Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammation influences thrombus burden in STEMI?

Inflammation is the new frontier in the treatment of coronary artery disease. Following the seminal works by Libby et al. [1], recent trials such as CANTOS [2] and COLCOT [3] have shown the benefit of targeting inflammation to reduce cardiovascular events. However, not all were positive suggesting different types of inflammation may be in play [4]. In this issue of Acta, Dolu et al. present an observational study in which they correlate thrombus burden observed in STEMI with CRP and a simple inflammatory parameter, the systemic immune-inflammation index (SII) defined by the product of platelet and neutrophil counts divided by the lymphocyte count. This correlation implies that thrombus burden and therefore the mechanism of myocardial infarction is not only related to plaque characteristics but also to the general systemic inflammatory milieu. In other words, different mechanisms of acute coronary syndrome may be associated with different types and variable degrees of inflammation. Notwithstanding, myocardial infarctions with larger thrombi may also activate a different inflammation or a greater release of catecholamines. Thus, these findings might also be a consequence of the severity of the myocardial infarction rather than related to its cause. The clinical utility of the SII is reduced in the setting of primary PCI where results of haematology tests are usually obtained after coronary angiography and PCI, where thrombus burden is apparent and when the consequences of this thrombotic load are appreciated. Therefore, these findings probably pertain more to understanding how to prevent acute coronary syndromes than actually treating them. Nonetheless, this new data represent yet another stepping-stone on our way to understanding acute coronary syndromes.
A simple noninvasive biomarker can reflect both the acute and chronic pulmonary impact of patent ductus arteriosus shunting

The SFR (SpO2/FiO2 ratio) offers a continuous, noninvasive reflection of pulmonary function regardless of whether the baby is ventilated or breathing spontaneously. We hypothesized that significant patent ductus arteriosus (PDA) shunting would impair pulmonary oxygen diffusion, reflected by decreased SFR; and that early PDA related decreases in SFR predict subsequent chronic lung disease (CLD).
The HVCN1 voltage‐gated proton channel contributes to pH regulation in canine ventricular myocytes

Regulation of intracellular pH (pHi) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage‐sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+, while avoiding Na+ loading, as occurs during direct acid extrusion via Na+/H+ exchange or indirect acid extrusion via Na+–HCO3− cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage‐gated H+ current that was highly H+‐selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5‐chloro‐2‐guanidinobenzimidazole. Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1‐mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+/H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+ extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+‐independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport‐mediated CO2 disposal.
To Use the Back-up Cochlear Implant or Not? Using Intra-operative Impedance to Guide Your Decisions

Introduction: Intra-operative electrophysiological testing is being increasingly used to determine device functionality. Impedance abnormalities (open or short circuits) measured at time of surgery pose a dilemma: is it likely to resolve or is it a permanent fault? There is little in the literature on how to manage these intraoperative finding and if, at time of surgery, the back-up device should be used. Methods: We routinely undertake impedance testing twice intraoperatively, as well as at switch on, 1 and 3 months postoperatively. Retrospective impedance thresholds were analysed for one surgeon's cases between January 2018 and December 2019. Results: There were 235 cochlear implants performed for 217 patients (5,020 electrode contacts) analysed. Thirty-three electrodes had abnormal impedance thresholds on first intraoperative cycle of testing, 76% resolving with the second testing cycle electrode contacts that demonstrated abnormal impedance during both intraoperative test cycles were 16.54 times (95%CI 2.55–107.13, p = 0.003) more likely to be abnormal at three months. Fifty percent resolved by switch on. The intraoperative abnormalities made up 26% of electrode abnormalities seen at 3 months postoperatively. Discussion: This study demonstrates the utility of 2 cycles of intraoperative impedance testing, with persistently abnormal electrodes having 16 times the likelihood of persistent abnormalities of impedance, and 50% resolution. These persistent intra-operative abnormal electrodes are responsibly for 26% of electrode abnormalities at 3 months. This information is useful for the surgeon when considering use of the backup cochlear implant device.
Evolutive profile of hemodialysis vascular accesses Hemodialysisaccesses

Summary Introduction: Arterio-venous fistula (AVF) is the first-choice vascular access for hemodialysis (HD). Hemodialysis catheter (KT) may be a temporary or permanent alternative. Aim: To evaluate indications of KT and AVF and their predictive factors of complications. Methods: It's a retrospective multicentric study interesting KT and AVF in patients treated by hemodialysis, in the Kef Governorate in north-western Tunisia, during the period from 01/07/18 to 31/12/18. Results: We included 288 AVF and 148 KT that were created on 205 patients. The average age was 58.14 years, the sex ratio was 1.5. Hypertensive patients and diabetics represented respectively 83.9% and 27.3% of the population. Diabetic nephropathy was the most common (25.9%). For the KT, the main indication was the wait for AVF creation (68.9%). The overall incidence of immediate complications was 11.5%. Dysfunction was reported in 23.6% of cases with obesity and tunneled type of KT as contributing factors. KT infection was occuring in 39.2% of cases. It was promoted by prolonged duration of use and hemoglobin level < 8g/dl. The use of antiseptic lock reduced infections' risk (p=0.011). For AVF, the most common complications were thrombosis (36.2%), aneurysm (29.9%) and stenosis (22.6%). Survival rate was 60% at 2000 days. The AVF impairing factors were diabetes (p=0.05), obesity (p=0.05), anterior AVF creation (p=0.011), AVF grafts (p=0.016), and anticoagulant therapy (p=0.0001). Antiplatelet therapy improved AVF patency (p=0.02). Conclusion Much remained to be done to reduce KT complications, creation of AVF on time and prevention of their complications.
Blocking Cancer–Nerve Crosstalk for Treatment of Metastatic Bone Cancer Pain

The tumor microenvironment is a complex milieu where neurons constitute an important non‐neoplastic cell type. From “cancer neuroscience,” the crosstalk between tumors and neurons favors the rapid growth of both, making the cancer–nerve interaction a reciprocally beneficial process. Thus, cancer–nerve crosstalk may provide new targets for therapeutic intervention against cancer and cancer‐related symptoms. We proposed a nerve–cancer crosstalk blocking strategy for metastatic bone cancer pain treatment, achieved by Mg/Al layered‐double‐hydroxide nanoshells (Mg/Al‐LDH) with AZ‐23 loaded inside and alendronate decorated outside. The pain‐causing H+ is rapidly eliminated by the LDH, with neurogenesis inhibited by the antagonist AZ‐23. As positive feedback, the decreased pain reverses the nerve‐to‐cancer Ca2+ crosstalk‐related cell cycle, dramatically inhibiting tumor growth. All experiments confirm the improved pain threshold and enhanced tumor inhibition. The study may inspire multidisciplinary researchers to focus on cancer–nerve crosstalk for treating cancer and accompanied neuropathic diseases.
C-reactive protein testing to reduce antibiotic prescribing for acute respiratory infections in adults: a systematic review and meta-analysis

Background Antimicrobial resistance (AMR) has become a worldwide public health problem. Abuse of antibiotic in acute respiratory tract infections (ARI) contributes to the increasing AMR. C-reactive protein (CRP) testing may help reduce antibiotic overprescribing, but the available evidence quality varies widely. There is no meta-analysis of CRP testing to guide the antibiotic prescribing for adult ARI. Therefore, we conducted this meta-analysis to determine the effectiveness of CRP testing to guide antibiotic prescribing in adult ARI. Methods We searched the Cochrane Library, PubMed, and EMBASE databases for randomized controlled trials (RCTs) involving our meta-analysis from the establishment of these databases until January 16, 2021. Two reviewers extracted the data separately and pooled the data using RevMan5.3. The evidence quality was appraised strictly with GRADE system. Results Seven studies included with 3,614 patients. Compared with routine care, CRP testing reduced antibiotic prescribing rate at the index consultation significantly [risk ratio (RR) =0.76; 95% confidence interval (CI): 0.68–0.85; P<0.00001], and during 28 days follow-up (RR =0.77; 95% CI: 0.73–0.81; P<0.00001). There were no significant differences between CRP testing and routine care in clinical recovery of patients within 7 days (RR =0.95; 95% CI: 0.90–1.01; P=0.08). Moreover, adverse events were not significantly different between CRP testing and routine care. Discussion CRP testing can reduce the antibiotic prescribing rate at index consultation and during 28 days follow-up. These findings support the conclusion that CRP testing is valuable to guide the antibiotic prescribing for adult ARI.
Injection of YiQiFuMai powder protects against heart failure via inhibiting p38 and ERK1/2 MAPKs activation

Abstract Context Injection of YiQiFuMai (YQFM) powder, a modern Chinese plant-derived medical preparation, has a therapeutic effect in heart failure (HF). However, its therapeutic mechanism remains largely unknown. Objective To investigate the molecular mechanisms of YQFM in HF. Materials and methods Kinase inhibition profiling assays with 2 mg/mL YQFM were performed against a series of 408 kinases. In addition, the effects of kinase inhibition were validated in cardiomyocyte cell line H9c2. In vivo, HF with reduced ejection fraction (HFrEF) was induced by permanent left anterior descending (LAD) coronary artery ligation for 6 weeks in male Sprague-Dawley rats. Then, HFrEF mice were treated with 0.46 g/kg YQFM or placebo once a day for 2 weeks. Echocardiography, immunohistochemistry, histological staining and Western blotting analysis were performed to assess the myocardial damage and molecular mechanisms. Results Kinase inhibition profiling analysis demonstrated that mitogen-activated protein kinases (MAPKs) mediated the signalling cascades of YQFM during HF therapy. Meanwhile, p38 and extracellular signal-regulated kinases (ERK1/2) were inhibited after YQFM treatment in H9c2 cells. In rats, the control group had lower left ventricular ejection fraction (LVEF) at 37 ± 1.7% compared with the YQFM group at 54 ± 1.1% (p < 0.0001). Cardiac fibrosis levels in control group rats were significantly higher than YQFM group (30.5 ± 3.0 vs. 14.1 ± 1.0, p < 0.0001). Conclusions Our collective in vitro and in vivo experiments demonstrated that YQFM improves left ventricular (LV) function and inhibits fibrosis in HFrEF rats by inhibiting MAPK signalling pathways.
Possible reactivation of latent anal human papillomavirus associated with markers of immune dysfunction in gay and bisexual men.

It is unknown whether reactivation of human papillomavirus (HPV) after latency occurs in the anus. We measured incidence and predictors of incident anal HPV in sexually inactive gay and bisexual men (GBM) as a surrogate of HPV reactivation. The Study of the Prevention of Anal Cancer collected data on sexual behavior, anal cytology, HPV DNA, histology and HPV serology. HPV incidence when zero sexual partners were reported in the last six months at both the current and previous annual visit ("no sexual activity") was analysed by Cox regression (Wei-Lin-Weissfeld method) to determine univariable predictors. Results: Of 617 men enrolled, 525 had results for {greater than or equal to} 2 visits, of whom 58 (11%) had {greater than or equal to} one period of "no sexual activity". During sexually inactive periods, there were 29 incident HRHPV infections in 20 men, which occurred more commonly in older men (p trend = 0.010), HIV-positive men (HR=3.12, 95% CI: 0.91-16.65), longer duration of HIV (p trend= 0.028), history of AIDS defining illness (p=0.010), lower current (p=0.010) and nadir CD4 count (p=0.014). For 18 of 29 infections with available results, 12 men remained type-specific HRHPV L1 seronegative. None were consistently seropositive. A new HSIL diagnosis occurred in only two men, caused by an HPV type other than the incident type. Our findings suggest that in sexually inactive GBM, anal HRHPV incidence is relatively common, and is associated with increasing age and immune dysfunction, a pattern consistent with HPV reactivation. Reactivation of anal HPV may occur.
Effect of partially replacing soybean meal with sunflower meal with supplementation of multienzymes on growth performance, carcass characteristics, meat quality, ileal digestibility, digestive enzyme activity and caecal microbiota in broilers

Objective An experiment was conducted to evaluate the effects of partially replacing soybean meal (SBM) with sunflower meal (SFM) with added exogenous multienzymes (MEs) on various biological parameters in broilers. Methods One week-old, 400 broiler chicks were randomly divided into four treatments (control, 3SFM, 6SFM, and 9SFM) with 5 replicates/treatment (20 chicks/replicate). Control diet was without SFM and MEs, while diets of 3SFM, 6SFM, and 9SFM treatments were prepared by replacing SBM with SFM at levels of 3%, 6%, and 9%, respectively, and were supplemented with MEs (100 mg/kg). Feeding trial was divided into grower (8 to 21 day) and finisher phases (22 to 35 day). External marker method was used to measure the nutrient digestibility. At the end of trial, twenty birds (one birds per replicate) with similar body weight were slaughtered for samples collection. Results No significant effect of dietary treatments was found on all parameters of growth performance and carcass characteristics, except relative weight of bursa. Weight (25.0 g) and length (15.80 cm) of duodenum were significantly (p<0.05) higher in 3SFM than control. Lowest (p<0.05) villus height/crypt depth ratio was found in 3SFM and 9SFM than control. Most of meat quality parameters remained unaffected, however, highest pH of breast meat (6.16) and thigh meat (6.44) were observed in 9SFM and 3SFM, respectively. Lowest (p<0.05) cook loss of thigh meat was found in 6SFM (31.76%). Ileal digestibility of crude protein was significantly (p<0.05) higher in 3SFM (72.35%) than control (69.46%). In addition, amylase (16.87 U/mg) and protease (85.18 U/mg) activities were significantly (p<0.05) higher in 3SFM than control. However, cecal microbial count remained unaffected. Conclusion Partial replacement (up to 9%) of SBM with SFM, with added MEs can help to improve the nutrient digestibility, intestinal morphology, and digestive enzyme activities without affecting cecal microbial count and growth performance in broilers.
Computational Modeling on Binding Interactions of Cyclodextrins with the Human Multidrug Resistance P-glycoprotein Toward Efficient Drug-Delivery System Applications.

AIMS Herein, molecular docking approaches and DFT ab initio simulations were combined for the first time, to study the key interactions of cyclodextrins (CDs: α-CD, β-CD, and γ-CD) family with potential pharmacological relevance and the multidrug resistance P-gp protein toward efficient drug-delivery applications. BACKGROUND The treatment of neurological disorders and cancer therapy where the multiple drug-resistance phenomenon-mediated by the P-gp protein constitutes the fundamental cause of unsuccessful therapies. OBJECTIVE Undercover the docking mechanism of the CDs and the P-gp-. METHODS Use of the computational docking methodology to reach the main aim. RESULT The observed docking-mechanism of the CDs on the P-gp were fundamentally based on hybrid backbone/side-chain hydrophobic interactions, and also hybrid electrostatic/side-chain interactions of the OH-motifs of the CD-ligands with acceptor and donor properties which theoretically could induce local perturbations in the TMD/P-gp inter-residues network modulating to the ligand extrusion from the blood-brain-barrier. CONCLUSION These theoretical results open new horizons for the evaluation of new nanotherapeutic drugs with potential pharmacological relevance for efficient drug-delivery for nanomedicine applications. P-gp residues were conformationally favored. Despite the structural differences, all the cyclodextrins exhibit very close Gibbs free binding energy values (or affinity) by the P-gp binding site (transmembrane domains - TMDs). The obtained theoretical docking-mechanism of the CDs on the P-gp were fundamentally based on hybrid backbone/side-chain hydrophobic interactions, and also hybrid electrostatic/side-chain interactions of the OH-motifs of the CD-ligands with acceptor and donor properties which theoretically could induce allosteric local-perturbations in the TMDs-inter-residues network of P-gp modulating to the CD-ligand extrusion from the blood-brain-barrier (or cancer cells). Finally, these theoretical results open new horizons for the evaluation of new nanotherapeutic drugs with potential pharmacological relevance for efficient drug-delivery applications and precision nanomedicine.
Strategies and foundations for scientific discovery in longitudinal studies of bipolar disorder

Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical samples with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Insights of the role of estrogen in obesity from two models of ERα deletion

Sex hormones play a pivotal role in physiology and disease. Estrogen, the female sex hormone, has been long implicated in having protective roles against obesity. However, the direct impact of estrogens in white adipose tissue (WAT) function and growth are not understood. Here, we show that deletion of estrogen receptor alpha (ERα) from adipocytes using Adiponectin-cre does not affect adipose mass in male or female mice under normal or high-fat diet (HFD) conditions. However, loss of ERα in adipocyte precursor cells (APs) via PdgfRα-cre leads to exacerbated obesity upon HFD feeding in both male and female mice, with subcutaneous adipose (SWAT)-specific expansion in male mice. Further characterization of these mice revealed infertility and increased plasma levels of sex hormones, including estradiol in female mice and androgens in male mice. These findings compromise the study of estrogen signaling within the adipocyte lineage using the PdgfRα-cre strain. However, AP transplant studies demonstrate that the increased AP hyperplasia in male SWAT upon PdgfRα-cre-mediated ablation of ERα is not driven by AP-intrinsic mechanisms, but are rather mediated by off-target effects. These data highlight the inherent difficulties in studying models that disrupt the intricate balance of sex hormones. Thus, better approaches are needed to study the cellular and molecular mechanisms of sex hormones in obesity and disease.
Profil épidémiologique et anatomopathologique du cancer du sein dans la région du Nord-Ouest de la Tunisie

Résumé Introduction: Le cancer du sein est une affection fréquente et grave. Il représente la première cause de mortalité et de morbidité par cancer chez la femme en Tunisie et dans le monde. Notre objectif est d'analyser les caractéristiques clinico-pathologiques et évolutives des patientes suivies au pôle de carcinologie de la région du Nord-Ouest tunisien. Méthodes: Il s'agit d'une étude rétrospective, menée sur une période de 6 ans allant du 1er janvier 2011 au 31 décembre 2016 et qui a colligé 114 patientes présentant un carcinome mammaire invasif non métastatique traitées au pôle de Carcinologie du Nord-Ouest tunisien. Résultats: Parmi les 289 patientes traitées au service de carcinologie médicale de l'hôpital régional de Jendouba pour carcinome mammaire invasif sur une période de 6 ans 114 patientes avaient un carcinome mammaire localisé, elles ont fait l'objet de notre étude. L'âge moyen était de 51 ans. Le carcinome canalaire infiltrant était le type histologique le plus fréquent (95,6%). La taille histologique moyenne était de 29,3 mm. Le grade SBR II était majoritaire (57%). L'envahissement ganglionnaire histologique était retrouvé dans 50,9%. Des emboles vasculaires étaient identifiés dans 23,7% des cas et des engainements périnerveux dans 21,9% des cas. Le sous-type moléculaire le plus fréquent était le Luminal B. Après discussion en réunion de concertation pluridisciplinaire, les patientes ont reçu un traitement locorégional : chirurgie, radiothérapie et un traitement systémique : chimiothérapie, hormonothérapie. Après un suivi médian de 45 mois, la SG et la SSP à 5 ans étaient respectivement de 85,6% et de 79,2%. Conclusion: Le cancer du sein dans la région du Nord-Ouest de la Tunisie se caractérise par sa survenue à un âge jeune, l'importance de la taille tumorale et l'envahissement ganglionnaire, la fréquence de carcinome mammaire inflammatoire et surtout par la prédominance du profil moléculaire Luminal B et HER2 neu.