Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p<0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Since the 70s, many countries have adopted different CRC screening programs which has resulted in a decrease in mortality. However, current screening test options still present downsides. The commercialized stool-based tests present high false-positive rates and low sensitivity, which negatively affects the detection of early stage carcinogenesis. The gold standard colonoscopy has low uptake due to its invasiveness and the perception of discomfort and embarrassment that the procedure may bring.In this review, we collected and described the latest data about alternative CRC screening techniques that can overcome these disadvantages. Web of Science and PubMed were employed as search engines for studies reporting on CRC screening tests and future perspectives. The searches generated 555 articles, of which 93 titles were selected. Finally, a total of 50 studies, describing 14 different CRC alternative tests, were included. Among the investigated techniques the main feature that could have an impact on CRC screening perception and uptake was the ease of sample collection. Urine, exhaled breath and blood-based tests promise to achieve good diagnostic performance (sensitivity of 63-100%, 90-95%, 47-97%, respectively) while minimizing stress and discomfort for the patient.

Breast cancer is the most common malignancies in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence based live cell non-invasive apoptosis detection sensor (IADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.

A 17th century wall painting representing a Virgin between two Saints in a noble Italian renaissance palace, Palazzo Gallo in Bagnaia (Viterbo, Italy), was restored in 2021 in the context of a wider restoration campaign interesting the main room of the palace built by cardinal Sansoni Riario. Diagnostic analyses done with traditional characterization techniques (optical microscopy on micro-stratigraphic sections, X-ray fluorescence spectroscopy and Fourier transform infrared spectroscopy) provided the identification of both original painting and restoration materials, while imaging investigations as ultraviolet fluorescence photography, false color images and multispectral mapping provided by hypercolorimetric multispectral imaging (HMI) technique enabled the evaluation of the state of conservation, locating restoration interventions and supporting the monitoring of the cleaning procedure. An altered protective Paraloid-based coating dating from early 2000s had to be removed due to the unpleasant glossy finishing given to the painted surface, making the scene barely readable. To pursue a restoration protocol based on environmental sustainability and green chemistry, enzyme-based gels marketed by Nasier-Brenta© and CTS© companies were tested in different protocols for the cleaning of the mash covering the painting. Although some interesting results were observed, the enzymatic cleaning had a scarce effectiveness with timing beyond a reasonable interval. Traditional chemical solvents as Dowanol PM (methoxy-propanol) and benzyl alcohol were necessary to complete the cleaning of the painting surface.

Nonionizing millimeter-waves (MMW) are reported to interact with cells in a variety of ways. Possible mechanisms of the inhibited cell division effect were investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm² safety standards. ~1.0 mW/cm² exposure over 5-6 hours treatment on 50 cells/μl samples of Saccharomyces cerevisiae model organism, resulted in 62% growth rate reduction compared to control (sham). The effect was specific for 85-105 GHz range and energy dose and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deletion cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm²) and compared to that of a compact waveguide (17.17 mW/cm²) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. Combinations of MMW mediated Structure Resonant Energy Transfer (SRET), membrane modulations eliciting signaling effects, and energetic resonance with biomolecules were indicated to be responsible for the observations reported. Our results provide novel mechanistic insights enabling innovative applications of nonionizing radiation procedures for eliciting targeted biomedical outcomes.

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A total of 108 microRNAs were significantly differentially expressed between normal breast and breast cancer tissues. Using clinicopathological information and microRNA sequencing data of 430 patients with breast cancer from The Cancer Genome Atlas (TCGA), the differences in candidate microRNAs between low- and high-grade cases were compared. Comparing the expression of the 108 microRNAs between low- and high-grade cases, 25 and 18 microRNAs were significantly upregulated and downregulated, respectively, in high-grade cases. Clustering analysis of the TCGA cohort using these 43 microRNAs identified two groups strongly predictive of histological grade. miR-3677 is a microRNA upregulated in high-grade breast cancer. The outcome analysis revealed that patients with high miR-3677 expression had a significantly worse prognosis than those with low miR-3677 expression. This study showed that microRNAs were associated with histological grade in early-stage invasive breast cancer. These findings contribute to the elucidation of a new mechanism of breast cancer growth regulated by specific microRNAs.

Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.

Nonionizing millimeter-waves (MMW) interact with cells in a variety of ways. Here the inhibited cell division effect was investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm2 safety standards. Irradiation using a power density of about 1.0 mW/cm2 , SAR over 5-6 hours on 50 cells/μl samples of Saccharomyces cerevisiae model organism resulted in 62% growth rate reduction compared to the control (sham). The effect was specific for 85-105 GHz range, and was energy and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deleted cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause permanent genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm2) and compared to that of a compact waveguide (17.17 mW/cm2) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. We have shown that non-thermal MMW radiation has potential for future use in treatment of yeast related diseases and other targeted biomedical outcomes.

Continuous glucose monitoring devices allow diabetes condition management. However, when limited data is available, one option is to increase their size by generating synthetic samples. From a homemade wearable prototype was created a real dataset with 18 instances and 53 attributes that capture characteristics of capillary and venous blood glucose, oxygen concentration, pulse rate, skin temperature, and 24 modules and 24 phases related to bio-impedance. The objective of this article is to generate synthetic datasets, and also it investigates the ideal features subset and optimal model for non-invasive diabetes prediction. Gaussian-Copulas (GC), conditional generative adversarial networks (CG), variational autoencoders, and Copula-GAN techniques' were used to generate five synthetic datasets. Experiments show that GC1 and GC2 datasets follow min/max boundaries and are not copies of the original data. Multilayer perceptron regressor outperformed (train and test) with 2.17, 2.51 in MAE; 9.29, 13.59 in MSE; 3.05, 3.69 in RMSE, and 0.95, 0.92 in R2 in GC1, and 2.64, 3.02 in MAE; 11.43, 15.11 in MSE; 3.38, 3.89 in RMSE, and 0.94, 0.92 in R2 in GC2 with eight features. Future work is necessary to explore autoencoder and generative architectures, datasets with diverse characteristics, and the effect of the number of features.

In food industry, there is a growing demand for cost-effective methods for inline inspection of food items able to non-invasively detect small foreign bodies which may have contaminated the product during the production process. Microwave imaging may be a valid alternative to the existing technologies, thanks to its inherently low-cost and its capability of sensing low-density contaminants. In this paper, a low-complexity microwave imaging system specifically designed to enable the inspection of a large variety of food products is presented. The system consists of two Circularly Loaded Antipodal Vivaldi Antennas, having a very large operative band, from 1 to 15 GHz, thus allowing a suitable spatial resolution for different food products from mostly fatty to high water-content ones. The antennas are arranged in such a way to collect the signal useful to exploit a recently proposed real-time microwave imaging strategy, leveraging the inherent symmetries usually characterizing food items. The system is experimentally characterized, and the achieved results compare favorably with the design specifications and the numerical simulations. Relying on these positive results, a first experimental proof of the effectiveness of the whole system is presented, which confirms its efficacy.

The present study provides an observation and documentation on the effect of static magnetic field on the growth of Triticum aestivum. The seeds are allowed to germinate and the seedlings are grown in an environment of the controlled static magnetic field while other physical factors such as temperature, light exposure, soil pH, etc. are held constant. Also, a comparison of influence on the average height between both the poles of the magnet is estimated and north pole oriented magnet is found to imply a significant difference. Finally some of the potential applications of the study in non-invasive protein silencing, GMO production, Vertical farming and Terraforming are briefly discussed.

This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.

Cancer cachexia is a multifactorial syndrome that is identified by ongoing muscle atrophy, along with functional impairment, anorexia, weakness, fatigue, anemia, reduced tolerance to antitumor treatments. Thus, reducing the patients’ quality of life. Cachexia alone causes about 22-25% of cancer deaths. This review covers the symptoms, mediators, available treatment, and prospects of 3D bioprinting for cancer cachexia. Studies about cachexia have shown several factors that drive this disease – protein breakdown, inflammatory cytokines activation, and mitochondrial alteration. Even with proper nutrition, physical exercises, anti-inflammatory agents, chemotherapy, and grafting attempts, standard treatment has been unsuccessful for cachexia. But the use of 3D bioprinting shows much promise compared to conventional methods by attempting to fabricate 3D constructs mimicking the native muscle tissues. In this review, some 3D bioprinting techniques with their advantages and drawbacks, along with their achievements and challenges in in-vivo applications have been discussed. Constructs with neural integration or muscle-tendon units aim to repair muscle atrophy. But it is still difficult to properly bio-print these complex muscles. Although progress can be made by developing new bio-inks or 3D printers to fabricate high-resolution constructs. Using secondary data, this review study shows prospects of why 3D bioprinting can be a good alternate approach to fight cachexia.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

Introduction: The transcranial direct current stimulation (tDCS) is a promising technique for brain modulation after cerebrovascular accident (CVA). This treatment modality has been previously studied in the recovery of patients. The aim of this review is to analyze the evidence in the ap-plication of tDCS in the recovery of gait disturbance in stroke patients. Methods: This review was conducted according to the recommendations of the PRISMA statement. Three different elec-tronic databases were searched for relevant results: PubMed, Scopus, and Cochrane. We included reviews and meta-analyses that only considered randomized controlled trials (RCTs) that inves-tigated the effects of transcranial direct electrical stimulation, in combination or not with other physiotherapy treatment, on gait recovery. Results: Thirteen studies with a total of 195 RCTs were included. Data on population, outcome measures, protocols and outcomes were extracted. The Amstar-2 scale and the GRADE system of certainty of evidence were used. Only one study re-ceived high certainty of evidence, 5 received low certainty of evidence and 7 received critically low certainty of evidence. Conclusions: Although the tDCS produces positive changes in gait recovery in spatio-temporal parameters, mobility, endurance, strength and motor function, there is insuf-ficient evidence to recommend this treatment.

Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence and statistical learning. The visuomotor Serial Reaction Time Task (SRTT) can measure these fundamental cognitive processes. In this review, we sought to answer whether repetitive transcranial magnetic stimulation (rTMS) is suitable for modulating visuomotor sequence learning and which factors mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain areas, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over the M1 usually weaken performance, but the results are less consistent for the DLPFC. These inconsistencies (at least in part) may be due to the current frequency-based heuristics of rTMS effects developed for explaining local stimulation effects in the motor cortex. Although this review cannot provide an ultimate answer about the optimal stimulation and task parameters, it comprehensively discusses the behavioral effects of six factors that are crucial for designing future studies to modulate sequence learning with rTMS. Moreover, we conclude that synergistically combining functional neuroimaging with rTMS could adequately link the rTMS-induced network effects with the behavioral findings that are crucial to develop a unified cognitive model of visuomotor sequence learning.

The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

Our prior studies have shown that B type Natriuretic Peptide (BNP) decreases absorption from the gastrointestinal (GI) tract. Since non-muscle myosin-type II (NMM-II) is known to have a role in epithelial tight junction regulation, we aimed to test whether BNP has an effect on the localization and expression of NMM-II in the intestinal villi. We treated wild type mice with a 10 ng/g intravenous bolus of BNP followed by infusion of BNP at 1ng/g/minute vs. vehicle control. The mice were then euthanized and intestinal tissue isolated and sectioned. The tissue was immune-stained for NMM-II and examined using fluorescence microscopy. The tissue section not treated with antibody to NMM-II was used as a methodological control to evaluate the non-specific binding. Scanning electron micrographic images were taken to compare structural differences between the two groups. Western blotting was performed to compare the regional protein expression of NMM-II and associated proteins including smooth muscle actin, kinesin, and E cadherin in small intestinal tissue between BNP vs. vehicle infused mice. Fluorescence microscopy revealed markedly increased localization of NMM-II at the crypts and core of intestinal villi of the jejunum, ileum and colon of BNP treated mice compared to vehicle. Transmission electron microscopy revealed that the microvilli of BNP treated mice assumed the distinctive appearance of ‘relaxed’ microvilli compared to vehicle. Such decrease in contractility was previously shown to decrease para-cellular permeability of epithelia. Our observation indicates that BNP alters the localization of NMM-II in intestinal villi and makes the intestinal villi structures assume a state of decreased permeability of the apical junctional complex. Further characterization of this process and understanding the specific mediators involved could lead to the identification of novel therapeutic targets for various disease states such as heart failure and malabsorption.

Background: Pancreatic invasive ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in Japan. The early diagnosis of pancreatic cancer, which will increase the number of patients with resectable tumors, is urgently needed. The purpose of the present study was to examine the earliest signs of pancreatic abnormalities on CT in order to facilitate the diagnosis and treatment of PDAC. Methods: Forty-one patients with pancreatic cancer and their 154 CTs were selected for the present study. We used the images that were acquired prior to the diagnosis and examined the pancreas in these images to observe serial changes in the morphology of the pancreas after selecting CT images in which PDAC was suspected. We also confirmed whether the main pancreatic duct was observed around that area of the pancreas. Four thousand two hundred seventy-seven patients without pancreato-biliary disease with 4630 CTs were selected for the control group. Results: Two pancreas shapes were detected: localized constriction of the pancreatic parenchyma referred to as the K-shaped sign, and localized fatty changes. Twenty-four (58.5%) of 41 patients showed the K-shaped sign. The main pancreatic duct without dilatation was noted around the K-shaped sign in 9 of the 24 patients. Eight of 41 patients (19.5%) showed localized fatty changes. Nine of 41 patients (21.9%) showed no abnormality. In the control group, only seven of 4277 patients (0.16%) showed the K-shaped sign. Conclusions: The K-shaped sign including localized fatty changes is the earliest CT sign that presents with pancreatic abnormalities. The K-shaped sign does not indicate PDAC itself but may predict its future development.

Respiratory therapist(RT)internet-supervised At-Home Telespirometry(AHT)was validated in pilot 22/95=23% ALS Clinic population. Erect, supine Vital Capacity(eFVC, sFVC)were measured longitudinally using ZephyRx smartphone interface and database recording in-clinic-conventional(Viaire-Vyasis-)and at-home-portable(MIR-Spirobank-Smart-)spirometers. Bland-Altman(BA)analysis supported content validity-precision and 7-day-test-re-test-validity [mean difference=0.15L(conventional–portable;95%CI -0.40L, 0.70L); = 2.7% predicted (conventional-portable;95%CI -12.1%, 17.5%) ]meeting ATS-ERS performance standards. RT Internet-supervised AHT measured sFVC was more frequently obtained[35/52=67.3 %]in-home-vs-in-clinic sFVC[9/21=42.9 %](Chi-Square;P=0.0533). Monthly mean eFVC slope decline for the eFVC > 60 % predicted baseline cohort was – 1.24% predicted per month[95% CI -2.15 ,-0.33% predicted]statistically significantly(P=0.015)less compared with the – 5.86% predicted per month[95% CI -9.44, -2.29 % predicted]decline for the eFVC < 60 % predicted baseline cohort and in this cohort was associated with statistically significant decreased survival(P=0.0219). RT Internet-supervised AHT facilitated initiation of non-invasive ventilation(NIV)in 5/22[23%]patients including 3/4[75%] homebound subjects. RT Internet-supervised AHT can be deployed for ALS patients stratified according to baseline eFVC for earlier detection of eFVC and sFVC decreases between clinic visits. A prospective research study[NCT05106569]is ongoing to further define the capability of online deployment of Respiratory therapist(RT)internet-supervised AHT in the timely initiation of NIV use to improve ALS respiratory care in larger numbers of ALS subjects.

Abstract: Background: Non-invasive acquistion of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r=0.64) and PCS (r=0.55) (p<0.01), as well as MAPIBP/DBPIBP for PES (r=0.6/0.55) and PCS (r=0.5/0.45) (p<0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease(0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

This paper presents a critical review and comparison of the results of recently published studies in the fields of human-machine interface and the use of sonomyography (SMG) for the control of upper limb prothesis. For this review paper, a combination of the keywords "Human Machine Interface", "Sonomyography", "Ultrasound", "Upper Limb Prosthesis", "Artificial Intelligence" and "Non-Invasive Sensors" was used to search for articles on Google Scholar and PubMed. Sixty-one articles were found, of which 59 were used in this review. For a comparison of the different ultrasound modes, feature extraction methods, and machine learning algorithms, 16 articles were used. It was found that various modes of ultrasound devices for prosthetic control, various machine learning algorithms for classifying different hand gestures, as well as various feature extraction methods for increasing the accuracy of artificial intelligence used in their controlling systems are reviewed in this article. The results of the review article show that ultrasound sensing has the potential to be used as a viable human-machine interface in order to control bionic hands with multiple degrees of freedom. Moreover, different hand gestures can be classified by different machine learning algorithms trained with extracted features from collected data with an accuracy of around 95%.

The present essay illustrates the methodological and theoretical premises of an emerging research area carrying out both ethological and (bio)ethical implications: the ethology of the freed animal (EFA). Unlike existing ethological fields, EFA focuses neither on non human (NH) animals in natural conditions of freedom in their own environment, nor on NH animals kept in conditions of “captivity”. Rather, EFA consists of a comparative study of NH animals that are released from a condition of more or less abusive captivity and instead relocated in an environment more appropriate to their species-specific and individual characteristics and inclinations. Ideal places for this study are contexts like “Animal sanctuaries” and parks/reserves provided with a camp or station for researchers, where a previously-captive NH animal can be reintroduced in his/her natural habitat. Even though EFA exists already, as a de facto practice of the specialized and/or volunteer personnel running sanctuaries and parks, the field still lacks a recognizable scholarly paradigm, and it is yet to be acknowledged at institutional/academic level. By consequence, one important aim for creating a field like this lies in the establishment of an active interaction between the two parties involved (researchers and sanctuaries/parks operators).

Breast cancer develops from cells lining the milk ducts and slowly grows into a lump or a tumour. Breast cancer may be invasive or non-invasive. Invasive cancer spreads from the milk duct or lobule to other tissues in the breast, whereas, non-invasive ones lack the ability to invade other breast tissues. Non-invasive breast cancer is called in situ and may remain inactive for entire lifetime. Due to heterogeneity nature of breast, density as well as masses is variable in size and shape. A dataset of 18056 patients are collected from 20 Government Hospitals and 50 Private Hospitals in West Bengal before COVID-19 and after COVID-19. The classification of patients are made on three classes- Normal, Sign of Abnormality and Abnormality. The reports of MRIs of patients in January 2020 and February 2020 are collected from different hospitals. It is treated as dataset before COVID-19 . MRIS of patients in April 2020 and May 2020 are dataset during COVID-19. The entire datasets are accumulated for testing of any change in patients MRIS after the official announcement of new virus COVID-19 in March 2020. The aim of the paper is to make a comparison of any change in size and shape of masses of MRIs of patients before and after COVId-19. All collected MRIs reports are diagnosed by radiologists of hospitals.

Background: Evidences on the effects of chemotherapy treatment cycles on measures of muscle, mental state, social and cognitive performance are scarce. Objective: To analyze the effects of chemotherapy cycles on muscle strength and activation, functional capacity, quality of life, fatigue and anxiety of women with breast cancer. Methods: Twenty-two women divided into a treatment group (n = 10; 46.6 ± 9.6 years) and control group (n = 12; 51.6 ± 7.0 years) participated in the study. Analysis of muscle performance, quality of life, fatigue and anxiety after the 2nd and 4th cycle of chemotherapy with anthracyclines and cyclophosphamide were performed in women with breast cancer (TRA) and compared to healthy women (CTR). Two-way ANOVA was used to compare the variance of the means and the significance level was set as p≤0.05. Results: Differences were found in the muscular activation of the vastus medialis between the groups at post time (p = 0.038), as well as in the sit and stand test in the baseline (p<0.001) and post moment (p<0.001). Functional capacity performance was different between baseline (p<0.001) and post-time (p<0.001) groups. Additionally, the TRA group worsened the quality of life in the domains of functional capacity (p<0.001) and limitation of physical aspects (p=0.002), besides presenting negative changes in fatigue. Conclusion: Anthracycline and cyclophosphamide chemotherapy cycles reduce muscular performance and affect biopsychosocial variables in women with breast cancer.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables show promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plum (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Treatment of myocytes with plum extract increased the cell size by ~3-fold (p<0.05) and stimulated myoblast differentiation by ~2-fold (p<0.05). Plum extract induced total protein synthesis by ~50% (p<0.05), reduced serum deprivation- induced total protein degradation by ~30% (P<0.05), and increased expression of IGF-1 by ~2-fold (p<0.05). Plum extract also reduced TNFα-induced NFkB activation by 80% (p<0.05) in A549/NFkB-luc cells. In addition, plum extract inhibited growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggest that plum extract may have pluripotent health benefits on muscle based on its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Breakthrough invasive fungal infections (bIFI) cause significant morbidity and mortality. Their diagnosis can be challenging due to reduced sensitivity of conventional culture techniques, serologic tests, and PCR-based assays in patients on antifungal therapy, and their diagnosis can be delayed contributing to poor patient outcomes. In this review, we provide consensus recommendations on behalf of the European Confederation for Medical Mycology (ECMM) for the diagnosis of bIFI caused by invasive yeasts, molds, and endemic mycoses, to guide diagnostic efforts in patients receiving antifungals and support the design of future clinical trials in the field of clinical mycology. The cornerstone of lab-based diagnosis of breakthrough infections for yeast and endemic mycoses remain conventional culture, to accurately identify the causative pathogen and allow for antifungal susceptibility testing. The impact of non-culture-based methods are not well-studied for the definite diagnosis of breakthrough invasive yeast infections. Non-culture-based methods have an important role for the diagnosis of breakthrough invasive mold infections, in particular invasive aspergillosis, and a combination of testing involving conventional culture, antigen-based assays, and PCR-based assays should be considered. Multiple diagnostic modalities, including histopathology, culture, antibody and/or antigen tests and occasionally PCR-based assays may be required to diagnose breakthrough endemic mycoses. A need exists for diagnostic tests that are effective, simple, cheap, and rapid to enable the diagnosis of bIFI in patients taking antifungals.

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

Biological invasions represent a threat to ecosystems, through competition and habitat destruction, which may result in significant changes of the invaded community. Asparagopsis armata is a red macroalgae (Rodophyta) globally recognized as an invasive species. It is found from the intertidal to shallow subtidal areas, on rock or epiphytic, forming natural vegetation belts on exposed coasts. This study evaluated the variations on native intertidal seaweed and macroinvertebrate assemblages inhabiting rock pools with and without the presence of the invasive macroalgae A. armata. To achieve this, manipulation experiments on Atlantic (Portugal) rock pools were done. Three rock pools were maintained without A. armata by manual removal of macroalgae, and three others were not experimentally manipulated during the study period and A. armata was freely present. In this study the variations between different rock pools were assessed. Results showed different patterns in the macroalgae composition of assemblages but not for the macrobenthic communities. Ellisolandia elongata was the main algal species affected by the invasion of A. armata. Invaded pools tended to show less species richness, showing a more constant and conservative structure, with lower variation of its taxonomic composition than the pools not containing A. armata, where the variability between samples was always higher. Despite the importance of the achieved results, further data based on observation of long-term series are needed, in order to further understand more severe effects of the invader A. armata on native macroalgal assemblage.

(1) Background: This case report focuses on a 46-year-old female patient diagnosed with a rare and aggressive form of breast cancer known as rapidly growing, ulcerated breast cancer. The patient exhibited rapid progression of the disease, experiencing discomfort and noticeable changes in the size and texture of the affected breast over a short period of time; (2) Methods: An intensive neoadjuvant chemotherapy regimen was employed as the primary treatment approach. The patient's response to this treatment was closely monitored and assessed. Various diagnostic tests and imaging techniques were utilized to evaluate the extent of the disease and track its response to the chemotherapy; (3) Results: The patient's response to the neoadjuvant chemotherapy regimen was remarkable, resulting in a complete pathologic response. This outcome, although unusual in rapidly growing, ulcerated breast cancers, highlights the effectiveness of neoadjuvant chemotherapy in managing large, locally advanced breast cancers; (4) Conclusions: The multidisciplinary approach employed in managing this complex breast cancer case proved to be crucial to the patient's favorable outcome. Despite the aggressive nature of the disease and the challenges posed by the rapid growth and ulceration, the patient achieved a positive result. This case contributes to the limited clinical literature on such unusual and aggressive breast cancer cases, providing valuable insights for future clinical practice.8

(1) Background: Previous systematic review suggested a beneficial effect of progressive muscle relaxation (PMR) for cancer patients receiving chemotherapy. However, poor quality of eligible studies impaired the reliability and validity of findings. Moreover, additional potential studies with good quality published in Chinese language have been published recently. The aim of the present systematic review was to investigate the value of PMR training in preventing and alleviating nausea and vomiting caused by chemotherapy among cancer patients. (2) Methods: We assigned two independent investigators to search all potential studies in PubMed, Cochrane Controlled Register of Trial (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang data. We used data extraction sheet extracted all essential information, and used the Cochrane risk of bias assessment tool to appraise the quality of eligible studies. Finally, we qualitatively summarized the results of all included studies. (3) Results: Six studies enrolling 288 patients were considered to meet our selection criteria finally. Of these 6 studies, three were labeled as moderate quality, and the remaining studies were low quality. All included studies consistently suggested that PMR has a positive impact on nausea and vomiting caused by chemotherapy among cancer patients especially alleviating the incidence, frequency and degree of delayed nausea and vomiting. (4) Conclusions: Independent studies indicated that PMR was a beneficial approach to prevent and alleviate nausea and vomiting caused by chemotherapy among cancer patients. However, further studies considering other types of primary tumors should be designed in order to increase the generality of PMR because studies included in the present systematic review mainly enrolled lung cancer and breast cancer.

Gross strap muscle invasion (gSMI) in patients with differentiated thyroid cancer (DTC) was defined as high-risk recurrent group in the 2015 American Thyroid Association guidelines. However, controversy persists because several studies suggested gSMI had little effect on disease outcome. Herein, a systematic review and meta-analysis was conducted to investigate impact of gSMI on outcome of DTC. Methods: A systematic search of electronic databases (PubMed, EMBASE, Cochrane Library, and MEDLINE) for studies published until February 2020 was performed. Case-control studies and randomized controlled trials that studied the impact of gSMI on outcome of DTC were included. Results: Six studies (all retrospective studies) involving 13639 patients met final inclusion criteria. Compared with no extrathyroidal extension (ETE), patients with gSMI were associated with increased risk of recurrence (P=0.0004,OR, 1.46; 95% CI: 1.18 to 1.80) and lymph node metastasis (LNM) (P<0.00001,OR 4.19;95% CI. 2.53 to 6.96). For mortality (P=0.34,OR 1.47;95% CI:0.67 to 3.25), ten-year disease-specific survival (P=0.80, OR 0.91;95% CI:0.44 to 1.88) and distant metastasis (DM) (P=0.21, OR 2.94;95% CI. 0.54 to 15.93), there was no significant difference between gSMI and no ETE group. In contrast with maximal ETE, patients with gSMI were associated with decreased risk of recurrence (P<0.0001,OR, 0.58; 95% CI: 0.44 to 0.76) , mortality (P=0.0003,OR 0.20;95% CI:0.08 to 0.48), LNM (P=0.0003,OR 0.64;95% CI. 0.50 to 0.81) and DM (P=0.0009,OR 0.28;95% CI. 0.13 to 0.59). Conclusions: DTC patients with gSMI had a higher risk of recurrence and LNM than those without ETE. However, in contrast with maximal ETE, a much better prognosis was observed in DTC patients with only gSMI. The findings of our meta-analysis provide supportive evidence for the validity of the T category changes in the 8th edition American Joint Committee on Cancer system. The actual impact of gSMI should be re-evaluated and revised in the recurrent risk stratification system in the future.

Over the last two months, as oncology specialists, we have frequently been contacted for estimating prognosis for cancer patients affected by COVID-19 infection. Until now, there have been no clear markers to guide decision making regarding the appropriateness of invasive ventilation in cancer patients affected by COVID-19 infection. Therefore, we developed a practical tool encompassing a prognostic score. We aimed at identifying a subgroup of patients likely to have a better outcome and therefore may be potential candidates for invasive ventilation, "The Milano Policlinico ONCOVID-ICU score". The score is composed by three groups of variables: patient’s characteristics such as sex, age, BMI and comorbidities; oncological variables (treatment intent, life expectancy, on or off-treatment status) and clinical parameters in association with laboratory values (SOFA score and D-dimer). The SOFA score includes six different clinical parameters and during the first few days of ICU admissions has an important prognostic role. The oncological history should never represent, per se, a contraindication to intensive care and must be considered together with other variables, such as laboratory values, clinical parameters and patient characteristics, in order to make the hardest but best possible choice. The Milano Policlinico ONCOVID-ICU score, to our knowledge, is the first prognostic score proposed in this setting of patients and may be a useful tool to assess the prognosis of cancer patients being in this critical condition.

Burn patients still represent an important challenge in critical care medicine today. These patients can develop significant neurological conditions up to intracranial hypertension, but as they find themselves hospitalized outside of neurocritical care and are often subjected to sedation for the complex management, they are sometimes underestimated. The aim of this study is to evaluate the feasibility of non-invasive methods for the early diagnosis of intracranial hypertension in these patients. In this prospective observational study, adult burn patients admitted to intensive care within the first 8 hours of the event were enrolled. These patients were studied through ultrasound measurement of optic nerve sheath diameter and intracranial vessel velocimetry with transcranial Doppler. In the 20 patients studied, no frankly pathological values were identified in the 3 different measurement stages (within 8 hours of the burn, then at 48 and 96 hours) and no correlations were identified between the measured values and the extension of the burn with the related risk of mortality. However, this study, one of a kind, demonstrates that these non-invasive methods are applicable to this specific patient population, and can represent an effective method for reducing the incidence of complications that are dangerous for survival.

In this study we used a recently developed ex vivo-in vitro model to assess the effect of feeding older adults a casein protein hydrolysate (CPH) compared with non-bioactive non-essential amino acid (NEAA) supplement on Muscle Protein Synthesis (MPS) and Breakdown (MPB). Serum from six healthy older males following overnight fast and 60 min postprandial ingestion of CPH or NEAA (0.33 g.kg^-1 body mass) was used to condition C2C12 myotube media. CPH-fed serum significantly increased MPS compared to fasted serum. In addition, CPH-fed serum induced myotube growth and markedly suppressed atrogin-1, but not MuRF1, expression. Comparatively, no change in MPS, myotube growth and gene expression was observed following NEAA-fed serum treatment. CPH-fed serum from older adults stimulated de novo MPS, suppressed markers of protein breakdown and resulted in myotube growth, indicating a potential role for CPH as a dietary protein source to prevent age-related sarcopenia.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

Much has been learned about the interaction between myosin and actin through biochemistry, in vitro motility assays and cryo-electron microscopy of F-actin decorated with myosin heads. Comparatively less is known about actin-myosin interactions within the filament lattice of muscle, where myosin heads function as independent force generators and thus most measurements report an average signal from multiple biochemical and mechanical states. All of the 3-D imaging by electron microscopy that has revealed the interplay of the regular array of actin subunits and myosin heads within the filament lattice has been accomplished using the flight muscle of the large waterbug Lethocerus sp. Lethocerus flight muscle possesses a particularly favorable filament arrangement that enables all the myosin cross-bridges contacting the actin filament to be visualized in a thin section. This review covers the history of this effort and the progress toward visualizing the complex set of conformational changes that myosin heads make when binding to actin in several static states as well as fast frozen actively contracting muscle. The efforts have revealed a consistent pattern of changes to the myosin head structures determined by X-ray crystallography needed to explain the structure of the different acto-myosin interactions observed in situ.

The purpose of this work was to evaluate a novel methodology developed by Digital Blood Corporation (DBC) to calculate critical blood values using four non-invasive measured values as input. The values obtained using a point-of-care testing (POCT) device were utilized for comparison and reference. Radial arterial blood was collected for the POCT comparator analysis using the Abbott i-STAT^® device. The non-invasive methodology from DBC requires four parameters to be directly measured: temperature, hemoglobin, pO2, and pCO2. Subsequently, sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation are calculated using an algorithm. The agreement between the POCT and DBC’s methodology was analyzed using Bland-Altman difference plots. For a second data set, pO2 and pCO2 values collected with the POCT were used as input for DBC’s algorithm to test its robustness. Data from 37 healthy ambulatory individuals, mean age: 42.4 + 13 years; range: 18-64 years, were included in the primary analysis. In the case of the non-invasive gained four input values the greatest variation between POCT and DBC’s approach was observed for pO2 and consequently for algorithm values that depend upon pO2 precision. Replacing transcutaneous pO2 and pCO2 with POCT values demonstrates the principal ability of DBC’s algorithm to predict the additional 8 blood values in sufficient agreement with a standard POCT device in healthy patients. The algorithm developed by DBC appears to be robust in the case of healthy patients but does need the four measured input values with preciseness comparable to a POCT device to give reliable and clinically relevant results. The present study thus serves as a proof of concept to facilitate future study and further development of this methodology into a non-invasive device.

Although cancers account for over 16% of all global deaths annually, at present, no reliable therapies exist for most types of the disease. As protein folding facilitators, heat shock proteins (Hsps) play an important role in cancer development. Not surprisingly, Hsps are among leading anticancer drug targets. Generally, Hsp70s are divided into two main subtypes: canonical Hsp70 (E. coli Hsp70/DnaK homologues) and the non-canonical (Hsp110 and Grp170) members. These two main Hsp70 groups are delineated from each other by distinct structural and functional specifications. Non-canonical Hsp70s are considered as holdase chaperones, while canonical Hsp70s are refoldases. This distinct characteristic feature is mirrored by the distinct structural features of these two groups of chaperones. Hsp110/Grp170 members are larger as they possess an extended acidic insertion in their substrate binding domains. While the role of canonical Hsp70s in cancer has received a fair share of attention, the roles of non-canonical Hsp70s in cancer development has received less attention in comparison. In the current review, we discuss the structure-function features of non-canonical Hsp70s members and how these features impact on their role in cancer development. We further mapped out their interactome and discussed the prospects of targeting these proteins in cancer therapy.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

This study analyzes the natural and social factors influencing the emergence and publicization of the invasive status of a fast growing bush, gorse (Ulex europaeus), by comparison between countries on a global scale. We used documents collected on the web in a standardized way. The results show that in all the countries studied, there are several public statuses attributed to gorse. The invasive status is the one that is most shared. The other most frequently encountered status are those of noxious weed, and of economically useful. The invasive status is publicized in nearly all countries, including those where gorse is almost absent. We quantified the publicization of the invasive gorse status of gorse by an indicator with 5 levels, and then performed a multivariate analysis that combines natural and social explanatory variables. The results lead us to propose the concept of invasive niche: the set of natural and social parameters that allow a species to be considered invasive in a given socio-ecosystem.

From the formalism of the thermodynamics of irreversible processes and the theory of complex systems, characterization of longevity and aging and its relationship with the emergence and evolution of cancer was carried out. It was found that: 1. The rate of entropy production can be used as an index of robustness, plasticity, the aggressiveness of cancer, and as a measure of biological age; 2. The aging process, as well as the evolution of cancer, goes through what we have called “biological phase transition”; 3. The process of metastasis, which occurs through epithelial-mesenchymal transition (EMT), appears as a phase transition far from thermodynamic equilibrium and exhibits Shilnikov chaos-like dynamic behavior. This dynamic guarantees the robustness of the process and, in turn, its unpredictability; 4. It was shown that as the ferroptosis process is strengthened, the complexity of the dynamics associated with the emergence and evolution of cancer decreases. The theoretical framework developed contributes to a better understanding of the biophysical-chemical phenomena of longevity and aging and their relationship with cancer.

In this review, we will cover a general overview of the current panorama on lncRNAs with an actual or potential role as biological markers in cancer. We will discuss examples of multi-omics approaches that integrates information on somatic aberrations, gene expression and epigenomics, with the scope of providing a more comprehensive view of the functional impact of lncRNA profiles and how these paradigm can be exploited for the discovery and selection of lncRNAs with a functional role and their use as variables informing on progression and prognostic and help guiding the selection of therapeutic strategies for cancers. Finally, we propose a perspective for future evolution of the study of lncRNAs and the discovery of their functional and harnessing their potential to assist in clinical management of malignancies.

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

The purpose of the present study was to examine the relationships between bat swing speed (BSS) and muscle thickness and lateral asymmetry of the trunk and limbs in collegiate baseball players. Twenty-four collegiate baseball players participated in this study. The maximum BSS in hitting a teed ball was measured using a motion capture system. The muscle thicknesses of the trunk (upper abdominal rectus, central abdominal rectus, lower abdominal rectus, abdominal wall, and multifidus lumborum), upper limb, and lower limb were measured using a B-mode ultrasonography. Lateral asymmetry between each pair of muscles was determined as the ratio of the thickness of the dominant side to that of the non-dominant side. Significant positive correlations were observed between BSS and muscle thicknesses of the abdominal wall and multifidus lumborum on the dominant side (r = 0.426 and 0.431, respectively; p < 0.05), while nearly significant positive correlations were observed between BSS and muscle thicknesses on the non-dominant side. No significant correlations were found between BSS and lateral asymmetry of all muscles. These findings indicate the importance of the trunk muscles for bat swing, and the lack of association between BSS and lateral asymmetry of muscle size.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

Arrhythmic sudden cardiac death (SCD) has an annual prevalence of 1 per 1000 while 75% of the victims suffer from ischemic and 10% from non-ischemic or hypertrophic cardiomyopathy. Altogether, these three entities account for more than 80% of the total SCD victims. Guidelines for implantable cardiac defibrillators are still dominated by LVEF<30% from the MADIT II study. In terms of arrhythmic risk stratification, the PRESERVE-EF study restored in clinical practice the two-step arrhythmic risk stratification approach based on Electrocardiographic non-invasive risk factors (NIRFs) guiding to electrophysiological study. In our times with the multiple cardiac imaging methods and artificial intelligence applications availability, this two-step approach based on integrated arrhythmia mechanisms detection, emerges as an efficient SCD risk stratification paradigm for these three entities but also for the patients with congenital heart disease.

Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize latest works providing in vivo evidence available for LncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target LncRNAs. The evidence discussed here strongly suggests that investigation of LncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open a new avenue for cancer treatment.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

This study aimed to investigate the effects of forearm postures and elbow joint angles on muscle torque and mechanomyography (MMG) signals. The torque about the elbow and MMG of the biceps brachii (BB) muscle were measured in 36 healthy subjects using an in-house elbow flexion testbed and Neuromuscular electrical stimulation (NMES) of the BB muscle. The BB muscle received stimulation intensity while the forearm was positioned in the neutral, pronation or supination. The elbow was flexed at angles 10°, 30°, 60° and 90°. (0° = full elbow extension). The study analyzed the impact of forearm posture(s) and elbow joint angle(s) on the root mean square value of torque (TQ_RMS). Subsequently, MMG parameters such as the root mean square value (MMG_RMS), the mean power frequency (MMG_MPF), and the median frequency (MMG_MDF), were analyzed in the longitudinal, lateral, and transverse axes of the BB muscle fibers. Forearm posture and elbow flexion angle were found to significantly influence TQ_RMS (P < 0.05). Similarly, MMG_RMS, MMG_MPF and MMG_MDF exhibited a significant difference for all postures and angles (P < 0.05). However, the combined main effect of forearm postures and elbow joint angles was insignificant in the longitudinal axis (P > 0.05). The study also found that MMG_RMS and TQ_RMS increased with the joint angle to 60° and decreased to the other angle(s). However, during this investigation,MMG_MPF and MMG_MDF exhibited a consistent decrease in response to joint angles. This finding suggests that the muscle contraction evoked by NMES may be influenced by the interplay between actin and myosin filaments, which are responsible for muscle contraction and are in turn influenced by muscle length. As restoring the function of limbs is a common goal in rehabilitation services, it becomes imperative to develop methods that may enable the real-time tracking of exact muscle dimensional changes and activation levels.

Background: Evaluating muscle mass and function among stroke patients is important. However, evaluating muscle volume and function is not easy due to the disturbance of consciousness and paresis. Temporal muscle thickness (TMT) has been introduced as a novel surrogate marker for muscle mass, function, and nutritional status. We herein performed a narrative literature review on temporal muscle and stroke to understand the current meaning of the TMT in the clinical stroke practice. Methods: The search was performed in PubMed, last updated in October 2021. Report on temporal muscle morphomics and stroke-related diseases or clinical entities were collected. Results: Four studies reported on TMT and subarachnoid hemorrhage, 2 intracerebral hemorrhage, 2 ischemic stroke, 2 standard TMT values, and 2 nutritional status. TMT was reported as a prognostic factor for several diseases, surrogate markers for skeletal muscle mass, and an indicator of nutritional status. Computed tomography, magnetic resonance imaging, and ultrasonography were used to measure TMT. Conclusions: TMT is gradually used as a prognostic factor of stroke or surrogate marker for skeletal muscle mass and nutritional status. Establishing standard methods to measure TMT and large prospective studies to investigate the further relationship between TMT and diseases are needed.

Skin cancer is a condition characterized by the abnormal growth of skin cells, primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Different types of skin cancer include melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite the advancements in targeted therapies, there is still a need for a safer, highly efficient approach to preventing and treating cutaneous malignancies. Spices have a rich history dating back thousands of years and are renowned for their ability to enhance the flavor, taste, and color of food. Derived from various plant parts like seeds, fruits, bark, roots, or flowers, spices are important culinary ingredients. However, their value extends beyond the culinary realm. Some spices contain bioactive compounds, including phenolic compounds, which are known for their significant biological effects. These compounds have attracted attention in scientific research due to their potential health benefits, including their possible role in disease prevention and treatment, such as cancer. This review focuses on examining the potential of spice-derived phenolic compounds as preventive or therapeutic agents for managing skin cancers. By compiling and analyzing the available knowledge, this review aims to provide insights that can guide future research in identifying new anticancer phytochemicals and uncovering additional mechanisms for combating skin cancer.

Lean body mass (LBM) is correlated with powerlifting performance in athletes competing in different bodyweight classes. However, it remains unknown whether changes in LBM are correlated with performance changes in powerlifters preparing for a competition. Aim of the study was to investigate the changes in LBM and performance in powerlifters preparing for a competition. Eight male powerlifters (age 31.7±9.8years, height 1.77±0.06m, weight 99.2±14.6kg) and three female powerlifters (age 32.7±16.3years, height 1.54±0.06m, weight 66.6±20.9kg), participated in the study. Athletes followed individualized periodized training programs for 12 weeks aiming to maximize their performance for the national championship. Maximum strength (1-RM) in squat, bench press, and deadlift, body composition, grip strength, anaerobic power, quadriceps’ cross sectional area and vastus lateralis muscle architecture were measured before and after the training period. Significant increases were found after the training period in squat (5.8±7.0%, P

At present, the applications and efficacy of non-ionizing radiations (NIR) in oncotherapy are limited. In terms of potential combinations, the use of biocompatible magnetic nanoparticles as heat mediators has been extensively investigated. Nevertheless, the development of more efficient heat nanomediators that may exhibit high specific absorption rates still is an unsolved problem. Our aim was to investigate if externally applied magnetic fields and a heat-inducing NIR affect tumor cell viability. To this end, under in vitro conditions, different human cancer cells (A2058 melanoma, AsPC1 pancreas carcinoma, MDA-MB-231 breast carcinoma) were treated with the combination of electromagnetic fields (EMFs, using solenoids) and hyperthermia (HT, using a thermostated bath). The effect of NIR was also studied in combination with standard chemotherapy and targeted therapy. An experimental device combining EMFs and high intensity focused ultrasounds (HIFU)-induced HT was tested in vivo. EMFs (25 T, 4h) or HT (52C, 40 min) showed a limited effect on cancer cell viability in vitro. However, their combination decreased viability to approx. 16%, 50%, and 21% of controls values in A2058, AsPC1, and MDA-MB-231 cells, respectively. Increased lysosomal permeability, release of cathepsins into the cytosol and mitochondria-dependent activation of cell death are the underlying mechanisms. Cancer cells could be completely eliminated combining EMFs, HT and standard chemotherapy or EMFs, HT and anti-Hsp70-targeted therapy. As a proof of concept, in vivo experiments performed in AsPC1 xenografts showed that combination of EMFs, HIFU-induced HT, standard chemotherapy and a lysosomal permeabilizer induces a complete cancer regression.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

Invasive fungal infections, notably candidemia, have been associated with COVID-19. The epidemiology of candidemia has significantly changed during the COVID-19 pandemic. We aim to identify the microbiological profile, resistance rates, and outcomes of COVID-19 associated candidemia (CAC) compared to patients with candidemia not associated with COVID-19. We retrospectively collected data on patients with candidemia admitted to the American University of Beirut Medical Center between 2004 and 2022. We compared the epidemiology of candidemia during and prior to the COVID-19 pandemic. Additionally, we compared the outcomes of critically ill patients with CAC to those with candidemia without COVID-19 from March 2020 till March 2022. Among 245 candidemia episodes, 156 occurred prior to the pandemic and 89 during the pandemic. Of the latter, 39 (43.8%) were CAC, most of which (82%) were reported from intensive care units (ICU). Non-albicans Candida (NAC) spp. were predominant throughout the study period (67.7%). Candida auris infection was the most common cause of NAC spp. in CAC. C. glabrata had decreased susceptibility rates to fluconazole and caspofungin during the pandemic period (46.1% and 38.4% respectively). Mortality rate in the overall ICU population during the pandemic was 76.6%, much higher than the previously reported mortality of candidemia from previous studies at our center. There was no significant difference in 30-day mortality between CAC and non-CAC (75.0% vs 78.1%; P =0.76). Performing ophthalmic examination (P = 0.002), CVC removal during the 48 hours following the candidemia (P = 0.008) and identifying the Candida spp. (P = 0.028) were significantly associated with a lower case-fatality rate. The epidemiology of candidemia has been significantly affected by the COVID-19 pandemic at our center. Rigorous infection control measures and proper antifungal stewardship are essential to combat highly resistant species like C. auris.

Background: Recently, minimally invasive access via right-anterolateral mini-thoracotomy (RAMT) has been gaining popularity in cardiac surgery. This approach is also an option for sur-geons performing aortic surgery. Aim of the study is to present our surgical method highlighting the total endoscopic minimally invasive approach via RAMT for replacement of the ascending aorta (AAR) with or without involvement of the aortic root and the aortic valve. Methods: Clini-cal data of 44 patients from three participating institutions with AAR with or without involving the aortic valve or aortic root via RAMT between April 2017 and February 2024 were retrospec-tively analyzed. According to surgical procedure patients were divided in group A with only AAR and group B with concomitant valve or root replacement. Operative time, length of ventila-tion, perioperative outcome, length of intensive care unit (ICU) as well as postoperative hospital stay, and mid- and long-term results were retrospectively analyzed. Results: Mean age was 61.4 ± 10.7 years old with a frequency of male gender (63.6%). Mean cardiopulmonary bypass (CBP) time and aortic cross-clamping time was 94.9 ± 32.5 min. and 63.8 ± 25.9 min., respectively. CPB and aortic clamp time were significantly lower in group A. In the first 24 hours the mean drain-age volume was 790.3 ± 423.6 ml. Re-thoracotomy due to bleeding was zero. Sternotomy could be avoided in all patients. Patients stayed 35.9 ± 23.5 hrs at ICU and were discharged 7.8 ± 3.0 days following surgery from hospital. Mean ventilation time was 5.8 ± 7.6 hrs. All patients survived and 30-day mortality was 0.0%. At a median follow-up time of 18.2 months, all patients were alive. The results were similar in both groups. Conclusions: The full endoscopic RAMT approach with 3D visualization is a safe and feasible technique which can be transferred in the field of aor-tic surgery without compromising surgical quality, postoperative outcomes, or patient safety when performed by an experienced team in a high-volume center.

Computers and artificial intelligence affect every field of life nowadays. In medical image interpretation automatic decision making using algorithms are used increasingly in every sub-field and computer aided diagnosis (CAD) is one of the main tools available to medical science today. CAD systems are used as an augmented option for both the medical practitioner and the patients, with image analysis and interpretation being of primary importance. In particular, spatial relations are used in knowledge representation, and these relations can be used for effective medical image interpretation. In this paper, we put forth an algorithm for defining non-small cells lungs cancer (NSCLC) stages in lungs images interpretation using topological spatial relations. We show an application case study in event motion predictions for lung cancer staging scoring - tumor, nodes and metastasis (TNM) - with combined topological and directional relations.

We aimed to determine whether A-mode ultrasound (US) can provide accurate and reliable measurements comparable to those obtained through B-mode US, under diverse conditions. Thirty healthy participants (15 female, 15 male) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscle with both US modes after and before exercises designed to stimulate the respec-tive muscles. In three key indices, the results demonstrated high validity of A-mode, with min-imal mean differences between the two devices less than 0.91mm and intraclass correlation coef-ficients exceeding 0.95 at all measures. Also, Correlation coefficients between error scores and average scores for the trapezius and biceps brachii muscles suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and biceps brachii MT significantly in-creased after exercise (p<0.05). Notably, both A-mode and B-mode exhibited the same tendency in these post-exercise changes in muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to more expensive, high-resolution B-mode imaging. A-mode US can serve as an affordable and portable alternative for muscle assessment.

Near-Infrared Spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity. The current method requires as many as 22 short ischemic occlusions to generate a recovery curve for mitochondrial capacity. PURPOSE: To determine the effectiveness of using a 6-occlusion analysis protocol to study muscle mitochondrial capacity. METHOD: Two independent, unidentified data sets were analyzed (bicep n=48, forearm n=41) from previous studies using a NIRS device (Artinis, Ltd.). Both data sets had two recovery tests that included 22 ischemic occlusions. A recovery rate used to indicate mitochondrial capacity was calculated two different ways (simultaneously). Each sample was analyzed with a MATLAB program; with a curve-fit for the 22 ischemic occlusions and curve matching for the first six ischemic cuffs and an end resting value. The two resulting rate constants were compared using correlations, both for the two data sets, good and bad fitting data, using the best 5 of 6 points for the 6 cuff approach. RESULTS: The rate constants were not significantly different between the 22 cmuff and 6 cuff for the total data sets: bicep (1.43+0.32min^-1, 1.44+0.35min^-1, p=0.56), forearm (1.94+0.42min^-1, 1.95+0.44min^-1, p=0.76). The average bicep rate constants, when compared to each other, had an equation of y=1.07x-0.09, R²=0.90. The average forearm rate constants, when compared to each other, had an equation of 0.98x+0.02, R²=0.93. CONCLUSIONS: The 6-Cuff analysis provided the same results as the longer 22-cuff. The 6-cuff approach is both shorter in time and uses less ischemic occlusion periods, increasing the practicality of the NIRS mitochondrial capacity test.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

Minimally invasive approaches to the aortic valve have been described since 1993, with great hopes that they would become universal and facilitate day-case cardiac surgery. The literature has shown that these procedures can be undertaken with equivalent mortality, similar operative time, comparative cost and some benefits in hospital length of stay. The competing efforts of the transcatheter aortic valve implantation for these same outcomes have provided an excellent range of treatment options for patients from the Heart Team. We describe the current state of the art, including technical considerations, caveats and complications of minimal access aortic surgery and predict future directions in this space.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

Background: Objectives. The objective of this study was to compare the efficacy of direct current stimulation (DCS) applied at the transcranial, suboccipital and spinal level on experimental sensory modalities and pain outcome measures in healthy subjects. The hypothesis of this study was that systematic analysis of the efficacy of DCS on modulating evoked thermal and mechanical pain modalities and mechanisms such as endogenous pain modulation in healthy individuals would reveal sensitive outcome measures help develop this technique for the control of chronic pain. Materials and Methods. Database searches were conducted up to December 2019 for randomized controlled trials that performed sham-controlled DCS of experimental sensory modalities and pain outcomes following transcranial, suboccipital and spinal locations in healthy participants. Standardized mean differences with 95% confidence intervals were calculated for sensory modalities, including random-effect metanalysis. Results: Thirty-one studies were included for analysis (647 participants). A significant decrease in pain intensity for active vs sham transcranial stimulation was identified for pain intensity (n=158; SMD=0.79; 95% CI=0.56 to 1.02), a significant increase in heat pain threshold (n=222; SMD=1.16; 95% CI=0.95 to 1.37), and a significant increase in cold pain threshold (n = 155; SMD = 0.77, 95% CI 0.53 to 1.01). No significant modulation of pressure pain threshold was identified with DCS and only a limited number of studies focused on experimental pain modulation following neuromodulation at the suboccipital or spinal level. Conclusions: These results show significant transcranial DCS neuromodulation of pain intensity and on thermal pain modalities. Future studies should focus on endogenous pain and sensory modality modulation with sham-controlled DCS applied at transcranial, suboccipital and spinal locations.

This paper discusses a cross-disciplinary, international collaboration aimed at researching a series of 15th century choir books at the abbey of San Giorgio Maggiore on the homonymous island in Venice. Produced for the abbey itself, the books have never left the island during their 500-years history, thereby allowing a unique opportunity to analyse historic artefacts, which have undergone little modification over time. Prompted by ongoing cataloguing work on the manuscripts, a week-long analytical campaign using a combination of non-invasive analytical methods used in portable configuration allowed the comprehensive characterisation of ten volumes. The manuscripts’ palette and painting techniques were analysed using near-infrared imaging, reflectance spectroscopy in the UV-vis-NIR range, Raman spectroscopy, X-ray fluorescence mapping and digital microscopy. The paper will discuss the challenges linked to the fragility and the large dimensions of the volumes as well as the most interesting results of the investigation. These include the detection of unusual painting materials such as bismuth ink, as well as the discovery of a less homogeneous palette than originally expected, which prompted a partial revision of the attribution of the decoration in one of the volumes to a single artist.

The correlation between pain and emotional status in subjects with temporomandibular disorders (TMD) is known. Regardless of that up to date these findings were seldomly confronted with the objective assessment of pain using a digital algometer on the mastication muscles. The aim of the study was to investigate the relationship between the emotional status, chronic pain pain pressure threshold (PPT). 38 subjects were screened for the existence of temporomandibular disorders with the 3Q/TMD questionnaire, for chronic pain (GCPS) and emotional status (PHQ-9 and GAD-7). The results were confronted with the PPT measured with the digital algometer on the masseter muscles. Each subject was examined three times (after 1 month and after 7 months from the initial exami-nation session. Chronic pain scores (GCPS) were found to be higher in the TMD group in all three examination sessions (p<0,05). The pain, depression and anxiety levels were higher in females de-spite the existence of TMD, but only some were significant.A correlation between chronic orofacial pain scores and PPT was found in 2 out of 3 examination sessions. The PPT scores on the masseter muscles did not correlate with the emotional state in the study population.

Objective: The main purpose of the study is to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Methods: Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline, PDRN, ESWT, PDRN injection before ESWT, and PDRN injection after ESWT. Following 2 weeks of cast immobilization, the respective treatments were administered to the atrophied calf muscles. Radial ESWT was performed twice weekly. The evaluation included measurements of calf circumference, tibial nerve compound muscle action potential (CMAP), and gastrocnemius (GCM) muscle thickness after 2 weeks of treatment. Histological and immunohistochemical staining, as well as Western blot analysis, were conducted 2 weeks post-treatment. Staining intensity and extent were assessed using semi-quantitative scores. Results: Groups 4 and 5 demonstrated significantly greater calf muscle circumference, GCM muscle thickness, tibial nerve CMAP, and GCM muscle fiber cross-sectional area (types I, II, and total) than in the remaining three groups (p < 0.05), while they did not did not differ significantly in these parameters. Groups 2 and 3 showed the higher values for all the observations compared to group 1 (p < 0.05). Group 4 had the greatest ratio of vascular endothelial growth factor (VEGF) to platelet endothelial cell adhesion molecule-1 (PECAM-1) in the gastrocnemius muscle fibers than in the other four groups (p < 0.05). Western blot analysis revealed significantly higher expression of angiogenesis cytokines in groups 4 and 5 than in the remaining (p < 0.05). Conclusion: The combination of ESWT and PDRN injection demonstrated superior regenerative efficacy for atrophied calf muscle tissue in rabbit models than these techniques alone or saline. Particularly, administering ESWT after PDRN injection yielded the most favorable outcomes in specific parameters.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis. Echocardiographic data of 45 patients (25 thoracotomy vs. 20 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue doppler imaging. No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE (mm): 17.90 ± 3.80 vs. 20.60 ± 3.50, p &lt; 0.018; TASV (cm/s): 12.40 ± 2.90 vs. 14.60 ± 2.50, p &lt; 0.010; RVFWGLS (%): −11.50 ± 8.50 vs. −17.50 ± 9.70, p &lt; 0.033), respectively]. Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

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.

Cancer is a complex and devastating disease that has engaged scientists and researchers for decades. Despite tremendous efforts, previous hypotheses about cancer development have not achieved significant breakthroughs. Evolutionary Cancer Cell Biology (ECCB) is a novel and emerging branch of oncological science that provides an evolutionary perspective on the origin of cancer. It reveals that the cancer genome evolved hundreds of millions of years ago, long before multicellular organisms such as metazoans and humans emerged. ECCB aims to unify all evolutionary insights, hypotheses, and theories into a cohesive framework. It investigates the intricate relationship between cancer genomics and ancient pre-metazoan genes that emerge when normal cells transform into cancer cells. It challenges the conventional wisdom of cancer research by suggesting that cancer could arise through intrinsic cellular mechanisms without genetic alterations and mutations. Furthermore, it postulates that somatic mutations are only secondary, downstream events in the process of oncogenesis.

Lynch syndrome (LS) is an inherited disorder in which affected individuals have a significantly higher-than-average risk of developing colorectal and non-colorectal cancers, often before the age of 50 years. In LS, mutations in DNA repair genes lead to a dysfunctional post-replication repair system. As a result, the unrepaired errors in coding regions of the genome produce novel proteins, called neoantigens. Neoantigens are recognised by the immune system as foreign and trigger an immune response. Due to the invasive nature of cancer screening tests, universal cancer screening guidelines unique for LS (including colonoscopy) are poorly adhered to by LS variant heterozygotes (LSVH). Currently, it is unclear whether immunogenomic components produced as a result of neoantigen formation can be used as novel biomarkers in LS. We hypothesize that: (i) LSVH produce measurable and dynamic immunogenomic components in blood, and (ii) these quantifiable immunogenomic components correlate with cancer onset and stage. Here, we discuss feasibility and propose the potential to: (a) identify personalised novel immunogenomic biomarkers, (b) reduce invasive cancer screening tests and thus increase non-invasive cancer surveillance, (c) improve compliance and adherence to recommended cancer screening guidelines in LSVH.

Box tree moth, Cydalima perspectalis is native to East Asia where it occurs on Buxus trees. Its natu-ral distribution includes China, Japan, Korea and India, and it was accidentally introduced into Europe, Middle East, North America and north Africa through the trade in Buxus spp., where it can cause considerable damage. In the native range of C. perspectalis, three tachinids (Diptera, Tachinidae) are known to parasitize larvae of C. perspectalis, including Exorista sp., Pseudoperichaeta nigrolineata (Walker 1853) and Compsilura concinnata (Meigen 1824). Data on tachinid parasitoids parasitizing C. perspectalis on the European continent include only P. nigrolineata. Field collection of mature larvae and pupae of C. perspectalis during July 2020 in four locations in Split – Dalmatia County in Croatia resulted in collection of live tachinid larvae that were reared to adults. The tachinid specimens were identified at the Natural History Museum, London, UK, as Nemorilla flo-ralis (Fallén, 1810) (Diptera, Tachinidae). Conservatively, 1.2 – 2.4 % parasitism rate was achieved. This is the first world record of N. floralis parasitism on C. perspectalis larvae, which can be added as a potential tool for C. perspectalis biological control.

Birds are highly social and need pairing in order to increase their welfare. Most bird species are monomorphic, therefore, molecular sexing helps to provide appropriate welfare for birds. Moreover, early sex determination can be of great value for bird owners. The aim of this study was to demonstrate that sex identification in birds by molecular methods, using samples collected by minimally invasive methods is fast, efficient and accurate. A total of 100 samples (29 paired samples of feathers - oral swab and 14 tripled samples of feathers - oral swab - blood) from 43 birds were taken into study, as follows: wild birds (Falconiformes, Accipitriformes, landfowl – Galliformes, waterfowl– Anseriformes), companion birds (Passeriformes, Psittaciformes – large, medium and small size parrots). Amplification of CHD1-Z and CHD1-W genes was performed by conventional PCR. The results obtained from feathers were compared to those obtained from oral swabs and with those obtained from blood samples, where was the case. The obtained results show that all types of samples can be used for molecular sexing of all studied species of birds. According to our knowledge, the present study reports for the first time the molecular sex identification in: Red Siskin (Carduelis cucullata) and Goldfinch (Carduelis carduelis major). For higher accuracy, our recommendation is to use minimally invasive samples (swab-feathers) and to test both types of samples, for each bird, instead of blood samples.

Abstract: (1) Background: Minimally-invasive sacroiliac joint (SIJ) fusion is the preferred surgical intervention to treat chronically severe pain associated with SIJ degeneration and dysfunction. (2) Methods: This paper details the ten-step surgical procedure associated with the postero-inferior approach using the PsiF™DNA Sacroiliac Joint Fusion System. (3) Results: The posterior surgical approach with an inferior operative trajectory (postero-inferior) utilizes easily identifiable landmarks to provide the safest, most direct access to the articular joint space for transfixing device placement. Implanting the device through the subchondral bone, provides maximum fixation and stabilization of the joint by utilizing an optimal amount of cortical bone-implant interface. Approaching the joint from the inferior trajectory also places the implant perpendicular to the S1 endplate at a “pivot point” near the sacral axis of rotation, which addresses the most significant motion of the joint. (4) Conclusions: Further observational data from real-world clinical use are encouraged to further validate this procedure as the surgical preference for minimally-invasive SIJ fusion.

Striated muscle thick filaments are composed of myosin II and several non- myosin proteins which define the filament length and modify its function. Myosin II has a globular N-terminal motor domain comprising its catalytic and actin-binding activities and a long α-helical, coiled-coil tail that forms the dense filament backbone. Myosin alone polymerizes into filaments of irregular length, but striated muscle thick filaments have defined lengths that with the thin filament define the sarcomere structure. The motor domain structure and function are well understood but the myosin filament backbone is not. Here we report a structure of the flight muscle thick filaments from Drosophila melanogaster at 4.7 Å resolution which eliminates previous ambiguities in the non-myosin densities. The full proximal S2 region is resolved as are the connecting densities between the Ig domains of stretchin-klp. The proteins, flightin and myofilin are resolved in sufficient detail to build an atomic model based on an AlphaFold prediction. Our results suggest how flightin and myofilin cooperate to define the structure of the thick filament and explains a key myosin mutation that affects flightin incorporation. Drosophila is a genetic model organism for which our results can define strategies for functional testing.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcomes measures selected: the myostatin inhibition story thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models has failed to translate into clinical benefit to patients has been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.

Adaptation to external forces relies on a well-functioning proprioceptive system including muscle spindle afferents. Muscle length-tension control in reaction to external forces is most important regarding the Adaptive Force (AF). This study investigated the effect of different procedures, which are assumed to influence the function of muscle spindles, on the AF. 19 elbow flexors of 12 healthy participants were assessed by an objectified manual muscle test (MMT) with different procedures: regular MMT, MMT after pre-contraction (self-estimated 20% MVIC) in lengthened position with passive return to test position (CL) and MMT after CL with a second pre-contraction in test position (CL-CT). During regular MMTs, muscles maintained their length up to 99.7±1.0% of the maximal AF (AFmax). After CL, muscles started to lengthen at 53.0±22.5% of AFmax. For CL-CT, muscles were again able to maintain the isometric position up to 98.3±5.5% of AFmax. AFisomax differed highly significantly between CL vs. CL-CT and regular MMT. CL is assumed to generate a slack of muscle spindles which led to a substantial reduction of the holding capacity. This was immediately erased by a pre-contraction in test position. The results substantiate that muscle spindle sensitivity seems to play an important role for neuromuscular functioning and musculoskeletal stability.

Invasive alien plant species (IAPS) pose one of the most significant threats to native biodiversity. Swietenia macrophylla, or big leaf mahogany, is among the most threatening invasive plants in the Philippines. This article aimed to formally document the presence of S. macrophylla along the edges of Mt. Banahaw de Nagcarlan, a protected area on Luzon Island, Philippines. The study also sought to identify the management strategies being implemented by various government institutions for addressing big leaf mahogany and other invasive plants. A total of 1591 individuals of S. macrophylla were documented in mixed land-use areas and roadsides. These were found to have been introduced by the Department of Environment and Natural Resources in 1991 as a reforestation species. Fortunately, no individuals were observed beyond the buffer zone towards the protected area. The identification of management strategies for big leaf mahogany and other IAPS revealed that there is no established approach specifically addressing the presence of S. macrophylla at the site. However, some institutions advocate for the conservation of native plants through tree planting activities and educational campaigns. Furthermore, no collaborative efforts were observed among stakeholders and institutions. The results of this study highlight the urgent need for managing the S. macrophylla population. Planning and enforcement of strategies require collaborative efforts among stakeholders to prevent its entry into the protected area and ensure the preservation of native biodiversity.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol® modified citrus pectin (P-MCP) is a food supplement generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is a competitive inhibitor of galectin-3 protein, involved in cancer pathogenesis. P-MCP treatment of BRPC-M0 patients for 6 months led to a 75% prostate-specific antigen doubling time (PSADT) improvement. To determine the longer-term effects of P-MCP we investigated an additional 12 months of treatment (phase II) with oral P-MCP at 4.8 grams X 3/day in patients with no disease progression in the previous 6 months. Of the 46 patients that entered the second phase, 7 patients withdrew consent and continued therapy independently, and 39 received another 12 months of therapy. After a total of 18 months P-MCP treatment, 62% (n=24) had a decreased/stable PSA, 90% (n=35) had improved PSADT, and 85% (n=33) had a durable long-term response, with a decreased/stable PSA, and/or improvement of PSADT, and negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long term durable efficacy, and is safe, in BRPC-M0.

Background: The thoracolumbar fascia (TLF) is thought to play a role in the development of LBP, but it is not yet clear which factor of TLF changes is a cause and which is an effect. Therefore, some studies used the cross-correlation function (CCR) to reveal time-dependent relationships between biomechanical and neuromotor factors. Methods: Ten patients with acute low back pain (aLBP) were matched to healthy controls. Simultaneous recording of surface electromyography (sEMG) of the erector spinae muscle (ES) and dynamic ultrasound (US) images of TLF deformation were performed during trunk extension. CCR functions and Granger causality were used to describe the relationship between the two measures. Results: CCR time lags were significant higher in the aLBP group (p = 0.04). Granger causality (GC) showed a direct effect of TLF deformation on ES activation only in the aLBP group (p &lt; 0.03). Conclusions: The results suggest that in aLBP, ES activity is significantly affected by TLF, whereas this relation-ship is completely random in healthy subjects studied with CCR and GC comparisons of dynamic US imaging and sEMG data signals. Fascia-related disturbances in neuromotor control, particularly due to altered muscle spindle functions, are suspected as a possible mechanism behind this.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.