Very well into the dawn of the fourth industrial revolution (industry 4.0), we hardly distinguish between what is artificial and what is natural (e.g. man-made virus and natural virus). Thus, the level of discombobulation among people, companies or countries is indeed unprecedented. The fact that industry 4.0 is explosively disrupting or retrofitting each and every industrial sector, makes industry 4.0 the famous buzzword amongst researchers today. However, the insight of industry 4.0 disruption in the industrial sectors remains ill-defined in both academic and non-academic literature. The present study aimed at identifying industry 4.0 neologisms, understanding the industry 4.0 disruption and illustrating the disruptive technologies convergence in the major industrial sectors. A total of 99 neologisms of industry 4.0 were identified. Industry 4.0 disruption in Education industry (Education 4.0), Energy industry (Energy 4.0), Agriculture industry (Agriculture 4.0), Healthcare industry (Healthcare 4.0), and Logistics industry (Logistics 4.0) are described. The convergence of 12 disruptive technologies including 3D printing, Artificial intelligence, Augmented reality, Big Data, Blockchain, Cloud computing, Drones, Internet of things, Nanotechnology, Robotics, Simulation and Synthetic biology in agriculture, healthcare and logistics industries are illustrated.

The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p < 0.045), Work with COVID patients - Traumatic stress (p < 0.001) and Total number of COVID patients per day – Traumatic stress (p < 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.

Objectives: This study aimed to analyze the awareness of local residents regarding healthcare projects and to suggest some ideas for the revision of local ones. Methods: To delve into the opinions of local residents, the author of this study created a questionnaire composed of eight questions on the general characteristics of the respondents, eight questions on satisfaction with health centers, 16 questions on the awareness of healthcare projects, and 22 questions on local healthcare. The survey was conducted for 409 residents who visited public centers in Gimcheon from 15 March to 14 April 2021. Results: Data analysis revealed the following: The proportion of local residents who use health centers was 39.1%, and those users visit health centers, on average, 3.92 times a year. Among healthcare projects, the project known by the highest proportion of people was vaccinations (84.5%), which was also the project that was most used (38.1%). Among healthcare projects needed in the with-COVID-19 age, respondents awarded the highest score to vaccinations (4.15 points on a five-point Likert scale) and the second highest score to infectious disease management (4.12). Conclusions: For healthcare projects, central and local governments should focus on activating vaccinations, solving the problem of medical accessibility through untact remote treatment and establishing national infectious disease-specializing hospitals and local infectious disease management based on such national hospitals.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

Contact tracing has become an indispensable tool of various extensive measures to control the spread of COVID-19 pandemic due to novel coronavirus. This essential tool helps to identify, isolate and quarantine the contacted persons of a COVID-19 patient. However, the existing contact tracing applications developed by various countries, health organizations to trace down the contacts after identifying a COVID-19 patient suffers from several security and privacy concerns. In this work, we have identified those security and privacy issues of several leading contact tracing applications and proposed a blockchain-based framework to overcome the major security and privacy challenges imposed by the applications. We have discussed the security and privacy measures that are achieved by the proposed framework to show the effectiveness against the security and privacy issues raised by the existing mobile contact tracing applications.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Based on the demographic shift and the related challenges resulting from the growing number of elderly and persons with chronic diseases, the idea of smart home that supports its inhabitants in the daily life, gains importance. The purpose of this paper was to examine in a prototypic Ambient Assisted Living environment if users after interaction with different health-supporting applications intend to use such in the future. Two experimental studies exemplary show possible applications of home-integrated technology that can support, assist and accompany the target group in different contexts, and examine to what extent participants are willing to future use such sophisticated technology at home. The results show that people in general, but especially the old and chronically ill ones are quite fascinated of health-supporting ambient technology and the majority intends to use such ambient assistance in the future (study I). Moreover, serious games for healthcare are shown as a hedonic use of technology in smart homes that have a great potential to retain or improve the physical health, mobility and the overall well-being of the inhabitants (study II). The article provides two examples of ambient technology to leverage the demographic change and presents important user factors for facilitating high user acceptance.

Blockchain technology enables a decentralized and distributed environment with no need for a central authority. Transactions are simultaneously secure and trustworthy due to the use of cryptographic principles. In recent years, blockchain technology has become very trendy and penetrated different domains, mostly due to the popularity of cryptocurrencies. One field where blockchain technology has tremendous potential is healthcare, due to the need for a more patient-centric approach to healthcare systems and to connect disparate systems and increase the accuracy of electronic healthcare records (EHRs). In this systematic review, an analysis of state-of-the-art blockchain research in the field of healthcare is conducted. The aim is to reveal the potential applications of the technology and to highlight the challenges and possible directions of blockchain research in healthcare. First, background information is discussed, followed by a description of the exact methodology used in this paper. Next, an analysis of the results is given, which includes a bibliometric overview, an analysis of gathered data and its properties, and the results of a literature quality assessment. Lastly, there is a discussion of the results from the analysis. The findings indicate that blockchain technology research in healthcare is increasing and it is mostly used for data sharing, managing health records and access control. Other scenarios are very rare. Most research is aimed at presenting novel structural designs in the form of frameworks, architectures or models. Findings also show that technical details about the used blockchain elements are not given in most of the analyzed publications and that most research does not present any prototype implementation or implementation details. Often even with a prototype implementation, no details about blockchain elements are given.

Background: Over 900,000 cases of COVID-19 and 23,000 deaths have been reported till 13 July in India. Preserving the limited healthcare workforce is part of the strategy against the pandemic. Mortality and morbidity data have a role in customising this strategy. At this time, there is no published study on COVID-related mortality among doctors or other healthcare workers in India. Methods: A multi-pronged search was made for all reported deaths linked with COVID-19 among doctors in India. Details of COVID-linked deaths reported by mainstream media and by multiple professional social media sources were collected, screened, verified and analysed. Violent deaths occurring in the setting of pandemic-related work were separately listed. Deaths from other diseases were excluded. Results: Among 108 COVID-linked deaths among doctors, there were four pandemic-related violent deaths including three road accidents and a suicide. Of the 104 non-violent deaths, 55.5% were below 60 years of age, while 29.6% and 21% were below the age of 50 and 40 respectively. The average age at death was 56.3 (range 22 - 96). Over half of the deaths occurred among general practitioners, while surgical specialties accounted for 27% of the mortality. The geographic distribution of deaths of doctors correlated with the reported number of COVID-19 patients in each state. The total number of COVID-related healthcare worker deaths was 136, out of which eight (5.8%) were violent, and occurred in young individuals with an average age of 27.8 years. Conclusions: The majority of the 104 COVID-related non-violent deaths among doctors (55.5%) occurred below the age of 60. The average at death was 56.6 years. The states with highest number of COVID-19 cases had greater number of doctor deaths. Violent deaths among young healthcare workers in the setting of the pandemic requires special attention.

Adeno-associated viruses (AAVs, genus dependoparvovirus) are promising gene therapy vectors. In strains AAV1-12, the capsid gene VP1 encodes a recently discovered protein, MAAP, in an overlapping frame. MAAP binds the cell membrane by an unknown mechanism. We discovered that MAAP is also encoded in bovine AAV and in porcine AAVs (which have shown promise for gene transfer into muscle tissues), in which it is probably translated from a non-canonical start codon. MAAP is predicted to be mostly disordered except for a predicted C-terminal, membrane-binding amphipathic α-helix. MAAP has a highly unusual composition. In particular, it lacks internal methionines, and is devoid of tyrosines in most strains. Unexpectedly, we discovered that the N-terminus of VP1 also lacks several amino acids. In all AAVs that encode MAAP, the first 200 aas of VP1 are devoid of internal methionines, probably owing to a selection against ATG codons that could prevent translation of MAAP and of capsid isoforms (VP2, VP3). The N-terminus of VP1 also lacks cysteines, likely to avoid the formation of disulfide bridges when it becomes exposed outside of the capsid during post-endocytic trafficking. Finally, the region common to VP1 and VP2 lacks tyrosine in the vast majority of AAVs that encode MAAP. Avoiding these "forbidden" aas in MAAP and VP1 when creating recombinant AAV capsids might increase the efficiency of capsid design. Conversely, the presence of "forbidden" aas in some rare strains probably indicates that they have unusual properties that could help us understand the viral cycle.

Reflection in healthcare education is an emergent topic with many studies and reviews being published. The purpose of the present review is to map the literature in this field by performing a systematic review of reviews (umbrella review) and to explore which definitions and models are currently in use, how reflection impacts on design, evaluation and assessment and future challenges. Nineteen reviews were identified that satisfied inclusion criteria. Emerging themes were: reflection is currently portrayed as self-reflection and critical reflection with the epistemology-of-practice notion not being as much as expected in tandem with the evidence-based-medicine paradigm modern science advocates. Reflective techniques were recognised in multiple settings (e.g. summative, formative, group vs individual etc.) and have been associated with learning but assessment remains a research topic with issues of validity, reliability and replicability. Future challenges involve the epistemology of reflection in healthcare education and how to practice and assess reflection without losing its theoretical background.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

In the context of the COVID-19 pandemic, countries around the world varied in the strength and timeliness of their responses. In Romania, specific challenges were faced with regards to managing the spread and limiting the impact of the disease, ranging from healthcare infrastructure to demographic and sociocultural aspects. As the country has a sizeable diaspora, major difficulties were faced when large numbers of individuals from highly affected areas returned to Romania. However, the fast implementation of control measures successfully averted a surge in the number of COVID-19 cases. This delayed the overburdening of an already challenged healthcare system during the initial phases of the epidemic. Furthermore, early control was facilitated by the exploitation of communication channels that penetrated all layers of society, from ordinary citizens to governmental authorities and high-ranking religious figures. The management of the COVID-19 crisis in Romania illustrates the importance of a fast initial response which takes into account the role played by sociocultural aspects in the context of an epidemic. As the challenges faced by Romania are not unique, these results could inform future public health strategies worldwide.

COVID-19 has affected 212 countries around the world, killing nearly 300,000 and infecting more than 4.4 million by May 14, 2020. Bangladesh, a South Asian low-middle-income economy, has experienced a demographic and epidemiological transition with rapid urbanization and a gradual increase in life expectancy. It is the seventh most populous country in the world and population of the country is expected to be nearly double by 2050. The increasing burden of communicable diseases in Bangladesh can be attributable to rapid urbanization and nearly 50% of all slum dwellers of the country live in Dhaka division. In 2017, National Rapid Response Team of IEDCR investigated 26 incidents of disease outbreak. The joint survey of the Power and Participation Research Centre and BRAC Institute of Governance and Development reveals that per capita daily income of urban slum and rural poor drops by 80% due to present countrywide shutdown enforced by the government to halt the spread of Covid-19. 40%-50% of these population took loans to meet the daily expenses. However, the country has just 127,000 hospital beds, 91,000 of them in government-run hospitals. Researchers say, the country’s economy is economy is losing BDT 33 billion every day from its service and agriculture sectors during the nationwide shutdown.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Background: Fluoride toothpaste (FT) has recently been included in the World Health Organization’s (WHO) Model List of Essential Medicines. Whereas it is essential for preventing dental caries, its current affordability around the globe remains unclear. This study aimed to analyse the affordability of FT in as many as possible countries worldwide. Methods: A standardized protocol was developed to collect country-specific information about the characteristics of the cheapest FT at a common point of purchase. 82 members of the WHO Global Oral Health Network of Chief Dental Officers (CDOs), directors of WHO Collaborative Centres and other oral health experts collected data using mobile phone technology. The Fluoride Toothpaste Affordability Ratio (FTAR) was calculated as the price associated with the recommended annual consumption of FT, relative to the daily wage of the lowest-paid unskilled government worker (FTAR >1 = unaffordable spending on fluoride toothpaste). The daily expenditure per capita of the poorest 15% of the income distrubition was used as the main proxy of the daily wage, using World Bank data. Alternatively, we used the daily minimum wage as a proxy of the daily wage. Stratified descriptive statistics were undertaken with respect to different World Bank Income Groups and WHO Regions. Results: There are significant discrepancies in the affordability of FT across 78 countries. FT was strongly affordable in high-income countries, relatively affordable in upper middle-income countries, and strongly unaffordable in lower middle-income and low-income countries. The affordability of FT across WHO Regions was dependent upon the economic mix of WHO Regions’ member states. Conclusion: FT is still unaffordable for many people, particularly in low-resource settings. Health policy members should develop better strategies to address and improve the universal affordability of FTs, for the incidence of dental caries to be reduced at a global level.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.

In service economy, scholars and practitioners focus on the development and the appliance of innovative services. The importance of service innovation is rising in many sectors and among different organizations. Several disciplines (e.g. marketing, management, operations research, etc.) focus on this innovation, a concept widely used, but with different definitions. In this paper, service innovation has been analyzed according to SD Logic and a service ecosystem perspective. Literature still call for a deeper understanding of how new or renewed resources’ combination affect the shaping of service ecosystems. To contribute to fill this gap, the study explores the practices that different actors, internal and external to a healthcare service ecosystem, enact to co-create value in novel ways that is service innovation. The paper is structured as follows. In the next section, the main academic contributions on service research have been reviewed, focusing on healthcare service innovation. Follows, the research method and the discussion of research findings. Finally, theoretical and managerial implications have been detailed and an agenda for future research suggested. The paper offers interesting insights to develop new or renewed practices that foster the reshaping and maintaining of a healthcare service ecosystem. Some recommendations are included to support managers in the development of service innovation strategies.

With an increasing demand for quality of care and lower costs, hospitals are looking for industry-based methods to improve efficiency in their processes. This study aims to reduce waste in a public hospital in Mexico by improving the medical supply process for the operating room. To this end, a lean healthcare (LH) implementation following the DMAIC approach (Define-Measure-Analyze-Improve-Control) is carried out. We analyze the value stream of the supply process, including main surgical procedures and their related medical supplies, and identify different causes of inefficiency, which are evaluated and controlled through different tools, including a value stream map, Kanban, and the 5S program. As a result, five types of waste were reduced. Over-processing requests were reduced by 15.3%, defective identification numbers were reduced by 46.5%, redundant processing was improved by 94.8%, near 2.8% of the unnecessary inventory was reduced, and transportation waste was reduced by up to 16.7%. Finally, the lead-time for the main supplies was reduced by 33 days. This work demonstrates that LH and DMAIC are effective in reducing waste and are highly conducive to improving sustainability in healthcare processes. Moreover, it provides practical insights for practitioners regarding the implementation of LH in public hospitals in developing countries.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

With Internet of Things (IoT) gaining presence throughout different industries a lot of new technologies have been introduced to support this undertaking. Implications on one such technology, wireless systems allowed for the use of different communication methods to achieve the goal of transferring data reliably, with more cost efficiency and over longer distances. Anywhere from a single house with only a few IoT devices such as a smart light bulb or a smart thermostat connected to the network, all the way to a complex system that can control power grids throughout countries, IoT has been becoming a necessity in everyday lives. This paper presents an overview of the devices, systems and wireless technologies used in different IoT architectures (Healthcare, Vehicular Networks, Mining, Learning, Energy, Smart Cities, Behaviors and Decision Making), their upbringings and challenges to this date and some foreseen in the future.

Background: The healthcare workers are exposed to dangerous pathogen agents during the outbreak of the new coronavirus COVID-19. To minimize the risk of becoming infected by this virus, healthcare workers need to wear the most appropriate personal protective equipment (PPE). Objective: The objective of this study was to analyze the guidelines that the World Health Organization (WHO) and the Centers for the Disease Control and Prevention (CDC) recommend for the rational use of EPP to protect healthcare workers against the novel coronavirus COVID-19.Methodology: To learn how to effectively protect healthcare workers against the COVID-19, a detailed analysis and comparison of the WHO and CDC guidelines related to the proper use of personal protection equipment (PPE) in different healthcare settings was carried out. Results: The results of this study based on an analysis of PPE recommended by the World Health Organization (WHO) and the Centers for the Disease Control and Prevention (CDC) indicated that the safety and protection of healthcare workers can be maximized if the guidelines suggested by these institutions are followed. In general, the WHO and CDC recommendations based on medical practices are similar, and depending on the healthcare activities and settings where the healthcare workers perform their work, suggest wearing medical/surgical facemasks, respirators, googles and face shields (eye protection), gloves, gowns and aprons. Conclusions: The protection and safety of the healthcare workers can be maximized during the outbreak of COVID-19 by following the WHO and CDC recommendations described in this study. The general guidelines offered by these institutions are similar and based on medical practices.

The radar sensor described realizes healthcare monitoring capable of detecting subject chest-wall movement caused by cardiopulmonary activities, and wirelessly estimating the respiration and heartbeat rates of the subject without attaching any devices to the body. No conventional Doppler only can capture Doppler signatures because of a lack of bandwidth information with noncontact sensors. In contrast, we take full advantages of impulse radio ultra-wideband (IR-UWB) radar to achieve low power consumption and convenient portability, with a flexible detection range and desirable accuracy. A noise reduction method based on improved ensemble empirical mode decomposition (EEMD) and a vital sign separation method based on continuous-wavelet transform (CWT) are proposed jointly to improve the signal-to-noise ratio (SNR) in order to acquire accurate respiration and heartbeat rates. This noncontact healthcare sensor system proves the commercial feasibility and considerable accessibility of using compact IR-UWB radar for emerging biomedical applications. Compared with traditional contact measurement devices, experimental results utilizing a 2.3 GHz bandwidth transceiver, demonstrate 100% similar results.

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

Infection control among patients is critical for diseases like COVID-19. The concentration of patients in a few facilities burdens healthcare providers and the healthcare system. This study examined the operations of an extended anteroom in a dedicated COVID-19 hospital. It presents issues to consider in the deployment and operation of an extended anteroom through discussions by expert working groups. The subjects covered included efficient space, staffing, equipment management, and education. The process involved wearing personal protective equipment (PPE; in this case, Level D), and if necessary, wearing additional powered air purification respirators (PAPR), after moving from the preparation room to the dressing room, and when entering the hospital through the entrance passage. When leaving the hospital, personnel used a mandatory exit-only passage; in the dressing room, they undressed, and then went outside, in this order. The efficient spatial composition of the anteroom facilitated entry and exit and the separation of contaminated areas and non-contaminated areas using colors and lines. It is necessary to develop operational guidelines for hospitals that treat infectious diseases and conduct research to improve care. The study indicated the need to develop educational programs and use educational simulations to address regionally spread infectious diseases

After conducting a detailed survey among the villagers of Pallissery and Karukutty, it was observed that in most of the villages the native people have to travel long distances for their basic health needs. Also most of the villagers lack knowledge regarding live health updates. At times, these problems have even resulted in death of many people including pregnant women and children. The objective of our research is to propose an integrated and easy to use Medical Kiosk that can be installed at various locations in rural areas. The Kiosk will provide an integrated environment for all medical related activities and would perform numerous functions like sending notifications regarding medical camps, mobile medical help, important dates for vaccinations, child care, insurance policies and provide other live medical updates to the villagers. It would also support the basic facilities for measurement of body parameters like height, weight, BMI, blood pressure, and heartbeat and also facilitate live consultation facilities with specialized doctors through video and voice chats.

When all countries are battling Covid-19 by adopting different policies, it could help address the issue of government response policy efficiency. This study examines the efficiency of government intervention policies in 19 countries, the efficiency of preventing the spread, and also the mortality caused by the virus. The policies are categorized based on the Oxford COVID-19 Government Response Tracker, which combines various indicators, including Containment and closure, Economic response, and Health systems. Given that the governments apply a top-down approach to design these policies, the current research evaluates the efficiency of policies based on the same approach. Here, two different models have been used to calculate the efficiency of policies. We designed a combined index in both models and applied Window DEA method to determine the output quantities in the efficiency ratio. The results of our study show that in both models, Japan, Finland and Thailand had the highest level of government response efficiency. The countries with the lowest government response efficiency were the United States, Spain, and Russia in the first model, and China, Italy, and Spain in the second.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs) include anti-mitotic agents (e.g auristatin and its derivatives) which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested to identify a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau) which binds specifically to tubulin and modulates the stability of microtubules thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g cancer and inflammatory cells) an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

In this ‘New Normal' post-COVID-19 modern world, people's health is becoming increasingly important to track. An advanced technology that uses sensory instruments to track and record critical parameters and communicates with others is the need of the time. It's difficult to keep track of all of the medical parameters and post-operative data of people with non-communicable diseases like diabetes and heart disease on a continuous basis. The system discussed here to be designed for patients who are confined to their homes, particularly when going out and being exposed to the outer world is prohibited. This paper proposed a groundbreaking health management system based on the Internet of Things (IoT) for accessing patient medical parameters in both local and remote areas. When a person's wellbeing becomes urgent, this initiative seeks to send an emergency alert to family members or loved ones. A cloud server records data from the patient's temperature sensor and pulse sensor; the data is analyzed using support vector machine algorithms to identify irregular conditions, and an emergency message is sent to the rest of the family via a mobile application, as well as a warning message to the nearest hospital.

The excited-state lifetimes of the anticoagulant drug warfarin (W) in water and in the absence and presence of methyl-β-cyclodextrins (Me-β-CD) were recorded using time-resolved fluorescence measurements. Selective excitation of the open and cyclic protonated isomers of W were acquired with laser emitting diodes (LED) producing 320 and 280 nm excitation pulses, respectively. Formation of the inclusion complex was checked by UV–visible absorption spectroscopy, and the values of binding constants (2.9 × 10³ M^–1 and 4.2 × 10² M^–1 for protonated and deprotonated forms, respectively) were extracted from the spectrophotometric data. Both absorption and time-resolved fluorescence results established that the interior of the macromolecular host binds preferentially the open protonated form, red shifts the maximum of its absorption of light at ~305 nm, extends its excited-state lifetime, and decreases its emission quantum yield (ФF). Collectively, sequestration of the open guest molecules decreases markedly their radiative rate constants (kr), likely due to formation of hydrogen-bonded complexes in both the ground and excited states. Due to lack of interactions, no change was observed in the excited-state lifetime of the cyclic form in the presence of Me-β-CD. The host also increases the excited-state lifetime and ФF of the drug deprotonated form (W¯). These later findings could be attributed to the increased rigidity inside the cavity of Me-β-CD. The pKa values extracted from the variations of the UV–visible absorption spectra of W versus the pH of aqueous solution showed that the open isomer is more acidic in both ground and excited states. The positive shifts in pKa values induced by three derivatives of cyclodextrins: HE-β-CD, Ac-β-CD, and Me-β-CD supported the preferential binding of these hosts to open isomers over cyclic.

Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.

Malaysia implemented a movement control order (MCO) to curb the spread of the SARS-CoV-2 virus in March 2020. Despite healthcare services remaining operational, rising COVID-19 infections and MCO restrictions have forced healthcare professionals to seek a compromise between service capacity and standard operating procedure compliance. A cross-sectional survey was conducted among public and private sector doctors, dentists and pharmacists to determine how lockdown measures impacted healthcare services. Responses from 413 doctors, 193 dentists, and 163 pharmacists were analysed. Pharmacy services remained mostly unaffected throughout the MCO. In contrast, operational capacities for surgical and dental services were severely affected during the MCO. All service sectors reported restricting patients or accompanying individuals at the workplace, reductions in staffing capacity, and shortened patient contact time at various degrees. Many pharmacy and medical participants reported supplying extended medication supplies to patients. Adoption of virtual healthcare services was generally poor. All private service sectors suffered financial losses ranging between 59 to 75%. Periodic assessments of the healthcare system throughout the pandemic are required to identify which patients have their treatment compromised so that healthcare managers and policy makers can plan and implement appropriate interventions that help alleviate pressure within the health system.

Implications of the novel usage adoption of the internet of things in various sectors of works and life are researched and documented at pace. This is related to the overall high rate at which new technologies are adopted in modern society. Healthcare is a vital aspect of everyday activities and as such overlaps with the increasingly important role played by use of the internet and associated technologies. The purpose of this review article is to draw attention to the potential social, ethical, legal and professional limitations to using IoT in the context of healthcare. The social and ethical aspects in particular, focus on IoT usage in care of the elderly with relevant case studies as reference.

This paper presents an effective heart disease prediction model through detecting the anomalies, also known as outliers, in healthcare data using the unsupervised K-means clustering algorithm. Most existing approaches for detecting anomalies are based on constructing profiles of normal instances. However, such techniques require an adequate number of normal profiles to justify those models. Our proposed model first evaluates an \textit{optimal} value of K using Silhouette method. Next, it intends to locate anomalies that are far from a certain threshold distance with respect to their clusters. Finally, the five most popular classification techniques such as K-Nearest Neighbor (KNN), Random Forest (RF), Support Vector Machines (SVM), Naive Bayes (NB), and Logistic Regression (LR) are applied to build the resultant prediction model. The effectiveness of the proposed methodology is justified using a benchmark dataset of heart disease.

Machine learning has become an increasingly ubiquitous technology, as big data continues to inform and influence everyday life and decision-making. Currently in healthcare, as well as in most other industries, the two most prevalent machine learning paradigms are supervised learning and transfer learning. Both practices rely on large-scale, manually annotated datasets to train increasingly complex models. However, the requirement of data to be manually labeled leaves an excess of unused, unlabeled data available in both public and private data repositories. Self-supervised learning (SSL) is a growing area of machine learning that has the ability to take advantage of unlabeled data. Contrary to other machine learning paradigms, SSL algorithms create artificial supervisory signals from unlabeled data and pretrain algorithms on these signals. The aim of this review is two-fold: firstly, we provide a formal definition of SSL, divide SSL algorithms into their four unique subsets, and review the state-of-the-art published in each of those subsets between the years of 2014-2020. Second, this work surveys recent SSL algorithms published in healthcare, in order to provide medical experts with a clearer picture of how they can integrate SSL into their research, with the objective of leveraging unlabeled data.

While it is not new that Nigeria is challenged by a huge infrastructure deficit, the COVID-19 pandemic has exposed the country’s comatose healthcare system. Given the country’s dwindling revenue, massive debt profile and the inability of the public-sector to efficiently manage public facilities in the country, this paper examines how the public-private partnership model of infrastructure procurement can be deployed as a solution for Nigeria’s healthcare crisis. In addition to the above, this paper takes a look at how a partnership with the private sector can aid Nigeria’s quest towards achieving healthcare-related Sustainable Development Goals. The paper also considers two healthcare-based projects as case studies to serve as lessons for future projects in the country. Among others, the paper recommends a holistic long-term solution for the country’s healthcare needs.

Progressive supranuclear palsy (PSP) is a sporadic parkinsonism tauopathy characterised by the deposition of aggregations of abnormal, hyperphosphorylated four-repeat tau (4R-tau). A revised clinical diagnostic criterion for PSP allows early presentations for the full spectrum of clinical phenotypes to be recognised enabling doctors to make a more accurate diagnosis. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT). Research into the biochemical and pathological pathways of tau is vital to improve the chances of developing an effective diagnostic biomarker to monitor tau pathogenesis. Neuroimaging biomarkers, such as tau PET ligands, are proving the most successful tool in providing a differential diagnosis between neurodegenerative disorders. There are currently no effective treatments for PSP, however tau-directed therapies in the last five years have rapidly advanced. Latest tau therapies are proposed to have disease-modifying effects by reducing toxic aggregations of tau through manipulating tau gene expression. After encouraging results from long awaited trials, additional funding is being injected into this field and with new results expected, this proves an exciting area for scientific discovery. This paper reviews advances in pathophysiology, diagnosis, biomarkers and disease-modifying therapeutic treatments for PSP.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

— Big Data analytics has come a long way since its inception. This field is growing day by day. With the advent of large handling capacity of computational analysis of modern computing systems as well as Internet of Things (IoT), this field has revolutionized the way we think about data. It has influenced the major domains such as healthcare, automobile, computing, climatology, and space communications. Of late, the health care sector has been largely influenced by this. This communication deals with the areas of healthcare where big data analytics has been largely influential. Encompassing the basics of Big Data Analytics (BDA) driven by IoT, the applications of it in healthcare sector are outlined, accompanied by future expectations. Additionally, it also presents a comprehensive analysis of recent application with special reference to Covid-19 in this sector.

The term dehumanisation refers to the ways in which a person is perceived to be less than human or treated as if they are less than human. It involves treating a person as if they are a child or infant, like an animal or non-living object, or as if they are dead, or any other way in which someone fails to be treated like a human being with an adult identity. Dehumanisation is widespread in dementia care; it is a major obstacle to person-centred care and has poor outcomes for people with dementia. This article proposes a new model of dehumanisation. The New Model presents a new way of describing dehumanisation that has been synthesised from current understanding about the phenomenon and reflects what is presently known about the subject. The model aims to summarise existing theories and models of dehumanisation and make dehumanisation theory accessible to students and trainees in healthcare. This article describes the new model, discusses existing models and theories in the literature, and explores the potential role of the new model in solutions for reducing dehumanisation in dementia care.

The burnout syndrome, which affects so many healthcare workers, has recently awakened wide interest due to the severe repercussions related to its appearance. Even though job factors are determinant to its development, not all individuals exposed to the same work conditions show burnout, which demonstrates the importance of individual variables such as personality. The purpose of this study was to determine personality characteristics of a sample of nursing professionals based on the Big Five model, and then, having determined the personality profiles, analyze the differences in burnout and engagement based on those profiles. The sample was made up of 1236 nurses. An ad hoc questionnaire was prepared to collect the sociodemographic data, and the Brief Burnout Questionnaire, the Utrecht Work Engagement Scale and the Big Five Inventory-10 were used. The results showed that the existence of burnout in this group of workers, is associated negatively with extraversion, agreeableness, conscientiousness and openness to experience, and positively with the neuroticism personality trait. These personality factors showed the opposite pattern with regard to engagement. Three different personality profiles were also found in nursing personnel, in which professionals who had a profile marked by strong neuroticism and low scores on the rest of the personality traits where those who were most affected by burnout.

Objective: The private healthcare providers (PHCP) are believed to improve access to healthcare services in Public-Private Mix (PPM) projects, as they are considered first point of contact for healthcare. The purpose of this study was to know the satisfaction level of TB patients. Design: A questionnaire-based, cross-sectional study was carried out during November and December 2017 for 572 under-treatment patients registered with PHCPs in the PPM project. Lot quality assurance sampling technique was used to randomly select 19 districts from sample frame of 75 districts. In each selected district, data collector retrieved TB register of 8 months (Jan – Aug 2017) and systematically selected patients by fixed periodic interval. SPSS (version 24.0) was used to analyze the data. Results: Study included 53% (n=301) of males and 47% (n=271) of females, with mean age of 38 years (SD, ±18). Almost half of the participants were illiterate (51%, n=289) and 64% (n=365) were non-earning members of the family. In practice, most of the participants visit private providers (71%, n=407), including private hospital/clinic (44%) and traditional practitioners (27%; n=153). 55% of participants visited the current doctor because of clinic’s proximity to residence. 82% of the participants (n=469) were satisfied with the TB care services and 85% (n=488) said that they would recommend this clinic to others. Conclusion: PHCPs are preferred providers for individuals, which is consistent with findings of other studies. Though they are satisfied with TB care and services, interventions should be introduced to reduce the financial burden on the patient. Partnering PHCP is a way forward to ensure universal health coverage, health system strengthening and better health outcomes of the population.

Purpose: The ongoing COVID-19 crisis has created the need for social distancing between medical staff and patients, therefore, healthcare robotics is increasingly important as regards infectious control. The purpose of this study was to design and fabricate a remote controlled transport robot that could provide an optimum technology base for developing countries, having dual functions of telepresence and delivery operations inside or outside buildings, is easy to assemble and also easily able to be cleaned using standard chemical agents.Methods: This machine was designed and fabricated to incorporate two main functions; delivery and telepresence. The robot consists of a base frame, DC motors for driving and steering systems, actuator motor for driving wheel elevation, Wi-Fi AP/Repeater, network camera, and a necessary a back-up power system.Results: This robot can be used both indoors and outdoors. It can carry loads of more than 80 kg. The machine can cross obstacles greater than 3 cm. It can be cleaned by disinfectant agents. An actuator motor can lift the driving wheels above the surface to prevent gear damage. Conclusion: This article demonstrates the concept of a healthcare telepresence and delivery robot that can provide distancing during the present COVID-19 crisis, using optimum technology for low and middle-income countries. In the future, the researcher should consider development of the delivery controls, combined with the telepresence system using the internet of things, to improve the navigation system, the manipulator system for supporting multi-floor transportation, and also other multi-functional purposes.

COVID-19 has been a major issue in most countries throughout the world with 213 countries being affected till date due to the disease. The pandemic has raised concerns over the healthcare facilities available in various countries and question the government decisions made during this period of outbreak. Despite having the best healthcare facilities several countries across Europe and America have found it difficult to contain the disease outbreak questioning the available solutions to contain an area. This paper focuses on presenting information on solutions available to control outbreaks in order to prevent another pandemic occurring in the future. The paper also highlights the strategies and plans implemented by various governments who have been successful in combatting the disease with minimum damage. By using available resources such as technology, scientific innovation and digitalized healthcare this paper focuses on providing solutions which are already available to be utilized in the right manner.

The burden of COVID-19 pandemic on health systems and the physical and mental health of healthcare workers (HCWs) has been substantial. This cross-sectional study aims to assess the effects of Covid-19 on the psychological wellbeing of mental health workers who provide care to a vulnerable patient population that have been particularly affected during this crisis. A total of 387 HCWs from across a large urban mental health service completed a self-administered questionnaire consisting of socio-demographic, lifestyle and work-based information and validated psychometric scales. Depression and anxiety were measured using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7) respectively, sleep problems with the Athens Insomnia Scale (AIS), burnout with the Maslach Burnout Inventory (MBI) and resilience with the Resilience Scale-14 (RS-14). Multivariable logistic regression analysis was performed to determine potential mediating factors. Prevalence of burnout was notable, with 52% recording moderate/severe in Emotional Exhaustion, 19.5% moderate/severe in Depersonalisation and 55.5% low/moderate Personal Accomplishment. Over half of all respondents (52%) experienced sleep problems; the presence of depressive symptoms was a significant predictor of insomnia. An increase in potentially harmful lifestyle changes, such as smoking, alcohol consumption and over-eating was also observed. However, high Resilience was reported by 70% of the sample and the importance of this is highlighted. Female gender was associated with increased levels of depression and emotional exhaustion while those with a history of mental health conditions were most at risk of affective symptoms, insomnia and burnout. Overall, our study revealed considerable levels of psychological distress and maladaptive coping strategies but also resilience and satisfaction with organizational support provided. Findings can inform tailored interventions in order to mitigate vulnerability and prevent long-term psychological sequelae.

Health information technology has been widely used in healthcare, which has contributed a huge amount of data. Health data has four characteristics: high volume; high velocity; high variety and high value. Thus, they can be leveraged to i) discover associations between genes, diseases and drugs to implement precision medicine; ii) predict diseases and identify their corresponding causal factors to prevent or control the diseases at an earlier time; iii) learn risk factors related to clinical outcomes (e.g., patients’ unplanned readmission), to improve care quality and reduce healthcare expenditure; and iv) discover care coordination patterns representing good practice in the implementation of collaborative patient-centered care. At the same time, there are major challenges existing in data-driven healthcare research, which include: i) inefficient health data exchanges across different sources; ii) learned knowledge is biased to specific institution; iii) inefficient strategies to evaluate plausibility of the learned patterns and v) incorrect interpretation and translation of the learned patterns. In this paper, we review various types of health data, discuss opportunities and challenges existing in the data-driven healthcare research, provide solutions to solve the challenges, and state the important role of the data-driven healthcare research in the establishment of smart healthcare system.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Background: Health Care Workers (HCWs) are at increased risk of acquiring and transmitting COVID-19 infection. Also, they present role models for communities with regards to attitudes towards COVID-19 vaccination. Hence, hesitancy of HCWs towards vaccination can crucially affect the efforts aiming to contain the pandemic. Previously published studies paid little attention to HCWs in Arab countries, which has a population of over 440 million. Objectives: to assess the rates of COVID-19 vaccine hesitancy in Arabic-speaking HCWs residing in and outside the Arab countries, and their perceived barriers towards vaccination. Methods: a cross-sectional study based on an online survey was conducted from 14-Jan 2021 to 29-Jan 2021, targeting Arabic-speaking HCWs from all around the world. Results: the survey recruited 5,708 eligible participants (55.6% males, 44.4% females, age 30.6±10 years) from 21 Arab countries (87.5%) and 54 other countries (12.5%). Our analysis shows a significant rate of vaccine hesitancy among Arabic-speaking HCWs residing in and outside Arab countries (25.8% and 32.8%, respectively). The highest rates of hesitancy were among participants from the west region of the Arab world (Egypt, Morocco, Tunisia, and Algeria). The most cited reasons for hesitancy were concerns about side effects and distrust in vaccine expedited production and healthcare policies. Factors associated with higher hesitancy included age of 30-59, previous or current suspected or confirmed COVID-19, female gender, not knowing the vaccine type authorized in the participant’s country, and not regularly receiving the influenza vaccine. Conclusion: this is the first large-scale, multinational, post-vaccine-availability study on COVID-19 vaccine hesitancy among HCWs. It reveals high rates of hesitancy among Arab-speaking HCWs. Unless addressed properly, this hesitancy can impede the efforts for achieving widespread vaccination and collective immunity.

The recent Zika virus (ZIKV) outbreak in Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies and Guillain-Barré syndrome. In responding to this global health outcry, unprecedented and world-wide efforts are taking place to study the ZIKV etiology. Much have been learned about this virus in the areas of epidemiology, clinical manifestation, viral sequences and protein structures, as well as effects of ZIKV infection on fetal brain development and microcephaly. However, the molecular mechanism underlying ZIKV-mediated neurologic disorders remains elusive. Some critical questions include: 1) what type of virologic changes has taken place that increased the viral virulence? 2) which ZIKV protein(s) is responsible for the enhanced viral pathogenicity? And 3) how the newly adapted and pathogenic ZIKV strains alter their interactions with host cells leading to neurologic disorders? The goal of this review is to explore the molecular insights into the ZIKV-host interactions with special focuses on host cell receptor usage for viral entry, host cellular and immune antiviral responses, ZIKV counteraction and ZIKV-induced cytopathic effects. Our hope with this literature review is to inspire additional studies focusing on molecular studies of ZIKV-host Interactions.

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, the lack of suitable in vitro models to study VZV latency have seriously hampered molecular studies of viral latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and have redefined our understanding of VZV latency and factors that initiate reactivation. Together, these findings pave the way for a new era of research that may finally unravel the precise molecular mechanisms that govern latency. In this review, we will summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

Technology advancements are evident in the healthcare field; numerous new opportunities and applications have emerged during the last years based on embedded intelligence and related to real-time diagnosis of medical issues, tele-care and telemedicine, remote monitoring of patients, computer-assisted “smart” transportation in case of emergencies, as well as new types of remotely controlled surgical operations. This paper aims to provide an overview of the application of embedded intelligence in the field of healthcare; it gathers the main critical requirements, related technologies and research advancements up to date, and it presents the most important challenges that are yet to be faced. The main focus is given in the development and optimization of Body Area Networks (BANs) based on advanced embedded sensing devices, the optimization of smart gateways in such networks, and the provision of holistic scalable and secure solutions in the healthcare domain. In addition, the paper presents two principal use cases that stem from the combination of novel information and communication technologies with classic healthcare practices, explaining the functional and non-functional requirements, as well as the mixed criticality characteristics of the associated systems.

The novel coronavirus pneumonia epidemic is still raging around the world. Therefore, during the period of a global pandemic, maintaining the normal circulation of medicine and health fields is the key to fight against the epidemic. This paper based on relevant data such as the export volume of cross-border e-commerce in Hangzhou, China from 2015 to 2019, the article uses system dynamics modeling to explore the impact of overseas warehouse services on cross-border e-commerce export transactions. Studies have shown that the introduction of overseas warehouses has significantly improved customer satisfaction and improved the quality of cross-border logistics services, which has a positive impact on cross-border e-commerce export transactions. Through sensitivity analysis, it can be seen that under the same conditions, the efficiency of customs clearance has the greatest impact on overseas warehouse services. Therefore, when allocating various investments in overseas warehouses, you can favor the customs clearance process to enhance the competitiveness of the cross-border e-commerce market and provide a feasible experience for healthcare supplies export from cross-border e-commerce.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

WHO was informed on 31 December 2019 of cases of unknown cause pneumonia in Wuhan City, China. On 7 January 2020 Chinese authorities reported a novel coronavirus as the cause and was temporarily labeled "2019-nCoV." Coronaviruses (CoV) are a wide family of viruses which cause diseases ranging from common cold to more serious illnesses. A novel coronavirus (nCoV) is a new strain not previously found in humans. Countries around the globe have stepped up their surveillance to quickly detect any new 2019-nCoV cases. Blockchain is developing into a safe and efficient network for secure data sharing in applications such as the financial industry, operations management, food industry, energy market, the Internet of Things and healthcare. In this paper, we are using blockchain technology as a mean to share authentic data, tracking of relevant information and help speed up the treatment process. At the same time it will preserve person’s identity. Timely deployment and suitable implementation of the proposed model have the opportunity to curb COVID-19 transmissions and associated mortality, especially in environments with inadequate access to testing facilities. This work will also facilitate in the treatment of other infectious diseases. Smart contract have been designed and implemented using the ethereum blockchain platform which has been presented in this paper. This work would facilitate multiple stakeholders who are involved within the medical system to curb the transmission of this disease.

The Internet of Things (IoT) has a growing presence in society's daily lives. These lightweight devices can be easily deployed and maintained, enabling extensive adoption in different environments. Furthermore, one of the most promising areas for using IoT devices is healthcare, comprising devices referred to as the Internet of Medical Things (IoMT). Several examples of healthcare services are supported by IoMT devices, e.g., continuous health monitoring. Conversely, there is an increasing concern with the cybersecurity aspects of these devices, and several attacks against IoT infrastructures have been launched in the past few years. These cybersecurity concerns also apply to healthcare applications, where the tradeoff between the benefits and security of IoMT devices must be observed. Given the complexity and amount of data IoMT network traffic generates, advanced methods become especially useful in these environments. Although Machine Learning (ML) brings various techniques and solutions to improve cyberattack detection, prevention, and mitigation, essential features are not addressed in the current state-of-the-art benchmark dataset contributions. Thereupon, the main goal of this research is to propose a realistic benchmark dataset to enable the development and evaluation of IoMT security solutions. In order to accomplish this, 18 attacks were executed against an IoMT testbed composed of 40 IoMT devices (25 real devices and 15 simulated devices), considering the plurality of protocols used in healthcare (e.g., Wi-Fi, MQTT, and Bluetooth). These attacks are categorized into five classes: DDoS, DoS, Recon, MQTT, and spoofing. This effort aims to establish a baseline complementary to the state-of-the-art contributions. The outcome supports researchers in investigating and developing new solutions to make healthcare systems more secure using different mechanisms (e.g., machine learning - ML). This research goes beyond merely conducting attacks on IoMT devices. We also attempt to capture the lifecycle of these devices in different vital phases, from the moment they join the network until they leave, which is called profiling. Profiling allows the different classifiers to identify anomalies of each device individually in the healthcare network. The CICIoMT2024 dataset has been published on CIC's dataset page, making it available for other researchers to use.

Artificial Intelligence (AI) refers to the simulation of human intelligence in machines, using machine learning, deep learning and neural networks. AI enables machines to learn from experience and perform human-like tasks. The field of AI research has been developing fast over the past five to ten years, due to the rise of ‘big data’ and increasing computing power. In the medical area, AI can be used to improve diagnosis, prognosis, treatment, surgery, drug discovery, or for other applications. Therefore, both academia and industry are investing a lot in AI. This review investigates the biomedical literature (in the PubMed and Embase databases) by looking at bibliographical data, observing trends over time and occurrences of keywords. Some observations are made: AI has been growing exponentially over the past few years; it is used mostly for diagnosis; COVID-19 is already in the top-5 of diseases studied using AI; the United States, China, United Kingdom, South Korea and Canada are publishing the most articles in AI research; MIT is the world’s leading university in AI research; and convolutional neural networks are by far the most popular deep learning algorithms at this moment. These trends could be studied in more detail, by studying more literature databases or by including patent databases. More advanced analyses could be used to predict in which direction AI will develop over the coming years. The expectation is that AI will keep on growing, in spite of stricter privacy laws, more need for standardization, bias in the data, and the need for building trust.

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.

A significant attention has been made to the accurate detection of diabetes which is a big challenge for the research community to develop a diagnosis system to detect diabetes in a successful way in the IoT e-healthcare environment. Internet of Things (IOT) has emerging role in healthcare services which delivers a system to analyze the medical data for diagnosis of diseases applied data mining methods. The existing diagnosis systems have some drawbacks, such as high computation time, and low prediction accuracy. To handle these issues, we have proposed a IOT based diagnosis system using machine learning methods, such as preprocessing of data, feature selection, and classification for the detection of diabetes disease in e- healthcare environment. Model validation and performance evaluation metrics have been used to check the validity of the proposed system. We have proposed a filter method based on the Decision Tree (Iterative Dichotomiser 3) algorithm for highly important feature selection. Two ensemble learning Decision Tree algorithms, such as Ada Boost and Random Forest are also used for feature selection and compared the classifier performance with wrapper based feature selection algorithms also. Machine learning classifier Decision Tree has been used for the classification of healthy and diabetic subjects. The experimental results show that the Decision Tree algorithm based on selected features improves the classification performance of the predictive model and achieved optimal accuracy. Additionally, the proposed system performance is high as compared to the previous state-of-the-art methods. High performance of the proposed method is due to the different combinations of selected features set and GL, DPF, and BMI are more significantly important features in the dataset for prediction of diabetes disease. Furthermore, the experimental results statistical analysis demonstrated that the proposed method would be effectively detected diabetes disease and can easily be deployed in IOT wireless sensor technologies based e-healthcare environment.

Several factors enhance the possibility of vertical HIV transmission in the pediatric population. Unfortunately, the data of the prevalence of HIV and associated risk factors in these populations remain limited in Rwanda. The study aimed to assess HIV prevalence and risk factors for infants born to mothers on ARV treatment at CHUB/Rwanda. MethodsA cross-sectional study was carried out on infants who were born to mothers under ARV treatment at CHUB. The associated risk factors were retrospectively assessed using prevention vertical HIV transmission records, and Dried Blood spots (DBS) were prospectively tested using Polymerase Chain Reaction (PCR). Data were analyzed by logistic regression. Ethical clearance (Ref: CMHS/IRB/198/2017) was issued by University of Rwanda to fulfill research ethical consideration.ResultsAmong 185(100%) infants born to HIV-positive mothers under ARV treatment, 5(2.7%) were HIV positive. The most associated risk factors were increased to over 1log copies/ml mother’s viral load (OR 9.3, 95% CI 1.01-85.45, P= 0.04) and mother’s CD4 count lower than 350 cells/µl (OR 6.4, 95% CI 1.03-40.06, P=0.04). The factors found to reduce the rate of vertical transmission of HIV were health facility as a delivery place (P=0.03), exclusive breastfeeding for 6 months (P= 0.006), and attending the antenatal care (P=0.01) while feeding children and vaginal delivery were associated risks but not statistically significant.ConclusionThe current study supports that the more mothers’ viral load and CD4 count decrease, so does the risk of HIV to their infants. A fact which indicates that both prevalence and risk factors remain an alarming issue. Much effort and multi-disciplinary approach are highly recommended.

Human Activity Recognition (HAR) is a process to automatically detect human activities based on stream data generated from various sensors, including inertial sensors, physiological sensors, location sensors, cameras, time, and many others. Unsupervised contrastive learning has been excellent, while the contrastive loss mechanism is less studied. In this paper, we provide a temperature (τ) variance study affecting the loss of SimCLR model and ultimately full HAR evaluation results. We focus on understanding the implications of unsupervised contrastive loss in context of HAR data. In this work, also regulation of the temperature(τ) coefficient is incorporated for improving the HAR feature qualities and overall performance for downstream tasks in healthcare setting. Performance boost of 1.3% is observed in experimentation.

Tinnitus is a complex and heterogeneous psycho-physiological disorder responsible for causing a phantom ringing or buzzing sound albeit the absence of an external sound source. It has a direct influence on affecting the quality of life of its sufferers. Despite being around for a while, there hasn’t been a cure for tinnitus, and the usual course of action for its treatment involves use of tinnitus retaining and sound therapy, or Cognitive Behavioral Therapy (CBT). One positive aspect about these therapies is that they can be administered face-to-face as well as delivered via internet or smartphone. Smartphones are especially helpful as they are highly personalized devices, and offer a well-established ecosystem of apps, accessible via respective marketplaces of differing mobile platforms. Note that current therapeutic treatments such as CBT have shown to be effective in suppressing the tinnitus symptoms when administered face-to-face, their effectiveness when being delivered using smartphones is not known so far. A quick search on the prominent market places of popular mobile platforms (Android and iOS) yielded roughly 250 smartphone apps offering tinnitus-related therapies and tinnitus management. As this number is expected to steadily increase due to high interest in smartphone app development, a contemporary review of such apps is crucial. In this paper, we aim to review scientific studies validating the smartphone apps, particularly to test their effectiveness in tinnitus management and treatment. We use the PRISMA guidelines for systematic identification of studies on major scientific literature sources and delineate the outcomes of identified studies.

Very little is known about laboratory confirmed blood stream infections (LCBIs) in neonatal intensive care units (NICUs) in resource-limited settings. The aim of this cohort study was to determine the incidence, risk factors, and causative agents of LCBIs in a level-2 NICU in India. The diagnosis of LCBIs was established using the Centre for Disease Control, USA criteria. A predesigned questionnaire containing risk factors associated with LCBIs was filled-in. A total of 150 neonates (43% preterm) were included in the study. The overall incidence of LCBIs was 31%. The independent risk factors for LCBIs were: preterm neonates (relative risk (RR) 2.23), duration of NICU stay more than 14 days (RR 1.75), chorioamnionitis in the mother (RR 3.18), premature rupture of membrane in mothers (RR 2.32), neonate born through meconium-stained amniotic fluid (RR 2.32), malpresentation (RR 3.05), endotracheal intubation (RR 3.41), umbilical catheterization (RR 4.18), and ventilator-associated pneumonia (RR 3.17). The initiation of minimal enteral nutrition was protective from LCBIs (RR 0.22). The predominant causative organisms were gram-negative pathogens (58%). The results of the present study can be used to design antibiotic interventions to reduce LCBIs in resource-limited settings.

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

We performed an epi and molecular characterization of two healthcare workers MPXV occupational infection. Five days after the sampling collection, nurses developed typical MPXV infection symptoms. Infection was confirmed by qPCR and whole genome sequencing. The most likely transmission route was through contact with fomites in the patient belonging/house.

Background: Disability and caste are two different forms of oppression, however Dalits and people with disabilities commonly face similar types of marginalities. Dalit women with disabilities may experience double discrimination because of the intersectionality of disability and caste. This study examines whether the disability and caste identity of women together affects and compounds the utilization of maternal healthcare services. Methods: A cross-sectional survey was conducted using a semi-structured questionnaire among a total of 354 Dalit and non-Dalit women, with and without a disability aged between 15 – 49 years. Maternal healthcare service utilization was assessed by Ante-Natal Care (ANC), health facility (HF) delivery, and Post-Natal Care (PNC) during the last pregnancy. Logistic regression was performed to detect the predictors of service utilization and identify whether disability and caste were associated with service utilization. First, disability and caste were fitted separately in models. Secondly, the intersectionality of disability and caste was tested by the inclusion of disability*caste interaction term. Finally, the confounding effect of socio-demographic factors was investigated. Results: Out of surveyed women, 73% had 4+ ANC visits, 65% had HF delivery and 29% had a PNC visit during their last pregnancy. Women with a disability had lower odds of HF delivery (OR 0.50, CI 0.30 – 0.84) and PNC (OR 0.47, CI 0.25 – 0.88) than women without a disability. Adjustment for women’s age and household wealth explained associations in HF delivery by women with disabilities. There was no association between caste and service utilization. Disability overrode caste and there was no other evidence of effect modification by women’s caste status in the utilization. However, a weak interaction effect in the utilization of ANC services was found in the caste group by their education (OR 0.19, 95% CI 0.05 – 0.74). Conclusions: Disabled women – whether Dalit or non-Dalit - had lower rates of utilizing all maternal healthcare services than non-disabled women. However, Dalit women with disabilities were more likely to receive PNC than non-Dalit women with disabilities. Increasing equity in maternal healthcare service utilization requires that traditional approaches to service development and program intervention to be re-examined and more nuanced interventions considered to ensure improved access and outcome among all vulnerable groups.

Background: Simulation plays a crucial role in health studies, as it helps medical students apply their theoretical knowledge in real-life situations. Moulage is one of the techniques that helps in making simulation more realistic or high-fidelity. It uses special effects to emulate wounds for a better understanding of what the wound is like visually. Still, moulage is expensive, time-consuming, resource-intensive, and requires the training of staff, which is why we need to find low-cost substitutes for moulage materials. Method: When searching the database “PubMed” for the terms “Low-cost and Medical moulage”, we retrieved 222 studies, out of which when excluding results not related to low-cost, we obtained 62 studies, from which when removing studies that do not contain information regarding moulage, we found two papers, after referring to citations and cited articles of those papers, we ended up with six studies. Based on the selected articles and additional articles sourced from their reference list, a total of 11 studies were included in the review. Results: We understand that moulage is a technique that helps make simulations come alive, but the resources required to use it are at times, expensive, which is why we need to find methods to do low-cost moulage, and many studies address that it can be as simple as using homemade ingredients. Students from a previous study have talked about their opinions regarding the realistic component of moulage and whether if it is any different from other moulages. Most of the students agreed that the moulage ranked well in face and content validity. However, further innovations must be introduced in the field to be widely spread and lead to newer opportunities. Conclusion: Although the research done under moulage is limited, it is accepted that moulage is helpful for simulation-based studies and that low-cost moulage can help make medical studies a better experience for students studying it. Students have a favorable opinion on the realistic aspect of the low-cost moulage applied to them. Newer methods can be introduced to moulage, and it can be implemented in low-income countries.

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

Recent reports have it that over 85\% of data breaches are still caused by the human element, of which healthcare is one of the suitable organizations mostly targeted by cybercriminals. The work of healthcare staff is often associated with high workloads, high emergency cases, and a broad range of psychological, social, and cultural factors. The significance of these factors could undermine conscious care information security (IS) practice leading to serious violations. This study comprehensively examined the correlation between the psycho-social-cultural factors, work factors with IS and privacy behaviour in a hospital that has fully adopted electronic health records (EHR) management system. The findings are to facilitate the decision-making process towards improving the cyber-security practice in healthcare. A quantitative approach was adopted where we collected responses from 212 healthcare staff through an online questionnaire survey. A broad range of constructs was selected from psychological, social, cultural perception and work factors based on earlier review work. These were therefore related to some security practices, to assess the IS knowledge, attitude and behaviour gaps among healthcare staff in a comprehensive way. From the study, IS self-reported conscious care behaviour (ISCCB) risk was relatively higher as compared to information security knowledge (ISK) risks and information security attitude (ISA) risk. Furthermore, the study revealed that work emergency has a positive correlation with ISCCB (r=1.95, p-value =0.001) risk. Conscientiousness also had positive correlation with ISCCB risk (r=0.157, p-value=0.05) however agreeableness negatively correlated with ISK risk (r=-0.166, p-value =0.05), and ISA risk (r=-0.140, p-value =0.05). Based on these findings, intrinsic and extrinsic motivation methods combined with cutting-edge technologies can be explored to discourage IS risks behaviours while enhancing conscious care security practice.

Blackcurrant leaf chlorosis associated virus (BCLCaV) was detected recently by next-generation sequencing (NGS) and proposed as a new and distinct species in the genus Idaeovirus. Genomic components of BCLCaV that were detected and confirmed include: 1) RNA-1 that is monocistronic and encodes the replicase complex; 2) a bicistronic RNA-2 that encodes a movement protein (MP) and the coat protein (CP) of the virus, with open reading frames (ORF) that overlap by a single adenine (A) nucleotide (nt) representing the third position of an opal stop codon of the MP ORF2a and the first position of the start codon of the CP ORF2b; 3) a subgenomic form of RNA-2 (RNA-3) that contains ORF2b; and 4) a concatenated form of RNA-2 that consists of a complementary and inverted RNA-3 conjoined to the full-length RNA-2. Analysis of NGS-derived paired-end reads revealed the existence of bridge reads encompassing the 3’-terminus and 5’-terminus of RNA-2 or RNA-3 of BCLCaV. The full RNA-2 or RNA-3 could be amplified using outward facing or abutting primers; also RNA-2/RNA-3 could be detected even after three consecutive RNase R enzyme treatments with denaturation at 95 ^oC preceding each digestion. Evidence was obtained indicating that there are circular forms of BCLCaV RNA-2 and RNA-3.

The rise in the volume, variety and complexity of data in healthcare has made it as a fertile-bed for Artificial intelligence (AI) and Machine Learning (ML). Several types of AI are already being employed by healthcare providers and life sciences companies. The review summarises a classical machine learning cycle, different machine learning algorithms; different data analytical approaches and successful implementation in haematology. Although there are many instances where AI has been found to be great tool that can augment the clinician’s ability to provide better health outcomes, implementation factors need to be put in place to ascertain large-scale acceptance and popularity.

Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.

With the availability of wearable health monitoring sensor modules like 3-Lead Electrocardiogram (ECG), Pulse Oximeter (SpO2), Galvanic Skin Response (GSR), Hall effect sensor (for measuring Respiratory Rate), Blood Pressure and Temperature measuring and sensing elements, it has now become possible to device a composite health status monitoring kit that can measure vital signs and other physiological parameters pertaining to human health in real time. Traditionally, the physiological parameters along with vital signs related examination was possible only in a hospitalized or ambulatory environment, however due to advances in sensing and embedded system technology and miniaturization of data acquisition and processing elements health monitoring has become possible even when individuals remain engaged in their day to day activities at the convenience of space and location. The patients or individuals subject to monitoring may suffer from a traumatic experience due to their medical condition and may need emergent incidence response and the critical care team may have to prepare for the treatment only after the patient arrives, which often is too late, as in case of cardiac arrests or severe injuries. The research focused on real-time health status monitoring and trauma scoring using standard physiological parameters along with standard telemetry protocols to make the critical care team aware of an emergent situation and prepare for a medical emergency. Vital signs and physiological parameters (heart rate, temperature, respiratory rate, and blood pressure, SpO2) were measured in real time from human subjects non-invasively. In order to enable monitoring of the patients engaged in day to day activities, errors due to the motion were removed using stationary wavelet transform correction (correlation coefficient of 0.9 after correction) and signals from various sensors were denoised, filtered and were encoded in a format suitable for further data analysis. A composite sensor kit capable of monitoring vital signs and physiological parameters can be very useful in incident response when an individual undergoes a traumatic experience related to stroke, cardiac arrest, fits or even injury, as along with monitoring information the kit can calculate scores related to trauma like the Injury Severity Score (ISS), National Early Warning Signs (NEWS), Revised Trauma Score (RTS). Trauma Injury Severity Score (TRISS), Probability of Survival (Ps) score. An open access database of vital signs and physiological parameters from Physionet, MIMIC 2 Numerics (mimicdb/numerics) database was used to calculate NEWS and RTS and to generate correlation and regression models using the vital signs/physiological parameters for a clinical class of patients with respiratory failure and admitted to Intensive Care Unit (ICU). NEWS and RTS scores showed no significant correlation (r = 0.25, p<0.001) amongst themselves, however together NEWS and RTS showed significant correlation with Ps (blunt) (r = 0.70, p<0.001). RTS and Ps (blunt) scores showed some correlation (r = 0.63, p<0.001) and NEWS score showed significant correlation (r = 0.79, p<0.001) with Ps (blunt) scores. Furthermore, since individuals have to be monitored regardless of location, these kits have to have a built-in capability to locate the individual so that the incident response team can locate the individual based on Global Positioning System coordinates (GPS). A Quantum GIS (Geographical Information System) application using real-time GPS coordinates (OpenStreetMap coordinates) was used to calculate the shortest path using QGIS Network Analysis tool to demonstrate the calculation of shortest path and direction to locate the nearest service provider in shortest time. Along with locating the nearest healthcare service provider, it would help if the critical care team could be made aware of the physiological parameters and trauma scores using standard protocols accepted across the globe. The physiological parameters from the sensors along with the calculated trauma scores were encoded according to a standard Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) coding system and International Code of Diseases (ICD) codes and the trauma information was logged to Electronic Health Records (EHR) using Fast Health Interoperability Resources (FHIR) servers. FHIR servers provided interoperable web services to log the event information in real time. It could be concluded that analytical models trained on existing datasets can help in analyzing a traumatic experience or an injury and the information can be logged using a standard telemetry protocol as a telemedicine initiative. These scores enable the healthcare service providers to estimate the extent of trauma and prepare for medical emergency procedures and find applications in general and military healthcare.

This study presents three forms of interdisciplinary expertise in the healthcare design context to approach a particular multifaceted problem around the current healthcare for older adult patients with chronic low-back pain (LBP). Using an interdisciplinary co-design framework, first, our design approach performs the role of an initiator to define the problem by exploring the current context of healthcare. Second, it facilitates the experiences of experts and patients to reach the roots of the problem by functioning as a mediator. Third, our approach fulfills the primary role of healthcare design in producing new meanings considering the principles of patient-centeredness. These roles significantly contributed to the design of healthcare innovations. Our framework transformed the distributed disciplinary knowledge developed while tackling the multifaceted problem into new forms of expertise for collaboration in healthcare innovation.

The history of health records (later also called medical records), including ones regarding individual patients, is thousands of years old. It finds it roots in the first ancient civilisations. Up until the 19^th century the records’ purpose was mainly an educational one. In the 19^th and 20^th century they started becoming significant in other roles as well, including those not strictly limited to medicine. In particular, to account for medical procedures, insurance proceeds or legal action. Currently we are living in a revolutionary era when it comes to health records, in which their character has changed from a “paper-based” to an electronic one. This paper presents the development of health records from the ancient to modern times, mainly in Europe and North America. Other cultures and civilisations, including China and India, are not discussed. An analysis of available sources was conducted, inter alia digital versions of manuscripts up to hundreds of years old. The analysis was based on PubMed and Google Scholar (several key words, all the available sources). Sources published in non-international languages (e.g. Dutch) were also investigated. Overall, approximately 600 articles were analysed, 158 of which were used and cited in this paper. The conclusions drawn from the analysis are as follows: (1) Health records, priorly used mostly for educational purposes, for about 100 years now have acquired a fully formal status. (2) We are currently facing the most revolutionary changes regarding the transformation of paper-based records into electronic ones. (3) The consequences of this process include systematic applications of solutions within the area of e-health, which allow us to make medical services more flexible, improve the health of individual patients and entire populations and potentially limit expenditure. (4) In the light of the ongoing COVID-19 pandemic, introducing electronic health records could be beneficial in terms of limiting the potential sources of contamination (physical copies of health records), saving time and resources, and improving the network of communication between medical centres.

Background: Healthcare attention is sometimes considered purely technical, but communication has proven to be closely related to clinical results and patient satisfaction. Therefore, evaluation of communication in the scope of healthcare is a priority. The purpose of this study was to validate and adapt, if necessary, the Spanish version of the Communication Styles Inventory (CSI) in a sample of nursing professionals. (2) Methods: The sample was made up of 2313 nursing professionals selected at random from various medical centers in Spain, and is therefore a sample actively employed at the time data were acquired. We started out from the Communication Style Inventory, a questionnaire for evaluating the predominance of certain individual communication behaviors on six scales (expressiveness, preciseness, verbal aggressiveness, questioningness, emotionality and impression manipulativeness). (3) Results: Confirmatory Factor Analysis of the model proposed showed god fit indices. The reliability of the model shown by the Cronbach’s alpha of α=.81 was adequate, and so was single-level and aggregate consistency. Finally, in the analysis of variance by type of contract, configural, metric and scalar invariance was acceptable, but not strict invariance. (4) Conclusions: This instrument progresses in measuring non-technical attributes, such as communication styles, in nursing personnel.

Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed-Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They are invisible to antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation, and “educate” (i.e., reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies, targeting not only tumor cells but also the tumor microenvironment, are being developed. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become protective or immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.

Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

An artificial intelligence (AI)-based conversational large language model (LLM) was launched in November 2022 namely, “ChatGPT”. Despite the wide array of potential applications of LLMs in healthcare education, research and practice, several valid concerns were raised. The current systematic review aimed to investigate the possible utility of ChatGPT and to highlight its limitations in healthcare education, research and practice. Using the PRIMSA guidelines, a systematic search was conducted to retrieve English records in PubMed/MEDLINE and Google Scholar under the term “ChatGPT”. Eligibility criteria included the published research or preprints of any type that discussed ChatGPT in the context of healthcare education, research and practice. A total of 280 records were identified, and following full screening, a total of 60 records were eligible for inclusion. Benefits/applications of ChatGPT were cited in 51/60 (85.0%) records with the most common being the utility in scientific writing followed by benefits in healthcare research (efficient analysis of massive datasets, code generation and rapid concise literature reviews besides utility in drug discovery and development). Benefits in healthcare practice included cost saving, documentation, personalized medicine and improved health literacy. Concerns/possible risks of ChatGPT use were expressed in 58/60 (96.7%) records with the most common being the ethical issues including the risk of bias, plagiarism, copyright issues, transparency issues, legal issues, lack of originality, incorrect responses, limited knowledge, and inaccurate citations. Despite the promising applications of ChatGPT which can result in paradigm shifts in healthcare education, research and practice, the embrace of this application should be done with extreme caution. Specific applications of ChatGPT in health education include the promising utility in personalized learning tools and shift towards more focus on critical thinking and problem-based learning. In healthcare practice, ChatGPT can be valuable for streamlining the workflow and refining personalized medicine. Saving time for the focus on experimental design and enhancing research equity and versatility are the benefits in scientific research. Regarding authorship in scientific articles, as it currently stands, ChatGPT does not qualify to be listed as an author unless the ICJME/COPE guidelines are revised and amended. An initiative involving all stakeholders involved in healthcare education, research and practice is urgently needed to set a code of ethics and conduct on the responsible practices involving ChatGPT among other LLMs.

Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in unintended damage to the microbiome and an epidemic of chronic disorders [e.g., noncommunicable diseases and conditions (NCDs)]. Along with NCDs came loss of colonization re-sistance, increased susceptibility to infectious diseases, and increasing multimorbidity and polypharmacy over the life course. To move toward sustainable healthcare, the human micro-biome needs to be front and center. This paper presents microbiome-human physiology from the view of systems biology regulation. It also details the ongoing NCD epidemic including the role of existing drugs and other factors that damage the human microbiome. Examples are provided for two entryway NCDs, asthma and obesity, regarding their extensive network of comorbid NCDs. Finally, the challenges of ensuring safety for the microbiome are detailed. Under Microbiome First Medicine and considering the importance of keystone bacteria and critical windows of development, changes in even a few microbiota-prioritized medical decisions could make a significant difference in health across the life course.

The tribal belt of Pakistan-the Pak-Afghan border region is famous for its unique culture, ethnography and wild food plants and traditional knowledge. People of these regions gather wild plants for number of purposes including plants or plant parts for direct use, use it in the traditional cuisines and selling in local markets. However, there is huge lack of documentation of food system particularly the Wild Food Plants (WFPs). In current study we have focused on the uses and contributions of the WFPs in the tribal traditional food system. The ethnobotanical data were gathered through questionnaire surveys with Eighty-four informants 69 men and 15 women belonging to 21 different villages. We documented Sixty-three WFP species belonging to 34 botanical families, of which 27 were used as vegetables, 24 as fruits, 6 in different kinds of chutneys (starters) formation and six as fresh food species. Fruits were the mostly used part (40%) followed by leaves (24%), aerial parts (24%), seeds (7%), stem (3%), legume (2%) and young inflorescence (1%). Use of Carthamus oxycanthus & Pinus roxburghii seeds and Marsillea quadrifolia leaves were the novel reports for the gastronomy of Pakistan. The results elucidate that WFPs have a significant contribution in the Tribal Food Systems. Tribal people use WFPs not only due to their nutritional importance but also as a cultural practice - an inseparable component of the tribal communities. This important traditional Knowledge about the consumption of WFPs has been eroding with an alarming speed among the younger generations due to introduction of fast food chains, modernization, and globalization. Therefore, appropriates strategies are imperative not only to safeguard traditional knowledge but also the cultural heritage, food security and hence public healthcare via food supplement in the region.

Tumor-associated macrophages are a key component in the tumor microenvironment, secreting extracellular vesicles (EVs) such as exosomes and other various factors for intercellular communication. However, macrophage-derived EVs heterogeneity and their cytotoxicity to cancer cells has not been well understood. Here, we aimed to separately isolate various types of macro-phage-EVs by size exclusion chromatography (SEC) method and investigate EV transmission and cytotoxicity to oral cancer cells. For fluorescence-labeling of cellular and EV membranes, palmitoylation signal-fused GFP and tdTomato were expressed in THP-1 monocytic cells and HSC-3 oral cancer cells, respectively. We found that fluorescence-labeled EVs secreted by macrophages were highly transmissive to oral cancer cells than those from parental monocytic cells. In a co-culture system and conditioned medium (CM), a macrophage-secreted unidentified factor was cytotoxic to oral cancer cells. We fractionated macrophage-derived EVs by the SEC method and performed western blotting to characterize various EV types. Three fractions were characterized: small exosomes (EXO-S: < 50 nm) fraction containing HSP90α, HSP90β, CD63 (EV marker) and β-actin; large exosomes (EXO-L: 50-200 nm) fraction containing CD9 (EV marker) and HSP90β; large EVs (100-500 nm) fraction. Notably, the macrophage-derived small exosomes fraction was cytotoxic to oral cancer cells, while large exosomes and large EVs were not. There-fore, it was implicated that macrophage-derived small exosomes are cytotoxic with high trans-mission potential to cancer cells.

Background: The practices of various health-care professionals have been improvised to accommodate the on-going covid-19 pandemic situation. Different guidelines have been set in place to ease the process of re-opening of non-elective healthcare services like out-patient physiotherapy clinics. Although the measures taken should be guided by evidence based information, major consensus amongst practicing therapists needs to guide the India physiotherapy clinics. Objective: To identify and present the opinions of different physiotherapists about the various strategies for re-opening the out-patient physiotherapy clinics. Methods: An online cross-sectional survey was conducted. Over 169 participants were selected to participate in the survey according to the pre-decided inclusion and exclusion criteria. The data was collected and saved via google forms. Result and conclusion: A majority of respondents had a consensus over different strategies for re-opening the physiotherapy OPDs. These were regarding different measures to be adapted including modifications in the clinic infrastructure and the practice pattern. This would help in smoothly re-instating the physiotherapy services post the covid-19 lockdown.

Artificial Intelligence (AI) describes computer systems able to perform tasks that normally require human intelligence, such as visual perception, speech recognition, decision-making, and language translation. Examples of AI techniques are machine learning, neural networks and deep learning. AI can be applied in many different areas, such as econometrics, biometry, e-commerce and the automotive industry. In recent years, AI has found its way into healthcare as well, helping doctors to make better decisions (‘clinical decision support’), localizing tumors in magnetic resonance images, reading and analyzing reports written by radiologists and pathologists, and much more. However, AI has one big risk: it can be perceived as a ‘black box’, limiting trust in its reliability, which is a very big issue in an area in which a decision can mean life or death. As a result, the term Explainable Artificial Intelligence (XAI) has been gaining momentum. XAI tries to ensure that AI algorithms (and the resulting decisions) can be understood by humans. In this narrative review, we will have a look at the current status of XAI in healthcare, describe several issues around XAI, and discuss whether it can really help healthcare to advance, for example by increasing understanding and trust. Finally, alternatives to increase trust in AI are discussed, as well as future research possibilities in the area of XAI.

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation, and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.

Background: Sudden changes in clinical practice and the altered ability to care for patients due to the COVID-19 pandemic have been associated with moral distress and mental health concerns in healthcare workers internationally. This study aimed to investigate the severity, prevalence, and predictors of moral distress experienced by Australian healthcare workers during the COVID-19 pandemic. Methods: A nationwide, voluntary, anonymous, single time-point, online survey of self-identified frontline healthcare workers was conducted between 27th August and 23rd October 2020. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts, and national media. Results: 7846 complete responses were received from nurses (39.4%), doctors (31.1%), allied health staff (16.7%) or other roles (6.7%). Many participants reported moral distress related to resource scarcity (58.3%), wearing PPE (31.7%) limiting their ability to care for patients, exclusion of family going against their values (60.2%), and fear of letting co-workers down if they were infected (55.0%). Many personal and workplace predictors of moral distress were identified, with those working in certain frontline areas, metropolitan locations, and with prior mental health diagnoses at particular risk of distress. Moral distress was associated with an increased risk of adverse mental health outcomes. Feeling appreciated by the community mitigated this risk in healthcare workers. Conclusions: Safeguarding healthcare workforces during crises is important for both patient safety and workforce longevity. Targeted interventions are required to prevent or minimise moral distress and associated mental health concerns in healthcare workers during COVID-19 and other crises.

The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have been recently developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments on radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors such as primary liver and gastro-entero-pancreatic cancer, or in regions with unfavorable tumor-to-background ratio at FDG-PET/CT (i.e. brain), as well as in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at presents, and definitive conclusion about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center, prospective studies powered for efficacy are needed.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

Background: Cancer patients may fail to distinguish COVID-19 symptoms such as anosmia, dysgeusia/ageusia, anorexia, headache, and fatigue, which are frequent after cancer treatments. We aimed to identify symptoms associated with COVID-19 and to assess the strength of their association in cancer and cancer-free populations. Methods: The prospective multicenter cohort study PAPESCO-19 included 878 cancer patients and 940 healthcare workers (HCWs) systematically tested for SARS-CoV-2-specific antibodies. Participants reported the results of routine screening RT-PCR and thirteen COVID-19 symptoms. Backward logistic regression identified the symptom combinations significantly associated with COVID-19. Results: COVID+ proportions were similar in patients (8%) and HCWs (9.5%, p=0.26), whereas symptomatic proportions were lower in patients (32%) than HCWs (52%, p&lt;0.001). Anosmia, anorexia, fever, headache, and rhinorrhea together accurately discriminated (c-statistic=0.7027) COVID-19 cases in patients. Anosmia, dysgeusia/ageusia, muscle pain, intense fatigue, headache, and chest pain better discriminated (c-statistic=0.8830) COVID-19 cases in HCWs. Anosmia had the strongest association in patients (OR=7.48, 95% CI: 2.96–18.89) and HCWs (OR=5.71, 95% CI: 2.21–14.75). Conclusions: COVID-19 symptoms and their diagnostic performance differ in cancer patients and HCWs. Anosmia is associated with COVID-19 for patients, while dysgeusia/ageusia are not. Cancer patients deserve tailored preventive measures due to their particular COVID-19 symptom pattern.

Healthcare sector is a truly dynamic and multidisciplinary system. Progressive practice of computational technologies in healthcare has enhanced electronic therapeutic measures in the care units. The healthcare decision-makers are accenting on the operational usage of digital technology in the system, to improve the health service by reducing human error and excessive load also by increasing possibility to attend more patients simultaneously. Sophisticated medical instruments are using advanced robotics, artificial intelligence to enhance their efficacy. Virtual treatments, self-diagnostics is increasing over time with the advancement of technical support in health. Electronic Health Records (EHR) of patients has created huge medical data (clinical information), which is undoubtedly a good resource for health professionals to take critical decisions and implement them accordingly. The aim of this article is to elucidate how technological developments are associated with clinical improvements in terms of constructing an upgraded health ecosystem. It is imperative to analyze how recent digital paradigms in health are helping to tackle regular and rare clinical challenges.

Background: COVID-19 booster uptake remained poor among healthcare workers (HCW) despite evidence of improved immunity against Delta and Omicron variants. While most studies used a questionnaire to assess hesitancy, this study aimed to identify factors affecting true booster hesitancy by examining actual vaccine uptake across time. Method: COVID-19 vaccination database records among HCW working at 7 Singaporean public primary care clinics between January to December 2021 were extracted, with gender, profession, place of practice, vaccination type and dates. Time to booster was calculated from the date of vaccination minus date of eligibility. Chi-square test was used to compare relationship between 1st dose and booster hesitancy, Kaplan-Meier method and Log-rank test were adopted to evaluate differences in cumulative booster uptake. Multivariate cox regression was used to investigate predictors for timely booster vaccination. Vaccination rate was charted across time and corroborated with media releases pertaining to legislative changes. Results: 877 of 891 (98.9%) primary care HCW were fully vaccinated, 73.8% of eligible HCW had taken the booster. HCW were less booster hesitant [median 16 (5-31.3) days] compared to the 1st dose [median 39 (13-119.3) days]. 1st dose hesitant HCW were more likely to be booster hesitant (OR=3.66, 95%CI 2.61-5.14). Adjusting for sex, workplace and time to 1st dose, ancillary (HR=1.53, 95%CI 1.03-2.28), medical (HR=1.8, 95%CI 1.18-2.74) and nursing (HR=1.8, 95%CI 1.18-2.37) received boosters earlier compared with administrative staff. No temporal relationship was observed between booster uptake, legislative changes and COVID-19 infection numbers. Conclusion: Vaccine hesitancy among HCW had improved from booster to 1st dose, with timely booster vaccination among medical and nursing staff. Tailored education, risk messaging and strategic legislation might help to reduce delayed booster vaccination.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point-patterns were generated, which were then used to perform spatial analyses using a normalized Ripley's K function at a radius of 25μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups, and multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) <6 months, and therapy response was defined as PFS >9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19; caspase-3 1.05; P = .04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs 37μm, respectively; P < .001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT response. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

Apomictic plants (reproducing via asexual seeds), unlike sexual individuals, avoid meiosis and egg cell fertilization. Consequently, apomixis is very important for fixing maternal genotypes in the next plant generations. Despite the progress in the study of apomixis, molecular and genetic regulation of the latter remains poorly understood. So far APOLLO (Aspartate Glutamate Aspartate Aspartate histidine exonuclease) is one of the very few described genes associated with apomixis in Boechera species. The centromere-specific histone H3 variant encoded by CENH3 gene is essential for cell division. Mutations in CENH3 disrupt chromosome segregation during mitosis and meiosis since the attachment of spindle microtubules to a mutated form of the CENH3 histone fails. This paper presents in silico characteristic of APOLLO and CENH3 genes, which may affect apomixis. Also, we characterize the structure of CENH3, study expression levels of APOLLO and CENH3 in gynoecium/siliques of the natural diploid apomictic and sexual Boechera species at the stages of before and after fertilization. While CENH3 was a single copy gene in all Boechera species, the APOLLO gene have several polymorphic alleles associated with sexual and apomictic reproduction in the Boechera genera. Expression of the APOLLO apo-allele during meiosis was upregulated in gynoecium of apomict B. divaricarpa downregulating after meiosis until 4th day after pollination (DAP). On the 5th DAP, expression in apomictic siliques increased again. In sexual B. stricta gynoecium and siliques APOLLO apo-allele did not express. Expression of the APOLLO sex-allele during and after meiosis in gynoecium of sexual plants was several times higher than that in apomictic gynoecium. However, after pollination the sex-allele was downregulated in sexual siliques to the level of apomicts and increased sharply on the 5th DAP, while in apomictic siliques it almost did not express. At the meiotic stage, the expression level of CENH3 in the gynoecium of apomicts was two times lower than that of the sexual Boechera, decreasing in both species after meiosis and keep remaining very low in siliques of both species for several days after artificial pollination until the 4th DAP, when the expression level raised in sexual B. stricta siliques exceeding 5 times the level in apomictic B. divaricarpa siliques. We also discuss polymorphism and phylogeny of the APOLLO and CENH3 genes.

(1) Background: Factors reported in literature associated with inappropriate prescribing of antimicrobials, such as physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians' decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing `antimicrobials would minimize the risk of resistance and, consequently, improve patients' clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. (2) Methods: Cross-sectional study conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed validated and piloted survey specific with closed-ended questions. A value of P &lt;0.05 was considered for statistical significance. All data analysis was performed using Statistical Package for Social Sciences (IBM SPSS version 23.0). (3) Results: 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All the respondents acknowledged effectiveness and previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) were key factors influencing physicians’ choice during antimicrobial prescribing. (4) Conclusion: The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials, were reported to be common practices. Further, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials and using antimicrobials without physician prescription (self-medication) were the key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.