bluuebunny/crossref_metadata_2025 huggingface dataset:
Sudapyridine (WX-081), a Novel Compound against Mycobacterium tuberculosis
Authors: Yao Rong , Wang Bin , Fu Lei , Li Lei , You Kejun , Li Yong-Guo , Lu Yu
Published: February 2022

This study is aimed at chemotherapy for multidrug-resistant tuberculosis (MDR-TB), mainly to develop new anti-TB drugs to kill
Mycobacterium tuberculosis
, a microorganism with strong drug resistance. In this study, the structure of a potent antituberculosis compound, bedaquiline (BDQ), was optimized to generate a new compound, sudapyridine (WX-081).
Rifting of the Indian passive continental margin: Insights from the Langjiexue basalts in the central Tethyan Himalaya, southern Tibet
Authors: Wang Chao , Ding Lin , Cai Fulong , Zhang Liyun , Li Zhenyu , Yue Yahui
Published: February 2022

The Triassic tectonic setting of the Tethyan Himalaya in southern Tibet remains controversial and is key to revealing the mechanism of Neo-Tethys Ocean opening and the breakup history of Gondwana. This paper reports 227–225 Ma mafic volcanic rocks interbedded within the Tethyan Himalaya sequence in southern Tibet, which were formed in a typical passive continental margin setting. The basalts are tholeiitic with high TiO2 (3.20–3.38 wt%) and moderate MgO (4.05–5.40 wt%) contents and exhibit enrichment in light rare earth elements and weak negative Nb, Ta, Eu, and Ti anomalies. These geochemical compositions, combined with uniform whole-rock εNd(t) (+1.50 to +2.70) values, indicate that the magmas were derived by low-degree melting of a deep-seated garnet source that was heterogeneously modified by an oceanic island basalt-type of component. Given the other geological evidence, we propose that the magmatic evolution of the Tethyan Himalaya during the late Paleozoic–Mesozoic was generally a lithospheric thinning process, that is, it evolved from a fully developed continental rift system during the Late Permian to wane during the Triassic. This interpretation further supports the hypothesis that the Neo-Tethys Ocean opened in a passive pattern and that the breakup of Gondwana in the late Paleozoic was initiated by lithospheric thinning. Therefore, the subsequent magmatism was related to the passive upwelling of normal asthenospheric materials.
Supplemental Material: Evidence for large departures from lithostatic pressure during Late Cretaceous metamorphism in the northern Snake Range metamorphic core complex, Nevada
Authors: Hoiland Carl , al. et
Published: February 2022

Table S1A: Detrital zircon U-Pb geochronology data at University of California–Santa Cruz, Table S1B: Detrital zircon U-Pb geochronology data at the University of Arizona Laserchron Center, Table S2: Finite strain data, and Table S3: Raman spectroscopy of carbonaceous material data
Impact of virtual care on health-related quality of life in children with diabetes mellitus: a systematic review protocol
Authors: Rajan Raeesha , Kshatriya Maya , Banfield Laura , Athale Uma , Thabane Lehana , Samaan M Constantine
Published: February 2022

Introduction

Diabetes mellitus is the most common endocrine disorder in children, and the prevalence of paediatric type 1 and type 2 diabetes continue to rise globally. Diabetes clinical care programs pivoted to virtual care with the COVID-19 pandemic-driven social distancing measures. Yet, the impact of virtual care on health-related quality of life in children living with diabetes remains unclear. This protocol reports on the methods that will be implemented to conduct a systematic review to assess the health-related quality of life and metabolic health impacts of virtual diabetes care.

Methods and analysis

We will search MEDLINE, Embase, EMCare, PsycInfo, Web of Science, and the grey literature for eligible studies. We will screen title, abstract, and full-text papers for potential inclusion and assess the risk of bias and the overall confidence in the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. A meta-analysis will be conducted if two studies report similar populations, study designs, methods, and outcomes.

This systematic review will summarise the health-related quality of life outcomes for virtual diabetes care delivery models.

Ethics and dissemination

No ethics approval is required for this systematic review protocol as it does not include patient data. The systematic review will be published in a peer-reviewed journal and presented at international conferences.

PROSPERO registration number

CRD42021235646.
Variation in appropriate diabetes care and treatment targets in urban and rural areas in England: an observational study of the ‘rule of halves’
Authors: Mason Thomas , Whittaker William , Dumville Jo C , Bower Peter
Published: February 2022

Objectives

To estimate the ‘rule of halves’ for diabetes care for urban and rural areas in England using several data sources covering the period 2015–2017; and to examine the extent to which any differences in urban and rural settings are explained by population characteristics and the workforce supply of primary care providers (general practices).

Design

A retrospective observational study.

Setting

Populations resident in predominantly urban and rural areas in England (2015–2017).

Participants

N=33 336 respondents to the UK Household Longitudinal Survey in urban and rural settings in England; N=4913 general practices in England reporting to the National Diabetes Audit and providing workforce data to NHS Digital.

Outcomes

Diabetes prevalence; administrative records of diagnoses of diabetes; provision of (all eight) recommended diabetes care processes; diabetes treatment targets.

Results

Diabetes prevalence was higher in urban areas in England (7.80% (95% CI 7.30% to 8.31%)) relative to rural areas (7.24% (95% CI 6.32% to 8.16%)). For practices in urban areas, relatively fewer cases of diabetes were recorded in administrative medical records (69.55% vs 71.86%), and a smaller percentage of those registered received the appropriate care (45.85% vs 49.32%). Among estimated prevalent cases of diabetes, urban areas have a 24.84% achieving these targets compared with 25.16% in rural areas. However, adjusted analyses showed that the performance of practices in urban areas in providing appropriate care quality was not significantly different from practices in rural areas.

Conclusions

The ‘rule of halves’ is not an accurate description of the actual pattern across the diabetes care pathway in England. More than half of the estimated urban and rural diabetes population are registered with clinical practices and have access to treatment. However, less than half of those registered for treatment have achieved treatment targets. Appropriate care quality was associated with a greater proportion of patients with diabetes achieving treatment targets.
The Childhood Cancer Diagnosis (CCD) Study: a UK observational study to describe referral pathways and quantify diagnostic intervals in children and young people with cancer
Authors: Shanmugavadivel Dhurgshaarna , Liu Jo-Fen , Ball-Gamble Ashley , Polanco Angela , Vedhara Kavita , Walker David , Ojha Shalini
Published: February 2022

Introduction

Childhood cancer is diagnosed in 400 000 children and young people (CYP) aged 0–19 years worldwide annually. In the UK, a child’s cumulative cancer risk increases from 1 in 4690 from birth to aged 1, to 1 in 470 by age 15. Once diagnosed, access to treatments offers survival to adulthood for over 80%. Tumour diagnoses are at a later stage and mortality is higher when compared with those in other parts of Europe. This means higher risk, more intensive therapies for a cure. Some CYPs are known to experience delays to diagnosis which may further contribute to poor outcomes. This study aims to understand the current pathway of childhood cancer referrals and diagnosis and quantify diagnostic intervals in the UK.

Methods and analysis

This is a prospective multicentre observational study including all tertiary childhood cancer treatment centres in the UK. CYP (0–18 years) with a new diagnosis of cancer over the study period will be invited to participate. Data will be collected at initial diagnosis and 5 years after diagnosis. Data will include demographic details, clinical symptoms, tumour location, stage and clinical risk group. In addition, key diagnostic dates and referral routes will be collected to calculate the diagnostic intervals. At 5 years’ follow-up, data will be collected on refractory disease, relapse and 1-year and 5-year survival. Population characteristics will be presented with descriptive analyses with further analyses stratified by age, geographical region and cancer type. Associations between diagnostic intervals/delay and risk factors will be explored using multiple regression and logistic regression.

Ethics

The study has favourable opinion from the York and Humber, Leeds West REC (19/YH/0416).

Dissemination

Results will be presented at academic conferences, published in peer-reviewed journals and disseminated through public messaging in collaboration with our charity partners through a national awareness campaign (ChildCancerSmart).

Study registration

researchregistry.com (researchregistry5313).
Assessment of emergency physicians’ performance in identifying shockable rhythm in out-of-hospital cardiac arrest: an observational simulation study
Authors: Derkenne Clément , Jost Daniel , Roquet Florian , Corpet Pascal , Frattini Benoit , Kedzierewicz Romain , Bellec Guillaume , Rajon Benjamin , Fernandez Marianne , Loeb Thomas , Pierantoni Emmanuel , Lamblin Antoine , Prunet Bertrand
Published: February 2022

Background

Emergency physicians can use a manual or an automated defibrillator to provide defibrillation of patients who had out-of-hospital cardiac arrest (OHCA). Performance of emergency physicians in identifying shockable rhythm with a manual defibrillator has been poorly explored whereas that of automated defibrillators is well known (sensitivity 0.91–1.00, specificity 0.96–0.99). We conducted this study to estimate the sensitivity/specificity and speed of shock/no-shock decision-making by prehospital emergency physicians for shockable or non-shockable rhythm, and their preference for manual versus automated defibrillation.

Methods

We developed a web application that simulates a manual defibrillator (https://simul-shock.firebaseapp.com/). In 2019, all (262) emergency physicians of six French emergency medical services were invited to participate in a study in which 60 ECG rhythms from real OHCA recordings were successively presented to the physicians for determination of whether they would or would not administer a shock. Time to decision was recorded. Answers were compared with a gold standard (concordant answers of three experts). We report sensitivity for shockable rhythms (decision to shock) and specificity for non-shockable rhythms (decision not to shock). Physicians were also asked whether they preferred manual or automated defibrillation.

Results

Among 215 respondents, we were able to analyse results for 190 physicians. 57% of emergency physicians preferred manual defibrillation. Median (IQR) sensitivity for a shock delivery for shockable rhythm was 0.91 (0.81–1.00); median specificity for no-shock delivery for non-shockable rhythms was 0.91 (0.80–0.96). More precisely, sensitivities for shock delivery for ventricular tachycardia (VT) and coarse ventricular fibrillation (VF) were both 1.0 (1.0–1.0); sensitivity for fine VF was 0.6 (0.2–1). Specificity for not shocking a pulseless electrical activity (PEA) was 0.83 (0.72–0.86), and for asystole, specificity was 0.93 (0.86–1). Median speed of decision-making (in seconds) were: VT 2.0 (1.6–2.7), coarse VF 2.1 (1.7–2.9), asystole 2.4 (1.8–3.5), PEA 2.8 (2.0–4.2) and fine VF 2.8 (2.1–4.3).

Conclusions

Global sensitivity and specificity were comparable with published automated external defibrillator studies. Shockable rhythms with the best clinical prognoses (VT and coarse VF) were very rapidly recognised with very good sensitivity. The decision-making for fine VF or asystole and PEA was less accurate.
Isolation of lipopeptide antibiotics from Bacillus siamensis: a potential biocontrol agent for Fusarium graminearum
Authors: Huang Yanhong , Zhang Xingrong , Xu Hui , Zhang Fan , Zhang Xuelin , Yan Yongheng , He Lianzhi , Liu Jianjun
Published: February 2022

Fusarium head blight (FHB), a destructive fungal disease that can cause damage to various crops and reduce yield and quality, is primarily caused by several species of the soil-borne fungal genus Fusarium, which produce mycotoxins that contaminate grains and may cause various severe chronic diseases in humans and livestock. In recent years, Bacillus spp. have been reported to be good producers of antifungal antibiotics against FHB. This study aimed to explore the potential role of a newly identified Bacillus strain, designated as CU-XJ-9, against FHB. This strain, which was isolated from traditional Chinese fermented food, was identified as Bacillus siamensis and confirmed to produce lipopeptide biosurfactants, which according to the analysis by quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS/MS) may belong to the iturin lipopeptide family. At 100 μg/mL, the isolated antifungal compounds completely inhibited conidial germination. Observation of the effects of the isolated antifungal compounds on the mycelia of F. graminearum by scanning electron microscopy revealed obvious nodes in the middle of the mycelia and destroyed mycelial structures, and these changes became more pronounced with increasing dose. Overall, this study provides important information regarding the ability of Bacillus siamensis to produce lipopeptide biosurfactants, which showed significant antagonistic activity against F. graminearum.
Reconsidering holographic dark energy in Brans–Dicke theory
Authors: Pinki  , Kumar Pankaj , Beesham Aroonkumar
Published: February 2022

In this paper, we reconsider the concept of holographic dark energy in the framework of Brans–Dicke theory in the formalism of the flat Friedmann–Lemaitre–Robertson–Walker metric. Firstly, we demonstrate how the assumption $$\phi \propto a^n$$

ϕ
∝

a
n

, where $$\phi $$
ϕ
and a stand for the Brans–Dicke scalar field and scale factor, respectively, naturally leads to a constant deceleration parameter, irrespective of the energy content of the universe. Secondly, we consider interacting holographic dark energy with Hubble horizon as IR cut-off, and find the value of the Hubble parameter and corresponding value of the scale factor. Further, we find the value of the Brans–Dicke scalar field $$\phi $$
ϕ
for the obtained value of the Hubble parameter and holographic dark energy. We obtain the corresponding value of the deceleration parameter and show that it can explain the phase transition of the universe. Moreover, statefinder diagnostics has been applied to compare the model with existing models. On the other hand, we consider the viscous behavior of holographic dark energy and show that the viscous holographic dark energy can play the role of interacting holographic dark energy as it is able to explain the phase transition of the universe. Further, we find the value of the Brans–Dicke scalar field $$\phi $$
ϕ
for this viscous holographic dark energy. In this model also, we apply the statefinder diagnostic.
Some properties of balanced hyperbolic compact complex manifolds
Authors: Marouani Samir , Popovici Dan
Published: February 2022

We prove several vanishing theorems for the cohomology of balanced hyperbolic manifolds that we introduced in our previous work and for the [Formula: see text] harmonic spaces on the universal cover of these manifolds. Other results include a Hard Lefschetz-type theorem for certain compact complex balanced manifolds and the non-existence of certain [Formula: see text] currents on the universal covering space of a balanced hyperbolic manifold.
Towards a discovery of BSM physics from the Cabibbo angle anomaly
Authors: Seng Chien-Yeah
Published: February 2022

New developments in both the theories and experiments related to the extraction of the top-row Cabibbo–Kobayashi–Maskawa matrix elements [Formula: see text] and [Formula: see text] led to a series of new anomalies, for instance, the apparent violation of the top-row unitarity relation. It is important to further reduce all the associated Standard Model theory uncertainties in order to better understand whether such observations point towards the possibility of physics beyond the Standard Model, or rather some unexpectedly large Standard Model effects. This requires improved studies of tree-level and higher-order Standard Model corrections that enter the beta decays of pions, neutron, nuclei and kaons. We will briefly review the recent progress along this direction and discuss possible improvements in the future.
A Class of Parameter-Free Filled Functions for Unconstrained Global Optimization
Authors: Pandiya Ridwan , Salmah  , Widodo  , Endrayanto Irwan
Published: February 2022

The deficiencies of existing filled functions have been extensively reviewed in the literature. Their use of an exponent function, the existence of adjustable parameters, their discontinuities, and their difficulty in determining an initial minimization point are significant issues that must be addressed. Although a new generation of filled functions, i.e., parameter-free filled functions, has been proposed, these filled functions still include an exponential term or some discontinuous points in their feasible domains. In this paper, these two adverse effects were diminished by providing a more general form, a new parameter free, and nonexponential filled function, which is continuously differentiable. The results of the analysis demonstrated that, under a specific condition, the properties of the filled functions presented in this paper meet the definition of a filled function. A comparison of numerical results confirmed that the proposed filled function performs better compared to some other parametric and nonparametric filled functions.
Evaluation of an Intervention Program Based on Mobile Apps to Learn Sexism Prevention in Teenagers
Authors: Morillo Pedro , Navarro-Pérez José J. , Orduña Juan M. , Fernández Marcos
Published: February 2022

The fight against sexism is nowadays one of the flagship social movements in western countries. Adolescence is a crucial period, and some empirical studies have focused on the socialization of teenagers, proving that the socialization with the surrounding environment prevent sexist practices. In a previous work, we developed and tested the effectiveness of a mobile app, called
Liad@s
, with the goals of helping teenagers to prevent sexism and build healthy couple relationships. In this article, we carry out a study where (using a real situation) we compare the effectiveness of the Liad@s app in front of traditional interventions like a workshop about sexism for teenagers. Also, we evaluate the usability of the app and the user satisfaction with this application. In this study, our primary hypothesis is that the effectiveness of using our mobile application, in terms of knowledge acquired about sexism, would be at least as good as attending the workshop. Our secondary hypothesis is that the user satisfaction with the mobile application would be higher than the one with the workshop, causing a preference for the app. The results of this study show significant differences in learning appeared between gender and between the two different procedures when separately evaluating the data collected from both hostile sexism (HS) and benevolent sexism (BS) questionnaires. These results validate our primary hypothesis. Also, most of the population under study preferred the mobile app in front of the traditional workshop, validating also our secondary hypothesis.
Understanding and Creating Art with AI: Review and Outlook
Authors: Cetinic Eva , She James
Published: February 2022

Technologies related to artificial intelligence (AI) have a strong impact on the changes of research and creative practices in visual arts. The growing number of research initiatives and creative applications that emerge in the intersection of AI and art motivates us to examine and discuss the creative and explorative potentials of AI technologies in the context of art. This article provides an integrated review of two facets of AI and art: (1) AI is used for art analysis and employed on digitized artwork collections, or (2) AI is used for creative purposes and generating novel artworks. In the context of AI-related research for art understanding, we present a comprehensive overview of artwork datasets and recent works that address a variety of tasks such as classification, object detection, similarity retrieval, multimodal representations, and computational aesthetics, among others. In relation to the role of AI in creating art, we address various practical and theoretical aspects of AI Art and consolidate related works that deal with those topics in detail. Finally, we provide a concise outlook on the future progression and potential impact of AI technologies on our understanding and creation of art.
Transform, Warp, and Dress: A New Transformation-guided Model for Virtual Try-on
Authors: Fincato Matteo , Cornia Marcella , Landi Federico , Cesari Fabio , Cucchiara Rita
Published: February 2022

Virtual try-on has recently emerged in computer vision and multimedia communities with the development of architectures that can generate realistic images of a target person wearing a custom garment. This research interest is motivated by the large role played by e-commerce and online shopping in our society. Indeed, the virtual try-on task can offer many opportunities to improve the efficiency of preparing fashion catalogs and to enhance the online user experience. The problem is far to be solved: current architectures do not reach sufficient accuracy with respect to manually generated images and can only be trained on image pairs with a limited variety. Existing virtual try-on datasets have two main limits: they contain only female models, and all the images are available only in low resolution. This not only affects the generalization capabilities of the trained architectures but makes the deployment to real applications impractical. To overcome these issues, we present
Dress Code
, a new dataset for virtual try-on that contains high-resolution images of a large variety of upper-body clothes and both male and female models. Leveraging this enriched dataset, we propose a new model for virtual try-on capable of generating high-quality and photo-realistic images using a three-stage pipeline. The first two stages perform two different geometric transformations to warp the desired garment and make it fit into the target person’s body pose and shape. Then, we generate the new image of that same person wearing the try-on garment using a generative network. We test the proposed solution on the most widely used dataset for this task as well as on our newly collected dataset and demonstrate its effectiveness when compared to current state-of-the-art methods. Through extensive analyses on our
Dress Code
dataset, we show the adaptability of our model, which can generate try-on images even with a higher resolution.
Electrochemical Pressure Impedance Spectroscopy for Polymer Electrolyte Membrane Fuel Cells: A Combined Modeling and Experimental Analysis
Authors: Schiffer Lutz , Shirsath Anantrao Vijay , Raël Stéphane , Bonnet Caroline , Lapicque François , Bessler Wolfgang G.
Published: February 2022

Electrochemical pressure impedance spectroscopy (EPIS) has recently been developed as a potential diagnosis tool for polymer electrolyte membrane fuel cells (PEMFC). It is based on analyzing the frequency response of the cell voltage with respect to an excitation of the gas-phase pressure. We present here a combined modeling and experimental study of EPIS. A pseudo-two-dimensional PEMFC model was parameterized to a 100 cm2 laboratory cell installed in its test bench, and used to reproduce steady-state cell polarization and electrochemical impedance spectra (EIS). Pressure impedance spectra were obtained both in experiment and simulation by applying a harmonic pressure excitation at the cathode outlet. The model shows good agreement with experimental data for current densities

≤

0.4 A cm−2. Here it allows a further simulative analysis of observed EPIS features, including the magnitude and shape of spectra. Key findings include a strong influence of the humidifier gas volume on EPIS and a substantial increase in oxygen partial pressure oscillations towards the channel outlet at the resonance frequency. At current densities

≥

0.8 A cm−2 the experimental EIS and EPIS data cannot be fully reproduced. This deviation might be associated with the formation and transport of liquid water, which is not included in the model.
Factors mediating spaceflight-induced skeletal muscle atrophy
Authors: Lee Peter H. U. , Chung Michael , Ren Zhanping , Mair Devin B. , Kim Deok-Ho
Published: February 2022

Skeletal muscle atrophy is a well-known consequence of spaceflight. Because of the potential significant impact of muscle atrophy and muscle dysfunction on astronauts and their mission, a thorough understanding of the mechanisms of this atrophy and the development of effective countermeasures is critical. Spaceflight-induced muscle atrophy is similar to atrophy seen in many terrestrial conditions, and therefore our understanding of this form of atrophy may also contribute to the treatment of atrophy in humans on Earth. The unique environmental features humans encounter in space include the weightlessness of microgravity, space radiation, and the distinctive aspects of living in a spacecraft. The disuse and unloading of muscles in microgravity are likely the most significant factors that mediate spaceflight-induced muscle atrophy and have been extensively studied and reviewed. However, there are numerous other direct and indirect effects on skeletal muscle that may be contributing factors to the muscle atrophy and dysfunction seen as a result of spaceflight. This review offers a novel perspective on the issue of muscle atrophy in space by providing a comprehensive overview of the unique aspects of the spaceflight environment and the various ways in which they can lead to muscle atrophy. We systematically review the potential contributions of these different mechanisms of spaceflight-induced atrophy and include findings from both actual spaceflight and ground-based models of spaceflight in humans, animals, and in vitro studies.
The role of Cl− and K+ efflux in NLRP3 inflammasome and innate immune response activation
Authors: Koumangoye Rainelli
Published: February 2022

Inflammation is part of innate immunity and is a natural response of the body to bacteria, virus, and any other pathogen infections or to damaged tissues. However, too much inflammation or chronic inflammation contributes to a wide variety of diseases such as inflammatory bowel disease, cancer, type 2 diabetes, heart disease, and autoimmune diseases such as rheumatoid arthritis. Recent studies underscored the critical role of K+ and Cl− efflux in the activation of the inflammasome. The NLRP3 inflammasome is a multiprotein complex that mediates the production of the proinflammatory cytokines IL-1β and IL-18 and initiates the inflammatory cell death or pyroptosis. The NLRP3 inflammasome can be activated by multiple stimuli such as extracellular ATP, microbial toxins, ROS, mitochondrial DNA, or particulate matter. Although the precise mechanisms of NLRP3 activation and regulation by these diverse agonists remain unclear, multiple reports indicate that all NLRP3 agonists ultimately lead to a drop in intracellular concentration of potassium (K+ efflux) and chloride (Cl− efflux). The WNK-SPAK/OSR1-[N]KCC pathway plays a critical role in maintaining K+ and Cl− ion concentrations in the cell. Recent advances indicate that the WNK-SPAK-[N]KCC pathway plays a role in the activation of the innate immune response. This review highlights recent discoveries detailing how ion transport regulates innate immune cell response to inflammatory stimuli.
Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation
Authors: Halder Sourav , Acharya Shashank , Kou Wenjun , Campagna Ryan A. J , Triggs Joseph R. , Carlson Dustin A. , Aadam Abdul Aziz , Hungness Eric S. , Kahrilas Peter J. , Pandolfino John E. , Patankar Neelesh A.
Published: February 2022

Blown-out myotomy (BOM) is a complication observed after myotomy, which is performed to treat achalasia. In silico simulations were performed to identify the factors leading to BOM formation. We found that a short myotomy that is not transmural and has some structural architecture intact reduces the risk of BOM formation. In addition, we found that high esophagogastric junction tone due to fundoplication is found to increase the risk of BOM formation.
Intestinal secretory mechanisms and diarrhea
Authors: Keely Stephen J. , Barrett Kim E.
Published: February 2022

One of the primary functions of the intestinal epithelium is to transport fluid and electrolytes to and from the luminal contents. Under normal circumstances, absorptive and secretory processes are tightly regulated such that absorption predominates, thereby enabling conservation of the large volumes of water that pass through the intestine each day. However, in conditions of secretory diarrhea, this balance becomes dysregulated, so that fluid secretion, driven primarily by Cl− secretion, overwhelms absorptive capacity, leading to increased loss of water in the stool. Secretory diarrheas are common and include those induced by pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis, or as a side effect of many drugs. Here, we review the cellular and molecular mechanisms by which Cl− and fluid secretion in the intestine are regulated, how these mechanisms become dysregulated in conditions of secretory diarrhea, currently available and emerging therapeutic approaches, and how new strategies to exploit intestinal secretory mechanisms are successfully being used in the treatment of constipation.
IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis
Authors: Auyeung Vincent C. , Downey Michael S. , Thamsen Maike , Wenger Talia A. , Backes Bradley J. , Sheppard Dean , Papa Feroz R.
Published: February 2022

After lung injury, damage-associated transient progenitors (DATPs) emerge, representing a transitional state between injured epithelial cells and newly regenerated alveoli. DATPs express profibrotic genes, suggesting that they might promote idiopathic pulmonary fibrosis (IPF). However, the molecular pathways that induce and/or maintain DATPs are incompletely understood. Here we show that the bifunctional kinase/RNase—IRE1α—a central mediator of the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress is a critical promoter of DATP abundance and function. Administration of a nanomolar-potent, monoselective kinase inhibitor of IRE1α (KIRA8)—or conditional epithelial IRE1α gene knockout—both reduce DATP cell number and fibrosis in the bleomycin model, indicating that IRE1α cell-autonomously promotes transition into the DATP state. IRE1α enhances the profibrotic phenotype of DATPs since KIRA8 decreases expression of integrin αvβ6, a key activator of transforming growth factor β (TGF-β) in pulmonary fibrosis, corresponding to decreased TGF-β-induced gene expression in the epithelium and decreased collagen accumulation around DATPs. Furthermore, IRE1α regulates DNA damage response (DDR) signaling, previously shown to promote the DATP phenotype, as IRE1α loss-of-function decreases H2AX phosphorylation, Cdkn1a (p21) expression, and DDR-associated secretory gene expression. Finally, KIRA8 treatment increases the differentiation of Krt19CreERT2-lineage-traced DATPs into type 1 alveolar epithelial cells after bleomycin injury, indicating that relief from IRE1α signaling enables DATPs to exit the transitional state. Thus, IRE1α coordinates a network of stress pathways that conspire to entrap injured cells in the DATP state. Pharmacological blockade of IRE1α signaling helps resolve the DATP state, thereby ameliorating fibrosis and promoting salutary lung regeneration.
The dynamic range of voltage-dependent gap junction signaling is maintained by Ih-induced membrane potential depolarization
Authors: Stein Wolfgang , DeMaegd Margaret L. , Braun Lena Yolanda , Vidal-Gadea Andrés G. , Harris Allison L. , Städele Carola
Published: February 2022

Electrical synapses and voltage-gated ionic currents are often studied independently from one another, despite mounting evidence that their interactions can alter synaptic behavior. We show that the hyperpolarization-activated inward ionic current shifts the voltage dependence of an electrical synaptic transmission through its depolarizing effect on the membrane potential, enabling it to lie within the functional membrane potential range of a motor neuron. Thus, the electrical synapse’s function critically depends on the voltage-gated ionic current.
Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes
Authors: Beghelli Daniela , Zallocco Lorenzo , Barbalace Maria Cristina , Paglia Simona , Strocchi Silvia , Cirilli Ilenia , Marzano Valeria , Putignani Lorenza , Lupidi Giulio , Hrelia Silvana , Giusti Laura , Angeloni Cristina
Published: February 2022

Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results.
Improved Approximate Expectation Propagation Massive MIMO Detector with Second-Order Richardson Iteration
Authors: Deng Qian , Chen Xuehui , Fu Wanting , Liang Xiaopeng , Xie Shilong , Shu Feng , Wu Yuan Yuan
Published: February 2022

The expectation propagation (EP) detector achieves significantly better performance than the linear detectors (such as minimum mean squared error detector) in massive MIMO systems, which has drawn great attention recently. EP’s approximation (EPA) algorithm simplifies the update formula of the EP algorithm by reexpressing the moment matching condition so that the number of matrix inversions in the EP algorithm is reduced to one. However, the expense is that the EPA algorithm requires higher accuracy for this inversion; otherwise, the bit-error-rate (BER) performance will suffer serious losses. To tackle this issue, the SORI iterative algorithm is introduced to obtain the high-precision result of this inversion to ensure the good BER performance of the EPA algorithm. First, the new expression of the SORI iterative algorithm is derived under the equivalent real-valued system. Second, the improved EPA-SORI algorithm is then introduced by the SORI algorithm, which is used to approximate the initial value of the EPA algorithm under the real-valued system. Finally, by designing the initial solution and the relaxation factor of the EPA-SORI iterative algorithm, the convergence rate can be quickly increased without increasing the complexity. Simulation and complexity results exhibit that in various massive MIMO system configurations, the proposed EPA-SORI algorithm can achieve the same BER performance as the Exact EP algorithm with significantly lower complexity. At the same time, compared with MMSE and the existing EPA algorithms, the proposed EPA-SORI algorithm has a better performance-complexity trade-off advantage, which is more obvious in scenarios with high modulation order and a large number of users.
Magnitudes and Correlates of Human Immunodeficiency Virus, Hepatitis B Virus, and Syphilis among Pregnant Mothers Attending Antenatal Care in Addis Ababa, Ethiopia
Authors: Genetu Kassa , Abere Kerebih , Tachbele Erdaw
Published: February 2022

Background. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis are major sexually transmitted infections (STIs) among the general population in Ethiopia, which in turn result in a wide range of adverse pregnancy outcomes. Hence, it is important to determine the seroprevalence and risk factors of HIV, HBV, and syphilis infection among pregnant mothers attending antenatal care in Addis Ababa, Ethiopia. Method. A cross-sectional study was conducted among 286 pregnant women from February 1, 2021, to March 30, 2021, in four selected public hospitals in Addis Ababa. Sociodemographic, risky sociocultural, behavioral, and hospital-related factors were collected using an interview-administered questionnaire. Detection of anti-HIV antibodies, hepatitis B surface antigen (HBsAg), and rapid plasma reagin (RPR) for syphilis was conducted. A binary logistic regression analysis was used to determine predictors of STIs using SPSS version 25. Result. A total of 281 pregnant mothers with a mean age of 27.5 (SD 4.6) completed the study. Among the participants, the seroprevalence rates of HIV, HBV, and syphilis were 15 (5.3%), 9 (3.2%), and 5 (1.8%), respectively. Twenty six (9.3%) of the participants tested positive for any one of the STIs, and 3 (1.1%) of the women had HIV and syphilis coinfections. History of multiple sexual partners (AOR 3.42, 95% CI: 1.6-11.63) and STIs (AOR 3.7; 95% CI: 1.70-13.45) were significantly associated with HIV infection. Likewise, history of abortion (AOR 7.65, 95% CI: 1.17-49.74), tattooing (AOR 9.72, 95% CI: 1.41-66.73), and rape (AOR 9.72, 95% CI: 1.41-66.73) were significantly associated with hepatitis B virus infection. Husband history of multiple sexual partners (AOR 20.9, 95% CI: 1.8-241.8) was significantly associated with syphilis infection. The educational level of participants, history of tattooing (AOR 6.24, 95% CI: 1.79-21.7), and history of multiple sexual partners (AOR 5.15, 95% CI: 1.68-15.7) were independent predictors of infection with any one of the STIs. Conclusion. There is still a high burden of HIV, HBV, and syphilis among pregnant mothers in Ethiopia. History of multiple sexual partners, abortion, rape, and tattooing was a significant predictor of STIs.
Comprehensive Pan-Cancer Analysis of IRAK Family Genes Identifies IRAK1 as a Novel Oncogene in Low-Grade Glioma
Authors: Li Jing , Sun Yuchen , Ma Yuan , Zhao Xu , Sun Xuanzi , Wang Yuzhu , Zhang Xiaozhi
Published: February 2022

Background. The interleukin-1 receptor-associated kinases (IRAK) family genes, indispensable mediators of interleukin-1 receptor (IL1R) and Toll-like receptor (TLR)-inflammatory signaling, may be involved in the biological function of human cancers due to the crucial roles of inflammation in tumor development. Though a little research has demonstrated the function of individual IRAK family members in specific tumors, comprehensive analysis is still lacking in pan-cancer. Methods. We analyzed the mRNA expression landscape, mutation, and prognosis value of IRAK genes based on The Cancer Genome Atlas (TCGA), cBioPortal, GlioVis, and Rembrandt databases. The correlation between the expression of IRAK genes and tumor microenvironment (TME), Stemness score, and immune subtypes was explored. Western blot, cell proliferation, apoptosis, migration assays, and xenograft models were utilized in this study. Results. We found that the expression of IRAK genes extensively changed and was related to patient survival in pan-cancer. Besides, IRAK family genes were correlated with TME, Stemness score, and immune subtypes in most cases. Given that high expression of all IRAK family members predicted poor prognosis in low-grade glioma (LGG), the oncogenic function of the highest expressed IRAK1 in LGG has been confirmed in vitro and in vivo. IRAK1 was uncovered to inhibit cell apoptosis and augment malignancy of LGG in vitro and in vivo. Conclusion. These findings revealed the potential targets of IRAK family genes in pan-cancer and provided insights for further investigation of IRAK1 as a novel oncogenic gene in LGG.
A Highly Selective Fluorescent Probe for Hypochlorous Acid in Living Cells Based on a Naphthalene Derivative
Authors: Sun Jingguo , Xu Junhong , Ma Qiujuan , Mao Guojiang , Zhu Nannan , Tian Meiju , Li Linke , Liu Shuzhen
Published: February 2022

Hypochlorous acid (HOCl) was crucial for maintaining the homeostasis in cells and plays vital roles in many physiological and pathological processes. In this work, a highly selective fluorescent probe for hypochlorous acid in living cells was constructed and prepared based on a naphthalene derivative. A naphthalene derivative was utilized as the fluorescent group, and N,N-dimethylthiocarbamate was applied as the selective recognition site for HOCl. Before adding HOCl, the fluorescent probe exhibited weak fluorescence. Upon adding HOCl, the fluorescent probe displayed remarkable fluorescence enhancement. The fluorescence intensity at 502 nm showed a linear response to the concentration of HOCl from 3.0 × 10−7 to 1.0 × 10−5 mol·L−1. The detection limit was estimated to be 1.5 × 10−7 mol·L−1 for HOCl. The fluorescent probe showed fast response and outstanding selectivity toward HOCl. It owned good biocompatibility and had also been successfully applied in the confocal imaging of exogenous and endogenous HOCl in living cells.
The lncRNA-AK046375 Upregulates Metallothionein-2 by Sequestering miR-491-5p to Relieve the Brain Oxidative Stress Burden after Traumatic Brain Injury
Authors: Tang Wei , Chai Weina , Du Donglin , Xia Yongzhi , Wu Yifan , Jiang Li , Cheng Chongjie , Guo Zongduo , Sun Xiaochuan , Huang Zhijian , Zhong Jianjun
Published: February 2022

We previously discovered that traumatic brain injury (TBI) induces significant perturbations in long noncoding RNA (lncRNA) levels in the mouse cerebral cortex, and lncRNA-AK046375 is one of the most significantly changed lncRNAs after TBI. lncRNA-AK046375 overexpression and knockdown models were successfully constructed both in vitro and in vivo. In cultured primary cortical neurons and astrocytes, lncRNA-AK046375 sequestered miR-491-5p, thereby enhancing the expression of metallothionein-2 (MT2), which ameliorated oxidative-induced cell injury. In addition, upregulated lncRNA-AK046375 promoted the recovery of motor, learning, and memory functions after TBI in C57BL/6 mice, and the underlying mechanism may be related to ameliorated apoptosis, inhibited oxidative stress, reduced brain edema, and relieved loss of tight junction proteins at the blood-brain barrier in the mouse brain. Therefore, we conclude that lncRNA-AK046375 enhances MT2 expression by sequestering miR-491-5p, ultimately strengthening antioxidant activity, which ameliorates neurological deficits post-TBI.
100 anos de Paulo Freire, o patrono da educação brasileira
Authors: Vaz Filho Pedro Serico
Published: February 2022

Resenha do livro "O Educador. Um perfil de Paulo Freire", assinado pelo professor e historiador Sergio Haddad, sobre o educador Paulo Freire, que completaria 100 anos em 19/09/2021.
Resposta a necessidades em saúde mental de estudantes universitários: uma revisão rápida
Authors: Gaiotto Emiliana Maria Grando , Trapé Carla Andrea , Campos Celia Maria Sivalli , Fujimori Elizabeth , Carrer Fernanda Campos de Almeida , Nichiata Lucia Yassuko Izumi , Cordeiro Luciana , Bortoli Maritsa Carla de , Yonekura Tatiana , Toma Tereza Setsuko , Soares Cassia Baldini
Published: February 2022

OBJETIVO Apresentar opções estratégicas para apoiar a adoção de políticas de fortalecimento da saúde mental de universitários da área da saúde, a serem implementadas por instituições universitárias. MÉTODOS Revisão rápida, sem delimitação de período, com buscas realizadas de maio a junho de 2020, em 21 fontes de dados bibliográficos, incluindo literatura cinzenta. Utilizaram-se as palavras-chave: saúde mental, estudantes e universidade. O processo de seleção priorizou revisões sistemáticas sobre intervenções em saúde mental para estudantes universitários em cursos da área da saúde, e considerou, também, outros tipos de revisão e estudos primários relevantes. RESULTADOS Foram incluídos 45 estudos: 34 revisões sistemáticas, uma síntese de evidências, um overview, uma revisão de escopo, três revisões narrativas, três relatos de experiência e dois artigos de opinião. As evidências desses estudos apoiaram a elaboração de quatro opções: 1) estabelecer e apoiar políticas de fortalecimento da saúde mental de estudantes dos cursos da área da saúde; 2) integrar programas de atenção à saúde mental, ampliar sua oferta e facilitar seu acesso pelos estudantes; 3) promover programas educacionais e estratégias de comunicação relacionadas ao sofrimento psíquico contemporâneo e ao seu enfrentamento, para que os estudantes conheçam os serviços e recursos e identifiquem práticas de fortalecimento; 4) monitorar e avaliar continuamente as necessidades em saúde mental dos estudantes dos cursos da área da saúde. CONCLUSÕES As opções são desafiadoras e exigem que as universidades estabeleçam comissões institucionais para implementar uma política de fortalecimento da saúde mental dos estudantes universitários da área da saúde, com capacidade de reconhecer as diversas necessidades em saúde, incluindo as manifestações de sofrimento psíquico; integrar ações internas da universidade entre si e aos serviços do Sistema Único de Saúde; implementar e monitorar as ações que compõem a política de saúde mental.
Política Nacional de Saúde Bucal: metassíntese dos estudos sobre a Rede de Saúde Bucal
Authors: Costa Junior Sylvio da , Araujo Pierre Guedes , Frichembruder Karla , Hugo Fernando Neves
Published: February 2022

OBJETIVO Analisar o desempenho da rede de cuidados em saúde bucal orientada a partir sua implantação, em 2004 até 2020, segundo publicações sobre o tema. MÉTODOS Trata-se de uma pesquisa com descrição metodológica de metassíntese. RESULTADOS As buscas resultaram em 600 publicações completas (586 na primeira busca e mais 14 na segunda busca), de acordo com os critérios estabelecidos. Foram excluídos 539 artigos: 151 artigos após análise de duplicidade, 236 artigos após a leitura do título, 45 pelo tipo de publicação e 107 artigos após leitura do resumo, por não se enquadrarem na temática da pesquisa. Dessa forma, foram selecionadas e analisadas 61 publicações originais e mais 29 publicações em snowball sampling, totalizando 90 publicações. A partir dessa seleção,optou-se por usaro modelo proposto pelo Projeto de Avaliações de Desempenho de Sistemas de Saúde – PROADESS. O estudo se utilizará de seus princípios norteadores sobre a dimensão “Desempenho dos Serviços de Saúde”. CONCLUSÃO O conjunto analisado permitiu identificar que a forma como o Estado brasileiro organiza e financia o atendimento em saúde bucal possibilitou a ampliação do acesso e do número de procedimentos realizados, mas não da criação de uma efetiva Rede de cuidados integrais, após mais de uma década de implementação do Brasil Sorridente.