Miracle-dz/UniFAR-FTUs huggingface dataset:
A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release

Significance Mechanical forces are important for normal gastrointestinal tract function. The enterochromaffin cells in the gastrointestinal epithelium have been proposed, but not previously shown, to be specialized sensors that convert forces into serotonin release, and serotonin released from these cells is important for normal gastrointestinal secretion and motility. The findings in this study show that some enterochromaffin cells are indeed mechanosensitive, and that they use mechanosensitive Piezo2 channels to generate an ionic current that is critical for the intracellular Ca2+ increase, serotonin release, and epithelial fluid secretion. Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca2+ increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology.
Understanding the Role of Alcohol, Anxiety, and Trait Mindfulness in the Perpetration of Physical and Sexual Dating Violence in Emerging Adults

This study examines alcohol consumption, anxiety, trait mindfulness, and physical and sexual dating violence aggression (PDV and SDV) among 735 emerging adults (18-25 years) in an urban emergency department. Of the total sample, 27.2% perpetrated PDV and 16.5% perpetrated SDV. Alcohol was positively associated with PDV/SDV. Anxiety was positively associated with PDV. Mindfulness was negatively associated with PDV/SDV. Interaction analyses revealed women had lower PDV with higher nonjudgment facet of mindfulness. Higher act aware was associated with lower PDV regardless of high versus low alcohol. Findings indicate different contributing factors among perpetrators of PDV/SDV; some factors may be attenuated by mindfulness.
Accurate estimation of cardiovascular risk in a non-diabetic adult: detecting and correcting the error in the reported Framingham Risk Score for the Systolic Blood Pressure Intervention Trial population

Objectives To understand the discrepancy between the published 10-year cardiovascular risk and 10-year cardiovascular risk generated from raw data using the Framingham Risk Score for participants in the Systolic Blood Pressure Intervention Trial (SPRINT). Design Secondary analysis of SPRINT data published in The New England Journal of Medicine (NEJM) and made available to researchers in late 2016. Setting SPRINT clinical trial sites. Participants Study participants enrolled into SPRINT. Results The number of SPRINT study participants identified as having ≥15% 10-year cardiovascular risk was not consistent with what was reported in the original publication. Using the data from the trial, the Framingham Risk Score indicated ≥15% 10-year cardiovascular risk for 7089 participants compared with 5737 reported in the paper, a change from 61% to 76% of the total study population. Conclusions The analysis of the clinical trial data by independent investigators identified an error in the reporting of the risk of the study population. The SPRINT trial enrolled a higher risk population than was reported in the initial publication, which was brought to light by data sharing.
Comparison of factors predicting nursing skills between general and psychiatric nurses

PURPOSE I examined whether nursing skills are related to occupational stress, self-focus, and other-consciousness, and whether these relationships differ between general and psychiatric nurses. DESIGN AND METHODS Two hundred seventy-one general and 317 psychiatric nurses completed a questionnaire assessing the aforementioned variables. Regression analysis was used to explore the predictors of nursing skills. FINDINGS Internal and fantastic aspects (other-consciousness subscales) and psychological burden (occupational stress subscale) predicted nursing skills in both groups, while lower rumination and higher reflection scores predicted them only in psychiatric nurses. PRACTICE IMPLICATIONS Nursing education should facilitate other-consciousness in general nurses, but self-focus in psychiatric nurses.
Corticomotoneuronal Model for Intraoperative Neurophysiological Monitoring During Direct Brain Stimulation

Intraoperative neurophysiological monitoring during brain surgery uses direct cortical stimulation to map the motor cortex by recording muscle activity induced by the excitation of alpha motor neurons (MNs). Computational models have been used to understand local brain stimulation. However, a computational model revealing the stimulation process from the cortex to MNs has not yet been proposed. Thus, the aim of the current study was to develop a corticomotoneuronal (CMN) model to investigate intraoperative stimulation during surgery. The CMN combined the following three processes into one system for the first time: (1) induction of an electric field in the brain based on a volume conductor model; (2) activation of pyramidal neuron (PNs) with a compartment model; and (3) formation of presynaptic connections of the PNs to MNs using a conductance-based synaptic model coupled with a spiking model. The implemented volume conductor model coupled with the axon model agreed with experimental strength-duration curves. Additionally, temporal/spatial and facilitation effects of CMN synapses were implemented and verified. Finally, the integrated CMN model was verified with experimental data. The results demonstrated that our model was necessary to describe the interaction between frequency and pulses to assess the difference between low-frequency and multi-pulse high-frequency stimulation in cortical stimulation. The proposed model can be used to investigate the effect of stimulation parameters on the cortex to optimize intraoperative monitoring.
Association of zinc level and polymorphism in MMP-7 gene with prostate cancer in Polish population

Introduction Prostate cancer is one of the most commonly diagnosed malignancies among men in Western populations. Evidence reported in the literature suggests that zinc may be related to prostate cancer. In this study we evaluated the association of serum zinc levels and polymorphisms in genes encoding zinc-dependent proteins with prostate cancer in Poland. Methods The study group consisted of 197 men affected with prostate cancer and 197 healthy men. Serum zinc levels were measured and 5 single nucleotide polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13, MT2A genes were genotyped. Results The mean serum zinc level was higher in prostate cancer patients than in healthy controls (898.9±12.01 μg/l vs. 856.6±13.05 μg/l, p<0.01). When compared in quartiles a significant association of higher zinc concentration with the incidence of prostate cancer was observed. The highest OR (OR = 4.41, 95%CI 2.07–9.37, p<0.01) was observed in 3rd quartile (>853.0–973.9 μg/l). Among five analyzed genetic variants, rs11568818 in MMP-7 appeared to be correlated with 2-fold increased prostate cancer risk (OR = 2.39, 95% CI = 1.19–4.82, p = 0.015). Conclusion Our results suggest a significant correlation of higher serum zinc levels with the diagnosis of prostate cancer. The polymorphism rs11568818 in MMP-7 gene was also associated with an increased prostate cancer risk in Poland.
Dengue Cerebellitis: A Case Report and Literature Review

Patient: Male, 60 Final Diagnosis: Dengue cerebellitis Symptoms: Dizziness • fever • headaches • vomiting Medication: — Clinical Procedure: Lumbar puncture Specialty: Neurology Objective: Unusual clinical course Background: Dengue-associated neurological manifestations have recently been on the rise. Cerebellar syndrome complicating dengue fever has rarely been reported in the literature. We present a case report of dengue-associated cerebellar syndrome and performed a literature review to draw attention to this rare neurological complication. Case Report: A 60-year-old man presented with 4 days of fever, myalgia, arthralgia, headaches, and warning symptoms (persistent diarrhea and vomiting). He was admitted with serologically-confirmed dengue fever. He had been well until day 8 of illness, when he developed cerebellar signs and symptoms. The temporal relationship with the recent dengue fever suggested that he had dengue cerebellitis. He recovered well, with no neurological sequelae upon our clinic visit. Conclusions: Dengue cerebellitis is a rare but recognized manifestation, which should be considered in patients from endemic areas of dengue fever who develop cerebellar syndrome.
Nonlinear couplings and energy transfers in micro- and nano-mechanical resonators: intermodal coupling, internal resonance and synchronization

Extensive development of micro/nano-electromechanical systems (MEMS/NEMS) has resulted in technologies that exhibit excellent performance over a wide range of applications in both applied (e.g. sensing, imaging, timing and signal processing) and fundamental sciences (e.g. quantum-level problems). Many of these outstanding applications benefit from resonance phenomena by employing micro/nanoscale mechanical resonators often fabricated into a beam-, membrane- or plate-type structure. During the early development stage, one of the vibrational modes (typically the fundamental mode) of a resonator is considered in the design and application. In the past decade, however, there has been a growing interest in using more than one vibrational mode for the enhanced functionality of MEMS/NEMS. In this paper, we review recent research efforts to investigate the nonlinear coupling and energy transfers between multiple modes in micro/nano-mechanical resonators, focusing especially on intermodal coupling, internal resonance and synchronization. This article is part of the theme issue ‘Nonlinear energy transfer in dynamical and acoustical systems’.
Further Defining the 2012 Multi-Society Task Force Guidelines for Surveillance of High-risk Adenomas

Supplemental Digital Content is available in the text. Goals: We set out to determine whether variation from this 3-year follow-up interval was associated with the finding of subsequent high-risk adenoma (HRA). Background: HRAs include the following: (1) an adenoma measuring ≥10 mm, (2) ≥3 adenomas found during a single procedure, and (3) an adenoma with high-grade dysplasia or villous architecture. The current Multi-Society Task Force guideline for timing of surveillance colonoscopy after removal of a HRA is 3 years. Study: In 2016, we analyzed 495 patients who had a HRA removed during a 2008 colonoscopy. We compared the frequency of finding another HRA at follow-up intervals. We used the current guidelines as our referent group and performed logistical regression to identify whether any patient characteristics, procedural factors, or type of HRA predicted the development of HRAs on follow-up colonoscopy. Results: Individuals who followed-up at a median of 4.5 years did not have more HRA on follow-up compared with those who followed-up at 3 years (25.2% vs. 21.0%, P=0.062). These groups had similar baseline characteristics. Older individuals, male gender, having a history of polyps, and piecemeal resection of an HRA predicted future HRAs. The removal of ≥3 adenomas in 2008 as well as a combination of multiple, large, and advanced polyps showed a higher risk of future HRAs. Conclusions: The 2012 Multi-Society Task Force recommendation of 3-year follow-up after removal of HRAs may not apply to all patients. We showed that a combination of patient demographics, procedural factors, and pathology best determines the surveillance colonoscopy interval.
Non-Coding RNAs in Endometrial Physiopathology

The Human Genome Project led to the discovery that about 80% of our DNA is transcribed in RNA molecules. Only 2% of the human genome is translated into proteins, the rest mostly produces molecules called non-coding RNAs, which are a heterogeneous class of RNAs involved in different steps of gene regulation. They have been classified, according to their length, into small non-coding RNAs and long non-coding RNAs, or to their function, into housekeeping non-coding RNAs and regulatory non-coding RNAs. Their involvement has been widely demonstrated in all cellular processes, as well as their dysregulation in human pathologies. In this review, we discuss the function of non-coding RNAs in endometrial physiology, analysing their involvement in embryo implantation. Moreover, we explore their role in endometrial pathologies such as endometrial cancer, endometriosis and chronic endometritis.
Plasticity of differentiated cells in wound repair and tumorigenesis, part I: stomach and pancreas

ABSTRACT For the last century or so, the mature, differentiated cells throughout the body have been regarded as largely inert with respect to their regenerative potential, yet recent research shows that they can become progenitor-like and re-enter the cell cycle. Indeed, we recently proposed that mature cells can become regenerative via a conserved set of molecular mechanisms (‘paligenosis’), suggesting that a program for regeneration exists alongside programs for death (apoptosis) and division (mitosis). In two Reviews describing how emerging concepts of cellular plasticity are changing how the field views regeneration and tumorigenesis, we present the commonalities in the molecular and cellular features of plasticity at homeostasis and in response to injury in multiple organs. Here, in part 1, we discuss these advances in the stomach and pancreas. Understanding the extent of cell plasticity and uncovering its underlying mechanisms may help us refine important theories about the origin and progression of cancer, such as the cancer stem cell model, as well as the multi-hit model of tumorigenesis. Ultimately, we hope that the new concepts and perspectives on inherent cellular programs for regeneration and plasticity may open novel avenues for treating or preventing cancers. Summary: Epithelial cells in diverse tissues have an innate plasticity program (recently dubbed ‘paligenosis’) such that differentiated cells can become regenerative upon large-scale insults to an organ. Thus, the proliferating, regenerative cells in an organ may not always derive directly from stem cells, which invites us to refine theories about the cell of origin of cancer such as the multi-hit model of tumorigenesis.
Population Pharmacokinetics of the Antimalarial Amodiaquine: a Pooled Analysis To Optimize Dosing

Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. ABSTRACT Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.
Anticancer potential of quercetin: A comprehensive review

Diet plays a key role to maintaining healthy life. Many natural products present in our diet, such as flavonoids, can prevent the progression of cancer. Quercetin, a distinctive bioactive flavonoid, is a dietary component that has attracted the attention of dietitians and medicinal chemists due to its numerous health‐promoting effects. It is an outstanding antioxidant that has a well‐documented role in reducing different human cancers. Quercetin exhibits direct proapoptotic effects on tumor cells and thus can inhibit the progress of numerous human cancers. The anticancer effect of quercetin has been documented in numerous in vitro and in vivo studies that involved several cell lines and animal models. On the other hand, the high toxic effect of quercetin against cancer cells is accompanied with little or no side effects or harm to normal cells. Accordingly, this review presents an overview of recent developments on the use of quercetin against different types of cancer along with mechanisms of action. In addition, the present review summarizes the literature pertaining to quercetin as an anticancer agent and provides an assessment of the potential utilization of this natural compound as a complimentary or alternative medicine for preventing and treating cancer.
Prioritize Technical Debt in Large-Scale Systems Using CodeScene

Large-scale systems often contain considerable amounts of code that is overly complicated, hard to understand, and hence expensive to change. An organization cannot address and refactor all of that code at once, nor should they. Ideally, actionable refactoring targets should be prioritized based on the technical debt interest rate to balance the trade-offs between improvements, risk, and new features. This paper examines how CodeScene, a tool for predictive analyses and visualizations, can be used to prioritize technical debt in a large-scale codebase like the Linux Kernel based on the most likely return on code improvements.
CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma

Somatic mutations in DNA repair genes have been clinically associated with chemosensitivity, although few studies have interrogated the nucleotide synthesis pathways that supply DNA repair processes. Previous work suggests that bladder urothelial carcinoma is uniquely enriched for mutations in nucleotide excision repair genes, and that these mutations are associated with response to platinum-based therapy and favorable survival. Conversely, the de novo pyrimidine synthesis pathway has recently emerged as a putative clinical target. This anabolic process is thought to supply DNA repair processes such as nucleotide excision repair; that is, DNA repair enzymes may require a sufficient nucleotide supply available to reverse the intended genotoxic damage of systemic chemotherapy in rapidly proliferating cancer cells. Therefore, we explored the prognostic complementarity between de novo pyrimidine synthesis and nucleotide excision repair expression in a total of 570 bladder urothelial carcinoma patients. Ultimately, we show that the de novo pyrimidine synthesis gene CAD is associated with poor survival (P = 0.008) and is co-altered with the nucleotide excision repair gene POLD2. High expression of POLD2 was also associated with poor overall survival (P = 0.019) and was significantly correlated with CAD expression in pre-treatment patient tumor samples (P = 2.44e-4). Expression of each gene was associated with cisplatin-based therapy resistance, and accordingly, CADhighPOLD2high patients were associated with worse survival than CADhighPOLD2low and CADlowPOLD2high patients. Together, these biomarkers could help elucidate mechanisms of chemoresistance to further personalize therapeutic strategies in bladder urothelial carcinoma.
The influence of multiple functional demands on morphological diversification: A test on turtle shells

Organismal parts are often involved in the performance of more than one function. The role of trade‐offs in influencing phenotypic evolution of such parts is well‐studied; less well‐understood is their role in influencing phenotypic diversity. Increases in the number of functions a part is involved in may inhibit subsequent diversification, as the number of trade‐offs increases. Alternately, such an increase might promote phenotypic diversification, by increasing adaptive landscape complexity and promoting specialization for different roles. We compare these predictions by testing whether aquatic turtle shells, which resist loads, act as hydrodynamic elements, facilitate self‐righting, and exchange heat with the environment, differ in phenotypic diversity from those of terrestrial species, which perform all the same functions except for hydrodynamics. We used 53 3D landmarks digitized on 2722 specimens of 274 hard‐shelled turtle species to quantify shell shape variation, and a set of phylogenetic hypotheses to examine evolutionary patterns. Terrestrial turtles consistently had higher phenotypic diversity than aquatic species. Differences are not due to differences in the rates of evolution between the two groups, but rather differences in evolutionary mode. Thus this study supports the traditional view of the role of multiple functions in determining phenotypic diversity.