Miracle-dz/UniFAR-FTUs huggingface dataset:
Swimming Training Does Not Affect the Recovery of Femoral Midshaft Structural and Mechanical Properties in Growing Diabetic Rats Treated with Insulin

Background: The effects of swimming training associated with insulin treatment on the cortical bone health in young rats with severe type 1 diabetes remain unclear, although there is evidence of such effects on the cancellous bone. This study examined the effects of swimming training combined with insulin therapy on the femoral midshaft structural and mechanical properties in growing rats with type 1 diabetes. Methods: Male Wistar rats were divided into six groups (n = 10): control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetic rats received an injection (60 mg/kg body weight) of streptozotocin (STZ). Exercised animals underwent a swimming program for eight weeks. Results: Diabetes induced by STZ decreased the bone mineral content (BMC) and density (BMD), and cortical thickness and maximum load and tenacity in the femoral midshaft. Insulin treatment partially counteracted the damages induced by diabetes on BMC, BMD and cortical thickness and tenacity. Swimming training did not affect the femoral structural and mechanical properties in diabetic rats. The combination of treatments did not potentiate the insulin effects. In conclusion, swimming training does not affect the benefits of insulin treatment on the femoral midshaft structural and mechanical properties in growing rats with severe type 1 diabetes.
Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

Simple Summary Although atezolizumab plus bevacizumab combination therapy was approved in September 2020 as the first immune-combined therapy for hepatocellular carcinoma, the efficacy and safety of this therapy are unclear in real-world practice. This study investigated the early antitumor effects of atezolizumab plus bevacizumab using imaging and tumor markers, and early safety using the frequency of adverse events and the change in hepatic reserve function, especially for patients with a history of previous systemic treatment. The decreased level of serum α-fetoprotein may reflect the early tumor response in atezolizumab plus bevacizumab, and this therapy is safe in all patients, including those in which it was used as a second-line or later treatment. Abstract The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37–649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.
Analytical Performance of NGS-Based Molecular Genetic Tests Used in the Diagnostic Workflow of Pheochromocytoma/Paraganglioma

Simple Summary The escalating use of Next Generation Sequencing in the routine clinical setting greatly facilitates the genetic diagnosis of hereditary cancer syndromes. However, these novel methods pose new and unique challenges. In our study we sought to demonstrate the evolution of these techniques, especially whole exome sequencing and targeted panel sequencing. This study highlights the multi-layered workflow and how each step affects the diagnostic outcome and demonstrates the effectiveness of an in-house developed targeted panel sequencing for hereditary endocrine tumor syndromes. Abstract Next Generation Sequencing (NGS)-based methods are high-throughput and cost-effective molecular genetic diagnostic tools. Targeted gene panel and whole exome sequencing (WES) are applied in clinical practice for assessing mutations of pheochromocytoma/paraganglioma (PPGL) associated genes, but the best strategy is debated. Germline mutations of at the least 18 PPGL genes are present in approximately 20–40% of patients, thus molecular genetic testing is recommended in all cases. We aimed to evaluate the analytical and clinical performances of NGS methods for mutation detection of PPGL-associated genes. WES (three different library preparation and bioinformatics workflows) and an in-house, hybridization based gene panel (endocrine-onco-gene-panel- ENDOGENE) was evaluated on 37 (20 WES and 17 ENDOGENE) samples with known variants. After optimization of the bioinformatic workflow, 61 additional samples were tested prospectively. All clinically relevant variants were validated with Sanger sequencing. Target capture of PPGL genes differed markedly between WES platforms and genes tested. All known variants were correctly identified by all methods, but methods of library preparations, sequencing platforms and bioinformatical settings significantly affected the diagnostic accuracy. The ENDOGENE panel identified several pathogenic mutations and unusual genotype–phenotype associations suggesting that the whole panel should be used for identification of genetic susceptibility of PPGL.
Causality in Reversed Time Series: Reversed or Conserved?

The inference of causal relations between observable phenomena is paramount across scientific disciplines; however, the means for such enterprise without experimental manipulation are limited. A commonly applied principle is that of the cause preceding and predicting the effect, taking into account other circumstances. Intuitively, when the temporal order of events is reverted, one would expect the cause and effect to apparently switch roles. This was previously demonstrated in bivariate linear systems and used in design of improved causal inference scores, while such behaviour in linear systems has been put in contrast with nonlinear chaotic systems where the inferred causal direction appears unchanged under time reversal. The presented work explores the conditions under which the causal reversal happens—either perfectly, approximately, or not at all—using theoretical analysis, low-dimensional examples, and network simulations, focusing on the simplified yet illustrative linear vector autoregressive process of order one. We start with a theoretical analysis that demonstrates that a perfect coupling reversal under time reversal occurs only under very specific conditions, followed up by constructing low-dimensional examples where indeed the dominant causal direction is even conserved rather than reversed. Finally, simulations of random as well as realistically motivated network coupling patterns from brain and climate show that level of coupling reversal and conservation can be well predicted by asymmetry and anormality indices introduced based on the theoretical analysis of the problem. The consequences for causal inference are discussed.
Comparison of skeletal muscle ultrastructural changes between normal and blood flow‐restricted resistance exercise: A case report

What is the main observation in this case? The main observation of this case report is that blood flow‐restricted exercise can cause myofibrils to have an aberrant wave‐like appearance that is accompanied by irregular pockets of sarcoplasm in the intermyofibrillar space, while traditional forms of damage to the Z‐discs and contractile elements are not as apparent. What insights does it reveal? Our findings indicate that blood flow restriction‐mediated fluid pooling might cause alterations in skeletal muscle ultrastructure after exercise that might be directly related to myofibre swelling.
The Association between School Climate and Aggression: A Moderated Mediation Model

While previous studies have shown evidence of an association between school climate and aggression, few have explored the mechanisms behind this association. As such, this cross-sectional study focused on both the mediating effects of self-control and the moderating effects of the parent-child relationship on the association between school climate and aggression. Data were obtained through an anonymous survey conducted among 1030 Chinese elementary and middle school students (52.72% male, average age = 11.53 years), who responded to items on school climate, aggression, self-control, and the parent-child relationship. First, the results showed that school climate was negatively associated with aggression. Second, a mediation analysis showed that self-control significantly mediated the association between school climate and aggression. Third, a moderated mediation analysis showed that the parent-child relationship significantly moderated the first stage of the indirect path (school climate → self-control). Specifically, this association was notably stronger among children and adolescents with better parent-child relationships. In sum, these findings constitute a valuable reference for both improving self-control and in the context of targeted interventions aimed at preventing aggression in children and adolescents in China.
Expression of Alternative Splice Variants of 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase-4 in Normoxic and Hypoxic Melanoma Cells

Cancer-specific isoenzyme of phosphofructokinase II (PFKFB4), as our previous research has shown, may be one of the most important enzymes contributing to the intensification of glycolysis in hypoxic malignant melanoma cells. Although the PFKFB4 gene seems to play a crucial role in the progression of melanoma, so far there are no complete data on the expression of PFKFB4 at the isoform level and the influence of hypoxia on alternative splicing. Using RT-qPCR and semi-quantitative RT-PCR, we presented the PFKFB4 gene expression profile at the level of six isoforms described in the OMIM NCBI database in normoxic and hypoxic melanoma cells. Additionally, using VMD software, we analyzed the structure of isoforms at the protein level, concluding about the catalytic activity of individual isoforms. Our research has shown that five isoforms of PFKFB4 are expressed in melanoma cells, of which the D and F isoforms are highly constitutive, while the canonical B isoform seems to be the main isoform induced in hypoxia. Our results also indicate that the expression profile at the level of the PFKFB4 gene does not reflect the expression at the level of individual isoforms. Our work clearly indicates that the PFKFB4 gene expression profile should be definitely analyzed at the level of individual isoforms. Moreover, the analysis at the protein level allowed the selection of those isoforms whose functional validation should be performed to fully understand the importance of PFKFB4 expression in the metabolic adaptation of malignant melanoma cells.
Genomic signatures of inbreeding and mutation load in a threatened rattlesnake

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their genetic load, but recent work suggests that the impact of load may be minimized by purging resulting from long‐term population bottlenecks. Empirical studies that examine this idea using genome‐wide estimates of inbreeding and genetic load in threatened species are limited. Here we use individual genome resequencing data to compare levels of inbreeding, levels of genetic load (estimated as mutation load) and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus), which exist in small isolated populations, and closely related yet outbred Western massasauga rattlesnakes (Sistrurus tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of runs of homozygosity of varying sizes, indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome‐wide levels of mutation load in the form of greater numbers of derived deleterious mutations compared to S. catenatus, presumably due to long‐term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped species‐level drift effects within S. catenatus populations were in general more frequent and more often found in homozygous genotypes than in S. tergeminus, suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations for most mutations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present, which impacts implementation of conservation actions such as genetic rescue.
MWNTs or PEG as Stability Enhancers for DNA–Cationic Surfactant Gel Particles

Cationic surfactants interact with DNA (Deoxyribonucleic acid), forming surfactant-DNA complexes that offer particularly efficient control for encapsulation and release of DNA from DNA gel particles. In the present work, DNA-based particles were prepared using CTAB (Cetyltrimethylammonium bromide) as the cationic surfactant and modified using two different additives: (Multi-Walled Carbon Nanotubes) MWNT or PEG (Poly Ethylene Glycol). The use of both additives to form composites increased the stability of the gel particles. The stability was monitored by the release of DNA and CTAB in different pH solutions. However, not much is known about the influence of pH on DNA–surfactant interaction and the release of DNA and surfactant from gel particles. It was observed that the solubilization of DNA occurs only in very acid media, while that of CTAB does not depend on pH and gets to a plateau after about 8 h. Within 2 h in contact with a pH = 2 solution, about 1% DNA and CTAB was released. Complete destruction for the gel particles was observed in pH = 2 solution after 17 days for PEG and 20 days for MWNT. The composite particles show a considerably enlarged sustained release span compared to the unmodified ones. The dehydration-rehydration studies show that the structure of the composite gel particles, as determined from SAXS (Small-Angle-X-Ray-Scattering) experiments, is similar to that of the unmodified ones. These studies will allow a better knowledge of these particles’ formation and evolution in view of possible applications in drug delivery and release.
Odiel River (SW Spain), a Singular Scenario Affected by Acid Mine Drainage (AMD): Graphical and Statistical Models to Assess Diatoms and Water Hydrogeochemistry Interactions

The Odiel River (SW Spain) is one of the most cited rivers in the scientific literature due to its high pollution degree, generated by more than 80 sulphide mines’ (mostly unrestored) contamination in the Iberian Pyritic Belt (IPB), that have been exploited for more than 5000 years. Along the river and its tributaries, the physico-chemical parameters and diatoms, from 15 sampling points, were analyzed in the laboratory. Physico-chemical parameters, water chemical analysis, together with richness and Shannon–Wiener indexes were integrated in a matrix. An initial graphical treatment allowed the definition and proposal of a functioning system model, as well as the establishment of cause–effect relationships between pollution and its effects on biota. Then, the proposed model was statistically validated by factor analysis. For acidic pH waters, high values of Eh, TDS, sulphate, ∑REE and ∑Ficklin were found, while diatomologic indicators took low values. Thus, factor analysis was a very effective tool for graphical treatment validation as well as for pollution–biota interaction models’ formulation, governed by two factors: AMD processes and water balance suffered by the studied river. As a novelty, the cause–effect relationships between high barium concentration and low diversity and richness were demonstrated in the IPB, for the first time.
Impact of Full Vaccination with mRNA BNT162b2 on SARS-CoV-2 Infection: Genomic and Subgenomic Viral RNAs Detection in Nasopharyngeal Swab and Saliva of Health Care Workers

SARS-CoV-2 infection was monitored in 1898 health care workers (HCWs) after receiving full vaccination with BNT162b2. Untill 30 June 2021, 10 HCWs tested positive for SARS-CoV-2 using real time RT-PCR, resulting in a 4-month cumulative incidence of 0.005%. The infection was mildly symptomatic in six (60%) and asymptomatic in four (40%) individuals. Among the infected HCWs, eight consenting individuals provided paired NPS and saliva during the course of infection, for the purpose of the analysis performed in the present study. Genomic and subgenomic viral RNAs were investigated using real-time RT-PCR in both biological specimens. The temporal profile of viral load was measured using ddPCR. Viral mutations were also analysed. Subgenomic viral RNA was detected in 8/8 (100%) NPS and in 6/8 (75%) saliva specimens at the baseline. The expression of subgenomic RNA was observed for up to 7 days in 3/8 (38%) symptomatic cases. Moreover, concordance was observed between NPS and saliva in the detection of viral mutations, and both N501Y and 69/70del (associated with the B.1.1.7 variant) were detected in the majority 6/8 (75%) of subjects, while the K417T mutation (associated with the P.1-type variants) was detected in 2/8 (25%) individuals. Overall, our findings report a low frequency of infected HCWs after full vaccination. It is, therefore, important to monitor the vaccinees in order to identify asymptomatic infected individuals. Saliva can be a surrogate for SARS-CoV-2 surveillance, particularly in social settings such as hospitals.
Thrombocytopenia and platelet count recovery in patients with sepsis-3: a retrospective observational study

Abstract Thrombocytopenia is common in critical illness. But there are no studies that focus on thrombocytopenia and platelet recovery in Sepsis-3 patients. We employed a large database to identify sepsis based on Sepsis-3 criteria. Patients were grouped by nadir platelet count during ICU, propensity score matching was used to eliminate covariates imbalance, multivariable cox proportional hazard model was used for evaluating mortality. A total of 9709 patients were enrolled based on Sepsis-3, 1794 (18%) patients developed thrombocytopenia, with 858 (8.8%) exhibiting thrombocytopenia at ICU admission (prevalent), 891 (9.2%) developed thrombocytopenia during ICU stay (incident). In the incident thrombocytopenia group, survivors exhibited higher nadir platelet count, higher rate in platelet count recovery and shorter time to platelet recovery compared to non-survivors. Platelet recovery was not observed until 1 days (IQR, 1–2) after weaning of mechanical ventilation and 1 days (IQR, 1–3) after discontinuation of vasopressor in survivors of incident thrombocytopenia. Furthermore, thrombocytopenia was associated with longer duration of ICU length of stay, longer duration of mechanical ventilation and vasopressor use compared to no thrombocytopenia. Moderate (20–50 × 109/L) and severe (<20 × 109/L) thrombocytopenia group showed increased 28 days mortality compared to no thrombocytopenia, while the mortality rate between mild (51–100 × 109/L) and no thrombocytopenia group (≥100 × 109/L) showed no significant difference. Taken together these data revealed that thrombocytopenia occurred in 18% Sepsis-3 patients; platelet recovery occurred more frequent and earlier in survivors; platelet recovery was not observed until clinical improvement. Thrombocytopenia in Sepsis-3 demonstrated increased disease severity, and patients with platelet count <50 × 109/L showed increased 28 days mortality.
Severe Cardiac and Metabolic Pathology Induced by Steroid Abuse in a Young Individual

Androgenic-Anabolic Steroids (AAS) abuse is known to play an important role in causing the systemic inflammatory response and multiple-organ dysfunction in healthy individuals. Although many of the undesirable effects of steroid abuse have been reported, at present, little is known about the effect of anabolic supplements and the correlation between cardiac and metabolic pathology. This paper presents a case of a 25 year old patient with a complex medical history after 6 months of steroid administration. Myocardial infraction, dyslipidemia, obesity, hyperuricemia, secondary diabetes, and chronic renal disease were identified after clinical and para-clinical examinations. The particularities of this case were interpreted in the context of a literature review, highlighting the effect of multi-organ damage as a result of the uncontrolled use of anabolic steroid supplements.
An Integrative Review of Recovery Services to Improve the Lives of Adults Living with Severe Mental Illness

There is an increasing call for recovery-oriented services but few reviews have been undertaken regarding such interventions. This review aims to synthesize evidence on recovery services to improve the lives of adults living with severe mental illness. An integrative review methodology was used. We searched published literature from seven databases: Medline, EMBASE, PsycINFO, CINAHL, Google Scholar, Web of Science, and Scopus. Mixed-methods synthesis was used to analyse the data. Out of 40 included papers, 62.5% (25/40) used quantitative data, 32.5% used qualitative and 5% (2/40) used mixed methods. The participants in the included papers were mostly adults with schizophrenia and schizoaffective disorder. This review identified three recovery-oriented services—integrated recovery services, individual placement services and recovery narrative photovoice and art making. The recovery-oriented services are effective in areas such as medication and treatment adherence, improving functionality, symptoms reduction, physical health and social behaviour, self-efficacy, economic empowerment, social inclusion and household integration. We conclude that mental health professionals are encouraged to implement the identified recovery services to improve the recovery goals of consumers.