bluuebunny/crossref_metadata_2025_split huggingface dataset:
GeneralizedDTA: combining pre-training and multi-task learning to predict drug-target binding affinity for unknown drug discovery
Authors: Lin Shaofu , Shi Chengyu , Chen Jianhui 
Published: September 2022

Abstract
Background
Accurately predicting drug-target binding affinity (DTA) in silico plays an important role in drug discovery. Most of the computational methods developed for predicting DTA use machine learning models, especially deep neural networks, and depend on large-scale labelled data. However, it is difficult to learn enough feature representation from tens of millions of compounds and hundreds of thousands of proteins only based on relatively limited labelled drug-target data. There are a large number of unknown drugs, which never appear in the labelled drug-target data. This is a kind of out-of-distribution problems in bio-medicine. Some recent studies adopted self-supervised pre-training tasks to learn structural information of amino acid sequences for enhancing the feature representation of proteins. However, the task gap between pre-training and DTA prediction brings the catastrophic forgetting problem, which hinders the full application of feature representation in DTA prediction and seriously affects the generalization capability of models for unknown drug discovery.

Results
To address these problems, we propose the GeneralizedDTA, which is a new DTA prediction model oriented to unknown drug discovery, by combining pre-training and multi-task learning. We introduce self-supervised protein and drug pre-training tasks to learn richer structural information from amino acid sequences of proteins and molecular graphs of drug compounds, in order to alleviate the problem of high variance caused by encoding based on deep neural networks and accelerate the convergence of prediction model on small-scale labelled data. We also develop a multi-task learning framework with a dual adaptation mechanism to narrow the task gap between pre-training and prediction for preventing overfitting and improving the generalization capability of DTA prediction model on unknown drug discovery. To validate the effectiveness of our model, we construct an unknown drug data set to simulate the scenario of unknown drug discovery. Compared with existing DTA prediction models, the experimental results show that our model has the higher generalization capability in the DTA prediction of unknown drugs.

Conclusions
The advantages of our model are mainly attributed to two kinds of pre-training tasks and the multi-task learning framework, which can learn richer structural information of proteins and drugs from large-scale unlabeled data, and then effectively integrate it into the downstream prediction task for obtaining a high-quality DTA prediction in unknown drug discovery.
Characterization of the CqCAMTA gene family reveals the role of CqCAMTA03 in drought tolerance
Authors: Zhu Xiaolin , Wang Baoqiang , Wei Xiaohong , Du Xuefeng 
Published: September 2022

Abstract
Background
Calmodulin-binding transcription activators (CAMTAs) are relatively conserved calmodulin-binding transcription factors widely found in eukaryotes and play important roles in plant growth and stress response. CAMTA transcription factors have been identified in several plant species, but the family members and functions have not yet been identified and analyzed in quinoa.

Results
In this study, we identified seven CAMTA genes across the whole quinoa genome and analyzed the expression patterns of CqCAMTAs in root and leaf tissues. Gene structure, protein domain, and phylogenetic analyses showed that the quinoa CAMTAs were structurally similar and clustered into the same three major groups as other plant CAMTAs. A large number of stress response-related cis-elements existed in the 2 kb promoter region upstream of the transcription start site of the CqCAMTA genes. qRT-PCR indicated that CqCAMTA genes were expressed differentially under PEG treatments in leaves, and responded to drought stress in leaves and roots. In particular, the CqCAMTA03 gene strongly responded to drought. The transient expression of CqCAMTA03-GFP fusion protein in the tobacco leaf showed that CqCAMTA03 was localized in the nucleus. In addition, transgenic Arabidopsis lines exhibited higher concentration levels of the antioxidant enzymes measured, including POD, SOD, and CAT, under drought conditions with very low levels of H2O2 and MDA. Moreover, relative water content and the degree of stomatal opening showed that the transgenic Arabidopsis lines were more tolerant of both stress factors as compared to their wild types.

Conclusion
In this study, the structures and functions of the CAMTA family in quinoa were systematically explored. Many CAMTAs may play vital roles in the regulation of organ development, growth, and responses to drought stress. The results of the present study serve as a basis for future functional studies on the quinoa CAMTA family.
A participatory practice study for the improvement of sub-regional health vulnerabilities: a qualitative study
Authors: Pyo Jeehee , Lee Haneul , Kang Yangwha , Oh Jaewook , Ock Minsu 
Published: September 2022

Abstract
Background
This study aimed to explore the experiences of the residents of Samho-dong with the health environment in the local community, and their in-depth opinions on health promotion using a photovoice methodology. Alternatives to improve health among the residents of Samho-dong were also discussed with the local residents, with the aim of translating suggestions from the discussion into practice.

Methods
A total of 195 photographs taken by the 15 participants over the course of 7 weeks were collected, along with 96 photovoice activity logs and transcription data from 5 rounds of focus group discussions. The photovoice activity logs consisted of the photographer’s name, the dates photos were taken, and a series of responses to the following SHOWeD questions: “What do you SEE here?”, “What is really HAPPENING?”, “How does this situation or scenario affect OUR lives/health?”, “WHY does this problem or strength Exist?”, “What can we DO about it?”. Direct content analysis was used for analysis.

Results
The analysis yielded a total of 247 semantic units, which were categorized into the themes, “the good, but insufficiency, living environment in Samho-dong,” “the health environment in Samho-dong needs improvement,” “small efforts to improve Samho-dong,” and “points of improvement for a better Samho-dong”. Samho-dong was found to have a poorer walking and transportation infrastructure than other regions, even though it was a town with a large elderly population. The dark streets in the residential complex made participants hesitate to engage in afternoon activities, and the insufficient traffic environment made it difficult to live a natural daily life by solving food, clothing, and shelter. Participants have made various attempts to solve areas that need improvement in the Samho-dong, which has led to actual improvement. It was analyzed that in order to make Samho-dong better, it was necessary to improve the perception of residents in Samho-dong and cooperate with the local community.

Conclusions
This study was significant in that it enabled the in-depth exploration and identification of areas of improvement from the participants’ perception of their health environment, considering that as residents, they are the direct stakeholders of the community health environment.
Mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy and its initial clinical application
Authors: Hong Yang , Wang Huanrui , Xu Qingquan , Chen Liang , Huang Xiaobo , Xiong Liulin 
Published: September 2022

Abstract
Background
To assess the outcome of the mini-track, mini-nephroscopy, mini ultrasonic probe percutaneous nephrolithotomy for upper ureteral and kidney stones.

Methods
We collected data of 53 patients (55 kidney units) who underwent mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy between September 2020 and March 2021. The study included single and upper ureteral stones from 12 kidneys, multiple stones from 28 kidneys, and staghorn stones from 15 kidneys.

Results
The mean operative duration was 50.6 min, ranging from 15 to 200 min, whereas the mean lithotripsy and stone removal time was 17.2 min (3–45 min). Moreover, the mean postoperative length of stay was 4.0 days (1–7 days). Besides, the stone-free rate (SFR) of discharge was 89.1% (49/55). The mean hemoglobin drop was 15.3 mg/dL, ranging 1–32 mg/dL. Out of the total cases, only 4 of them displayed minor complications. The outcomes of < 40 mm versus ≥ 40 mm calculi were compared by performing subgroup analysis. The results demonstrated a longer operation duration (65.2 vs. 40.2 min), higher complication rate (13.0% vs. 3.3%), and lower SFR in the ≥ 40 mm calculi subgroup.

Conclusions
In summary, mini-track, mini-nephroscopy, mini-ultrasonic probe percutaneous nephrolithotomy is an effective and safe method to treat patients with upper ureteral and kidney calculi. This is especially significant for the stone size of 20–40 mm, demonstrating excellent SFR and a lower complication rate.
The impact of a 12-hour educational program on nurses’ knowledge and attitudes regarding pain management: a quasi-experimental study
Authors: Innab Adnan , Alammar Kamila , Alqahtani Naji , Aldawood Fatima , Kerari Ali , Alenezi Ali 
Published: September 2022

AbstractBackgroundProper pain assessment is fundamental to effective pain management. Training nursing staff is critical for improvingpain assessment competence and patient clinical outcomes.However, there is a dearth of research examining interventions that can enhance nurses’ knowledge and attitudes toward pain management, especially in Saudi Arabia. Thus, this study aimed to evaluate the effectiveness of a structured education program on nurses’ knowledge and attitudes towards pain management.MethodsA quasi-experimental design was used. The study sample included 124 registered nurses working in intensive care or inpatient units in Saudi Arabia. Data were collected between March and September 2021 using a knowledge and attitudes survey regarding pain, satisfaction with and self-confidence in learning, and the learning self-efficacy scale for clinical skills.ResultsNurses showed moderate levels of knowledge and attitudes regarding pain before (M = 20.3, SD = 4.80) pain management education, which were significantly higher after the intervention (M = 22.2, SD = 5.09,t = 2.87,p < .01). Before the intervention, nurses with a baccalaureate degree had more knowledge and better attitudes regarding pain management than diploma nurses (t = 3.06,p < .01). However, there was no significant difference between the two groups after the intervention (p > .05), indicating that the education was effective in enhancing nurses’ knowledge and attitudes, regardless of nursing education level. Nurses in this study had high mean scores for self-confidence in learning (M = 35.6, SD = 4.68, range = 18–40), self-learning efficacy (M = 52.9, SD = 7.70, range = 25–60), and satisfaction with learning (M = 22.2, SD = 3.24, range: 10–25).ConclusionRegular pain education programs can improve nurses’ knowledge and attitudes. Increasing the breadth and depth of educational courses, alongside appropriate training, competency-based assessment, and pain education programs, is also recommended. Future research should consider the subjectivity and individualized nature of nursing by including patient satisfaction surveys to measure the improvement in nurses’ knowledge and attitudes from the patient perspective.
Lipophorin receptors regulate mushroom body development and complex behaviors in Drosophila
Authors: Rojo-Cortés Francisca , Fuenzalida-Uribe Nicolás , Tapia-Valladares Victoria , Roa Candy B. , Hidalgo Sergio , González-Ramírez María-Constanza , Oliva Carlos , Campusano Jorge M. , Marzolo María-Paz 
Published: September 2022

Abstract
Background
Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain.

Results
We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the mushroom bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurite arborization. This effect depends on LpRs and Dab, the Drosophila ortholog of the Reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events.

Conclusions
These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.
Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling
Authors: Lee Seul-Gee , Kim Darae , Lee Jung-Jae , Lee Hyun-Ju , Moon Ro-kyung , Lee Yong-Joon , Lee Seung-Jun , Lee Oh-Hyun , Kim Choongki , Oh Jaewon , Lee Chan Joo , Lee Yong-ho , Park Seil , Jeon Ok-Hee , Choi Donghoon , Hong Geu-Ru , Kim Jung-Sun 
Published: September 2022

Abstract
Background
Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function.

Methods
A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis).

Results
The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group.

Conclusions
Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.
TMBur: a distributable tumor mutation burden approach for whole genome sequencing
Authors: Titmuss Emma , Corbett Richard D. , Davidson Scott , Abbasi Sanna , Williamson Laura M. , Pleasance Erin D. , Shlien Adam , Renouf Daniel J. , Jones Steven J. M. , Laskin Janessa , Marra Marco A. 
Published: September 2022

Abstract
Background
Tumor mutation burden (TMB) is a key characteristic used in a tumor-type agnostic context to inform the use of immune checkpoint inhibitors (ICI). Accurate and consistent measurement of TMB is crucial as it can significantly impact patient selection for therapy and clinical trials, with a threshold of 10 mutations/Mb commonly used as an inclusion criterion. Studies have shown that the most significant contributor to variability in mutation counts in whole genome sequence (WGS) data is differences in analysis methods, even more than differences in extraction or library construction methods. Therefore, tools for improving consistency in whole genome TMB estimation are of clinical importance.

Methods
We developed a distributable TMB analysis suite, TMBur, to address the need for genomic TMB estimate consistency in projects that span jurisdictions. TMBur is implemented in Nextflow and performs all analysis steps to generate TMB estimates directly from fastq files, incorporating somatic variant calling with Manta, Strelka2, and Mutect2, and microsatellite instability profiling with MSISensor. These tools are provided in a Singularity container downloaded by the workflow at runtime, allowing the entire workflow to be run identically on most computing platforms. To test the reproducibility of TMBur TMB estimates, we performed replicate runs on WGS data derived from the COLO829 and COLO829BL cell lines at multiple research centres. The clinical value of derived TMB estimates was then evaluated using a cohort of 90 patients with advanced, metastatic cancer that received ICIs following WGS analysis. Patients were split into groups based on a threshold of 10/Mb, and time to progression from initiation of ICIs was examined using Kaplan–Meier and cox-proportional hazards analyses.

Results
TMBur produced identical TMB estimates across replicates and at multiple analysis centres. The clinical utility of TMBur-derived TMB estimates were validated, with a genomic TMB ≥ 10/Mb demonstrating improved time to progression, even after correcting for differences in tumor type (HR = 0.39, p = 0.012).

Conclusions
TMBur, a shareable workflow, generates consistent whole genome derived TMB estimates predictive of response to ICIs across multiple analysis centres. Reproducible TMB estimates from this approach can improve collaboration and ensure equitable treatment and clinical trial access spanning jurisdictions.
Human PMSCs-derived small extracellular vesicles alleviate neuropathic pain through miR-26a-5p/Wnt5a in SNI mice model
Authors: Lu Yitian , Zhang Jintao , Zeng Fanning , Wang Peng , Guo Xiangna , Wang Haitao , Qin Zaisheng , Tao Tao 
Published: September 2022

Abstract
Background
Mesenchymal stem cell (MSCs)-derived small Extracellular Vesicles (sEVs) are considered as a new cell-free therapy for pain caused by nerve injury, but whether human placental mesenchymal stem cell-derived sEVs relieve pain in sciatic nerve injury and its possible mechanism are still unclear. In this study, we investigated the roles of hPMSCs-derived sEVs and related mechanisms in neuropathic pain.

Methods
The spared nerve injury (SNI) mouse model was employed. Intrathecal injection of sEVs or miR-26a-5p agomir was performed on the seventh day of modeling, to study its anti-nociceptive effect. sEVs’ miRNA sequencing (miRNA-Seq) and bioinformatics analysis were performed to study the downstream mechanisms of miRNAs. RT-qPCR, protein assay and immunofluorescence were used for further validation.

Results
A single intrathecal injection of sEVs durably reversed mechanical hypersensitivity in the left hind paw of mice with partial sciatic nerve ligation. Immunofluorescence studies found that PKH26-labeled sEVs were visible in neurons and microglia in the dorsal horn of the ipsilateral L4/5 spinal cord and more enriched in the ipsilateral. According to miRNA-seq results, we found that intrathecal injection of miR-26a-5p agomir, the second high counts microRNA in hPMSCs derived sEVs, significantly suppressed neuropathic pain and neuroinflammation in SNI mice. Bioinformatics analysis and dual-luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR-26a-5p. The results showed that overexpression of miR-26a-5p in vivo could significantly reduce the expression level of Wnt5a. In addition, Foxy5, a mimetic peptide of Wnt5a, can significantly reverse the inhibitory effect of miR-26a-5p on neuroinflammation and neuropathic pain, and at the same time, miR-26a-5p can rescue the effect of Foxy5 by overexpression.

Conclusions
We reported that hPMSCs derived sEVs as a promising therapy for nerve injury induced neuropathic pain. In addition, we showed that the miR-26a-5p in the sEVs regulated Wnt5a/Ryk/CaMKII/NFAT partly take part in the analgesia through anti-neuroinflammation, which suggests an alleviating pain effect through non-canonical Wnt signaling pathway in neuropathic pain model in vivo.
COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction
Authors: Chen Yanting , Yang Wenren , Chen Feng , Cui Lili 
Published: September 2022

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. Although COVID-19 was initially described as a respiratory disease, there is growing evidence that SARS-CoV-2 is able to invade the brains of COVID-19 patients and cause cognitive impairment. It has been reported that SARS-CoV-2 may have invasive effects on a variety of cranial nerves, including the olfactory, trigeminal, optic, and vagus nerves, and may spread to other brain regions via infected nerve endings, retrograde transport, and transsynaptic transmission. In addition, the blood–brain barrier (BBB), composed of neurovascular units (NVUs) lining the brain microvasculature, acts as a physical barrier between nerve cells and circulating cells of the immune system and is able to regulate the transfer of substances between the blood and brain parenchyma. Therefore, the BBB may be an important structure for the direct and indirect interaction of SARS-CoV-2 with the brain via the blood circulation. In this review, we assessed the potential involvement of neuroinvasion under the SARS-CoV-2 infection, and the potential impact of BBB disorder under SARS-CoV-2 infection on cognitive impairment.