bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling
Authors: Maimets Martti , Pedersen Marianne Terndrup , Guiu Jordi , Dreier Jes , Thodberg Malte , Antoku Yasuko , Schweiger Pawel J. , Rib Leonor , Bressan Raul Bardini , Miao Yi , Garcia K. Christopher , Sandelin Albin , Serup Palle , Jensen Kim B. 
Published: February 2022

AbstractOrgans are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI.
Cryo-EM structures of human bradykinin receptor-Gq proteins complexes
Authors: Shen Jinkang , Zhang Dongqi , Fu Yao , Chen Anqi , Yang Xiaoli , Zhang Haitao 
Published: February 2022

AbstractThe type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-Gqin complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W2836.48, the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with Gqproteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and Gqproteins coupling of B2R.
Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain
Authors: Xie Rou-Gang , Chu Wen-Guang , Liu Da-Lu , Wang Xu , Ma Sui-Bin , Wang Fei , Wang Fu-Dong , Lin Zhen , Wu Wen-Bin , Lu Na , Liu Ying-Ying , Han Wen-Juan , Zhang Hui , Bai Zhan-Tao , Hu San-Jue , Tao Hui-Ren , Kuner Thomas , Zhang Xu , Kuner Rohini , Wu Sheng-Xi , Luo Ceng 
Published: February 2022

AbstractPostsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.
The elphbolt ab initio solver for the coupled electron-phonon Boltzmann transport equations
Authors: Protik Nakib H. , Li Chunhua , Pruneda Miguel , Broido David , Ordejón Pablo 
Published: February 2022

Abstract is a modern Fortran (2018 standard) code for efficiently solving the coupled electron–phonon Boltzmann transport equations from first principles. Using results from density functional and density functional perturbation theory as inputs, it can calculate the effect of the non-equilibrium phonons on the electronic transport (phonon drag) and non-equilibrium electrons on the phononic transport (electron drag) in a fully self-consistent manner and obeying the constraints mandated by thermodynamics. It can calculate the lattice, charge, and thermoelectric transport coefficients for the temperature gradient and electric fields, and the effect of the mutual electron–phonon drag on these transport properties. The code fully exploits the symmetries of the crystal and the transport-active window to allow the sampling of extremely fine electron and phonon wave vector meshes required for accurately capturing the drag phenomena. The feature of modern Fortran, which offers native and convenient support for parallelization, is utilized. The code is compact, readable, well-documented, and extensible by design.
Identifying schizophrenia stigma on Twitter: a proof of principle model using service user supervised machine learning
Authors: Jilka Sagar , Odoi Clarissa Mary , van Bilsen Janet , Morris Daniel , Erturk Sinan , Cummins Nicholas , Cella Matteo , Wykes Til 
Published: February 2022

AbstractStigma has negative effects on people with mental health problems by making them less likely to seek help. We develop a proof of principle service user supervised machine learning pipeline to identify stigmatising tweets reliably and understand the prevalence of public schizophrenia stigma on Twitter. A service user group advised on the machine learning model evaluation metric (fewest false negatives) and features for machine learning. We collected 13,313 public tweets on schizophrenia between January and May 2018. Two service user researchers manually identified stigma in 746 English tweets; 80% were used to train eight models, and 20% for testing. The two models with fewest false negatives were compared in two service user validation exercises, and the best model used to classify all extracted public English tweets. Tweets classed as stigmatising by service users were more negative in sentiment (t (744) = 12.02, p < 0.001 [95% CI: 0.196–0.273]). Our linear Support Vector Machine was the best performing model with fewest false negatives and higher service user validation. This model identified public stigma in 47% of English tweets (n5,676) which were more negative in sentiment (t (12,143) = 64.38, p < 0.001 [95% CI: 0.29–0.31]). Machine learning can identify stigmatising tweets at large scale, with service user involvement. Given the prevalence of stigma, there is an urgent need for education and online campaigns to reduce it. Machine learning can provide a real time metric on their success.
Neuro-adaptive augmented distributed nonlinear dynamic inversion for consensus of nonlinear agents with unknown external disturbance
Authors: Mondal Sabyasachi , Tsourdos Antonios 
Published: February 2022

AbstractThis paper presents a novel neuro-adaptive augmented distributed nonlinear dynamic inversion (N-DNDI) controller for consensus of nonlinear multi-agent systems in the presence of unknown external disturbance. N-DNDI is a blending of neural network and distributed nonlinear dynamic inversion (DNDI), a new consensus control technique that inherits the features of Nonlinear Dynamic Inversion (NDI) and is capable of handling the unknown external disturbance. The implementation of NDI based consensus control along with neural networks is unique in the context of multi-agent consensus. The mathematical details provided in this paper show the solid theoretical base, and simulation results prove the effectiveness of the proposed scheme.
Aerodynamic characteristics and genesis of aggregates at Sakurajima Volcano, Japan
Authors: Vecino M. C. Diaz , Rossi E. , Freret-Lorgeril V. , Fries A. , Gabellini P. , Lemus J. , Pollastri S. , Poulidis A. P. , Iguchi M. , Bonadonna C. 
Published: February 2022

AbstractAggregation of volcanic ash is known to significantly impact sedimentation from volcanic plumes. The study of particle aggregates during tephra fallout is crucial to increase our understanding of both ash aggregation and sedimentation. In this work, we describe key features of ash aggregates and ash sedimentation associated with eleven Vulcanian explosions at Sakurajima Volcano (Japan) based on state-of-the-art sampling techniques. We identified five types of aggregates of both Particle Cluster (PC) and Accretionary Pellet (AP) categories. In particular, we found that PCs and the first and third type of APs can coexist within the same eruption in rainy conditions. We also found that the aerodynamic properties of aggregates (e.g., terminal velocity and density) depend on their type. In addition, grainsize analysis revealed that characteristics of the grainsize distributions (GSDs) of tephra samples correlate with the typology of the aggregates identified. In fact, bimodal GSDs correlate with the presence of cored clusters (PC3) and liquid pellets (AP3), while unimodal GSDs correlate either with the occurrence of ash clusters (PC1) or with the large particles (coarse ash) coated by fine ash (PC2).
A highly accurate metadynamics-based Dissociation Free Energy method to calculate protein–protein and protein–ligand binding potencies
Authors: Wang Jing , Ishchenko Alexey , Zhang Wei , Razavi Asghar , Langley David 
Published: February 2022

AbstractAlthough seeking to develop a general and accurate binding free energy calculation method for protein–protein and protein–ligand interactions has been a continuous effort for decades, only limited successes have been obtained so far. Here, we report the development of a metadynamics-based procedure that calculates Dissociation Free Energy (DFE) and its application to 19 non-congeneric protein–protein complexes and hundreds of protein–ligand complexes covering eight targets. We achieved very high correlations in comparison to experimental binding free energies for these diverse sets of systems, demonstrating the generality and accuracy of the method. Since structures of most proteins are available owing to the recent success of prediction by artificial intelligence, a general free energy method such as DFE, combined with other methods, can make structure-based drug design a widely viable and reliable solution to develop both traditional small molecule drugs and biologic drugs as well as PROTACS.
A deep learning model to detect novel pore-forming proteins
Authors: Jacob Theju , Kahn Theodore W. 
Published: February 2022

AbstractMany pore-forming proteins originating from pathogenic bacteria are toxic against agricultural pests. They are the key ingredients in several pesticidal products for agricultural use, including transgenic crops. There is an urgent need to identify novel pore-forming proteins to combat development of resistance in pests to existing products, and to develop products that are effective against a broader range of pests. Existing computational methodologies to search for these proteins rely on sequence homology-based approaches. These approaches are based on similarities between protein sequences, and thus are limited in their usefulness for discovering novel proteins. In this paper, we outline a novel deep learning model trained on pore-forming proteins from the public domain. We compare different ways of encoding protein information during training, and contrast it with traditional approaches. We show that our model is capable of identifying known pore formers with no sequence similarity to the proteins used to train the model, and therefore holds promise for identifying novel pore formers.
The ACE genes in Aphelenchoides besseyi isolates and their expression correlation to the fenamiphos treatment
Authors: Hsu Jung-Kai , Weng Chia-Wei , Chen Jeremy J. W. , Chen Peichen Janet 
Published: February 2022

AbstractAphelenchoides besseyi could cause great yield losses of rice and many economically important crops. Acetylcholinesterase (AChE) inhibitors were commonly used to manage plant-parasitic nematodes. However, nematodes resistant to AChE inhibitors have been increasingly reported due to the extensive use of these chemicals. The current study was aimed to establish the correlation between fenamiphos (an AChE-inhibitor) sensitivities and acetylcholinesterase genes (ace) by analyzing two isolates of A. besseyi (designated Rl and HSF), which displayed differential sensitivities to fenamiphos. The concentrations of fenamiphos that led to the death of 50% (LD50) of Rl and HSF were 572.2 ppm and 129.4 ppm, respectively. Three ace genes were cloned from A. besseyi and sequenced. Sequence searching and phylogenic analyses revealed that AChEs of R1 and HSF shared strong similarities with those of various vertebrate and invertebrate species. Molecular docking analysis indicated that AChEs-HSF had much higher affinities to fenamiphos than AChEs-R1. Quantitative reverse transcriptase-PCR analyses revealed that expression of three ace genes were downregulated in HSF but were upregulated in Rl after exposure to 100 ppm fenamiphos for 12 h. The results indicated that the expression of the ace genes was modulated in response to fenamiphos in different nematode strains. An increased expression of the ace genes might contribute to fenamiphos-insensitivity as seen in the Rl isolate.
Effect of single tablet regimen on prescription trends for treatment-naïve patients with HIV/AIDS in Korea
Authors: Oh Kyung Sun , Seo Gi Hyeon , Choi Hee Kyoung , Han Euna 
Published: February 2022

AbstractSingle-tablet regimens (STRs) should be considered for patients with HIV/AIDS to increase medication compliance and improve clinical outcomes. This study compared variations in the prescription trends between STRs and multiple-tablet regimens (MTRs) for treatment-naïve patients with HIV/AIDS after the approval of the new STRs, a proxy indicator for improvement in medication adherence. The medical and pharmacy claim data were retrospectively obtained from the Health Insurance Review and Assessment service, which contains basic information on the patients’ sociodemographic characteristics and treatment information for the entire Korean population. From 2013 to 2018, a total of 6737 patients with HIV/AIDS were included. Most patients were men (92.8%, n = 6251) and insured through the National Health Insurance (95.1%, n = 6410). The mean number of pills in their antiretroviral treatment regimens decreased from 2.8 ± 1.2 in 2013 to 1.2 ± 1.0 in 2018. After the first STR (EVG/c/TDF/FTC) was approved in 2014, prescription transitions from MTR to STR were observed among more than 38% of patients. In 2018, most treatment-naïve patients were prescribed STRs (91.2%). There was a time lag for STR prescription trends in non-metropolitan hospitals compared with those in metropolitan cities. Our data provide a valuable perspective for evaluating ART regimen prescription patterns on a national scale.
Cancer as a risk factor for distress and its interactions with sociodemographic variables in the context of the first wave of the COVID-19 pandemic in Germany
Authors: Ernst Mareike , Beutel Manfred E. , Brähler Elmar 
Published: February 2022

AbstractThe COVID-19 pandemic poses a psychological challenge, especially for individuals with chronic illnesses. The aim of this study was to investigate associations of cancer with distress, including its interplay with further risk and protective factors. We conducted a representative survey of the German population (N = 2503, including N = 144 with a cancer diagnosis) during the first wave of the pandemic. In multiple linear and logistic regression analyses, we tested associations of cancer with depression and anxiety symptoms and suicidal ideation. We also investigated moderating effects of age, gender, income, living situation, marital status, and loneliness. Individuals with cancer were more likely to report anxiety symptoms (φ = .061), suicidal ideation (φ = .050), and loneliness (φ = .044) than other participants. In regression analyses that controlled for sociodemographic differences, cancer was still associated with anxiety symptoms. We also observed interaction effects, indicating that this relation was especially strong in men with cancer and that cancer survivors with a low income were particularly likely to report anxiety symptoms. The findings demonstrate that cancer survivors are a vulnerable group and that factors of different life domains interact in shaping well-being in the population, necessitating comprehensive risk assessment and support offers during the pandemic and beyond.
The high-intensity interval training introduced in physical education lessons decrease systole in high blood pressure adolescents
Authors: Popowczak Marek , Rokita Andrzej , Koźlenia Dawid , Domaradzki Jarosław 
Published: February 2022

AbstractIncreased resting blood pressure (BP) is a risk factor for many health complications. The prevalence of elevated BP is growing among adolescents. There is a need to investigate effective ways of decreasing excessive blood pressure in this age group. The study aim was to determine the effect of 10-weeks High-Intensive Interval Training (HIIT)—Tabata protocol—introduced in physical education (PE) lessons on resting blood pressure in adolescents. The sample included 52 boys aged 16.23 ± 0.33 years body height176.74 ± 6.07 (m), body weight 65.42 ± 12.51 (kg), BMI 20.89 ± 3.53 (kg/m2) and 89 girls aged 16.12 ± 0.42 years, body height 164.38 ± 6.54 (m), body weight 56.71 ± 10.23 (kg), BMI 20.93 ± 3.08 (kg/m2) from secondary school. Based on resting BP, the fractions of boys and girls with normal BP and high BP were identified and divided into experimental (EG) and control (CG) groups. EG completed a 10-weeks HIIT program (three cycles of Tabata protocol) implemented in one PE lesson during a week. The duration of the effort was 14 min. The intensity was at 75–80% of maximal heart rate. Changes in systolic and diastolic BP after the experiment were examined. The results indicated the improvement in SBP in EG with high BP compared to the rest of the groups (average reduction of 12.77 mmHg; p < 0.0001). The EG normotensive had a statistically significant higher reduction of SBP comparing CG normotensive (average decrease of 1.81 mmHG; p = 0.0089). HIIT effectively decreases BP in adolescents. Implementing HIIT in PE lessons in secondary school is recommended to improve BP parameters.
Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma
Authors: Okamoto Isaku , Tsukahara Kiyoaki , Sato Hiroki 
Published: February 2022

AbstractNivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.
Emergent players in renovascular disease
Authors: Barsom Samer H. , Glasstetter Logan M. , Siddiqi Sarosh , Rajagopalan Kamalnath Sankaran , Eirin Alfonso , Lerman Lilach O. 
Published: February 2022

Abstract
Renovascular disease (RVD) remains a common etiology of secondary hypertension. Recent clinical trials revealed unsatisfactory therapeutic outcomes of renal revascularization, leading to extensive investigation to unravel key pathophysiological mechanisms underlying irreversible functional loss and structural damage in the chronically ischemic kidney. Research studies identified complex interactions among various players, including inflammation, fibrosis, mitochondrial injury, cellular senescence, and microvascular remodeling. This interplay resulted in a shift of our understanding of RVD from a mere hemodynamic disorder to a pro-inflammatory and pro-fibrotic pathology strongly influenced by systemic diseases like metabolic syndrome (MetS), hypertension, diabetes mellitus, and hyperlipidemia. Novel diagnostic approaches have been tested for early detection and follow-up of RVD progression, using new imaging techniques and biochemical markers of renal injury and dysfunction. Therapies targeting some of the pathological pathways governing the development of RVD have shown promising results in animal models, and a few have moved from bench to clinical research. This review summarizes evolving understanding in chronic ischemic kidney injury.