This research illustrates modification of multi-walled carbon nanotubes (MWCNT) by ZrO2/Pb to construct nanocomposites (MWCNT/ZrO2/Pb-NCs) by simple precipitation technique and subsequently examine its ability for adsorption of Amido black (AB) and Eosin B (EB) dyes in binary system. The present nanocomposites investigation by FESEM, XRD, FTIR, and EDX analysis, reveal its as-synthesized crystalline nature with cubic morphology and average particle size 30–50 nm. The present nano-adsorbent represent high efficiency for AB and EB adsorption from aqueous solution, while dependency of variables including pH, initial concentration of dyes, contact time and MWCNT/ZrO2/Pb-NCs mass were analyzed by central composite design (CCD). The predicted maximum removal percentage was 95% removal for both dyes is consequence of adjustment of operational conditions at pH of 6.0; 0.05 g MWCNT/ZrO2/Pb-NCs; 15 min stirring at 15 mg L-1 for both dyes. The Langmuir as applicable for representation and description of reveal data of adsorption with adsorption capacity of 15.46 and 16.92 mg g-1 for AB and EB, respectively. Pseudo-first order model owing to its high correlation coefficient and closeness of experimental and theoretical data well represented behavior of corresponding adsorption system. Mechanism examination strongly proof high contribution of external mass transference as the main rate-controlling step. The successful regeneration of MWCNT/ZrO2/Pb-NCs suggested their usefulness in wastewater treatment and its ability of environmental management.

A quite energetic seismic excitation consisting of one main and additional three distinctive earthquake clusters that occurred in the transition area between the Kefalonia Transform Fault Zone (KTFZ) and the continental collision between Adriatic and Aegean microplates, is thoroughly studied after high–precision aftershocks’ relocation. The activated fault segments are in an area where historical and instrumental data have never claimed the occurrence of a catastrophic (M>6.0) earthquake. The relocated seismicity initially defines an activated structure extending from the northern segment of the Lefkada branch of KTFZ with the same NNE–SSW orientation and dextral strike-slip faulting and then keeping the same sense of motion its strike becomes NE–SW and its dip direction NW. This provides unprecedented information on the link between the KTFZ and the Collision front and sheds more light on the regional geodynamics. The earthquake catalog, which is specially compiled for this study, starts one year before the occurrence of the Mw5.4 mainshock and adequately provides the proper data source for investigating the temporal variation of the b–value, which might be used for discriminating foreshock and aftershock behavior.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

In January and February 2001, El Salvador was hit by two strong earthquakes that triggered thousands of landslides, causing 1,259 fatalities and extensive damage. The analysis of aerial and SPOT-4 satellite images taken a few days after the events allowed us to map 6,491 coesismic landslides, which occurred in 14 study areas extending for about 400 km2. Four different Multivariate Adaptive Regression Splines (MARS) models were produced by using different covariate sets and landslide inventories, the latter containing the slope failures triggered by an extreme rainfall event of November 2009 and those induced by the earthquakes of 2001. Moreover, two validation scenarios were employed, including the 25% and 95% of the mapped landslides, respectively. The results of our experiment revealed that: (i) MARS algorithm provides reliable predictions of coesismic landslides; (ii) models calibrated with rainfall-induced landslides predict with acceptable accuracy landslides caused by deep earthquakes and distributed over vast areas; (iii) the best accuracy is achieved by models trained with both preparatory and trigger variables; (iv) a small portion of the landslides produced by an earthquake can be used to calibrate MARS predictive models that help to identify slopes where yet unreported landslides may have occurred.

Subacute sclerosing panencephalitis (SSPE) is a progressive neurological complication that affects the central nervous system. It occurs as a late complication of the measles infection the young children and adolescents who are commonly affected present with personality changes and neurological deficits. The diagnosis can be done via clinical features, electroencephalography, and cerebrospinal fluid analysis. At present, there is no cure for SSPE. The immunisation against measles is the main strategy in preventing this condition. Here, we present a case of a 22-year-old Indian male diagnosed with Subacute sclerosing panencephalitis.

Deforestation brings vast and detrimental impact on the environment, economy, and social aspects of community. Thus, it is important to assess and analyze deforestation to inform the decision maker that oversees issued policy and development strategies. The present study aims to characterize deforestation in Central Kalimantan between 2006 - 2020. Utilized land cover map issued by Indonesian Ministry of Environment and Forestry, we analyzed the change in natural forest cover using Remote Sensing and Geographical Information System (GIS) to find the rate the trend, location, and land cover replacement of deforestation in Central Kalimantan Province, Indonesia. The research found that during the period Central Kalimantan lost 1.5 million ha of natural forest with the rate of deforestation 117,000 ha/year. In general, the deforestation shown decrease trend and fluctuated during the period. Deforestation majority takes place at secondary swamp and dry forest that are located at south part of the island. Most of deforestation resulted shrubs, plantations, and agriculture land. The finding of this research could be used as a base to determine the target location for rehabilitation strategy and approach to prevent further deforestation.

Background: Although triptorelin acetate (TA) is generally considered a safe medication, severe adverse drug reactions (ADRs) to triptorelin have occurred. In this study, we present the largest retrospective analysis of ADRs related to TA during the treatment of pediatric central precocious puberty. Methods: We describe a total of 38 suspected cases of TA-induced ADRs reported to the pharma-covigilance center of Shenzhen Children’s Hospital from September 2015 to December 2022. Causality assessment was carried out using the validated Kramer’s algorithm. The severity of ADRs was evaluated using the Modified Hartwig and Siegel Scale. Results: The most common ADRs attributed to TA were damage to the cutaneous tissues (29.3%) and reactions affecting the systemic and digestive systems (20.7%). The majority (61.1%) of ADRs occurred within 2 hours of administration. Among the 12 patients with severe ADRs, the three most frequent symptoms were anaphylactic reactions, hip synovitis, and arthralgia. Additional-ly, six patients experienced ADRs due to a change in the manufacturing process. Conclusion: The majority of ADRs observed in pediatric cases were type I anaphylactic reactions, which are rare but life-threatening. It is advisable to perform skin prick tests and intradermal tests when switching pharmaceutical manufacturers.

Abstract: Obstructive sleep apnea (OSA) is well known to often improve with non-supine positioning as opposed to su¬pine positioning. Emerging research supports a role for sleep position management in patients with central sleep apnea (CSA) as well. We report a case of de novo Complex Sleep apnea Syndrome (CompSAS) in a 78-year-old female, who presented after a car accident due to unclear syncope. Diagnostic polysomnography (PSG) showed a moderate OSA. A CompSAS developed under Automatic positive airway pressure (APAP), while download data of 4 years showed a good adherence. No significant benefit was reported under Adaptive Servo Ventilation (ASV) and BiPAP-ST, while a reduction of CSA in non-supine position was noticed. Oxygen and sleep positional therapy (SPT) were considered resulting in a significant improvement of CSA and sleep quality. Further research on the prevalence of positional CSA is needed.

This paper concerns about a stepwise modelling procedure for groundwater flow simulation in a complex carbonate, folded and faulted, multilayer aquifer, in the Apennine chain in Central Ita-ly, which constitutes a source of good quality water for human consumption. A perennial river acts as the main natural drain for groundwater while sustaining valuable water related ecosys-tems. The spatial distribution of recharge was estimated using the Thornthwaite-Mather method on 60 years of climate data. The system was conceptualized as three main aquifers separated by two locally discontinuous aquitards. Three numerical models were implemented by gradually adding complexity to the model grid: single layer (2D), three layers (Quasi-3D), and five layers (Fully-3D), using an equivalent porous medium approach, in order to find the best solution with a parsimonious model setting. To overcome dry-cell problems in the Fully-3D model, the New-ton-Raphson formulation for MODFLOW-2005 was invoked. Calibration results show that a Fully-3D model was required to match the observed distribution of aquifer outflow to the river baseflow. The numerical model demonstrated the major impact of folded and faulted geological structures on controlling the flow dynamics in terms of flow direction, water heads and spatial distribution of the outflows to the river and springs.

In this research, the accessibility in the footpath-level walkability condition of old core cities of India has been assessed, considering Central Kolkata, India as a case. Post-2015, after the implementation of Goal Number 11 of United Nations Sustainable Development Goals (i.e. Sustainable Cities and Communities), the significance of universal mobility has globally manifolded in the walkability sector. This research has been done in theoretical, ideological, and methodological patterns using Architectural Planning Research for promoting Universal Mobility in old Indian cities. The variables (categorical) used in this research are related to pedestrian infrastructure. The categorical variables are: 1) Building Typology of Stretch, 2) Footpath Dimensions, 3) Temporary Encroachment, 4) Permanent Encroachment, 5) Bus Stop, 6) Metro Rail Entrance, 7) Railings, 8) Storm Water Drains, 9) Public Toilet, 10) Trash Bins, 11) Street Lights, 12) Flooring, 13) Manholes, 14) Kerb, 15) Pedestrian Crossing, 16) Street Furniture, 17) Safety and Security, and 18) Additional Inclusive Features like signage. This research shows that the footpath stretches in Central Kolkata, India are inadequate in terms of ideal accessibility. In addition to this, the result of this research portrays complexities in the adaptability of accessible walkability-related considerations; thereby suggesting a new accessibility audit format for old core Indian cities for achieving Universal Mobility standards in the future. The authors also propose quantitative methods to conduct future research in the same domain.

In this research, users’ perception towards Universal Mobility in old core cities of India has been critically analyzed. Despite Universal Design guidelines from the United Nations and Union Government of India, old cities in India are seldom having Universal Mobility, in effect endangering the lifestyle of senior citizens and differently-abled people. The core of Kolkata Municipal Corporation in Kolkata, India has been considered as a case example for this research. This research has considered three types of data sets for analysis. First, the authors interviewed 310 respondents from the Indian design fraternity, with the objective of understanding their opinion on the concept of Universal Design. In the next investigative study of 125 respondents from different wards of Kolkata Municipal Corporation, the purpose was to comprehend people’s perception about walkability and mobility in an old Indian city. In the last visual survey of a stretch in Central Kolkata, the focus was identifying the hindrance in Universal Mobility in an old city core of Indian origin. Significant dissatisfaction was found in walkability amongst all user groups; which is linked to poor infrastructural conditions. Furthermore, accessing public transportation is difficult due to improper waiting facilities. However, the design fraternity in India suggests the need of separate accessibility guidelines for old and new cities in India. The design fraternity also recommends a customized rating system for accessing Universal Design. The result of this study indicates a need of recognizing the difficulty in imparting Universal Mobility in old core cities in India. This information can be used for preparing an Access Audit Checklist through Architectural Planning, which is the first step in proposing a framework for Universal Mobility in old core cities in India.

The brain, rather than being homogeneous, displays an almost infinite topological genus, because is punctured with a very high number of topological vortexes, i.e., .e., nesting, non-concentric brain signal cycles resulting from inhibitory neurons devoid of excitatory oscillations. Starting from this observation, we show that the occurrence of topological vortexes is constrained by random walks taking place during self-organized brain activity. We introduce a visual model, based on the Pascal’s triangle and linear and nonlinear arithmetic octahedrons, that describes three-dimensional random walks of excitatory spike activity propagating throughout the brain tissue. In case of nonlinear 3D paths, the trajectories in brains crossed by spiking oscillations can be depicted as the operation of filling the numbers of the octahedrons in the form of “islands of numbers”: this leads to excitatory neuronal assemblies, spaced out by empty area of inhibitory neuronal assemblies. These procedures allow us to describe the topology of a brain of infinite genus, to assess inhibitory neurons in terms of Betti numbers, and to highlight how non-linear random walks cause spike diffusion in neural tissues when tiny groups of excitatory neurons start to fire.

Several long-term monitoring of aerosol datasets from the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Terra/Aqua, Multi-angle Imaging SpectroRadiometer (MISR), Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) are used to derive the dust aerosol optical depth (DOD) in Central Asia based on the Angstrom exponent parameter and/or the particle shape. All sensors agree very well on the interannual variability of DOD. The seasonal analysis of DOD and dust occurrences identified the largest dust loading and the most frequent dust occurrence in the spring and summer, respectively. No significant trend is found during the research period in terms of both DOD and the dust occurrence. Further analysis of Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) aerosol products on a case-by-case basis in most dust months of 2007 suggested that the vertical structure is varying in terms of the extension and the dust loading from one event to another, although dust particles of most episodes have similar physical characteristics (the particle shape and size). Our analysis on the vertical structure of dust plumes, the layer-integrated color ratio and depolarization ratio indicates a varied climate effect (e.g., the direct radiative impact) by mineral dust, dependent on the event being observed in Central Asia.

The production of particles outside the region of nucleon-nucleon kinematics due to interactions involving dense cold clusters of quark-gluon matter in nuclei is calculated. The possibility of observing this process in the region of central rapidities and large transverse momenta in heavy ion collisions at low energies with MPD detector at the NICA collider has been demonstrated.

Exploring the spatio-temporal differentiation characteristics and coupling coordination relationship of the composite ecosystem of urban agglomerations is of great significance for promoting the synergistic development and integration construction of urban agglomerations. This paper is based on LUCC data, DEM, temperature, precipitation and other multi-source data, taking the central Yunnan urban agglomeration as an example. The entropy weight method is first used to determine the comprehensive weights to evaluate the regional economic and social development level. Then, the InVEST (Integrated Valuation of Ecosystem Services and Trade-offs)model was used to quantitatively calculate and analyze the spatial and temporal evolution characteristics of the four ecosystem services, including water conservation, soil conservation, carbon sequestration services, and habitat quality. The coupling coordination model was used to quantitatively analyze the evolution of the coupling coordination of the composite ecosystems in the central Yunnan urban agglomeration during the period of 2010-2020, and to reveal its development law. The results show the following: ①During the study period, the socio-economic subsystems in central Yunnan urban agglomeration demonstrated an outward radiative growth from Kunming City, marked by underdeveloped sub-centers and prevalent low-level areas. ②Trends in ecosystem services varied, with water and soil conservation showing fluctuating increases, carbon sequestration remaining stable, and habitat quality declining. The integrated ecosystem services critically important zone is mainly located in the northeastern region and southwestern edge of the study area. ③Economic, social and ecological subsystems are highly coupled, with consistent overall development trends and strong interactions. ④The increase in the degree of harmonization amounted to 7.82%, with lagging subsystems varying in different degree of harmonization subregions. The study can provide a scientific basis for urban agglomerations to formulate scientific and reasonable development policies, promoting regional sustainable development and optimizing the spatial pattern of the national territory.

Cerebrospinal fluid contacting neurons (CSF-cNs) are a specific type of neurons located around the ventricles in the brain and the central canal in the spinal cord and have been demonstrated to be intrinsic sensory neurons in the central nervous system (CNS). One of the important channels responsible for the sensory function is polycystic kidney disease 2-like 1 (PKD2L1) channel. Most of the studies concerning the distribution and function of the PKD2L1-expressing CSF-cNs in the spinal cord have previously been performed in non-mammalian vertebrates. In the present study immunohistochemistry was performed to determine the distribution of PKD2L1-immunoreactive (IR) CSF-cNs in the spinal cords of 4 mammalian species: mouse, rat, cat, and macaque monkey. Here, we found that PKD2L1-expressing CSF-cNs were present at all levels of the spinal cord in these animal species. Although the distribution pattern was similar across these species, differences existed. Mice and rats presented a clear PKD2L1-IR cell body labeling, whereas in cats and macaques the PKD2L1-IR cell bodies were more weakly labeled. Ectopic PKD2L1-IR neurons away from the ependymal layer were observed in all the animal species although the abundance and the detailed locations varied. The apical dendritic protrusions towards the lumen of the central canal were clearly seen in all the animal species, but the sizes of protrusion bulbs were different among the species. PKD2L1-IR cell bodies/dendrites were co-expressed with doublecortin, MAP2 (microtubule-associated protein 2) and aromatic L-amino acid decarboxylase, but not with NeuN (neuronal nuclear protein), indicating their immature property and ability to synthesis monoamine transmitters. In addition, in-situ hybridization performed in rats revealed PKD2L1 mRNA expression in the cells around the central canal. Our results indicate that the intrinsic sensory neurons are conserved across non-mammalian and mammalian vertebrates, and that this may play an essential role in the regulation of motor and sensory functions as well as in the maintenance of homeostasis in the CNS.

Background: Classical Hodgkin's lymphoma (cHL) is a lymph node disease, however, extranodal involvement is present in about 10% of affected individuals. Various forms of direct central nervous system (CNS) involvement have been reported, including intracranial, epidural, leptomeningeal, and intramedullary spinal cord cHL (Table 1). We hereby describe the clinical presentation, work up, and outcomes of two distinctive cases of cHL with intracranial extra-axial spread in patients receiving novel combination and traditional chemotherapy. Methods: This case series (n=2) was conducted following the CARE guidelines. Institutional review board (IRB) approved protocol #24-015 for HIPPA waiver of subjects in our retrospective study. Results: Patients with cHL exhibiting CNS symptoms or relapse refractory cases benefit from neuroimaging and excluding infectious etiologies. Suspicious lesions include iso- to hypointensity on T1 weighted and iso- to hyperintensity on T2 MR scans. Diagnosis is confirmed with biopsy. Treatment with A-AVD has shown more benefit than traditional ABVD chemotherapy. There has been shown progression free survival with nivolumab-AVD (N-AVD) over brentuximab-AVD (B-AVD). Conclusion: cHL with CNS involvement is rare and requires comprehensive workup to exclude infectious and other malignancies. Diagnosis relies on neuroimaging and subsequent brain biopsy. Treatment with novel N-AVD has shown greater PFS in patients with advanced cHL.

Background Corpus callosum abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosum abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications on the postnatal outcome. Methods In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. Results The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%) and hypoplasia with dysplasia (4.2%). Amongst them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. Conclusion The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a diagnosis suspected on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in the cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Ecuador is the world's fifth largest cocoa producer, generating hundreds of annual tons of residues from this fruit. This research aims to value this residual (cocoa pod husk) by using it as raw material to obtain pectin, which is widely used in the food and pharmaceutical industries. For them, the extraction of three different organic acids with GRAS status (and therefore safe for their use), citric, malic and fumaric acids, were studied. In addition, two other factors, temperature (70-90°C) and extraction time (60-90 min), were explored in a central composite design of experiments. Under the conditions of the experiment, it was obtained that the best yields were reached for citric acid, malic acid and fumaric acid and for ~86 min of extraction time. The temperature did not show a significant influence on the yield. The pectins obtained under optimal conditions were characterised, showing their similarity with commercial pectin. However, the equivalent weight and the esterification degree of the pectin obtained with fumaric acid classify it as having a high equivalent weight and a low degree of esterification. It differs significantly from the other two acids, perhaps due to the limited solubility of fumaric acid.

Intranasal (i.n.) administration became an alternative strategy to bypass the blood-brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions and thus, they could be beneficial in the treatment of different medical conditions.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demye-lination and motor and cognitive impairment due to the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intrave-nously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.

The genetic pool of valuable old ornamental cultivars and their in situ maintenance may be threated by climate change. Meanwhile, the ornamental plants like roses make up an important share of both gardens and urban green spaces, where they are particularly vulnerable to multistress growth conditions. The aim of this research was to evaluate the effect of changing climatic conditions on growth and flowering of 11 historic climber roses through long-term studies (2000-2017) conducted in Central Europe. The evaluation of plants consisted of assessment of frost damage and the timing of early phenological stages (starting of bud break, leaf unfolding) as well as gathering data on beginning, fullness and end of flowering and its abundance. Frost damage was not recorded in any year only in ‘Mme Plantier’, and did not occur for any cultivar after the winter in the years 2007, 2008, and 2014. Only a little damage to one-year shoots was recorded after the winter in the years 2015-2017. Frost damage to ‘Alberic Barbier’, ‘Albertine’, ‘Chaplin's Pink Climber’, ‘Orange Triumph clg’ and ‘Venusta Pendula’ led to pruning to ground level in every year excluding those listed above. Frost damage of once blooming roses limited their flowering; however, the many-year data-sets showed a trend for decreased frost damage and improved abundance of flowering, and these results can be interpreted as a response to the increase of average air temperature. The timing of bud breaking and leaf development in all climber roses was strictly correlated with average air temperature in the dormancy period. The reactions of climber roses to weather conditions confirmed the influence of climatic changes on ornamental crop plants in Central Europe, introducing the potential possibility for the wider application of climber roses, but without certainty of flowering every year.

Phantom Limb Pain (PLP) is a challenging condition affecting a significant proportion of amputees. In this article we describe the case of a 54-year-old Paralympic athlete with Phantom Limb Syndrome following right leg amputation and widespread sports-related enthesitic pain, who underwent a Whole Body Cryostimulation (WBC) cycle, an emerging treatment known for its rapid pain-relieving and anti-inflammatory effects. Assessments were conducted before and after a 10-session WBC cycle, including pain and quality of life assessment, and use of medications. A substantial reduction in enthesitic pain, PLP intensity, paresthesia, tingling related to atmospheric events and an improved function and quality of life were reported after the WBC cycle and lasted for two weeks. One month after WBC, the enthesitic pain following sports activity and PLP gradually returned but with lesser intensity. Similarly, the stump's sensitivity to atmospheric changes returned but with lower frequency. Pain at night remained lower than before WBC with significantly improved quality of sleep. This case study suggests that WBC could be a valuable adjuvant treatment for alleviating PLP. Controlled studies are warranted to validate the findings of this case-report and elucidate the mechanisms underlying the positive effects of WBC in this condition.

Background: As the world tends to recover from the crisis created by the COVID-19 pandemic, vaccines have served as one of the most valuable tools of combat and large-scale immunization has helped to tide over the catastrophe. However, several reports of post -vaccination neurological complications around the globe have surfaced up in recent literature. This study was conducted with an aim to describe the spectrum of neurological ailments requiring hospitalization following COVID-19 vaccination.Methods: An ambispective observational study was carried out from March 2021 to February 2022 at a tertiary care institute with 25 patients who satisfied the inclusion criteria of a new onset neurological illness requiring hospitalization within 4 days to 42 days of vaccination. The patients were duly followed upto months after discharge.Results: The median age of the sample was 36 years and the median latency of onset of neurological events was 14 days. Guillain-Barré syndrome was documented in 11 patients; majority were acute motor axonal neuropathy (45.45%) followed by acute inflammatory demyelinating polyradiculoneuropathy (36.36%) and acute motor sensory axonal neuropathy (18.18%). Central nervous system demyelination was reported in 9 patients; two patients had acute disseminated encephalomyelitis, 2 patients were diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease, one patient with aquaporin-4 positive neuromyelitis optica spectrum disorder , and the rest were labelled as seronegative central nervous system demyelination. Vascular events were noted in 5 patients comprising of 2 cases each of cerebral venous sinus thrombosis and intracerebral hemorrhage and a case of Moyamoya angiopathy. All patients were conservatively managed and had a complete to partial recovery suggestive of a favorable outcome after 3 months. Conclusion: The pathomechanisms of post -vaccination neurological complications is yet to be elucidatedand any causal association attributable to vaccination warrants further research. Compared to the enormity of the vaccinated population, the adverse effects are miniscule to hinder and discourage vaccination.

Vector-borne disease (VBD) accounts for more than 17% of the global infectious disease burden, disproportionately affecting developing nations within tropical and subtropical areas. As Aedes aegypti mosquitoes are the principal vector for the transmission of many Public Health pathogens, our study examined their population dynamics within the seasonal context of tropical dry biomes in El Salvador as incidence of VBD in this region has increased in recent years. Species that rely on sexual reproduction must maintain a balanced sex ratio (1:1) to support their population dynamics, however, our phenological analysis of field-collected A. aegypti specimens revealed significant sex ratio variations during dry and wet seasons. Interestingly, we detected a seasonal shift that favored female mosquitoes during the dry season, highlighting the dynamic nature of mosquito populations in highly urbanized environments like El Salvador. By linking sex ratio distortions to anthropogenic factors, our study underscores the importance of comprehensively characterizing the urban ecology of vectors for the development of effective biocontrol strategies. As such, we advocate for more nuanced vector control approaches that consider ecological factors as well as the human behaviors that influence mosquito breeding habitats to effectively combat the rise of VBDs amid global climate changes.

In this research, univariate and bivariate statistical methods were applied to rainfall, river and piezometric level datasets belonging to 24 years long time series (1986-2009). These methods, that often are used to understand the effects of precipitation on rivers and karstic springs discharge, have been used to assess, piezometric level response to rainfall and river level fluctuations in a porous aquifer. A rain gauge, a river level gauge and three wells, located in Central Italy along the lower Pescara river valley in correspondence of its important alluvial aquifer, provided the data. The statistical analysis has been used within a known hydrogeological framework, which has been refined by mean of a photo-interpretation and a GPS survey. Water-groundwater relationships were identified following the autocorrelation and cross-correlation analyses; the spectral analysis and mono-fractal features of time series were assessed, in order to provide information on multy-year variability, data distributions, their fractal dimension and the distribution return time within the historical time series. The statistical-mathematical results were interpreted through field work that identified distinct groundwater flowpaths within the aquifer and enabled the implementation of a conceptual model, improving the knowledge on water resources management tools.

We examined special roles of the Central Nervous System (CNS) in an attempt to resolve the puzzle that chronic diseases cannot be cured by medicine. By exploring a skill-learning model, we found that the CNS is able to remember certain information reflecting biochemical and cellular (B&C) processes in the body. From the skill using ability, we found that the CNS is able to control basic B&C processes that drive and power the skill. From the ability to adjust forces and force direction of a physical act, we found that the CNS is able to adjust B&C processes that drive the physical act. From this adjustment capability, we further inferred that the CNS must also store information on the baseline B&C processes. As a whole, we found that the CNS can maintain information on baseline B&C processes, up-regulate or down-regulate the processes, and make comparisons in performing its regulatory functions. We found that chronic diseases are the results of deviated baseline B&C processes. Per the proved hypothesis, the CNS maintains deviated baseline B&C processes, and thus protects the body states of fully developed diseases. We then used the three CNS roles to explain that cancer progresses with increasing malignancy, cancer quickly returns after a surgery, cancer cells repopulate after chemotherapy and radiotherapy, cancer develops drug resistance inevitably, immune cells rebound after suppression, generally poor benefits of cancer drugs such as beta-blockers, etc. We further showed that long-term exercises generally push most, if not all, baseline B&C processes in diametrical opposing directions against the diseased B&C processes, implying that exercises play unique roles in reversing chronic diseases. Finally, we proposed several strategical approaches to resetting the CNS’ state memory as the essential condition for curing chronic diseases.

Truffles are ascomycete hypogeous fungi belonging to the Tuberaceae family of the Pezizales order that grow in ectomycorrhizal symbiosis with tree roots and are known for their peculiar aromas and flavors. Axenic culture of truffle mycelium is problematic because it is not possible in many cases, and the growth rate is meager when it is possible. This limitation prompts searching and characterizing new strains that can be handled in laboratory conditions for basic and applied studies. In this work, a new strain of Tuber borchii (strain SP1) has been isolated and cultured, and its transcriptome has been analyzed under different in vitro culture conditions. The results show that the best T. borchii SP1 growth was obtained using maltose-enriched cultures made with soft-agar and in static submerged cultures made at 22ºC. The transcriptome analysis of this strain cultured in different media indicated that most of the gene transcription effort is due to a limited number of genes (20% of genes account for 80% of the transcription), that the transcription profile of the central metabolism genes was similar in the different conditions analyzed with a transcription signal detected for around 80% of the annotated genes. The gene expression profile suggests that T. borchii uses a fermentative rather than respiratory metabolism, even in aerobic conditions. Finally, there is a reduced expression of genes belonging to secondary metabolite clusters, whereas there is a significative transcription of those involved in producing volatile aromatic compounds.

A stable match, an intercuspated maxilla-mandible relation is the universally accepted goal for dental restorative interventions, yet the underlying sensorimotor mechanisms to achieve this goal in the natural jaw closure remains to be elucidated. Dentists have intuitively regarded peripheral sensory innervation from tooth contacts as a significant control element for jaw muscle actions, both in the state of health and in cases of pathological dysfunction. However, therapeutical interventions for reshaping the dental arch anatomy and jaw relations have not always been successful. Repetitive masticatory chewing cycles, swallowing, talking, as well as volitional jaw-opening and -closing involve stereotyped neural commands from the central nervous system that are modulated in reaction to the sensory afferent feedback from the peripheral neurons and their sensor organs. The aim of this article is to describe, on a fraction of a second time-scale, the minuscule tilts and kinematic events of mandible during the making of a stable match with maxilla. Evidence of the importance of tooth contacts as the sensorimotor motivation of each of the successive kinematic steps of the “mandible-meets-maxilla-narrative” are discussed.

This paper uses preliminary studies of archaeological sites (burial mounds and settlements) from the Iron Age through Medieval periods (ca. 800 BCE to 1200 CE) in the Juuku Valley on the South side of Lake Issyk-Kul to model land-use across vertical mountain zones. To do so, we have established a radiometric chronology, conducted test excavations of an Iron Age settlement and a Turkic period burial, undertaken preliminary archaeobotanical research, and pedestrian surveys. Seed remains of wheat (Triticum aestivum), barley (Hordeum vulgare), broomcorn millet (Panicum milaceum) and foxtail millet (Setaria italica) and legumes were recovered in very small quantities from an Iron Age upland settlement at 2100 m asl and a Turkic period burial mound at 1934 m asl. These preliminary archaeobotanical results are compared to the Talgar Iron Age settlements on the north side of the Tian Shan Mountain range in Kazakhstan studied earlier by Robert Spengler. Small samples of faunal remains found at the Turkic period kurgan and from a profile at the upland Iron Age settlement indicate livestock herding of sheep/goats, cattle, and horses in Juuku Valley. The goal of this paper is to test the hypothesis that pastoral transhumance and agropastoralism were economic strategies used by ancient societies during the Iron Age through Medieval periods in mountain-river valley areas between 750 m to 2500 m asl. These economic strategies that combined the pasturing of sheep, goats, cattle and horses with the cultivation of cereals were adapted to the use of different vegetational zones along a vertical gradient. This paper based on preliminary research of upland sites of the Juuku Valley in Kyrgyzstan, initiates a long-term research study of four millennia of settlements that ranged from pastoral transhumance, pastoral nomadism, and combined mountain agriculture using survey data and test excavations.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

Nowadays, the transactions carried out with digital currencies are increasing. Citizens are asked to respond to growing challenges related to the sustainable management of digital currencies in their daily lives. However, due to the lack of digital skills of users, the sustainable management of digital currencies hides risks. The methodology of this study was based on the Digital Competence Framework for Citizens (DigComp) and is applied through a questionnaire completed by 443 respondents. The main objective was to evaluate their digital skills from the perspective of digital currency use. The analysis of the responses was carried out by using Structural Equation Modeling (SEM). The most important result from this research reveals that users of digital currencies are significantly capable of developing sustainable communication to solve everyday problems. At the same time, users of digital currencies mostly detect digital threats and effectively manage fake news without being affected by them. However, users of digital currencies consider that security issues are important, but only for transactions and not for their supporting functions. The study concludes with suggestions for improving the experience of digital currency users through individual actions, thus having a positive impact on the state and banking institutions.

Mountain and pastoralist societies around the world have for centuries sustained their livelihoods and cultures by accumulating specialist knowledge about their local and regional socio-ecological environments. Developing traditional knowledge and customary practices takes time, sometimes spanning across generations. As macro-level changes to social and natural environment are now taking place, such as globalization and climate change, local communities could potentially also benefit from complementary, suitably adapted educational opportunities for sustainable development. However, access to education has often required moving to urban centres, which can weaken community structures and cohesion, and could also foster increased dependence on external specialists, providers or decision-makers. Careful introduction of emerging Educational Technologies could alleviate and possibly reverse such trends as mobile Internet access spreads to remote areas. This paper examines the role of education in sustainable development and specifically explores the potential for two educational innovations, open badges and blockchain, to provide a new construct for transformation in sustainable development amongst mountain and pastoralist societies. These technologies could not only facilitate education through online distance learning, but also allow geographically remote populations to highlight the value of their traditional knowledge and to engage more comprehensively in their changing worlds.

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization of movements. Their study, like that of any other scientific field, must use specific notions to get to grips with them. This review is therefore organized along a series of notions that are frequently used in motor control, and we will discuss them with particular emphasis on neurological conditions, which may disrupt normal motor functioning. We will start with a short description of the roles of space and time, in which movements take place. Subsequently we will deal with kinematics and kinetics (dynamics) of movements. Then, we will list the inputs to motoneurons (MNs), which, in different forms, convey signals from the central nervous system (CNS) to skeletal muscles and muscle spindles, including central pattern generators (CPGs), sensory inputs and supraspinal descending fiber systems. Some helpers in movement organization will be introduced, such as internal models and neuronal network models. A relatively brief section on sensory-motor learning will follow because learning abilities are required to endow the sensory-motor system with flexibility and adaptability. The major emphasis is placed on neurological processes, which result from genetic modifications, autoimmune diseases, neurodegenerative diseases, infections in the nervous system as well as vascular and traumatic lesions. These neurological diseases lead to a variety of impairments and symptoms, particularly movement derangements including cerebellar ataxia, spasticity, and (other) movement disorders such as Parkinson’s syndromes. The conclusion is that there is no unique top controller that controls ´motor control`.

Background: Central serous chorioretinopathy (CSC) is a common macular condition characterized by detachment of the neuroretina and is a frequent cause of central vision loss in adults. Among the various therapeutic strategies, subthreshold microsecond pulsed laser (SML) treatment has become a useful option. Despite the suggested involvement of choroidal circulatory disturbances in CSC, effects of this treatment on macular microperfusion have not been fully evaluated yet. Herein, we report the impact of SML on retinal and choroidal microvascular flow using non-invasive optical coherence tomography (OCT) angiography (OCTA). Methods: In this study, CSC patients with persistent subretinal fluid (SRF) with or without secondary choroidal neovascularization (CNV) were included (referred to as pachychoroid neovasculopathy (PNV) group and CSC group, respectively). SML was conducted using a yellow (577 nm) laser with duty cycle of 10%, spot size of 200 µm and duration of 200 ms. Best corrected visual acuity (BCVA) as well as OCT and OCTA images were evaluated at baseline and 4 weeks after SML. OCTA parameters of interest included full retinal perfusion (FRP), choriocapillaris perfusion (CCP), Sattler’s layer perfusion (SLP), and Haller’s layer perfusion (HLP), which were evaluated longitudinally and compared to unaffected fellow eyes. Results: 27 affected eyes and 17 fellow eyes from 27 patients were included. Before treatment, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) of affected eyes were significantly larger than in fellow eyes. Four weeks after SML, CRT decreased significantly, whereas perfusion parameters did not change. In subgroup analyses, the CSC group showed a significant decrease of SFCT, whereas the PNV group did not despite the decrease of CRT. Conclusion: Our results suggest that the SML may SFCT of CSC, but not of PNV patients at least within four weeks following treatment. This effect seems to be independent of the change in choroidal perfusion measured with OCTA.

Neurodevelopmental disorders are characterized by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the fetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioral phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterized solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behavior is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviors, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilized society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

Glial cells provide physical and chemical support and protection for neurons. Secreted neurotrophic factors, scaffolds and vesicles regulate in addition to normal homeostasis, repair following neural tissue injury or degeneration. We previously demonstrated that human CNS glia have revascularization capacity by inducing endothelial cell sprouting and microchanneling driven by glial cell secreted components. The clinical potential of using secreted factors and vesicles generated by glial cells in conditioned media was shown by their re-normalization of pathological blood vessels and 3D tissue wound healing and remodeling capacity. To identify secreted components of glial cells and how CNS and PNS glial cells differentially regulate neural tissue homeostasis, disease and injury response, we developed a novel culture method for various types of glial cells that allow for isolating and characterizing secreted glial components, free of animal factors and contaminants normally associated with serum-based culture conditions. Our culture method will enable to identify secreted components using ultrasensitive RNA, glycoconjugate and protein analysis technologies. The characterization of glial secreted factors involved microchanneling may help in development of new clinical therapies for glial and neural cells or axons to migrate and reform connections.

Background: This study examines the relationship between energy usage, health issues, and pro-environmental behavior (PEB) in Kyrgyzstan, amidst the country's commitment to transition from coal-based energy to renewable sources in line with the Paris Agreement. The purpose is to investigate citizens' attitudes towards PEB and their intentions to engage in environmentally friendly actions, focusing on gas, electricity, and coal. Methods: Drawing upon the Theory of Planned Behavior (TPB) framework, a survey was conducted among 1,455 respondents to explore attitudes towards PEB and energy sources' impact on health issues. Results: Decarbonization efforts in Kyrgyzstan and Central Asia are in their early stages, with coal remaining a primary energy source. The study emphasizes the importance of governmental policies and citizen action in achieving decarbonization goals. Rising electricity costs outweigh the increase in indirect energy costs for food, posing challenges for households in adapting to changing energy dynamics. Conclusions: Targeted interventions and communication strategies are crucial to promote pro-environmental behavior and facilitate the transition to sustainable energy sources. Understanding the relationships between health concerns, air pollution awareness, PEB, and energy source choices can inform policymakers and organizations in their efforts to ensure a sustainable and healthy future for Kyrgyzstan and other Central Asian countries.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Breast cancer is the most common cause of mortality due to cancer for woman both in Lithuania and worldwide. Chances of survival after diagnosis differ significantly depending on the stage of disease at the time of diagnosis and other factors. One way to estimate survival is to construct a Kaplan-Meier estimate for each factor value separately. However, in cases when it is impossible to observe a large number of patients (for example, in case of countries with lower numbers of inhabitants) dividing data into subsets, say, by stage at diagnosis may lead to results where some subsets contain too little data so that results of Kaplan Meier (or any other) method will become statistically incredible. The problem may become even more acute if the researcher would like to use more risk factors, such as stage at diagnosis, sex, place of living, treatment method, etc. Alternatively, Cox models are used to analyse survival data with covariates, and they don’t require dividing the data into subsets according to chosen risks factors (hazards).

This article provides a general overview of the bio-inspired computing method called DNA-Based Computing (DBC), including its theory and applications. The main theme of DBC is the central dogma of molecular biology (once information of DNA/RNA has got into a protein, it can’t get out again), i.e., DNA to RNA (sequences of four types of nucleotides) and DNA/RNA to protein (sequence of twenty types of amino acids) are allowed, not the reverse ones. Thus, DBC transfers few-element information (DNA/RAN-like) to many-element information (protein-like), solving a given cognitive problem. DBC can take many forms; this article elucidates two main forms, denoted as DBC-1 and DBC-2. Using arbitrary numerical examples, it is shown that DBC-1 can solve the following cognitive problems: “similarity indexing between seemingly different but inherently identical objects” and “recognizing regions of an image separated by a complex boundary.” DBC-2 can solve the following cognitive problem: “pattern recognition when the relevant information is insufficient.” Smart manufacturing-based systems (digital twins and big data analytics) must solve the abovementioned problems to make the manufacturing enablers (machine tools and monitoring systems) more self-reliant and autonomous. Consequently, DBC can improve the cognitive problem-solving ability of smart manufacturing-relevant systems and, thereby, can enhance its biologicalization.

Background: The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. Objective: Evaluate ex-ante whether the benefits of replacing peripheral venous catheters, peripherally inserted central catheters and midline catheters with ultrasound-guided peripherally inserted central catheters and midline catheters by a vascular access specialist team outweigh their costs. Methods: Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when replacing peripherally inserted central catheters, midline catheters and peripheral venous catheters with ultrasound-guided peripherally inserted central catheters and midlines, as well as the additional resources required for their use. Results: Each ultrasound-guided peripherally inserted central catheter replacing a peripherally inserted central catheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, each ultrasound-guided midline catheter replacing a midline, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96. Conclusion: The benefits of replacing peripheral venous catheters, peripherally inserted central catheters and midline catheters by introducing a vascular access specialist team trained in the implantation of ultrasound-guided peripherally inserted central catheters and midline catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of healthcare-associated infections. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.

Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a novel immunotherapy that has shown remarkable success in the treatment of adult relapsed or refractory (R/R) B-cell non-Hodgkin's lymphoma, adult R/R mantle cell lymphoma, and R/R acute paediatric lymphoblastic leukaemia. One barrier to the widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) with a variable grade of severity. The main manifestations of CRS are fever, hypotension, cytopenia, organ dysfunction among others. Neurological toxicities vary widely and range from headaches to encephalopathy. In addition, anti-CD19 CAR T-cell therapy provokes an array of less frequent events, such as coagulopathies, delayed cytopenia, and cardiovascular toxicities. In general, toxicities are usually reversible and resolve on their own in most cases, though severe cases may require intensive care and immunosuppressive therapy. Deaths due to CRS, neurologic toxicity and infectious complications have been reported, which highlights the gravity of these syndromes and the critical nature of appropriate intervention. In this paper, we look at all available FDA- and EMA-approved information about the pathophysiology, clinical manifestations, risk factor reviews of existing toxicity grading systems, current management strategies, and guidelines for anti-CD19 CAR T-cell toxicities. We also present new approaches, which are under investigation, to mitigate these adverse events.

The VEMoS AXL system is a new optical biometer based on spectral domain optical coherence tomography (SD-OCT) that has been tested in terms of intrasession repeatability and compared with a swept-source optical coherence tomography biometer (SS-OCT), which is considered the gold standard, for an agreement analysis. A biometric analysis was performed three consecutive times in 120 healthy eyes of 120 patients aged between 18 and 40 years with the SD-OCT system and afterwards a single measurement was obtained with the SS-OCT system. Within-subject standard deviations were 0.004 mm, 4.394 µm and 0.017 mm for axial length (AL), central corneal thickness (CCT), and anterior chamber depth (ACD) measures obtained with the SD-OCT biometer, re-spectively. The agreement between devices was good for AL (Limits of agreement, LoA: -0.04 to 0.03 mm) and CCT (LoA: -4.36 to 14.38 µm), whereas differences between devices were clinically relevant for ACD (LoA: 0.03 to 0.21 mm). In conclusion, the VEMoS AXL system provides consistent measures of anatomical parameters, being most of them interchangeable with those provided by the SS-OCT-based gold standard.

Non-ulcerated cutaneous leishmaniasis (NUCL) is an atypical and peculiar clinical form of the disease that was first described by Ponce et al. (1988) in Honduras (Central America), where iso-lated or disseminated popular and/or nodular skin lesions are commonly seen in adolescents and young adults. Leishmania (L.) chagasi was then incriminated as the causal agent of the disease, as well as of American visceral leishmaniasis (AVL), although NUCL has been shown to be more prevalent than AVL in the region. Considering, however, the dubious taxonomic character of the causal agent of NUCL, as there is no evidence of this form of disease associated with L. (L.) cha-gasi in South America, this study aimed to carry out a retrospective taxonomic analysis on a se-ries of studies on the diagnostic approach to the Honduran parasite in loco (El Tigre island, Amapala municipality, west coast of Honduras), where taxonomic characters of a biological (in vitro and in vivo), epidemiological (vector and canine reservoir), clinical-immunological (im-munopathological features of in situ skin lesion and systemic infection) and molecular (ge-nomic/phylogenetic analyses) nature were considered. The findings, particularly those of mo-lecular nature, such as: the Honduran parasite showed to be more ancestral (molecular clock analysis of the DNA polymerase alpha subunit gene) than all viscerotropic ones [L. (L.) chagasi, L. (L.) donovani and L. (L.) infantum], as well as presenting an absolutely unprecedented structural variation on chromosome 17 and the highest frequency of genomic SNPs (more than twice the number seen in the Brazilian parasite), in addition to representing a different phylogenetic lin-eage (mainly in the NJ - RNA Pol II tree) from those viscerotropic ones, have pointed to the characterization of a new leishmanine parasite, Leishmania (Leishmania) poncei n. sp. (Kinetoplas-tea: Trypanosomatidae), in honor of Professor Ponce, who was the first researcher to describe NUCL in Honduras.

The introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology is based on the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In such cases, the fact that the material design methods are based on fundamental scientific principles and have been proven in laboratories and through Accelerated Pavement Testing (APT), may be of little influence. However, the general acceptance of new disruptive technologies, e.g. telecommunications and Information Technologies (IT), have been based on the considerable advantages it presented. The same principles are applicable to the general acceptance and use of NME stabilisation/enhancement of materials in the road construction industry. This article is aimed at the practical cost-effective demonstration of the general application of the use of nanos-silane modified emulsions in the construction of the highest order roads, i.e. inter-city multi-lane highways, lower order roads (including Low-Volume-Roads (LVR)) and even local accesses to farms and in villages/townships. The implementation of NME technologies is directly associated with ease of use, time and cost savings and the addressing and reduction of risks applicable to the use thereof.

Loess provides a valuable terrestrial record of past environmental conditions, including the dynamics of air mass circulation responsible for dust transport. Here we explore variations in the luminescence characteristics of sedimentary quartz and feldspar – dominant minerals in loess-palaeosol sequences (LPS) - as possible tools for identifying changes in source. We investigate luminescence sensitivity, a rapidly measurable index which is the product of interplay between source lithology and the history of the mineral in question. Variations in sensitivity down profile may therefore reflect, among other factors such as pedogenesis and reworking, changes in sediment provenance. We undertake an empirical investigation of the luminescence sensitivity of quartz and feldspar from different grain-size fractions from the climatically sensitive Schwalbenberg LPS in the German Rhine valley, comparing samples from a 30 m core spanning the last full glacial cycle with samples of oxygen isotope stage (OIS) 3-2 age exposed within a c. 6 m profile downslope. The temporal overlap enables comparison of luminescence characteristics with respect to possible provenance change during that timeframe. We find an overall inverse relationship between quartz and feldspar sensitivity, as well as variability in sensitivity between different quartz grain sizes. There is some indication that feldspar sensitivity increases during periods of soil formation down the core. In particular, measurements of IR50 sensitivity on unprocessed sediments show correlation with down-profile trends in more established indicators of provenance. This suggests it may be used to provide a reliable, rapid scan of sensitivity changes, and may suggest source variability over millennial timescales.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.

In this paper we discuss a problem of generalization of binomial distributed triangle, that is sequence A287326 in OEIS. The main property of A287326 that it returns a perfect cube n as sum of n-th row terms over k; 0 ≤ k ≤ n−1 or 1 ≤ k ≤ n, by means of its symmetry. In this paper we have derived a similar triangles in order to receive powers m = 5; 7 as row items sum and generalized obtained results in order to receive every odd-powered monomial n^2m+1; m ≥ 0 as sum of row terms of corresponding triangle. In other words, in this manuscript are found and discussed the polynomials D_m(n,k) and U_m(n,k), such that, when being summed up over k in some range with respect to m and n returns the monomial n^2m+1.