Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes over time in the Chronic Liver Disease risk score predict liver-related outcomes: longitudinal analysis of the Whitehall II study

Abstract Background and Aims The Chronic Liver Disease (CLivD) risk score was recently shown to predict future advanced liver disease in the general population. We here investigated the impact of individual CLivD-score changes over time. Methods Participants of both phase 3 (baseline, 1991–1994) and phase 5 (follow-up, 1997–1999) examinations of the Whitehall II study were followed for liver-related outcomes (hospitalization, cancer, death) until December 2019 through linkage with electronic healthcare registers. The CLivD score, its modifiable components (alcohol use, waist–hip ratio [WHR], diabetes, and smoking), and their individual changes were studied. Results Among 6590 adults (mean age 50 years, 30% women) with a median 21-year follow-up, there were 80 liver outcomes. A rise in the CLivD score between baseline and follow-up examinations significantly increased the risk for liver-related outcomes (adjusted hazard ratio [aHR] 1.62, 95% confidence interval [CI] 1.01–2.60), more so in subjects with baseline intermediate–high CLivD scores (HR 2.4 for a CLivD-change) compared to minimal-low CLivD scores. Adverse changes over time in alcohol use and WHR, and new-onset diabetes also predicted liver outcomes. In contrast to WHR, changes in body weight (kg) showed a U-shaped association with liver outcomes. Conclusions A change in the CLivD score over time corresponds to a true change in the risk for liver-related outcomes, suggesting the usefulness of the CLivD score for assessing response to liver-directed lifestyle interventions. Changes in WHR predicted liver outcomes better than changes in body weight or waist circumference, independent of body mass index, supporting the WHR in assessing risk for future liver disease.
A Clinicopathologic and Molecular Analysis of Fumarate Hydratase–deficient Pheochromocytoma and Paraganglioma

Up to 40% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are hereditary. Germline mutations/deletions in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell carcinoma syndrome which manifests predominantly with FH-deficient uterine/cutaneous leiomyomas and renal cell carcinomas (RCCs)—tumors characterized by loss of immunohistochemical (IHC) expression of FH and/or positive staining for S-(2-succino)-cysteine. Occasional patients develop PCC/PGL. We investigated the incidence, morphologic, and clinical features of FH-deficient PCC/PGL. We identified 589 patients with PCC/PGLs that underwent IHC screening for FH and/or S-(2-succino)-cysteine. Eight (1.4%) PCC/PGLs were FH deficient (1.1% in an unselected population). The median age for FH-deficient cases was 55 (range: 30 to 77 y) with 50% arising in the adrenal. All 4 with biochemical data were noradrenergic. Two (25%) metastasized, 1 dying of disease after 174 months. Germline testing was performed on 7 patients, 6 of whom had FH missense mutations. None were known to have a significant family history before presentation or developed cutaneous leiomyomas, or FH-deficient RCC at extended follow-up. The patient wild-type for FH on germline testing was demonstrated to have somatic FH mutation and loss of heterozygosity corresponding to areas of subclonal FH deficiency in her tumor. One patient did not undergo germline testing, but FH mutation was demonstrated in his tumor. We conclude that FH-deficient PCC/PGL are underrecognized but can be identified by IHC. FH-deficient PCC/PGL are strongly associated with germline missense mutations but are infrequently associated with leiomyoma or RCC, suggesting there may be a genotype-phenotype correlation. FH-deficient PCC/PGL may have a higher metastatic risk.
Involvement of IKK/IkBα/NF-kB p65 Signaling into the Regulative Effect of Engeletin on MUC5AC Mucin Gene Expression in Human Airway Epithelial Cells

In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.
Unique genetic signature and selection footprints in Dutch population of German Longhaired Pointer dogs

Abstract The German Longhaired Pointer (GLP) breed is a versatile pointer dog breed. In the current study, we investigated the genetic diversity of these dogs based on SNP array data and compared it to 11 other pointer setter breeds. The results show that GLPs have a relatively low level of inbreeding among these pointer breeds. In addition, with the availability of pedigree information of the GLPs, we demonstrate that the correlation between pedigree‐based inbreeding and genotype‐based inbreeding coefficients was high (R = 0.89 and 0.85). By investigating population structure between these 12 pointer setter breeds we showed that GLP is a breed distinct from other pointers and shares common ancestry with a few other pointing breeds. Finally, we identified selection signatures in GLPs using the runs of homozygosity islands method. The most significant runs of homozygosity island was detected on chromosome 30 harboring the genes RYR3, FMN1, and GREM1. The RYR3 gene plays a role in skeletal muscle contraction while the FMN1 and GREM1 genes are involved in limb development. The selection on these three genes could have contributed to the excellent athletic performance of GLPs, which is an extremely important characteristic for this hunting dog.
Draft Genome Sequence of the Multiple Antibiotic Resistant Pseudomonas aeruginosa PAO1-UB Subline

We report the draft genome sequence and antibiotic susceptibility of Pseudomonas aeruginosa strain PAO1-UB, a subline of the common reference strain PAO1. This strain was sequenced in order to provide information on the genome dynamics of PAO1 sublines and their genes conferring resistance to multiple antibiotics. ABSTRACT We report the draft genome sequence and antibiotic susceptibility of Pseudomonas aeruginosa strain PAO1-UB, a subline of the common reference strain PAO1. This strain was sequenced in order to provide information on the genome dynamics of PAO1 sublines and their genes conferring resistance to multiple antibiotics.
Repolarization indicates electrical instability in ventricular arrhythmia originating from papillary muscle

Abstract Aims Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. Methods and results Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. Conclusion RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.
Blunted hypoxic pulmonary vasoconstriction in apnoea divers

What is the central question of this study? Does the hyperbaric, hypercapnic, acidotic, hypoxic stress of apnoea diving lead to greater pulmonary vasoreactivity and increased right heart work in apnoea divers? What is the main finding and its importance? Compared with sex‐ and age‐matched control subjects, divers experienced significantly less change in total pulmonary resistance in response to short‐duration isocapnic hypoxia. With oral sildenafil (50 mg), there were no differences in total pulmonary resistance between groups, suggesting that divers can maintain normal pulmonary artery tone in hypoxic conditions. Blunted hypoxic pulmonary vasoconstriction might be beneficial during apnoea diving.
Quality assurance and quality control in surgical oncology

Even though surgery has remained a key component within multi‐disciplinary cancer care, the expectations have changed. Instead of serving as a modality to free a patient of a mass at all means and at the risk of high morbidity, modern cancer surgery is expected to provide adequate tumor clearance with lowest invasiveness. This review summarizes the evidence on quality assurance in surgical oncology and gives a comprehensive overview of quality improvement tools.
Impact of labor characteristics on maternal and neonatal outcomes of labor: A machine-learning model

Introduction Since Friedman’s seminal publication on laboring women, numerous publications have sought to define normal labor progress. However, there is paucity of data on contemporary labor cervicometry incorporating both maternal and neonatal outcomes. The objective of this study is to establish intrapartum prediction models of unfavorable labor outcomes using machine-learning algorithms. Materials and methods Consortium on Safe Labor is a large database consisting of pregnancy and labor characteristics from 12 medical centers in the United States. Outcomes, including maternal and neonatal outcomes, were retrospectively collected. We defined primary outcome as the composite of following unfavorable outcomes: cesarean delivery in active labor, postpartum hemorrhage, intra-amniotic infection, shoulder dystocia, neonatal morbidity, and mortality. Clinical and obstetric parameters at admission and during labor progression were used to build machine-learning risk-prediction models based on the gradient boosting algorithm. Results Of 228,438 delivery episodes, 66,586 were eligible for this study. Mean maternal age was 26.95 ± 6.48 years, mean parity was 0.92 ± 1.23, and mean gestational age was 39.35 ± 1.13 weeks. Unfavorable labor outcome was reported in 14,439 (21.68%) deliveries. Starting at a cervical dilation of 4 cm, the area under receiver operating characteristics curve (AUC) of prediction models increased from 0.75 (95% confidence interval, 0.75–0.75) to 0.89 (95% confidence interval, 0.89–0.90) at a dilation of 10 cm. Baseline labor risk score was above 35% in patients with unfavorable outcomes compared to women with favorable outcomes, whose score was below 25%. Conclusion Labor risk score is a machine-learning–based score that provides individualized and dynamic alternatives to conventional labor charts. It predicts composite of adverse birth, maternal, and neonatal outcomes as labor progresses. Therefore, it can be deployed in clinical practice to monitor labor progress in real time and support clinical decisions.
Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis

Background High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). Methods A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. Results A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Conclusion Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.
The effects of testosterone on transgender males on carotid intima-media thickness and serum inflammatory markers compared within patients with polycystic ovary syndrome

Abstract Objective: To evaluate the effects of testosterone on carotid intima-media thickness (CIMT) and serum inflammatory markers compared within transgender males (TGM-Former called female-to-male) and polycystic ovary syndrome (PCOS). Methods: The prospective observational study included 30 TGM, 30 patients with PCOS, and 30 healthy women. Groups were compared for CIMT and hematologic inflammatory markers white blood cell (WBC), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean platelet volume (MPV). Results: The CIMT of the TGM group was 0.48 ± 0.09 mm was significantly higher than PCOS (0.41 ± 0.09 mm, p = .005) and the control group (0.38 ± 0.7 mm, p = .001). The mean NLR, LMR, and MPV values were similar (p > .05). TGM had higher WBC levels compared to control women (p = .029). TGM had significantly lower PLR compared to PCOS and the control group (p = .001). CIMT were related to age (r = .390, p = .04) and body mass index (BMI) (r = .392, p = .03) in TGM. Conclusion: Increased CIMT in TGM individuals is not associated with inflammation; it seems to be a deleterious effect of exogenous testosterone exposure. Since increased CIMT may be a sign of serious cardiovascular problems developing in the future, it is suggested that it will be beneficial for these individuals should undergo clinical and radiological evaluation at regular intervals.
Influence of Injury to the Kaplan Fibers of the Iliotibial Band on Anterolateral Rotatory Knee Laxity in Anterior Cruciate Ligament Injury: A Retrospective Cohort Study

Background: Biomechanical cadaveric studies have shown that Kaplan fibers (KFs) of the iliotibial band play a role in controlling anterolateral rotatory knee laxity in anterior cruciate ligament (ACL) injury. However, in the clinical setting, the contribution of injury to KFs on anterolateral rotatory laxity remains unclear. Purpose: To use magnetic resonance imaging (MRI) scans to detect concomitant KF injury in ACL-injured knees and to then examine the effect of KF injury on anterolateral rotatory laxity as measured by the pivot-shift test in a clinical setting. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The study enrolled 91 patients with primary ACL tears (mean age 25 ± 11 years; 46 male and 45 female) whose MRI was conducted within 90 days after injury. KF injury was assessed by MRI according to previously reported criteria, and the patients were allocated to a KF injury group and a no–KF injury group. At the time of ACL reconstruction, the pivot-shift test was performed with the patient under anesthesia and quantitatively evaluated by tibial acceleration using an electromagnetic measurement system. Manual grading of the pivot-shift test was assessed according to guidelines of the International Knee Documentation Committee. The data were statistically compared between the 2 groups using Mann-Whitney U test and Fisher exact test (P < .05). Results: KFs were identified in 85 patients (93.4%), and KF injury was detected in 20 of the 85 patients (23.5%). No significant differences were observed between the KF injury group (n = 20) and the no–KF injury group (n = 65) in demographic characteristics, the period from injury to MRI (8.0 ± 14.0 days vs 8.9 ± 12.1 days, respectively), the rate of meniscal injury (50.0% vs 53.8%), or the rate of anterolateral ligament injury (45.0% vs 44.6%). Regarding the pivot-shift test, no significant differences were observed in tibial acceleration (1.2 m/s2 [interquartile range, 0.5-2.1 m/s2] vs 1.0 m/s2 [interquartile range, 0.6-1.7 m/s2], respectively) or manual grading between the 2 groups. Conclusion: Concomitant KF injury did not significantly affect the pivot-shift phenomenon in acute ACL-injured knees. The findings suggest that the contribution of KF injury to anterolateral rotatory knee laxity may be limited in the clinical setting.
Spatial Extent of Amyloid-β Levels and Associations With Tau-PET and Cognition.

Importance Preventive trials of anti-amyloid agents might preferably recruit persons showing earliest biologically relevant β-amyloid (Aβ) binding on positron emission tomography (PET). Objective To investigate the timing at which Aβ-PET binding starts showing associations with other markers of Alzheimer disease. Design, Setting, and Participants This longitudinal multicentric cohort study included 3 independent cohorts: Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) (data collected from 2012-2020), Alzheimer Disease Neuroimaging Initiative (ADNI) (data collected from 2005-2019), and Harvard Aging Brain Study (HABS) (data collected from 2011-2019). In a 3-tiered categorization of Aβ-PET binding spatial extent, individuals were assigned as having widespread Aβ deposition if they showed positive signal throughout a designated set of brain regions prone to early Aβ accumulation. Those with binding in some but not all were categorized as having regional deposition, while those who failed to show any criterion Aβ signal were considered Aβ-negative. All participants who were cognitively unimpaired at their first Aβ PET scan. Main Outcomes and Measures Differences in cerebrospinal fluid (CSF), genetics, tau-PET burden, and cognitive decline. Results A total of 817 participants were included, including 129 from the PREVENT-AD cohort (mean [SD] age, 63.5 [4.7] years; 33 [26%] male; 126 [98%] White), 400 from ADNI (mean [SD] age, 73.6 [5.8] years; 190 [47%] male; 10 [5%] Hispanic, 338 [91%] White), and 288 from HABS (mean [SD] age, 73.7 [6.2] years; 117 [40%] male; 234 [81%] White). Compared with Aβ-negative persons, those with regional Aβ binding showed proportionately more APOE ε4 carriers (18 [64%] vs 22 [27%] in PREVENT-AD and 34 [31%] vs 38 [19%] in ADNI), reduced CSF Aβ1-42 levels (F = 24 and 71), and greater longitudinal Aβ-PET accumulation (significant β = 0.019 to 0.056). Participants with widespread amyloid binding further exhibited notable cognitive decline (significant β = -0.014 to -0.08), greater CSF phosphorylated tau181 (F = 5 and 27), and tau-PET binding (all F > 7.55). Using each cohort's specified dichotomous threshold for Aβ positivity or a visual read classification, most participants (56% to 100%, depending on classification method and cohort) with regional Aβ would have been classified Aβ-negative. Conclusions and Relevance Regional Aβ binding appears to be biologically relevant and participants at this stage remain relatively free from CSF phosphorylated tau181, tau-PET binding, and related cognitive decline, making them ideal targets for anti-amyloid agents. Most of these individuals would be classified as negative based on classical thresholds of Aβ positivity.
Postneoadjuvant treatment for triple-negative breast cancer

Purpose of review Triple-negative breast cancer (TNBC) has been conventionally associated with poor prognosis, as a result of limited therapeutic options. In the early setting, prognosis is informed by clinical–pathological factors; for patients receiving neoadjuvant treatments, pathological complete response (pCR) is the strongest factor. In this review, we mapped the landscape of clinical trials in the postneoadjuvant space, and identified three patterns of clinical trial design. Recent findings For patients at higher risk, effective postneoadjuvant treatments are of paramount importance to address a high clinical need. Postneoadjuvant risk-adapted treatments have demonstrated to improve survival in patients at high of recurrence. Summary Patients at high risk have indication for adjuvant treatment intensification, informed by baseline clinical, pathological or molecular factors (type 1 approach), on the presence, extent and molecular characteristics of the residual disease at the time of surgery (type 2) or on risk factors assessed in the postsurgical setting (type 3), for example, circulating tumour DNA. Most of the past trials were based on type 2 approaches, for example, with capecitabine and Olaparib. Few trials were based on a type 1 approach, notably pembrolizumab for early TNBC. The clinical validity of type 3 approaches is under investigation in several ongoing trials.
Virtual reality in pediatrics, effects on pain and anxiety: A systematic review and meta‐analysis update

Medical procedures are often accompanied by pain and anxiety in pediatric patients. A relatively new technique to reduce pediatric pain and anxiety is virtual reality. Virtual reality is both applied as a distraction tool and as an exposure tool to prepare patients for medical procedures. Research into the application of virtual reality in medical settings is rapidly evolving. This meta‐analysis is an update of the meta‐analysis of Eijlers et al. investigating the effectiveness of virtual reality as an intervention tool on pain and anxiety in pediatric patients undergoing medical procedures.
Spin-Hall effect in a disordered two-dimensional electron system

We calculate the spin-Hall conductivity for a two-dimensional electron gas within the self-consistent Born approximation, varying the strength and type of disorder. In the weak disorder limit we find both analytically and numerically a vanishing spin-Hall conductivity even when we allow a momentum dependent scattering. Separating the reactive from the dissipative current response, we find the universal value ${\ensuremath{\sigma}}_{sH}^{R}=e∕8\ensuremath{\pi}$ for the reactive response, which cancels however with the dissipative part ${\ensuremath{\sigma}}_{sH}^{D}=\ensuremath{-}e∕8\ensuremath{\pi}$.