Miracle-dz/UniFAR-FTUs huggingface dataset:
Prophylactic Topical Antibiotics in Fracture Repair and Spinal Fusion

Introduction The objective of this systematic review with meta-analysis is to determine whether prophylactic local antibiotics prevent surgical site infections (SSIs) in instrumented spinal fusions and traumatic fracture repair. A secondary objective is to investigate the effect of vancomycin, a common local antibiotic of choice, on the microbiology of SSIs. Methods An electronic search of PubMed, EMBASE, and Web of Science databases and major orthopedic surgery conferences was conducted to identify studies that (1) were instrumented spinal fusions or fracture repair and (2) had a treatment group that received prophylactic local antibiotics. Both randomized controlled trials (RCTs) and comparative observational studies were included. Meta-analysis was performed separately for randomized and nonrandomized studies with subgroup analysis by study design and antibiotic. Results Our review includes 44 articles (30 instrumented spinal fusions and 14 fracture repairs). Intrawound antibiotics significantly decreased the risk of developing SSIs in RCTs of fracture repair (RR 0.61, 95% CI: 0.40–0.93, I2 = 32.5%) but not RCTs of instrumented spinal fusion. Among observational studies, topical antibiotics significantly reduced the risk of SSIs in instrumented spinal fusions (OR 0.34, 95% CI: 0.27–0.43, I2 = 52.4%) and in fracture repair (OR 0.49, 95% CI: 0.37–0.65, I2 = 43.8%). Vancomycin powder decreased the risk of Gram-positive SSIs (OR 0.37, 95% CI: 0.27–0.51, I2 = 0.0%) and had no effect on Gram-negative SSIs (OR 0.95, 95% CI: 0.62–1.44, I2 = 0.0%). Conclusions Prophylactic intrawound antibiotic administration decreases the risk of SSIs in fracture surgical fixation in randomized studies. Therapeutic efficacy in instrumented spinal fusion was seen in only nonrandomized studies. Vancomycin appears to be an effective agent against Gram-positive pathogens. There is no evidence that local vancomycin powder is associated with an increased risk for Gram-negative infection.
Are There Limits in Explainability of Prognostic Biomarkers? Scrutinizing Biological Utility of Established Signatures

Prognostic biomarkers can have an important role in the clinical practice because they allow stratification of patients in terms of predicting the outcome of a disorder. Obstacles for developing such markers include lack of robustness when using different data sets and limited concordance among similar signatures. In this paper, we highlight a new problem that relates to the biological meaning of already established prognostic gene expression signatures. Specifically, it is commonly assumed that prognostic markers provide sensible biological information and molecular explanations about the underlying disorder. However, recent studies on prognostic biomarkers investigating 80 established signatures of breast and prostate cancer demonstrated that this is not the case. We will show that this surprising result is related to the distinction between causal models and predictive models and the obfuscating usage of these models in the biomedical literature. Furthermore, we suggest a falsification procedure for studies aiming to establish a prognostic signature to safeguard against false expectations with respect to biological utility.
The Role of Sodium Glucose Cotransporter-2 Inhibitors in Atherosclerotic Cardiovascular Disease: A Narrative Review of Potential Mechanisms

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication with broad cardiovascular benefits in those with type 2 diabetes, chronic kidney disease, and heart failure. These include reductions in major adverse cardiac events and cardiovascular death. The mechanisms that underlie their benefits in atherosclerotic cardiovascular disease (ASCVD) are not well understood, but they extend beyond glucose lowering. This narrative review summarises the ASCVD benefits of SGLT2 inhibitors seen in large human outcome trials, as well as the mechanisms of action explored in rodent and small human studies. Potential pathways include favourable alterations in lipid metabolism, inflammation, and endothelial function. These all require further investigation in large human clinical trials with mechanistic endpoints, to further elucidate the disease modifying benefits of this drug class and those who will benefit most from it.
Effects of intradialytic exercise for advanced-age patients undergoing hemodialysis: A randomized controlled trial

Previous reports have shown the benefits of intradialytic exercise to patients undergoing hemodialysis. However, most of those studies assessed the effects of exercise in middle-aged patients and little is known about advanced-age patients undergoing hemodialysis. Therefore, the present randomized controlled trial was performed to determine the effectiveness of exercise therapy in advanced-age patients undergoing hemodialysis. This non-blinded, randomized controlled parallel trial enrolled a total of 101 patients who were randomly assigned to intradialytic exercise (n = 51) or usual care (n = 50) groups. The training program included both resistance and aerobic exercises and was performed three times per week for 6 months. The aerobic exercise intensity was adjusted to a target Borg score of 13 for 20 minutes. Four types of resistance exercises were performed using elastic tubing, with three sets of 10 exercises performed at moderate intensity (13/20 on the Borg scale). The usual care group received standard care. Lower extremity muscle strength, Short Physical Performance Battery score, and 10-m walking speed were the outcomes and were evaluated before the hemodialysis session and after 6 months of training. There were statistically significant improvements in Short Physical Performance Battery score (effect size, 0.57; 95% confidence interval, 0.15‒1.95) in the exercise group relative to the control group. There were no statistically significant differences in lower extremity muscle strength or in the 10-m walking speed between the two groups. These findings suggest that 6 months of intradialytic training could improve physical function in older patients undergoing hemodialysis.
Hydroxy-Selenomethionine Improves the Selenium Status and Helps to Maintain Broiler Performances under a High Stocking Density and Heat Stress Conditions through a Better Redox and Immune Response

This study has determined whether hydroxy-selenomethionine (OH-SeMet) exerts a better protective action on broilers against environmental stress than sodium selenite (SS) or seleno-yeast (SY). Day-old male Cobb 500 broilers (12 cages/diet, 9 broilers/cage) were fed a selenium (Se)-deficient diet (0.047 mg/kg) supplemented with SS, SY or OH-SeMet at 0.3 mg Se/kg under a high stocking density and heat stress condition for six weeks. OH-SeMet improved the FCR and Se concentration in the tissues than SS and SY. SY and OH-SeMet both reduced the serum cortisol, T3, IL-6, IgA, IgM and LPS, more than SS, while only OH-SeMet further increased IL-10 and IgG. SY and OH-SeMet improved the intestinal morphology and increased the T-AOC, TXRND, SELENON and OCCLUDIN activities but decreased CLAUDIN2 in the jejunum than SS, while OH-SeMet further improved these values than SY. SY and OH-SeMet both increased SELENOS and TXNRD2 in the muscles than SS, and OH-SeMet further raised T-AOC, GPX4, SELENOP, SELENOW and TXNRD1, and reduced malondialdehyde and protein carbonyl in the muscles than SS and SY. OH-SeMet showed a better ability to maintain the performance and the redox and immune status of broilers under a high stocking density and heat stress challenge than SS and SY.
Clinical Characteristics and Outcomes in Immune Checkpoint Inhibitor Therapy-Associated Myocarditis

Immune checkpoint inhibitor (ICI) therapy has played an important role in the treatment of several groups of cancers. Although a life prolonging treatment, many side effects have been shown with ICI therapy. This study looked at individual level clinical characteristics and outcomes with ICI therapy in patients who developed ICI-related myocarditis. A comprehensive review of the National Library of Medicine PubMed database was performed. Inclusion criteria were all studies that were composed of case reports and case series of individual patients undergoing ICI therapy that developed myocarditis. To appreciate individual patient level data, observational studies, clinical trials, systematic reviews, and meta-analyses were excluded. Our search yielded 333 results with 71 cases reviewed of ICI therapy-related myocarditis. The findings included an average age of 68 years, higher incidence in men, and pretreatment cardiac history of hypertension. Melanoma was the most prevalent malignancy with nivolumab being the most used ICI therapy. Heart failure was the most prevalent adverse event that was co-prevalent with myocarditis. Corticosteroid therapy alone was the most utilized therapy to treat ICI-related myocarditis. Mortality was seen in nearly half of the patient population. Our study reviewed the preexisting literature of prior reported myocarditis secondary to ICI therapy. Periodic surveillance should be performed by the cardio-oncologist and internist. Due to the expanding role of ICI therapy in treating a variety of cancer patients, appreciation of its impact on the development of myocarditis is needed.
MicroRNAs and Metabolism: Revisiting the Warburg Effect with Emphasis on Epigenetic Background and Clinical Applications

Since the well-known hallmarks of cancer were described by Hanahan and Weinberg, fundamental advances of molecular genomic technologies resulted in the discovery of novel puzzle pieces in the multistep pathogenesis of cancer. MicroRNAs are involved in the altered epigenetic pattern and metabolic phenotype of malignantly transformed cells. They contribute to the initiation, progression and metastasis-formation of cancers, also interacting with oncogenes, tumor-suppressor genes and epigenetic modifiers. Metabolic reprogramming of cancer cells results from the dysregulation of a complex network, in which microRNAs are located at central hubs. MicroRNAs regulate the expression of several metabolic enzymes, including tumor-specific isoforms. Therefore, they have a direct impact on the levels of metabolites, also influencing epigenetic pattern due to the metabolite cofactors of chromatin modifiers. Targets of microRNAs include numerous epigenetic enzymes, such as sirtuins, which are key regulators of cellular metabolic homeostasis. A better understanding of reversible epigenetic and metabolic alterations opened up new horizons in the personalized treatment of cancer. MicroRNA expression levels can be utilized in differential diagnosis, prognosis stratification and prediction of chemoresistance. The therapeutic modulation of microRNA levels is an area of particular interest that provides a promising tool for restoring altered metabolism of cancer cells.
Reactive Oxygen Species and Antioxidative Defense in Chronic Obstructive Pulmonary Disease

The respiratory system is continuously exposed to endogenous and exogenous oxidants. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, leading to the destruction of lung parenchyma (emphysema) and declining pulmonary function. It is increasingly obvious that reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the progression and amplification of the inflammatory responses related to this disease. First, we described the association between cigarette smoking, the most representative exogenous oxidant, and COPD and then presented the multiple pathophysiological aspects of ROS and antioxidative defense systems in the development and progression of COPD. Second, the relationship between nitric oxide system (endothelial) dysfunction and oxidative stress has been discussed. Third, we have provided data on the use of these biomarkers in the pathogenetic mechanisms involved in COPD and its progression and presented an overview of oxidative stress biomarkers having clinical applications in respiratory medicine, including those in exhaled breath, as per recent observations. Finally, we explained the findings of recent clinical and experimental studies evaluating the efficacy of antioxidative interventions for COPD. Future breakthroughs in antioxidative therapy may provide a promising therapeutic strategy for the prevention and treatment of COPD.
The Pathophysiological Role of Heat Shock Response in Autoimmunity: A Literature Review

Within the last two decades, there has been increasing evidence that heat-shock proteins can have a differential influence on the immune system. They can either provoke or ameliorate immune responses. This review focuses on outlining the stimulatory as well as the inhibitory effects of heat-shock proteins 27, 40, 70, 65, 60, and 90 in experimental and clinical autoimmune settings.
Targeting PirAvp and PirBvp Toxins of Vibrio parahaemolyticus with Oilseed Peptides: An In Silico Approach

Acute hepatopancreatic necrosis disease (AHPND), caused by PirAvp- and PirBvp-releasing Vibrio parahaemolyticus strains, has resulted in massive mortality in shrimp aquaculture. Excessive use of antibiotics for AHPND management has led to antibiotic resistance, highlighting the urgency to search for alternatives. Using an in silico approach, we aimed to discover PirAvp/PirBvp-binding peptides from oilseed meals as alternatives to antibiotics. To search for peptides that remain intact in the shrimp digestive tract, and therefore would be available for toxin binding, we focused on peptides released from tryptic hydrolysis of 37 major proteins from seeds of hemp, pumpkin, rape, sesame, and sunflower. This yielded 809 peptides. Further screening led to 24 peptides predicted as being non-toxic to shrimp, fish, and humans, with thermal stability and low water solubility. Molecular docking on the 24 peptides revealed six dual-target peptides capable of binding to key regions responsible for complex formation on both PirAvp and PirBvp. The peptides (ISYVVQGMGISGR, LTFVVHGHALMGK, QSLGVPPQLGNACNLDNLDVLQPTETIK, ISTINSQTLPILSQLR, PQFLVGASSILR, and VQVVNHMGQK) are 1139–2977 Da in mass and 10–28 residues in length. Such peptides are potential candidates for the future development of peptide-based anti-AHPND agents which potentially mitigate V. parahaemolyticus pathogenesis by intercepting PirAvp/PirBvp complex formation.
Link between History of Childhood Maltreatment and Emotion Dysregulation in Adults Suffering from Attention Deficit/Hyperactivity Disorder or Borderline Personality Disorder

Childhood maltreatment (CM) may have a long-term effect on emotion regulation. This study aimed to explore the relationship between CM and emotion dysregulation (ED) in a heterogeneous population. Four hundred seventy French-speaking outpatients (N = 279 ADHD, N = 70 BPD, N = 60 ADHD + BPD, N = 61 clinical controls) completed the Emotion Reactivity Scale (ERS), the Cognitive Emotional Regulation Questionnaire (CERQ), the Childhood Trauma Questionnaire (CTQ), and the Relationship Scales Questionnaire (RSQ). Reports of childhood maltreatment experiences were significantly associated with increased levels of emotion reactivity in all our groups and in the whole population, with a greater use of non-adaptive cognitive emotion regulation strategies and insecure attachment patterns. Emotional abuse showed the strongest effect. Further analysis indicated that an anxious attachment style significantly mediated the relationship between CM and the use of non-adaptive cognitive emotion regulation strategies and emotion reactivity. The results of our study suggest an impact of CM on ED and a potentially marked effect of emotional abuse. They also indicate a potentially mediating role of insecure attachment in the relationship between a history of childhood abuse and emotion reactivity and a higher use of non-adaptive cognitive emotion regulation strategies in adulthood.
Which Tyrosine Kinase Inhibitors Should Be Selected as the First-Line Treatment for Chronic Myelogenous Leukemia in Chronic Phase?

Simple Summary This review discusses the optimal selection of BCR-ABL1 tyrosine kinase inhibitors (TKIs) as the first-line treatment for newly diagnosed chronic myelogenous leukemia in chronic phase (CML-CP). With the advent of TKIs, the treatment goals for CML-CP patients have changed from “simply survival” to “survival with adequate quality of life”, hence the number of CML-CP patients aiming to achieve treatment-free remission has increased, irrespective of age or comorbidities. Therefore, optimal selection of TKIs for maximizing the number of patients to achieve treatment-free remission is an important factor for consideration in future studies. To this end, we must understand the advantages and disadvantages of each TKI in terms of treatment response, disease risk at diagnosis, comorbidities, and medical expenses, and use of effective 2GTKIs based on patient background. This review provides insights into “shared decision-making” in individual cases, including the elderly population. Abstract With the use of tyrosine kinase inhibitors (TKIs), chronic myelogenous leukemia in chronic phase (CML-CP) has been transformed into a non-fatal chronic disease. Hence, “treatment-free remission (TFR)” has become a possible treatment goal of patients with CML-CP. Currently, four types of TKIs (imatinib, nilotinib, dasatinib, and bosutinib) are used as the first-line treatment for newly diagnosed CML-CP. However, the second-generation TKI (2GTKI), the treatment response of which is faster and deeper than that of imatinib, is not always recommended as the first-line treatment for CML-CP. Factors involved in TKI selection in the first-line treatment of CML-CP include not only patients’ medical background, but also patients’ choice regarding the desired treatment goal (survival or TFR? ). Therefore, it is important that clinicians select an appropriate TKI to successfully achieve the desired treatment goal for each patient, while minimizing the development of adverse events. This review compares the pros and cons of using imatinib and 2GTKI for TKI selection as the first-line treatment for CML-CP, mainly considering treatment outcomes, medical history (i.e., desire for pregnancy, aging factor, and comorbidity), and cost. The optimal use of 2GTKIs is also discussed.
Impact of Soil Microbes and Oxygen Availability on Bacterial Community Structure of Decomposing Poultry Carcasses

Simple Summary Decomposition is a complex process that involves several factors, such as temperature, pH, humidity, and microbes. Microbes play a significant role in the carcass decomposition process. Microcosm burial set-ups were prepared and poultry carcasses were decomposed for 60 days in unsterilized and sterilized soil, incubated under aerobic or anaerobic conditions. The moisture content, pH, alpha and beta diversity were affected by the soil microbial community and oxygen availability during the decomposition of poultry carcasses. The bacterial taxa composition was also altered during the poultry carcass decomposition. These changes suggested that the soil with an intact microbial community and oxygen availability influenced the bacterial community structure during the decomposition of poultry carcasses. The results of this study provided information on the different bacterial species which might be associated with the decomposition of poultry carcasses. Abstract The impact of soil with an intact microbial community and oxygen availability on moisture content, soil pH, and bacterial communities during decomposition of poultry carcasses was investigated. Poultry carcasses were decomposed in soil with or without a microbial community, under aerobic or anaerobic conditions. The samples collected in each microcosm burial set-up were analyzed by targeted 16S rRNA amplicon sequencing and Amplicon sequence variants (ASV) method. Our results showed that moisture was high in the burial set-ups under anaerobic conditions and pH was high in the burial set-ups under aerobic conditions. Meanwhile, the Chao1 and Shannon index significantly differed between the different burial set-ups and across different time points. In addition, bacterial taxa composition during the early period of decomposition differed from that of the late period. A total of 23 phyla, 901 genera, and 1992 species were identified. Firmicutes was the most dominant phyla in all burial set-ups throughout the decomposition. At day 60, Pseudogracilibacillus was dominant in the burial set-ups under aerobic conditions, while Lentibacillus dominated in the burial set-ups under anaerobic conditions. This study demonstrated that the soil microbial community and availability of oxygen significantly affected the changes in moisture content, pH, and bacterial composition during the decomposition process.
Multi-model mapping of phonemic fluency

Abstract The voluntary generation of non-overlearned responses is usually assessed with phonemic fluency. Like most frontal tasks, it draws upon different complex processes and systems whose precise nature is still incompletely understood. Many claimed aspects regarding the pattern of phonemic fluency performance and its underlying anatomy remain controversial. Major limitations of past investigations include small sample size, scant analysis of phonemic output and methodologically insufficient lesion analysis approaches. We investigated a large number of patients with focal unilateral right or left frontal (n = 110) or posterior (n = 100) or subcortical (n = 65) lesions imaged with magnetic resonance or computed tomography and compared their performance on the number of overall responses, words produced over time, extremely infrequent/unknown words and inappropriate words generated. We also employed, for the first time parcel‐based lesion-symptom mapping, tract-wise statistical analysis as well as Bayesian multi-variate analysis based on meta-analytically defined functional region of interest, including their interactions. We found that left frontal damage was associated with greater impairment than right frontal or posterior damage on overall fluency performance, suggesting that phonemic fluency shows specificity to frontal lesions. We also found that subcorticals, similar to frontals, performed significantly worse than posteriors on overall performance suggesting that subcortical regions are also involved. However, only frontal effects were found for words produced over time, extremely infrequent/unknown and inappropriate words. Parcel‐based lesion-symptom mapping analysis found that worse fluency performance was associated with damage to the posterior segment of the left frontal middle and superior gyrus, the left dorsal anterior cingulate gyrus and caudate nucleus. Tract-wise statistical analysis revealed that disconnections of left frontal tracts are critical. Bayesian multi-variate models of lesions and disconnectome maps implicated left middle and inferior frontal and left dorsomedial frontal regions. Our study suggests that a set of well localized left frontal areas together with subcortical regions and several left frontal tracts are critical for word generation. We speculate that a left lateralized network exists. It involves medial, frontal regions supporting the process of ‘energization’, which sustains activation for the duration of the task and middle and inferior frontal regions concerned with ‘selection’, required due to the competition produced by associated stored words, respectively. The methodology adopted represents a promising and empirically robust approach in furthering our understanding of the neurocognitive architecture underpinning executive processes.