Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Sensitivity Troponin I Assay for Differential Diagnosis of New-Onset Myocardial Infarction in Patients with Acute Decompensated Heart Failure.

PURPOSE Acute decompensated heart failure (ADHF) caused by ischemic heart disease is associated with higher mortality and requires immediate diagnosis. Recently, novel methods to diagnose non-ST elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin have been applied. We compared the clinical utility of high-sensitivity troponin I (hS-TnI), delta troponin I, and other traditional methods to diagnose NSTEMI in patients with ADHF. MATERIALS AND METHODS This retrospective cross-sectional study was conducted to analyze patients with ADHF who underwent hS-TnI evaluation of 0-2-h protocol in our emergency department. Patients were grouped according to a diagnosis of NSTEMI. RESULTS A total of 524 ADHF [ADHF with NSTEMI, n=109 (20.8%)] patients were enrolled in this analysis. The mean values of hS-TnI (ng/mL) in the ADHF with and without NSTEMI groups were 2.44±5.60 and 0.25±0.91, respectively. Multivariable analysis revealed that regional wall-motion abnormality, T-wave inversion/hyperacute T wave, and initial and delta hS-TnI were predictive factors for NSTEMI. Laboratory values related to cardiac biomarkers, including hS-TnI [odds ratio (OR) (95% confidence interval, CI): 2.18], and the delta hS-TnI [OR (95% CI): 1.55] were significant predictors of NSTEMI. Moreover, receiver operating characteristic analysis showed that the areas under receiver operating characteristic curves for electrocardiographic abnormalities, initial hS-TnI, and delta hS-TnI were 0.794, 0.802, and 0.773, respectively. CONCLUSION For diagnosis of suspected NSTEMI in patients with ADHF, initial hS-TnI assay has similar predictive value as ischemic changes on electrocardiogram and superior predictive value than delta hS-TnI calculated by the 0-2-h protocol.
The effect of sulphur on the yield and chemical composition of winter barley

The changeover from fertilizers containing calcium or ammonium sulphate to those containing little or no sulphur has led to the occurrence of sulphur deficiency in many areas of the world (McNaught & Christoffels, 1961). In the United Kingdom, it was thought that even in the absence of fertilizer sulphur, atmospheric inputs were sufficient to ensure an adequate supply for crops. Recent work in the north of Scotland has shown that this is not so, that many soils in the area are low in sulphur, and yield responses have been obtained following application of sulphur to grass (Soott et al. 1983; Scott, 1984). The purpose of the present experiments was to extend the work to cereals, in particular to examine the response to added sulphur of the grain yield of winter barley, and to measure the effect of sulphur on the chemical composition of plants.
Manipulation of Inflammasome: A Promising Approach Towards Immunotherapy of Lung Cancer

Abstract Chronic inflammation has emerged as a key player at different stages of cancer development. A prominent signaling pathway for acute and chronic inflammation is the activation of the caspase-1 inflammasomes. These are complexes that assemble on activation of certain nucleotide-binding domain, leucine-rich repeat containing proteins (NLRs), AIM2-like receptors (ALRs), or pyrin due to activation via PAMPs or DAMPs. Of these, five complexes—NLRP1, NLRP3, NLRC4, Pyrin, and AIM2 are of importance in the context of cancer for their activities in modulating immune responses, cell proliferation, and apoptosis. Inflammasomes have emerged as clinically relevant in multiple forms of cancer making them highly promising targets for cancer therapy. As lungs are a tissue niche that is prone to inflammation owing to its exposure to external substances, inflammasomes play a vital role in the development and pathogenesis of lung cancer. Therefore, manipulation of inflammasome by various immunomodulatory means could prove a full-proof strategy for the treatment of lung cancer. Here, in this review, we tried to explore the various strategies to target the inflammasomes for the treatment of lung cancer.
How disturbance history alters invasion success: biotic legacies and regime change

Abstract Disturbance is a key factor shaping ecological communities, but little is understood about how the effects of disturbance processes accumulate over time. When disturbance regimes change, historical processes may influence future community structure, for example, by altering invasibility compared to communities with stable regimes. Here, we use an annual plant model to investigate how the history of disturbance alters invasion success. In particular, we show how two communities can have different outcomes from species introduction, solely due to past differences in disturbance regimes that generated different biotic legacies. We demonstrate that historical differences can enhance or suppress the persistence of introduced species, and that biotic legacies generated by stable disturbance history decay over time, though legacies can persist for unexpectedly long durations. This establishes a formal theoretical foundation for disturbance legacies having profound effects on communities, and highlights the value of further research on the biotic legacies of disturbance.
Urm1: A Non-Canonical UBL

Urm1 (ubiquitin related modifier 1) is a molecular fossil in the class of ubiquitin-like proteins (UBLs). It encompasses characteristics of classical UBLs, such as ubiquitin or SUMO (small ubiquitin-related modifier), but also of bacterial sulfur-carrier proteins (SCP). Since its main function is to modify tRNA, Urm1 acts in a non-canonical manner. Uba4, the activating enzyme of Urm1, contains two domains: a classical E1-like domain (AD), which activates Urm1, and a rhodanese homology domain (RHD). This sulfurtransferase domain catalyzes the formation of a C-terminal thiocarboxylate on Urm1. Thiocarboxylated Urm1 is the sulfur donor for 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), a chemical nucleotide modification at the wobble position in tRNA. This thio-modification is conserved in all domains of life and optimizes translation. The absence of Urm1 increases stress sensitivity in yeast triggered by defects in protein homeostasis, a hallmark of neurological defects in higher organisms. In contrast, elevated levels of tRNA modifying enzymes promote the appearance of certain types of cancer and the formation of metastasis. Here, we summarize recent findings on the unique features that place Urm1 at the intersection of UBL and SCP and make Urm1 an excellent model for studying the evolution of protein conjugation and sulfur-carrier systems.
The Theory Crisis in Psychology: How to Move Forward

Meehl argued in 1978 that theories in psychology come and go, with little cumulative progress. We believe that this assessment still holds, as also evidenced by increasingly common claims that psychology is facing a “theory crisis” and that psychologists should invest more in theory building. In this article, we argue that the root cause of the theory crisis is that developing good psychological theories is extremely difficult and that understanding the reasons why it is so difficult is crucial for moving forward in the theory crisis. We discuss three key reasons based on philosophy of science for why developing good psychological theories is so hard: the relative lack of robust phenomena that impose constraints on possible theories, problems of validity of psychological constructs, and obstacles to discovering causal relationships between psychological variables. We conclude with recommendations on how to move past the theory crisis.
Enhanced Tendon-to-Bone Healing via IKKβ Inhibition in a Rat Rotator Cuff Model

Background: More than 450,000 rotator cuff repairs are performed annually, yet healing of tendon to bone often fails. This failure is rooted in the fibrovascular healing response, which does not regenerate the native attachment site. Better healing outcomes may be achieved by targeting inflammation during the early period after repair. Rather than broad inhibition of inflammation, which may impair healing, the current study utilized a molecularly targeted approach to suppress IKKβ, shutting down only the inflammatory arm of the nuclear factor κB (NF-κB) signaling pathway. Purpose: To evaluate the therapeutic potential of IKKβ inhibition in a clinically relevant model of rat rotator cuff repair. Study Design: Controlled laboratory study. Methods: After validating the efficacy of the IKKβ inhibitor in vitro, it was administered orally once a day for 7 days after surgery in a rat rotator cuff repair model. The effect of treatment on reducing inflammation and improving repair quality was evaluated after 3 days and 2, 4, and 8 weeks of healing, using gene expression, biomechanics, bone morphometry, and histology. Results: Inhibition of IKKβ attenuated cytokine and chemokine production in vitro, demonstrating the potential for this inhibitor to reduce inflammation in vivo. Oral treatment with IKKβ inhibitor reduced NF-κB target gene expression by up to 80% compared with a nontreated group at day 3, with a subset of these genes suppressed through 14 days. Furthermore, the IKKβ inhibitor led to enhanced tenogenesis and extracellular matrix production, as demonstrated by gene expression and histological analyses. At 4 weeks, inhibitor treatment led to increased toughness, no effects on failure load and strength, and decreases in stiffness and modulus when compared with vehicle control. At 8 weeks, IKKβ inhibitor treatment led to increased toughness, failure load, and strength compared with control animals. IKKβ inhibitor treatment prevented the bone loss near the tendon attachment that occurred in repairs in control. Conclusion: Pharmacological inhibition of IKKβ successfully suppressed excessive inflammation and enhanced tendon-to-bone healing after rotator cuff repair in a rat model. Clinical Relevance: The NF-κB pathway is a promising target for enhancing outcomes after rotator cuff repair.
Synaptic Scaling—An Artificial Neural Network Regularization Inspired by Nature

Nature has always inspired the human spirit and scientists frequently developed new methods based on observations from nature. Recent advances in imaging and sensing technology allow fascinating insights into biological neural processes. With the objective of finding new strategies to enhance the learning capabilities of neural networks, we focus on a phenomenon that is closely related to learning tasks and neural stability in biological neural networks, called homeostatic plasticity. Among the theories that have been developed to describe homeostatic plasticity, synaptic scaling has been found to be the most mature and applicable. We systematically discuss previous studies on the synaptic scaling theory and how they could be applied to artificial neural networks. Therefore, we utilize information theory to analytically evaluate how mutual information is affected by synaptic scaling. Based on these analytic findings, we propose two flavors in which synaptic scaling can be applied in the training process of simple and complex, feedforward, and recurrent neural networks. We compare our approach with state-of-the-art regularization techniques on standard benchmarks. We found that the proposed method yields the lowest error in both regression and classification tasks compared to previous regularization approaches in our experiments across a wide range of network feedforward and recurrent topologies and data sets.
Visceral Adiposity Index (VAI) in Children and Adolescents with Obesity: No Association with Daily Energy Intake but Promising Tool to Identify Metabolic Syndrome (MetS)

(1) Background. Visceral adiposity index (VAI) has been recently identified as a new cardiometabolic risk marker reflecting abdominal fat distribution and dyslipidaemia. The aim of the present paper was to evaluate the relationship between VAI, daily energy intake and metabolic syndrome (MetS) in a cohort of obese Caucasian children and adolescents, aged 8 to 15 years. (2) Methods. Consecutive Italian children and adolescents with obesity, according to World Health Organization were enrolled. Anthropometric parameters and blood pressure were measured. Fasting blood samples have been analyzed for lipids, insulin and glucose levels. MetS was diagnosed using identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) or International Diabetes Federation (IDF) criteria according to age. Homeostatic model assessment index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), A body shape index (ABSI) and VAI were calculated. Multivariable logistic regression analyses with sex, age and each anthropometric parameter (body mass index (BMI) z-score, ABSI, waist-to-height ratio (WHR)) or VAI was performed to predict MetS. Receiver operation curve (ROC) analysis was used to define the optimal VAI cut-off to identify MetS. Multiple regression was performed to predict the BMI z-score and VAI from daily energy intake after adjusting for age and sex. (3) Results. Six hundred and thirty-seven (313 boys and 324 girls) children and adolescents with obesity with median age 11 (interquartile range 10–13) years were included in the analysis. MetS was diagnosed in 79 patients. VAI correlated with BMI, WHR, ABSI, HOMA-IR, QUICKI, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides and triglycerides-to-HDL ratio (p < 0.050). Optimal VAI cut-off (AUC) values to identify MetS were 1.775 (0.774), 1.685 (0.776) and 1.875 (0.797) in the whole population, boys and girls, respectively. Energy intake was positively associated with BMI z-score but no association was found with VAI. (4) Conclusion. VAI is a promising tool to identify MetS in children and adolescents with obesity and should be used in the management of abdominal obesity together with dietary assessment.
Cardiac autonomic modulation in patients with type 2 diabetes

Recently we had the opportunity to read the article published by Vukomanovic et al. [1] in your journal. This study aimed to determine the autonomic nervous system function, assessed by heart rate variability (HRV), oxygen uptake (VO2), and heart rate kinetics, as well as the interaction between various clinical and glucose regulation parameters in individuals recently diagnosed with uncomplicated type 2 diabetes (T2D). Among the new and relevant results present by this study, the authors found that the only long-term HRV measure independently associated with all indexes of the cardiopulmonary exercise test was the standard deviation of all normal heart cycles (SDNN). This result is essential as this was the first time the association between HRV measure and cardiorespiratory fitness was demonstrated in individuals with T2D. Despite the clinical importance of the study findings, there is an issue that, in our opinion, are worthy of further discussion. Although the authors’ SDNN definition is according to the HRV guidelines [2] as well as the data collection and analysis methodology had been performed according to the standardisation checklist of procedures for HRV recently published [3], the clinical significance attributed to this HRV measure can be questioned. According to the Task Force’s publication [2], the SDNN reflects all the cyclical components responsible for the heartbeat variability in the registration period, encompassing both high and low-frequency variations of the heartbeats. In addition, as the variance is mathematically equal to the total power of the spectral analysis, SDNN is consequently correlated to the total power of HRV frequency domain analysis [2]. In this sense, it is established in the scientific literature that SDNN reflects both sympathetic and parasympathetic cardiac modulation [2,4]. Otherwise, in the discussion section, Vukomanovic et al. [1] considered that this HRV measure reflects the sympathetic function. This misinterpretation may have its origin in studies that showed a significant correlation between SDNN and spectral power component of low frequency (LF) as part of their results [5,6]. Vukomanovic et al. [1] cited a systematic review [7] which in turn cited a study published by Otzenberger et al. [5] which shown an association of SDNN not only with LF but also with spectral power component of high frequency (HF) during sleep in men, reinforcing our suspicious in respect to the cause of the misinterpretation. In conclusion, the existence of an association between these two HRV measures (SDNN and LF) in some studies did not mean that SDNN can be interpreted as a sympathetic activity measure. As the clinical interpretation of HRV measures is crucial to analyse the cardiac autonomic modulation properly, we hope that this letter could help interpret the study findings, especially concerning SDNN be recognised as an estimate of overall HRV.
The efficiency of progesterone/estradiol and progesterone/follicle ratio without elevated trigger-day progesterone levels on the reproductive outcomes of GnRH antagonist IVF/ICSI cycles

Abstract Aim To assess the predictive value of serum progesterone/estradiol (P/E2) and serum progesterone/follicle (P/F) ratios on the reproductive outcomes of women without elevated trigger-day progesterone levels undergoing GnRH-antagonist IVF (in vitro fertilization)/ICSI (intracytoplasmic sperm injection) cycles. Materials and methods This was a retrospective cohort study in a university teaching hospital conducted between January 2017 and December 2019. Couples who underwent assisted reproduction cycles were evaluated. Initially, 978 cycles were evaluated and only GnRH antagonist cycles (n = 505) without elevated trigger-day progesterone levels were analyzed after respecting exclusion criteria. Results A total of 505 cycles were analyzed after the exclusion criteria were met. The clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were 45.5%, 30.9%, and 27.8%, respectively. Cutoff values of P/E2 and P/F ratios that were discriminative for achieving or not achieving clinical pregnancy were 0.36 and 0.17, respectively. The clinical pregnancy rates were found to be significantly different between below and above P/E2 cutoff values (49.8% vs. 40.1%, respectively, p = .031), while there were no significant differences between below and above P/F cutoff values regarding the pregnancy outcomes. Conclusion The P/E2 and P/F ratios were found to be more efficient and reliable markers than serum progesterone level alone in predicting the reproductive outcomes of assisted reproduction cycles without a premature rise in serum progesterone levels. A P/E2 ratio ≤0.36 and a P/F ratio ≤0.17 significantly improved the cycle outcomes.
Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

Objective Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART. Methods Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing. Results The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively). Conclusion The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.
[Pregnancy-preserving and maternal-fetal management in a patient with rare large cell neuroendocrine carcinoma of the uterine cervix].

OBJECTIVE To explore the strategy of pregnancy-preserving and maternal- fetal management in patients with primary gynecologic neuroendocrine tumors (gNETs) during pregnancy. METHODS We performed whole genome sequencing (WGS) for analyzing maternal and fetal somatic and germline single nucleotide variations (SNVs) and small insertions and deletions (InDels) for a 29-year-old pregnant woman diagnosed with stage IB2 large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the cervix. A systematic literature review was performed to explore the strategies for treatment of such rare histological type while maintaining pregnancy. RESULTS Global case analysis of cervical NETs during pregnancy suggested that negative lymph node metastasis and an early FIGO stage were potentially associated with a good prognosis of the patients. In the case presented herein, a pregnancy-preserving strategy was adopted and favorable maternal-fetal outcomes were achieved after neoadjuvant chemotherapy, radical surgery and postoperative systemic chemotherapy. At 35+5 weeks, the fetus was delivered by caesarian section, and the patient has by now had a disease-free survival of 19 months postoperatively. WGS analysis revealed 6 missense somatic pathogenic mutations in two cancer tissues of the patient, and among them KARS and VEGFA were related with targeted therapy. Five pathogenic germline variants were detected in the patient and her son, suggesting the necessity of a long-term follow-up schedule including precise genetic counselling for both the mother and the child. CONCLUSIONS Although gNETs in pregnancy are rare and highly risky, pregnancy-preserving managements of gNETs can still be considered and favorable maternalfetal outcomes are possible with proper assessment of the clinical indications and implementation of multimodal treatments. Precise treatment and follow-up strategies based on the results of WGS for risk-reducing intervention of cancer recurrence or occurrence can potentially benefit the patient and the neonate.