Miracle-dz/UniFAR-FTUs huggingface dataset:
Impairment of Mitochondrial-Nuclear Cross Talk in Lymphocytes Exposed to Landfill Leachate

Landfill leachate, a complex mixture of different solid waste compounds, is widely known to possess toxic properties. However, the fundamental molecular mechanisms engaged with landfill leachate exposure inducing cellular and sub-cellular ramifications are not well explicated. Therefore, we aim to examine the potential of leachate to impair mitochondrial machinery and its associated mechanisms in human peripheral blood lymphocytes. On assessment, the significant increase in the dichlorofluorescein (DCF) fluorescence, accumulation of 8-Oxo-2′-deoxyguanosine (8-oxo-dG), and levels of nuclear factor erythroid 2–related factor 2 (Nrf-2) strongly indicated the ability of the leachate to induce a pro-oxidant state inside the cell. The decrease in the mitochondrial membrane potential and alterations in the mitochondrial genome observed in leachate-exposed cells further suggested the disturbances in mitochondrial machinery. Moreover, these mitochondrial-associated redox imbalances were accompanied by the increased level of NF-κβ, pro-inflammatory cytokines, and DNA damage. In addition, the higher DNA fragmentation, release of nucleosomes, levels of polyadenosine diphosphate ADP-ribose polymerase (PARP), and activity of caspase-3 suggested the involvement of mitochondrial mediated apoptosis in leachate exposed cells. These observations were accompanied by the low proliferative index of the exposed cells. Conclusively, our results clearly indicate the ability of landfill leachate to disturb mitochondrial redox homeostasis, which might be a probable source for the immunotoxic consequences leading to plausible patho-physiological conditions in humans susceptible to such environmental exposures.
Human hippocampal ripples signal encoding of 1 episodic memories 2

Recent human electrophysiology work has uncovered the presence of high frequency oscil- 9 latory events, termed ripples, during awake behavior. This work focuses on ripples in the 10 medial temporal lobe (MTL) during memory retrieval. Few studies, however, investigate 11 ripples during item encoding. Many studies have found neural activity during encoding 12 that predicts later recall, termed subsequent memory effects (SMEs), but it is unclear 13 if encoding ripples also predict subsequent recall. Detecting ripples in 124 neurosurgical 14 participants performing an episodic memory task, we do not find ripple SMEs in any MTL 15 region, even as these regions exhibit robust high frequency activity (HFA) SMEs. Instead, 16 hippocampal ripples increase during encoding of items leading to recall of temporally or 17 semantically associated items, a phenomenon known as clustering. This subsequent clus- tering effect (SCE) arises specifically when hippocampal ripples occur during both encod- ing and retrieval, suggesting that ripples mediate the encoding and future reinstatement 20 of episodic memories. P = 0.49; non-HPC 550 MTL, β = -0.0095±0.053, P = 0.86 (each FDR-corrected across 3 tests of Eq. 7). To directly assess if 551 hippocampal regions show a stronger relationship between SCE and clustering than non-HPC MTL, we 552 compare using a mixed model measuring the interaction between proportion of clustered recalls and re- 553 gion to predict SCE: CA1 vs. non-HPC MTL, β = 0.25±0.095, P = 0.017; CA3/DG vs. non-HPC MTL, 554 β = 0.11±0.12, P = 0.34 (FDR-corrected across 2 tests of Eq. 8). 555
Passive Surveillance as a Key Tool for African Swine Fever Eradication in Wild Boar: A Protocol to Find Carcasses Tested and Validated in the Mediterranean Island of Sardinia

African swine fever (ASF) is one of the most important and serious contagious hemorrhagic viral diseases affecting domestic pigs and wild boar and is associated with high mortality rates while also having an extensive sanitary and socioeconomic impact on the international trade of animal and swine products. The early detection of the disease is often hampered by inadequate surveillance. Among the surveillance strategies used, passive surveillance of wild boars is considered the most effective method for controlling the African swine fever virus (ASFV). Otherwise, the design of a sufficiently sensitive ASF surveillance system requires a solid understanding of the epidemiology related to the local eco-social context, especially in the absence of virus detection. Even if the number of carcasses needed to demonstrate ASF eradication has been established, the scientific context lacks detail compared to protocols applied in the active search for wild boar carcasses. The aim of this study was to describe the protocol applied in the active search for carcasses, providing detailed information on the number of people and dogs as well as the amount of time and space used within the Mediterranean area. Using a specific tool developed to record, trace, and share field data (the GAIA observer app), a total of 33 active searches for wild boar carcasses were organized during 2021–2023. Most of these searches were planned to find carcasses that had previously been reported by hunters. A total of 24 carcasses were found, with only 2 carcasses not previously reported. The final protocol applied involved four people, with an average speed of 1.5 km/h. When a carcass had been previously reported, about 2 km of distance had to be covered in about 1.5 h to find the carcass, and even less time was spent when a dog (untrained) was present. In conclusion, it can be stated that, when searching for carcasses, solid collaboration with local hunters or other forest visitors is necessary to ensure carcasses are reported. The process involves small groups of experts actively searching for carcasses, possibly with the use of hunting dogs without special training. The data presented could be of valid support for those countries characterized by Mediterranean vegetation that are faced with the need to plan active carcass searches.
Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry

Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. Methods: We described COVID-19 morbidity and mortality among patients with STS across ‘Omicron’ (15 December 2021–31 January 2022), ‘Pre-vaccination’ (27 February 2020–30 November 2020), and ‘Alpha-Delta’ phase (01 December 2020–14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR28) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders. Results: Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18–92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR28 was 25.8%, with 38% oxygen therapy requirement, 34% rate of complications, and 32.3% of hospitalizations due to COVID-19. CFR28 (29.5%, 21.4%, and 12.5%) and all indicators of COVID-19 severity demonstrated a trend toward a numerical improvement across the pandemic phases. Similarly, vaccinated patients demonstrated numerically improved CFR28 (16.7% versus 27.7%) and COVID-19 morbidity compared with unvaccinated patients. Patients who were on chemotherapy experienced comparable CFR28 (19.4% versus 26.0%, p = 0.4803), hospitalizations (50.0% versus 44.4%, p = 0.6883), complication rates (30.6% versus 34.0%, p = 0.7381), and oxygen therapy requirement (28.1% versus 40.0%, p = 0.2755) compared to those who were not on anticancer therapy at COVID-19, findings further confirmed by the IPTW-fitted multivariable analysis. Conclusion: In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.
Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy

Abstract Background The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. Methods This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. Results Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). Conclusion The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.
Effectiveness and safety of cefotaxime combined with avibactam for treating multidrug-resistant E coli infections: A systematic review and meta-analysis

Background: Multidrug-resistant Escherichia coli infections are a global health challenge, notably in North America, Europe, Asia, and Africa. This systematic review and meta-analysis evaluates the effectiveness and safety of cefotaxime combined with avibactam, aiming to mitigate these infections’ impact and lessen their burden on healthcare systems worldwide. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and PICO frameworks, we conducted a comprehensive literature search across 4 primary databases on May 6, 2023. Studies evaluating the efficacy and safety of cefotaxime and avibactam were included. Key outcomes included treatment success, adverse effects, and microbiological eradication. Quality assessment utilized the Cochrane Collaboration Risk of Bias instrument. Heterogeneity was analyzed using chi-square statistics and the I2 index. Both fixed- and random-effects models were applied as appropriate. Publication bias was rigorously evaluated using Egger linear regression test and funnel plot analysis, ensuring the study’s integrity and reliability. Results: The clinical cure rate derived from 8 studies showed no significant difference between the treatment groups (odds ratio [OR] = 1.97, 95% CI: 0.69 to 1.36, P = .86). Analysis of the bacterial clearance rate from the 5 studies also indicated no significant difference (OR = 0.97, 95% CI: 0.42 to 2.25, P = .36). Notably, a reduced mortality rate favoring the experimental group was observed in 6 studies (OR = 0.64, 95% CI: 0.44 to 0.92, P = .012). Comprehensive sensitivity analyses and the assessment of publication bias strengthened the reliability of the results. Conclusions: Ceftazidime combined with avibactam significantly reduced mortality among patients with multidrug-resistant Escherichia coli infections, indicating its potential as a therapeutic option, especially for carbapenem-resistant Enterobacteriaceae. However, extensive large-scale clinical trials are required to validate these findings.
Meta-analysis of risk factors for posttraumatic stress disorder in myocardial infarction

Background: The aim of this study was to identify the risk factors for posttraumatic stress disorder in patients with myocardial infarction. Methods: Cohort, case-control, and cross-sectional studies on posttraumatic stress disorder (PTSD) in patients with myocardial infarction were searched from PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and Technology Journal database. The Newcastle-Ottawa Quality Assessment Scale was used to score the quality of the included literature in the cohort and case-control studies, and the cross-sectional studies were scored using the American Agency for Health Care Quality and Research cross-sectional study quality evaluation criteria. The literature was screened independently by 2 researchers, and if there was no consensus, the inclusion was decided by a third party. The extraction content included first author, publication year, sample size, PTSD assessment tool, PTSD assessment time, PTSD incidence, influencing factors, and study type. Meta-analysis of data was performed using Stata17.0 software. Results: Ten studies were included, including 2 cohort studies, 7 cross-sectional studies, and 1 case-control study, with a total sample size of 2371 patients, including 26 influencing factors. The results of meta-analysis showed that the prevalence of PTSD in patients with myocardial infarction was 21.2%. Statistically significant influencing factors were gender (odd ratio [OR] = 3.124), neuroticism score (OR = 2.069), and age (OR = 0.913). Conclusions: The prevalence of PTSD in patients with myocardial infarction in China is higher than that in other countries. Female and neurotic personality are risk factors for developing PTSD in patients with myocardial infarction, and old age is protective factor for developing PTSD in patients with myocardial infarction. Targeted measures should be taken to prevent and reduce the occurrence and development of PTSD in patients with myocardial infarction in the future.
Strain-induced bands of Büngner formation promotes axon growth in 3D tissue-engineered constructs

Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75NTR. Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes.
Genotype–phenotype correlations in carriers of the PMS2 founder variant c.1831dup

Abstract Background Lynch syndrome represents one of the most common cancer predispositions worldwide and is caused by germline pathogenic variants (PV) in DNA mismatch repair (MMR) genes. We repeatedly identified a PV in the MMR gene PMS2, c.1831dup, accounting for 27% of all Swiss PMS2 PV index patients identified. Notably, 2/18 index patients had been diagnosed with colorectal cancer (CRC) before age 30. Methods In this study, we investigated if this PV could (i) represent a founder variant by haplotype analysis and (ii) be associated with a more severe clinical phenotype. Results Haplotype analysis identified a shared common region of about 0.7 Mb/1.3 cM in 13 (81%) out of 16 index patients. Genotype–phenotype correlations, combining data from the 18 Swiss and 18 literature‐derived PMS2 c.1831dup PV index patients and comparing them to 43 Swiss index patients carrying other PMS2 PVs, indicate that the PMS2 c.1831dup variant may be associated with earlier (<50 y) age at CRC diagnosis (55% vs. 29%, respectively; p = 0.047). Notably, 30% (9/30) of cancers from c.1831dup carriers displayed atypical MMR protein expression patterns on immunohistochemistry. Conclusion Our results suggest that the PMS2 c.1831dup PV represents a, probably ancient, founder mutation and is possibly associated with an earlier CRC diagnosis compared to other PMS2 PVs.
Cardiac Catheterization and Outcomes for Elderly Patients Hospitalized With Heart Failure

Background: Heart failure affects over 6 million people in the United States (US) with limited evidence to support the use of cardiac catheterization. The benefit of its use remains mostly as expert opinion. This study intends to assess the benefits and risks of cardiac catheterization in elderly patients admitted for heart failure. Methods: This was a retrospective study using data from the National Inpatient Sample, including admissions 65 years and older hospitalized for heart failure, between 2008 and 2016. The outcomes analyzed were in-hospital mortality, total hospital costs, and length of stay. Results: After controlling for covariates, cardiac catheterization was found to have a protective association with mortality (OR 0.87, 95% CI 0.833-0.912, P < .0001), an increased hospital length of stay by 2.88 days (95% CI: 2.84-2.92 days, P < .0001) and approximately $16 255 increase in cost. Conclusions: Cardiac catheterization was associated with decreased in-hospital mortality, longer length of stay and higher total costs in admissions with heart failure aged 65 years or older.
Advances in the transdermal delivery of antiretroviral drugs

Antiretroviral therapy regimens are successful in stopping the advancement of human immunodeficiency virus infection to acquired immunodeficiency syndrome, and other opportunistic infections. However, they do have significant disadvantages, including long-term treatment, limited oral bioavailability, inaccessibility to organs, non-adherence by patients, and the development of medication resistance. Because of the listed drawbacks of available routes and the availability of curative medicines for human immunodeficiency virus/acquired immunodeficiency syndrome, advanced solutions are required. Antiretroviral therapy transdermal delivery is one of the current strategies that have attracted much attention from many researchers. In this narrative review, various in vitro, in vivo, and ex vivo transdermal antiretroviral therapy delivery strategies were reviewed, such as transdermal patches and films, lipid-based nano-delivery systems, microneedles, chemical penetration enhancers, and iontophoresis, which showed promising results. Although the majority of studies on Antiretroviral transdermal delivery have produced hopeful findings, additional in-depth research on passive and physical enhancement techniques, both existing and new, is necessary to fully understand the potential of this route and to make it accessible to human immunodeficiency virus patients.
Effects of adding neuromuscular electrical stimulation to functional training on muscle recruitment, pain reduction, and knee joint function in patellofemoral pain syndrome patients

Background: Impaired lower extremity motor function and knee pain are common concerns in patients with patellofemoral pain syndrome (PFPS). It is essential to plan therapeutic techniques to therapy PFPS. The objective of this study was to determine the effect of neuromuscular electrical stimulation (NMES) combined with functional training on pain, lower extremity function and muscle recruitment in patients with PFPS. Methods: Twenty-four PFPS patients (male-13, female-11) were selected to conduct this study finally. Two groups were formed: the control group (n = 12) which included functional training only and the experimental group (n = 12) which functional training along with NMES-in both groups interventions were performed for 45 minutes/session, 3 days/weeks for 6 weeks. The functional training consisted of warm-up activities, strength training, balance training, and relaxation activities. All patients were evaluated with surface electromyography testing system for the root mean square and integrated electromyography of vastus medial oblique (VMO), vastus lateralis (VL), and VMO/VL ratio, visual analog scores (VAS) for pain, and Kujala functional score for knee joint function before and after 6 weeks. Normality was tested for all outcome variables using Shapiro–Wilk test. Nonparametric (Mann–Whitney U test and Wilcoxon signed-rank test) tests were used to analyze data. A 2-way analysis of variance with repeated measures (group*time) was applied to analyze the data. Results: A significant increases (P < .001) root mean square and integrated electromyography of VMO, VMO/VL ratio, and Kujala score in both groups, For VAS scores, significant decreases was observed in both groups. When both groups were compared, greater improvement (P < .05) was observed in the experimental group in comparison the control group for both knee pain, lower extremity function and muscle recruitment. However, there was no difference in VL muscle recruitment between the 2 groups. Conclusions: Functional training and NMES combined with functional training are helpful to improve pain, knee function and muscle recruitment of PFPS patients. NMES combined with functional training was more effective compared to the control group. This may help clinical trialists to use different NMES to synchronize other interventions in future studies to enhance rehabilitation efficacy in PFPS patients through passive training versus active stimulation.