bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states
Authors: Zhu Jiaqi , Salvatella Xavier , Robustelli Paul 
Published: October 2022

AbstractIntrinsically disordered proteins, which do not adopt well-defined structures under physiological conditions, are implicated in many human diseases. Small molecules that target the disordered transactivation domain of the androgen receptor have entered human trials for the treatment of castration-resistant prostate cancer (CRPC), but no structural or mechanistic rationale exists to explain their inhibition mechanisms or relative potencies. Here, we utilize all-atom molecular dynamics computer simulations to elucidate atomically detailed binding mechanisms of the compounds EPI-002 and EPI-7170 to the androgen receptor. Our simulations reveal that both compounds bind at the interface of two transiently helical regions and induce the formation of partially folded collapsed helical states. We find that EPI-7170 binds androgen receptor more tightly than EPI-002 and we identify a network of intermolecular interactions that drives higher affinity binding. Our results suggest strategies for developing more potent androgen receptor inhibitors and general strategies for disordered protein drug design.
Regulating the scaling relationship for high catalytic kinetics and selectivity of the oxygen reduction reaction
Authors: Zhou Wanlin , Su Hui , Cheng Weiren , Li Yuanli , Jiang Jingjing , Liu Meihuan , Yu Feifan , Wang Wei , Wei Shiqiang , Liu Qinghua 
Published: October 2022

AbstractThe electrochemical oxygen reduction reaction (ORR) is at the heart of modern sustainable energy technologies. However, the linear scaling relationship of this multistep reaction now becomes the bottleneck for accelerating kinetics. Herein, we propose a strategy of using intermetallic-distance-regulated atomic-scale bimetal assembly (ABA) that can catalyse direct O‒O radical breakage without the formation of redundant *OOH intermediates, which could regulate the inherent linear scaling relationship and cause the ORR on ABA to follow a fast-kinetic dual-sites mechanism. Using in situ synchrotron spectroscopy, we directly observe that a self-adjustable N-bridged Pt = N2 = Fe assembly promotes the generation of a key intermediate state (Pt‒O‒O‒Fe) during the ORR process, resulting in high reaction kinetics and selectivity. The well-designed Pt = N2 = Fe ABA catalyst achieves a nearly two orders of magnitude enhanced kinetic current density at the half-wave potential of 0.95 V relative to commercial Pt/C and an almost 99% efficiency of 4-electron pathway selectivity, making it one of the potential ORR catalysts for application to the energy device of zinc‒air cells. This study provides a helpful design principle for developing and optimizing other efficient ORR electrocatalysts.
Speech acoustic indices for differential diagnosis between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy
Authors: Daoudi Khalid , Das Biswajit , Tykalova Tereza , Klempir Jiri , Rusz Jan 
Published: October 2022

AbstractWhile speech disorder represents an early and prominent clinical feature of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), little is known about the sensitivity of speech assessment as a potential diagnostic tool. Speech samples were acquired from 215 subjects, including 25 MSA, 20 PSP, 20 Parkinson’s disease participants, and 150 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 26 speech dimensions related to phonation, articulation, prosody, and timing. A semi-supervised weighting-based approach was then applied to find the best feature combinations for separation between PSP and MSA. Dysarthria was perceptible in all PSP and MSA patients and consisted of a combination of hypokinetic, spastic, and ataxic components. Speech features related to respiratory dysfunction, imprecise consonants, monopitch, slow speaking rate, and subharmonics contributed to worse performance in PSP than MSA, whereas phonatory instability, timing abnormalities, and articulatory decay were more distinctive for MSA compared to PSP. The combination of distinct speech patterns via objective acoustic evaluation was able to discriminate between PSP and MSA with very high accuracy of up to 89% as well as between PSP/MSA and PD with up to 87%. Dysarthria severity in MSA/PSP was related to overall disease severity. Speech disorders reflect the differing underlying pathophysiology of tauopathy in PSP and α-synucleinopathy in MSA. Vocal assessment may provide a low-cost alternative screening method to existing subjective clinical assessment and imaging diagnostic approaches.
Seasonal increase of methane emissions linked to warming in Siberian tundra
Authors: Rößger Norman , Sachs Torsten , Wille Christian , Boike Julia , Kutzbach Lars 
Published: October 2022

AbstractWhile increasing methane emissions from thawing permafrost are anticipated to be a major climate feedback, no observational evidence for such an increase has previously been documented in the literature. Here we report a trend of increasing methane emissions for the early summer months of June and July at a permafrost site in the Lena River Delta, on the basis of the longest set of eddy covariance methane flux data in the Arctic. Along with a strong air temperature rise of 0.3 ± 0.1 °C yr−1 in June, which corresponds to an earlier warming of 11 d, the methane emissions in June and July have increased by roughly 1.9 ± 0.7% yr−1 since 2004. Although the tundra’s maximum source strength in August has not yet changed, this increase in early summer methane emissions shows that atmospheric warming has begun to considerably affect the methane flux dynamics of permafrost-affected ecosystems in the Arctic.
A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer
Authors: Inglebert Marine , Dettwiler Martina , Hahn Kerstin , Letko Anna , Drogemuller Cord , Doench John , Brown Adam , Memari Yasin , Davies Helen R. , Degasperi Andrea , Nik-Zainal Serena , Rottenberg Sven 
Published: October 2022

AbstractMammary tumors in dogs hold great potential as naturally occurring breast cancer models in translational oncology, as they share the same environmental risk factors, key histological features, hormone receptor expression patterns, prognostic factors, and genetic characteristics as their human counterparts. We aimed to develop in vitro tools that allow functional analysis of canine mammary tumors (CMT), as we have a poor understanding of the underlying biology that drives the growth of these heterogeneous tumors. We established the long-term culture of 24 organoid lines from 16 dogs, including organoids derived from normal mammary epithelium or benign lesions. CMT organoids recapitulated key morphological and immunohistological features of the primary tissue from which they were derived, including hormone receptor status. Furthermore, genetic characteristics (driver gene mutations, DNA copy number variations, and single-nucleotide variants) were conserved within tumor-organoid pairs. We show how CMT organoids are a suitable model for in vitro drug assays and can be used to investigate whether specific mutations predict therapy outcomes. Specifically, certain CMT subtypes, such as PIK3CA mutated, estrogen receptor-positive simple carcinomas, can be valuable in setting up a preclinical model highly relevant to human breast cancer research. In addition, we could genetically modify the CMT organoids and use them to perform pooled CRISPR/Cas9 screening, where library representation was accurately maintained. In summary, we present a robust 3D in vitro preclinical model that can be used in translational research, where organoids from normal, benign as well as malignant mammary tissues can be propagated from the same animal to study tumorigenesis.
Galerkin finite element analysis for magnetized radiative-reactive Walters-B nanofluid with motile microorganisms on a Riga plate
Authors: Shahzad Faisal , Jamshed Wasim , Usman  , Ibrahim Rabha W. , Aslam Farheen , Tag El Din El Sayed M. , Khalifa Hamiden Abd El-Wahed , ElSeabee Fayza Abdel Aziz 
Published: October 2022

AbstractIn order to understand the characteristics of bio-convection and moving microorganisms in flows of magnetized Walters-B nano-liquid, we developed a model employing Riga plate with stretchy sheet. The Buongiorno phenomenon is likewise employed to describe nano-liquid motion in the Walters-B fluid. Expending correspondence transformations, the partial differential equation (PDE) control system has been transformed into an ordinary differential equation (ODE) control system. The COMSOL program is used to generate mathematical answers for non-linear equations by employing the Galerkin finite element strategy (G-FEM). Utilizing logical and graphical metrics, temperature, velocity, and microbe analysis are all studied. Various estimates of well-known physical features are taken into account while calculating nanoparticle concentrations. It is demonstrated that this model's computations directly relate the temperature field to the current Biot number and parameter of the Walters-B fluid. The temperature field is increased to increase the approximations of the current Biot number and parameter of the Walters-B fluid.
Cold intolerance and associated factors: a population study
Authors: Khabbazi Alireza , Farzaneh Rojin , Mahmoudi Maryam , Shahi Mohammad , Jabbaripour Sarmadian Amirreza , Babapour Elaheh , Alizadeh Leila , Khabbazi Raha , Nouri-Vaskeh Masoud 
Published: October 2022

AbstractCold intolerance has been defined as a set of symptoms including pain, tingling, numbness, chills, stiffness, weakness, swelling or skin color changes on exposure to cold. Cold intolerance may have a profound effect on health-related quality of life. In this cross-sectional study, we investigated primarily the prevalence of cold intolerance and secondly associated factors in the general population of Tabriz. Simple random sampling of individuals aged ≥ 18 was performed from the population covered by Emamieh health center under the supervision of Tabriz University of Medical Sciences. A telephone interview was conducted with the participants by the general physician of that center. In participants with a positive response to each of two questions “I am oversensitive to cold” and “I experience pain or discomfort when exposed to cold” a Cold Intolerance Symptom Severity (CISS) questionnaire was filled. We used a cut off value 50 for defining cold intolerance. Of the 353 person who received telephone calls, 322 answered questions. Cold related symptoms and cold intolerance were reported in 144 (44.7%) and 38 (11.1%) persons, respectively. Cold intolerance was significantly more common in females and people with comorbidities. Cold intolerance led to a decrease in quality of job in 27 (8.4%) and a change in job in 6 (1.9%) persons. In conclusion, cold intolerance is a common problem in the general population of Tabriz.
Establishment of the diagnostic and prognostic nomograms for pancreatic cancer with bone metastasis
Authors: Liu Zongtai , Liu Haiyan , Wang Dalin 
Published: October 2022

AbstractBone metastasis (BM) is rare in patients with pancreatic cancer (PC), but often neglected at the initial diagnosis and treatment. Bone metastasis is associated with a worse prognosis. This study was aimed to perform a large data analysis to determine the predictors and prognostic factors of BM in PC patients and to develop two nomograms to quantify the risks of BM and the prognosis of PC patients with BM. In the present study, we reviewed and collected the data of patients who were diagnosed as PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression analyses were used together to screen and validate the risk factors for BM in PC patients. The independent prognostic factors for PC patients with BM were identified by Cox regression analysis. Finally, two nomograms were established via calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). This study included 16,474 PC patients from the SEER database, and 226 of them were diagnosed with BM. The risk factors of BM for PC patients covered age, grade, T stage, N stage, tumor size, and primary site. The independent prognostic factors for PC patients with BM included age, race, grade, surgery, and lung metastasis. The AUC of the diagnostic nomogram was 0.728 in the training set and 0.690 in the testing set. In the prognostic nomogram, the AUC values of 6/12/18 month were 0.781/0.833/0.849 in the training set and 0.738/0.781/0.772 in the testing set. The calibration curve and DCA furtherly indicated the satisfactory clinical consistency of the nomograms. These nomograms could be accurate and personalized tools to predict the incidence of BM in PC patients and the prognosis of PC patients with BM. The nomograms can help clinicians make more personalized and effective treatment choices.
Applicability of DRIS in bananas based on the accuracy of nutritional diagnoses for nitrogen and potassium
Authors: Villaseñor-Ortiz Diego , de Mello Prado Renato , Pereira da Silva Gilmara , Lata-Tenesaca Luis Felipe 
Published: October 2022

AbstractDRIS (Diagnosis Recommendation Integrated System) is a tool used in the interpretation of leaf analyses that values the balance of nutrients, an important fact for a better assessment of the nutritional status of banana plants. Its usefulness depends on the ability to identify the nutrients that limit productivity in order to correct possible nutritional imbalances, but there is a lack of research in all crops, including bananas, to assess the accuracy of these diagnoses, which have a worrying global implication. To this end, this study evaluates DRIS norms for banana cultivation in Ecuador and the use of accuracy measurements for nutritional diagnosis, verifying the capacity of DRIS to detect true nutritional status based on plant response. The database created here contains 233 results referring to productivity and leaf contents of N, P, K, Ca, Mg, S, Cl, Fe, Mn, Cu, B, and Zn for banana trees in 2018, 2019, and 2020. Then, a field experiment evaluated doses of nitrogen and potassium and the accuracy of DRIS norms for N and K. The results show that the DRIS of banana produced in Ecuador depends on the nutrient being variable according to the crop nutritional status. The DRIS norms for diagnosis of N and K result in an acceptable accuracy to identify only deficiencies and toxicities, respectively, indicating the need for adjustments in these standards for later use in the field. Thus, there is a need for more research aiming to adopt calibrated DRIS diagnostic norms to assess the nutritional status of bananas in Ecuador.
East Asian heatwaves driven by Arctic-Siberian warming
Authors: Kim Jeong-Hun , Kim Seong-Joong , Kim Joo-Hong , Hayashi Michiya , Kim Maeng-Ki 
Published: October 2022

AbstractThis study investigates the contributing factors of East Asian heatwaves (EAHWs) linked to the Arctic-Siberian Plain (ASP) over the past 42 years (1979–2020). EAHWs are mainly affected by two time scales of variabilities: long-term externally forced and interannual variabilities. The externally forced EAHWs are attributed to the increasing global warming trend, while their interannual variability is related to the circumglobal teleconnection (CGT) and the ASP teleconnection patterns. In addition to the CGT, the Rossby wave energy originating from the ASP propagates to East Asia through the upper troposphere, amplifying the EAHWs. The stationary high pressure in the ASP is generated by vorticity advection in the upper troposphere. Enhanced surface radiative heating and evaporation on the ASP surface increase the specific humidity and temperature, amplifying the thermal high pressure via positive water vapor feedback. Thermal high-pressure amplified by land–atmosphere interactions in the ASP during the peak summer season leads to EAHWs by the propagation of stationary Rossby wave energy. The results indicate that our enhanced understanding of the ASP teleconnection can improve forecasting of the EAHWs not only on a sub-seasonal time scale but also in future projections of global climate models.
Cross-sectional study of cholinergic urticaria subtypes and bronchial hyperresponsiveness
Authors: Katsurada Naoko , Nagano Tatsuya , Yamamoto Masatsugu , Kiriu Tatsunori , Dokuni Ryota , Kamiryo Hiroshi , Yoshioka Ai , Fukunaga Atsushi , Nishigori Chikako , Nishimura Yoshihiro , Kobayashi Kazuyuki 
Published: October 2022

AbstractCholinergic urticaria (CholU) is classified into several subtypes: (1) conventional sweat allergy-type CholU (conventional SAT-CholU), (2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd); 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the subtypes. We analyzed bronchial responsiveness using the methacholine dose indicator Dmin, respiratory symptoms, and exhaled nitric oxide (FeNO). Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU (n = 11), CholU-PA (n = 11), and CholU-Anhd (n = 11) was 0.381 (− 0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p = 0.516). Respiratory symptoms were less frequently observed in CholU-Anhd than in conventional SAT-CholU or CholU-PA. FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p = 0.237). Nine% of conventional SAT-CholU patients and more than half of CholU-PA patients required treatment for asthma. Log Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. CholU-PA might be associated with asthma.
Educational quality may be a closer correlate of cardiometabolic health than educational attainment
Authors: Cundiff Jenny M. , Lin Shayne S.-H. , Faulk Robert D. , McDonough Ian M. 
Published: October 2022

AbstractEducational quality may be a closer correlate of physical health than more commonly used measures of educational attainment (e.g., years in school). We examined whether a widely-used performance-based measure of educational quality is more closely associated with cardiometabolic health than educational attainment (highest level of education completed), and whether perceived control (smaller sample only), executive functioning (both samples), and health literacy (smaller sample only) link educational quality to cardiometabolic health. In two samples (N = 98 and N = 586) collected from different regions of the US, educational quality was associated with cardiometabolic health above and beyond educational attainment, other demographic factors (age, ethnoracial category, sex), and fluid intelligence. Counter to expectations, neither perceived control, executive function, nor health literacy significantly mediated the association between educational quality and cardiometabolic health. Findings add to the growing literature suggesting that current operationalizations of the construct of education likely underestimate the association between education and multiple forms of health. To the extent that educational programs may have been overlooked based on the apparent size of associations with outcomes, such actions may have been premature.
A hybrid numerical/machine learning model development to improve the bimetal performance in the electric circuit breakers
Authors: Mallah Abdul Rahman , Aljuraid Nawaf , Alawi Omer A. , Yaseen Zaher Mundher , Singh Kamaljeet , Ataki Adel 
Published: October 2022

AbstractBimetals are widely used as a thermal tripping mechanism inside the miniature circuit breakers (MCBs) products when an overload current passes through the circuit for a certain period. Experimental, numerical, and, recently artificial intelligence methods are widely used in designing electric components. However, developing the bimetal for MCB products somewhat differs from developing other conductor items since they are strongly related to the electrical, mechanical, and thermal performance of the MCB. The conventional experimental and numerical approaches are time-consuming processes that cannot be easily utilized in optimizing the product's performance within the development lead time. In this study, a simple, fast, robust, and accurate novel methodology has been introduced to predict the temperature rise of the bimetal and other related performance characteristics. The numerical model has been built on the time-based finite difference method to frame the theoretical thermal model of the bimetal. Then, the numerical model has been consolidated by the machine learning (ML) model to take advantage of the experiments to provide an accurate, fast and reliable model finally. The novel model agrees well with the experimental tests, where the maximum error does not exceed 8%. The model has been used to redesign the bimetal of a 32 A MCB product and significantly reduce the maximum temperature by 24 °C. The novel model is promising since it considerably reduces the required design time, provides accurate predictions, and helps to optimize the performance of the circuit breaker products.
Dementia and risk of visual impairment in Chinese older adults
Authors: Kwok Charlotte P. C. , Kwok Jessie O. T. , Yan Rachel W. K. , Lee Kaspar K. W. , Richards Marcus , Chan Wai C. , Chiu Helen F. K. , Lee Ruby S. Y. , Lam Linda C. W. , Lee Allen T. C. 
Published: October 2022

AbstractWe had previously identified visual impairment increasing risk of incident dementia. While a bi-directional vision-cognition association has subsequently been proposed, no study has specifically examined the longitudinal association between dementia and incidence of clinically defined visual impairment. In this territory-wide community cohort study of 10,806 visually unimpaired older adults, we examined their visual acuity annually for 6 years and tested if dementia at baseline was independently associated with higher risk of incident visual impairment (LogMAR ≥ 0.50 in the better eye despite best correction, which is equivalent to moderate visual impairment according to the World Health Organization definition). By the end of Year 6, a total of 3151 (29.2%) participants developed visual impairment. However, we did not find baseline dementia associating with higher risk of incident visual impairment, after controlling for baseline visual acuity, cataract, glaucoma, diabetes, hypertension, hypercholesterolemia, heart diseases, stroke, Parkinson’s disease, depression, hearing and physical impairments, physical, intellectual and social activities, diet, smoking, age, sex, educational level, and socioeconomic status. Among different covariables, baseline visual acuity appears to be more important than dementia in contributing to the development of visual impairment. Our present findings highlight the need for re-evaluating whether dementia is indeed a risk factor for visual impairment.