Miracle-dz/UniFAR-FTUs huggingface dataset:
Using cultured canine cardiac slices to model the autophagic flux with doxorubicin

Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 μm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.
A quadriceps femoris motor pattern for efficient cycling

In cycling, propulsion is generated by the muscles of the lower limbs and hips. After the first reports of pedal/crank force measurements in the late 1960s, it has been assumed that highly trained athletes have better power transfer to the pedals than recreational cyclists. However, motor patterns indicating higher levels of performance are unknown. To compare leg muscle activation between trained (3.5–4.2 W/kgbw) and highly trained (4.3–5.1 W/kgbw) athletes we applied electromyography, lactate, and bi-pedal/crank force measurements during a maximal power test, an individual lactate threshold test and a constant power test. We show that specific activation patterns of the rectus femoris (RF) and vastus lateralis (VL) impact on individual performance during high-intensity cycling. In highly trained cyclists, we found a strong activation of the RF during hip flexion. This results in reduced negative force in the fourth quadrant of the pedal cycle. Furthermore, we discovered that pre-activation of the RF during hip flexion reduces force loss at the top dead center (TDC) and can improve force development during subsequent leg extension. Finally, we found that a higher performance level is associated with earlier and more intense coactivation of the RF and VL. This quadriceps femoris recruitment pattern improves force transmission and maintains propulsion at the TDC of the pedal cycle. Our results demonstrate neuromuscular adaptations in cycling that can be utilized to optimize training interventions in sports and rehabilitation.
Meta-analysis of clinical risk factors of patients with systemic lupus erythematosus complicated with invasive fungal infection

Background: To systematically evaluate the clinical risk factors of patients with systemic lupus erythematosus (SLE) complicated with invasive fungal infection (IFI) among patients. Methods: A meta-analysis was performed of all the literatures germane to estimate the clinical risk factors of patients with SLE complicated with IFI from published clinical trials from 1990 to April 2022. Mean differences, odds ratio and 95% confidence intervals were calculated, and the meta-analysis was conducted with Stata 12.0 software (StataCorp, College Station, TX). Results: A total of 14 clinical research involving 1129 patients were included. The results of meta-analysis demonstrated that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors associated with IFI in SLE patients. However, age, sex, course of disease, leukopenia, lymphopenia, C- reactive protein and hypoproteinemia were not the risk factors associated with IFI in patients with SLE. Conclusion: Our results indicate that immunosuppressant, glucocorticoids, systemic lupus erythematosus disease activity index score, antibiotic were risk factors for IFI in SLE patients. However, high quality of multicenter, large sample size-controlled trials are needed to validate the result.
Study protocol: Neuro-inflammatory parameters as mediators of the relationship between social anxiety and itch intensity: A cross-sectional, controlled laboratory study in patients with psoriasis and healthy skin controls

Introduction Psoriasis (PSO) is a disease that in the majority of patients is accompanied by itch, which imposes a great burden and positively relates to anxiety. Social anxiety, a facet of anxiety associated with social withdrawal, may be a predictor of itch intensity in this patient group. Moreover, anxiety is linked to the secretion of neuroendocrine and inflammatory parameters such as substance P (SP), interleukin (IL)-6 and IL-17, which are also related to itch. In this research project, we investigate first, whether there is a direct relationship between social anxiety and itch intensity in patients with PSO and second whether the secretion of SP, IL-6 and IL-17 in the skin mediates this relationship. Additionally, PSO-patients are compared to healthy skin controls regarding their level of social anxiety, itch intensity and the secretion of SP, IL-6 and IL-17. Methods and analyses For study 1, we aim to recruit 250 psoriasis patients and 250 healthy skin controls who complete questionnaires to assess social anxiety, itch intensity and control variables (e.g. sociodemographic variables and severity of PSO). A linear hierarchic regression will be used to determine whether social anxiety significantly contributes to itch intensity. In study 2, we plan to apply the suction blister method to 128 patients and healthy skin controls recruited from study 1 to determine SP, IL-6 and IL-17 in tissue fluid extracted from the skin. A mediation analysis will be conducted using the SPSS-macro PROCESS to test whether the relationship between social anxiety and itch is mediated by SP, IL-6 and IL-17. Trial registration numbers DRKS00023621 (study 1) and DRKS00023622 (study 2).
Can neutrophil-lymphocyte ratio and mean platelet volume be used to predict metastasis in individuals with lung cancer?

Chronic inflammation plays an important role in the etiopathogenesis of many life-threatening chronic diseases, including cancer. Currently, the relationship between inflammation, native immunity and cancer is widely accepted; however, many of the mechanisms mediating this relationship remain undetermined and the clinical significance of these markers is unclear. The purpose of this study was to investigate the potential of neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV) to indicate the existence of metastasis in lung cancer. This retrospective cross-sectional study evaluated patients with lung cancer of any pathological type who was admitted to the Palliative Care Unit of the referral hospital in the region between January 2019 and February 2020. Patient characteristics, distant organ metastasis, treatments, NLR and MPV values were noted. Patients were grouped as with or without metastasis. Characters, NLR, MPV values were compared. One hundred twenty-six patients were included. The mean age of the patients was 61.17 ± 9.4 years and 7.9% (n = 10) were female. The patients with a history of chemotherapy were 47% (n = 60) and distant organ metastases were present in 38.9% (n = 49) of the patients. The mean MPV value of 49 patients with distant metastasis was 8.34 ± 0.8 fL. MPV values of those with metastasis were found to be significantly higher than those without (P = .010). There was no significant difference in NLR values between groups (P = .920). Lung cancer patients with metastasis were found with higher MPV values. MPV can be effective and most accessible test in prediction of metastasis in lung cancer patients regardless of the pathological type.
Correlates of self-reported and biomarker based adherence to daily oral HIV pre-exposure prophylaxis among a cohort of predominantly men who have sex with men in Nigeria

Introduction HIV pre-exposure prophylaxis (PrEP) significantly reduces the risk of HIV acquisition. However, studies have demonstrated discordance between self-reported measures and biomedical benchmarks of PrEP adherence. We estimated the correlation between self-reported PrEP adherence and PrEP biomarkers and explored factors associated with adherence among men who have sex with men (MSM) in Nigeria. Methods TRUST-PrEP, an open-label, prospective study; conducted in Abuja between April 2018 and May 2019. MSM ≥ 18 years with substantial HIV risk were enrolled. Participants reported PrEP adherence in the last month using a 4-point scale from “poor” to “perfect” and serum samples for PrEP biomarkers were collected at months 3 and 9. Serum tenofovir concentration was measured by liquid chromatography-tandem mass spectrometry and considered protective for adherence if ≥ 4.2 ng/ml. Spearman’s rank correlation was used to estimate correlation between self-reported adherence and measured tenofovir levels. Generalized estimating equations with a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between self-reported adherence and laboratory-measured adherence. Results A total of 219 MSM with median age 23 (interquartile range 20–27) years had at least one PrEP biomarker assay. Only 66/219 (30%) had at least one record of protective tenofovir concentration. Correlation between tenofovir and self-reported adherence at 3 and 9 months were 0.1 and 0.02 respectively. Furthermore, 17/219 (8%,) and 49/219 (22%) had serum tenofovir of 4.2–35.4 ng/mL and ≥ 35.5 ng/mL, corresponding to at least 4 and 7 days’ PrEP use in a week, respectively. PrEP adherence was higher among participants introduced to PrEP in the clinics compared with communities (aOR: 8.35, 95%CI: [3.24, 21.5]) and those with same-sex practices family disclosure (aOR: 3.60 95% CI: [1.73, 7.51]). Conclusion Self-reported PrEP adherence poorly correlated with biomarkers. Facilitating clinic-based PrEP introduction and disclosure of same-sex practices to family among MSM may improve PrEP adherence.
Adverse events of a third dose of BNT162b2 mRNA COVID-19 vaccine among Korean healthcare workers

Due to the urgency of controlling the coronavirus disease 2019 pandemic, coronavirus disease 2019 messenger ribonucleic acid (mRNA) vaccines have been expeditiously approved and introduced in several countries without sufficient evaluation for adverse events. We analyzed adverse events among Korean healthcare workers who received all 3 doses of the BNT162b2 mRNA vaccine. This survey was conducted among hospital workers of Inha University Hospital who had received the BNT162b2 mRNA vaccine for their first, second, third rounds, and using a diary card. The surveyed adverse events included local (redness, edema, and injection site pain) and systemic (fever, fatigue, headache, chill, myalgia, arthralgia, vomiting, diarrhea, pruritis, and urticaria) side effects and were divided into 5 grades (Grade 0 = none – Grade 4 = critical). Based on adverse events reported at least once after any of the 3 doses, the most common systemic adverse reactions were chills and headache (respectively, 62.6%, 62.4%), followed by myalgia (55.3%), arthralgia (53.4%), fatigue (51.6%), pruritus (38.1%), and fever (36.5%). The frequency and duration of adverse events were significantly greater in women (P < .05) than men. Except for redness, pruritus, urticaria, and most adverse reactions had a higher rate of occurrence after the third dose in subjects who also had reactions with the second dose. However, grade 4 adverse events did occur with the third dose in some patients, even if there were no side effects with the first and second doses. Adverse events experienced with the first and second doses of the BNT162b2 mRNA vaccine in Korean healthcare workers increased the incidence of adverse events at the time of the third dose. On the other hand, grade 4 adverse events could still occur with the third dose even though there were no side effects with the first and second doses.
Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing

Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person’s faecal flora (their gut “resistome”). Using this approach, we aimed to test the hypothesis that differences in antimicrobial use across different hospitals in the United Kingdom will result in observable differences in the resistome of individual patients. Three National Health Service acute Hospital Trusts with markedly different antibiotic use and Clostridioides difficile infection rates collected faecal samples from anonymous patients which were discarded after C. difficile testing over a period of 9 to 15 months. Metagenomic DNA was extracted from these samples and sequenced using an Illumina NovaSeq 6000 platform. The resulting sequencing reads were analysed for taxonomic composition and for the presence of AMR genes. Among 683 faecal metagenomes we found huge variation between individuals in terms of taxonomic diversity (Shannon Index range 0.10–3.99) and carriage of AMR genes (Median 1.50 genes/cell/sample overall). We found no statistically significant differences in diversity (median Shannon index 2.16 (IQR 1.71–2.56), 2.15 (IQR 1.62–2.50) and 2.26 (IQR 1.55–2.51)) or carriage of AMR genes (median 1.37 genes/cell/sample (IQR 0.70–3.24), 1.70 (IQR 0.70–4.52) and 1.43 (IQR 0.55–3.71)) at the three trusts respectively. This was also the case across the sample collection period within the trusts. While we have not demonstrated differences over place or time using metagenomic sequencing of faecal discards, other sampling frameworks may be more suitable to determine whether organisational level differences in antibiotic use are associated with individual-level differences in burden of AMR carriage.
Feline myocardial transcriptome in health and in hypertrophic cardiomyopathy—A translational animal model for human disease

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by primary left ventricular hypertrophy. Feline HCM closely resembles human HCM and is suggested as translational animal model for the human disease. A genetic cause is established in humans and suspected for cats, but little is known about the gene expression and pathways involved in the pathogenesis of HCM. To investigate the myocardial transcriptome changes in HCM, RNA sequencing was conducted on left ventricle (LV) and left atrium (LA) samples of healthy cats and cats with HCM (each n = 5; 20 samples). Ingenuity Pathway Analysis was used to determine functional pathways, regulators, and networks. Distinct gene expression profiles were identified in the LV and LA of the feline healthy and HCM myocardium. Analysis of differentially expressed mRNAs (>2 fold; FDR < 0.01) found chamber-specific (LV vs. LA) expression in both healthy and HCM groups, with higher transcriptional activity in the LA. Genes that contribute to the distinct structure and function of each chamber in health and HCM were identified in the regional comparison. The gene expression profiles of HCM compared to healthy hearts revealed disease related genes, including THBS4 and KLHL33 (LV), FAM177B and THRSP (LA), the latter 3 have not been reported for the myocardium so far, as the top differently expressed genes in the HCM heart. Differently expressed genes and functional pathways found in the HCM heart are associated with cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling and cardiac metabolism, with some regional differences. RhoGDI-RhoGTPase signaling, integrin and ILK signaling pathways, the LXR/RXR pathway in the LA, and the PPARα/RXRα, HIF1α and CXCR4 pathways in the LV might be of particular importance in the HCM disease process. This study identified region-specific myocardial gene transcription patterns as well as novel genes and pathways associated with HCM.
Acute coronary syndrome management in hemophiliacs: How to maintain balance?: A review

To analyze existing literature and understand how to balance the minimization of bleeding risk and ensuring adequate anticoagulation during coronary intervention treatment and long-term postoperative anticoagulation in hemophilia patients during the perioperative period, in order to provide guidance for healthcare professionals in developing effective treatment plans. This narrative review will analyze existing studies, case reports, and clinical guidelines to determine the most effective strategies for managing acute coronary syndrome in hemophilia patients. When evaluating the literature, factors such as patient age, medical history, and severity of the condition will be considered. The current management guidelines for acute coronary syndrome in hemophilia patients are not based on systematic evaluation and mainly rely on expert opinions. This article provides a comprehensive analysis of existing literature and recommends coagulation factor replacement therapy before anticoagulation and intervention treatment, as well as personalized anticoagulation treatment during the postoperative period for better management of hemophilia patients with acute coronary syndrome. These recommendations can help healthcare professionals develop more effective treatment plans for hemophilia patients.
PEMANFAATAN VISUALISASI VIDEO PERCOBAAN GRAVITY CURRENT UNTUK MENINGKATKAN PEMAHAMAN KONSEP FISIKA PADA MATERI TEKANAN HIDROSTATIS

Penelitian ini bertujuan untuk meningkatkan pemahaman konsep fisika siswa dengan memanfaatkan visualisasi serangkaian video percobaan gravity current pada materi pokok tekanan hidrostatis. Metode yang digunakan adalah One Group Pre-Test Post-Test Design dengan menggunakan satu kelas sampel penelitian. Pre-Test diberikan sebelum perlakuan untuk mengukur pemahaman awal siswa sedangkan Post-Test diberikan untuk mengukur pemahaman akhir siswa setelah diberikan perlakuan. Berdasarkan hasil Pre-Test dan Post-Test didapatkan nilai uji-t berpasangan sebesar 27,93. Nilai tersebut lebih besar dari sehingga Ho ditolak dengan reliabilitas 95%. Berdasarkan hasil tersebut dapat disimpulkan bahwa terdapat peningkatan pemahaman konsep siswa yang signifikan. Hasil dari analisis skor gain ternormalisasi didapatkan 22 siswa (64,7%) mendapatkan skor gain tinggi dan 12 siswa (35,3%) mendapatkan skor gain sedang serta skor gain rata-rata keseluruhan siswa sebesar 0,74 yang berkategori tinggi. Keterlaksanaan pembelajaran dengan memanfaatkan visualisasi video percobaan gravity current pada RPP 1 dan RPP 2 yang diamati oleh dua orang pengamat adalah terlaksana dengan baik. Siswa memberikan respons positif terhadap pembelajaran yang dilaksanakan. Kata kunci : tekanan hidrostatis, gravity current Abstract This research aims to develop and improve student’s understanding of physics relevant to the concept of hydrostatic pressure given to students Grade XI. The research was performed by visualizing clips made up from gravity current experiments. The method used is One Group Pre-Test Post-Test Design. Pre-Test was given before treatment to measure student’s initial understanding of the problem, while post-test was given to measure student’s final understanding. Paired sample t-test results in 27.93, which is greater than . Therefore, Ho is rejected by a score of reliability 95%. Based on the result, it can be concluded that there is a significant result in improving student’s understanding. Result of gain score are 22 students (64,7%) get high gain score, 12 students (35,3%) get medium gain score and average gain score for all students is 0,74 which is high. The feasibility of lesson by using visualization of gravity current experiment in laboratory on lesson plan 1 and lesson plan 2 by two observers are good. Students gave positive responses to the lesson had done. Keywords : hydrostatic pressure, gravity current.
Surgical outcome of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy

Abstract OBJECTIVES Ipsilateral reoperation after pulmonary lobectomy is often challenging because of adhesions from the previous operation. We retrospectively examined the surgical outcome and prognosis of ipsilateral anatomical resection for lung cancer after pulmonary lobectomy using a multicentre database. METHODS We evaluated the perioperative outcomes and overall survival of 51 patients who underwent pulmonary lobectomy followed by ipsilateral anatomical resection for lung cancer between January 2012 and December 2018. In addition, patients with stage I non-small-cell lung cancer (NSCLC) were compared with 3411 patients with stage I lung cancer who underwent pulmonary resection without a prior ipsilateral lobectomy. RESULTS Ipsilateral anatomical resections included 10 completion pneumonectomies, 19 pulmonary lobectomies and 22 pulmonary segmentectomies. Operative time was 312.2 ± 134.5 min, and intraoperative bleeding was 522.2 ± 797.5 ml. Intraoperative and postoperative complications occurred in 9 and 15 patients, respectively. However, the 5-year overall survival rate after anatomical resection followed by ipsilateral lobectomy was 83.5%. Furthermore, in patients with c-stage I NSCLC, anatomical resection followed by ipsilateral lobectomy was not associated with worse survival than anatomical resection without prior ipsilateral lobectomy. CONCLUSIONS Anatomical resection following ipsilateral lobectomy is associated with a high frequency of intraoperative and postoperative complications. However, the 5-year overall survival in patients with c-stage I NSCLC who underwent ipsilateral anatomical resection after pulmonary lobectomy is comparable to that in patients who underwent anatomical resection without prior pulmonary lobectomy.
Lasers for stone lithotripsy: advantages/disadvantages of each laser source

Purpose The purpose of this article was to make a narrative review of the literature in search of all articles regarding thulium:yttrium-aluminium-garnet (YAG), thulium laser fiber (TFL) and holmium:YAG (Ho:YAG) for lithotripsy from 2020 to 2023. A selection of articles of special interest and best evidence was made in order to give a better perspective on their advantages and disadvantages. Recent findings New Ho:YAG technologies of as high power, high frequency and pulsed modulations have shown promising results for lithotripsy by reducing retropulsion with good ablation efficiency. High peak power makes it particularly good for percutaneous nephrolithotomy. High intrarenal temperatures and correct setting are still concerning points. TFL has arrived to be one of the main players in flexible ureteroscopy. Being highly efficient and quick, and by producing micro-dusting the laser is quickly heading to become a gold standard. The new pulsed Thulium YAG is the newest laser. For now, only in-vitro studies show promising results with efficient lithotripsy. As the peak power lies between Ho:YAG and TFL it may be able to adequately perform when needing and low power lithotripsy. Summary Several new technologies have been developed in the last years for stone lithotripsy. All being efficient and safe if well used. Different advantages and disadvantages of each laser must be taken into consideration to give each laser the proper indication.