bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a specialty endoscopy online platform for continuing medical education for clinical endoscopists during the COVID-19 pandemic
Authors: Li Guofu , Yu Tingting , Zhang Lichao , Du Haiming , Zhang Wei , Hou Senlin 
Published: June 2022

Abstract
Background
To explore the use of a digestive endoscopy professional online platform by domestic endoscopists and its application effect on endoscopists’ continuing medical education, analyse the related problems of continuing medical education using this method, and propose targeted improvement suggestions.

Methods
Based on the “Doctor’s Circle” app, a questionnaire was sent to all members who successfully registered on the Hebei Biliary and Pancreatic Endoscopy Diagnosis and Treatment Alliance online platform. The questionnaire was available for 30 days. The questionnaire survey results were collected and counted for a grouping comparison.

Results
By the deadline, 703 completed questionnaires had been received. After the registered doctors joined the platform, 469 (66.7%) experienced a significant influence on their own endoscopic operation ability level, and 354 (50.3%) felt a significant improvement in their ability to diagnose biliary- and pancreatic-related diseases. The application effect of the platform on members’ continuing medical education was affirmed by the vast majority of registered doctors. The clinical specialty of registered doctors, the length of time they joined the platform, the length of time they participated in the platform activities each time, and whether they played back course videos after the live broadcast of the course on the platform were the main factors affecting the application effect on continuing medical education (P < 0.05). Registered doctors who benefited significantly from the platform used it for 6–12 months, participated in activities for 1–2 hours each time, and often played back course videos.

Conclusion
The new model of continuing medical education based on an online platform breaks through the constraints of traditional models and meets the individualized needs of every medical worker to improve their comprehension level. At present, the global outbreak of COVID-19 makes this learning mode increasingly popular among medical workers. We should constantly improve the organization of the content and methods of continuing medical education courses, make the online platform better serve the majority of medical workers, and effectively improve the comprehension levels of clinicians.
Data quality and associated factors in the health management information system at health centers in Shashogo district, Hadiya zone, southern Ethiopia, 2021
Authors: Getachew Nigusu , Erkalo Bereket , Garedew Muluneh Getachew 
Published: June 2022

Abstract
Background
Poor quality routine data contributes to poor decision-making, inefficient resource allocation, loss of confidence in the health system, and may threaten the validity of impact evaluations. For several reasons in most developing countries, the routine health information systems in those countries are described as ineffective. Hence, the aim of this study is to determine the quality of data and associated factors in the routine health management information system in health centers of Shashogo district, Hadiya Zone.

Methods
A facility-based cross-sectional study was conducted from June 1, 2021, to July 1, 2021, and 300 participants were involved in the study through simple random sampling. The data was collected with a self-administered questionnaire by trained data collectors. After checking its completeness, the data was entered into EPI data version 3.1 and exported to SPSS version 25 for statistical analysis. Finally, variables with p < 0.05 during multivariable analysis were considered significant variables.

Result
A total of 300(100%) participant were included in the interview and HMIS data quality was 83% in Shashogo district health centers. The data quality in terms of accuracy, completeness, and timeliness was 79%, 86%, and 84%, respectively. Conducting supportive supervision [AOR 3.5 (1.4, 8.9)], checking accuracy [AOR 1.3 (1.5, 3.5)], filling registrations [AOR 2.7 (1.44, 7.7)], and confidence level [AOR 1.9 (1.55, 3.35)] were all rated positively found to be factors associated with data quality.

Conclusion
The overall level of data quality in Shashogo district health centers was found to be below the national expectation level. All dimensions of data quality in the district were below 90% in data accuracy, content completeness, and timeliness of data. Conducting supportive supervision, checking accuracy, filling registrations and confidence level were found to be factors associated with data quality. Hence, all stakeholders should give all necessary support to improve data quality in routine health information systems to truly attain the goal of providing good quality data for the decision-making process by considering the identified factors.
A neuromechanical model for Drosophila larval crawling based on physical measurements
Authors: Sun Xiyang , Liu Yingtao , Liu Chang , Mayumi Koichi , Ito Kohzo , Nose Akinao , Kohsaka Hiroshi 
Published: June 2022

Abstract
Background
Animal locomotion requires dynamic interactions between neural circuits, the body (typically muscles), and surrounding environments. While the neural circuitry of movement has been intensively studied, how these outputs are integrated with body mechanics (neuromechanics) is less clear, in part due to the lack of understanding of the biomechanical properties of animal bodies. Here, we propose an integrated neuromechanical model of movement based on physical measurements by taking Drosophila larvae as a model of soft-bodied animals.

Results
We first characterized the kinematics of forward crawling in Drosophila larvae at a segmental and whole-body level. We then characterized the biomechanical parameters of fly larvae, namely the contraction forces generated by neural activity, and passive elastic and viscosity of the larval body using a stress-relaxation test. We established a mathematical neuromechanical model based on the physical measurements described above, obtaining seven kinematic values characterizing crawling locomotion. By optimizing the parameters in the neural circuit, our neuromechanical model succeeded in quantitatively reproducing the kinematics of larval locomotion that were obtained experimentally. This model could reproduce the observation of optogenetic studies reported previously. The model predicted that peristaltic locomotion could be exhibited in a low-friction condition. Analysis of floating larvae provided results consistent with this prediction. Furthermore, the model predicted a significant contribution of intersegmental connections in the central nervous system, which contrasts with a previous study. This hypothesis allowed us to make a testable prediction for the variability in intersegmental connection in sister species of the genus Drosophila.

Conclusions
We generated a neurochemical model based on physical measurement to provide a new foundation to study locomotion in soft-bodied animals and soft robot engineering.
Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation
Authors: Cypris Olivia , Franzen Julia , Frobel Joana , Glück Philipp , Kuo Chao-Chung , Schmitz Stephani , Nüchtern Selina , Zenke Martin , Wagner Wolfgang 
Published: June 2022

Abstract
Background
DNA methylation is involved in the epigenetic regulation of gene expression during developmental processes and is primarily established by the DNA methyltransferase 3A (DNMT3A) and 3B (DNMT3B). DNMT3A is one of the most frequently mutated genes in clonal hematopoiesis and leukemia, indicating that it plays a crucial role for hematopoietic differentiation. However, the functional relevance of Dnmt3a for hematopoietic differentiation and hematological malignancies has mostly been analyzed in mice, with the specific role for human hematopoiesis remaining elusive. In this study, we therefore investigated if DNMT3A is essential for hematopoietic differentiation of human induced pluripotent stem cells (iPSCs).

Results
We generated iPSC lines with knockout of either exon 2, 19, or 23 and analyzed the impact of different DNMT3A exon knockouts on directed differentiation toward mesenchymal and hematopoietic lineages. Exon 19−/− and 23−/− lines displayed an almost entire absence of de novo DNA methylation during mesenchymal and hematopoietic differentiation. Yet, differentiation efficiency was only slightly reduced in exon 19−/− and rather increased in exon 23−/− lines, while there was no significant impact on gene expression in hematopoietic progenitors (iHPCs). Notably, DNMT3A−/− iHPCs recapitulate some DNA methylation patterns of acute myeloid leukemia (AML) with DNMT3A mutations. Furthermore, multicolor genetic barcoding revealed growth advantage of exon 23−/− iHPCs in a syngeneic competitive differentiation assay.

Conclusions
Our results demonstrate that iPSCs with homozygous knockout of different exons of DNMT3A remain capable of mesenchymal and hematopoietic differentiation—and exon 23−/− iHPCs even gained growth advantage—despite loss of almost the entire de novo DNA methylation. Partial recapitulation of DNA methylation patterns of AML with DNMT3A mutations by our DNMT3A knockout iHPCs indicates that our model system can help to elucidate mechanisms of clonal hematopoiesis.
DEPDC1B collaborates with GABRD to regulate ESCC progression
Authors: Yuan Yunfeng , Ping Wei , Zhang Ruijie , Hao Zhipeng , Zhang Ni 
Published: June 2022

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide with a poor prognosis. Given that DEPDC1B plays a key role in multiple cancers, the role of this molecule in ESCC was explored to identify potential targets for ESCC patients.MethodThe expression level of DEPDC1B in ESCC was revealed based on the TCGA database and immunohistochemical experiments on clinical tissues. The correlation between DEPDC1B and survival of ESCC patients was analyzed by Kaplan–Meier method. Small hairpin RNA (shRNA)-mediated silencing of DEPDC1B expression in ESCC cells and performed a series of in vitro and in vivo functional validations.ResultDEPDC1B was overexpressed in ESCC. High expression of DEPDC1B was significantly negatively correlated with overall survival in patients with ESCC. Moreover, knockdown of DEPDC1B inhibited ESCC cell proliferation, clone formation, migration, tumor formation and promoted apoptosis. Furthermore, knockdown of DEPDC1B leaded to significant downregulation of GABRD in ESCC cells. Meanwhile, GABRD expression was upregulated in ESCC, and its silencing can inhibit the proliferation and migration of the tumor cells. Interestingly, there was a protein interaction between DEPDC1B and GABRD. Functionally, GABRD knockdown partially reversed the contribution of DEPDC1B to ESCC progression. In addition, GABRD regulated ESCC progression may depend on PI3K/AKT/mTOR signaling pathway.ConclusionDEPDC1B collaborated with GABRD to regulate ESCC progression, and inhibition of this signaling axis may be a potential therapeutic target for ESCC.
A perspective on the diagnosis of cracked tooth: imaging modalities evolve to AI-based analysis
Authors: Guo Juncheng , Wu Yuyan , Chen Lizhi , Long Shangbin , Chen Daqi , Ouyang Haibing , Zhang Chunliang , Tang Yadong , Wang Wenlong 
Published: June 2022

AbstractDespite numerous clinical trials and pre-clinical developments, the diagnosis of cracked tooth, especially in the early stages, remains a challenge. Cracked tooth syndrome is often accompanied by dramatic painful responses from occlusion and temperature stimulation, which has become one of the leading causes for tooth loss in adults. Current clinical diagnostical approaches for cracked tooth have been widely investigated based on X-rays, optical light, ultrasound wave, etc. Advances in artificial intelligence (AI) development have unlocked the possibility of detecting the crack in a more intellectual and automotive way. This may lead to the possibility of further enhancement of the diagnostic accuracy for cracked tooth disease. In this review, various medical imaging technologies for diagnosing cracked tooth are overviewed. In particular, the imaging modality, effect and the advantages of each diagnostic technique are discussed. What’s more, AI-based crack detection and classification methods, especially the convolutional neural network (CNN)-based algorithms, including image classification (AlexNet), object detection (YOLO, Faster-RCNN), semantic segmentation (U-Net, Segnet) are comprehensively reviewed. Finally, the future perspectives and challenges in the diagnosis of the cracked tooth are lighted.
Biomimetic and temporal-controlled nanocarriers with ileum transporter targeting for achieving oral administration of chemotherapeutic drugs
Authors: Liu Wei , Han Ying , Xin Xin , Chen Liqing , Liu Yanhong , Liu Chao , Zhang Xintong , Jin Mingji , Jin Jingzhe , Gao Zhonggao , Huang Wei 
Published: June 2022

Abstract
Background
Oral chemotherapy is preferred for patients with cancer owing to its multiple advantages, including convenience, better patient compliance, and improved safety. Nevertheless, various physical barriers exist in this route that hamper the development of oral chemotherapeutic formulations, including destruction of drugs in the gastrointestinal tract (GIT), low permeability in enterocytes, and short residence time in the intestine. To overcome these limitations, it is necessary to design an efficient oral drug delivery system with high efficacy and improved safety.

Results
Herein, we designed novel glycocholic acid (GCA)-functionalized double layer nanoparticles (GCA-NPs), which can act via an endogenous pathway and in a temporally controlled manner in the intestine, to enhance the oral bioavailability of hydrophobic chemotherapeutic drugs such as paclitaxel (PTX). GCA-NPs were composed of quercetin (Qu)-modified liposomes (QL) coated with GCA-chitosan oligosaccharide conjugate (GCOS). The GCA-NPs thus prepared showed prolonged intestinal retention time and good GIT stability due to the presence of chitosan oligosaccharide (COS) and enhanced active transportation via intestinal apical sodium-dependent bile acid transporter (ASBT) due to the presence of GCA. GCA-NPs also efficiently inhibited intestinal P-gp induced by Qu. PTX-loaded GCA-NPs (PTX@GCA-NPs) had a particle size of 84 nm and an entrapment efficiency of 98% with good stability. As a result, the oral bioavailability of PTX was increased 19-fold compared to that of oral Taxol® at the same dose. Oral PTX@GCA-NPs displayed superior antitumor efficacy and better safety than Taxol® when administered intravenously.

Conclusions
Our novel drug delivery system showed remarkable efficacy in overcoming multiple limitations and is a promising carrier for oral delivery of multiple drugs, which addresses several challenges in oral delivery in the clinical context.

Graphical Abstract
NEK2 promotes the migration and proliferation of ESCC via stabilization of YAP1 by phosphorylation at Thr-143
Authors: Su Wei , Hu Hao , Ding Qiurong , Wang Min , Zhu Yan , Zhang Zhaochao , Geng Zihan , Lin Shengli , Zhou Pinghong 
Published: June 2022

Abstract
Background
Esophageal Squamous Cell Carcinoma (ESCC) was characterized as a regional-prevalent and aggressive tumor with high morbidity and mortality. NIMA-related kinase 2 (NEK2) is an interesting oncogene, the alteration of which leads to patients-beneficial outcomes. We aimed to explore the role of NEK2 in ESCC and excavate its mechanism.

Methods
RNA-seq data were downloaded from TCGA and GEO and analyzed by R software. The protein levels were detected by immunohistochemistry (IHC) or western blot (WB), and mRNA expression was detected by qRT-PCR. The in vitro role of proliferation and migration was detected by Transwell migration assay and by colony formation assay, respectively. The in vivo roles were explored using a subcutaneous xenograft tumor model, where immunofluorescence (IF) and IHC were employed to investigate expression and localization. The interaction between proteins was detected by immunoprecipitation. The stability of proteins was measured by WB in the presence of cycloheximide.

Results
A higher level of NEK2 was found in ESCC than normal esophageal epithelia in GEO, TCGA, and tissue microarray, which was associated with worse prognoses. The NEK2 knockdown impaired the proliferation and migration of ESCC, which also downregulated YAP1 and EMT markers like N-cadherin and Vimentin in vitro. On the contrary, NEK2 overexpression enhanced the migration of ESCC and elevated the levels of YAP1, N-cadherin, and Vimentin. Additionally, the overexpression of YAP1 in NEK2 knocked down ESCCs partly rescued the corresponding decrease in migration. The knockdown of NEK2 played an anti-tumor role in vivo and was accompanied by a lower level and nucleus shuffling of YAP1. In mechanism, NEK2 interacted with YAP1 and increased the stability of both endogenous and exogenous YAP1 by preventing ubiquitination. Moreover, the computer-predicted phosphorylation site of YAP1, Thr-143, reduced the ubiquitination of HA-YAP1, strengthened its stability, and thus influenced the migration in vitro.

Conclusions
NEK2 is a prognostic oncogene highly expressed in ESCC and promotes the progression of ESCC in vitro and in vivo. Mechanistically, NEK2-mediated phosphorylation of YAP1 at Thr-143 protects it from proteasome degradation and might serve as a promising therapeutic target in ESCC.
Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study
Authors: Van Tassell Benjamin , Mihalick Virginia , Thomas Georgia , Marawan Amr , Talasaz Azita H. , Lu Juan , Kang Le , Ladd Amy , Damonte Juan Ignacio , Dixon Dave L. , Markley Roshanak , Turlington Jeremy , Federmann Emily , Del Buono Marco Giuseppe , Biondi-Zoccai Giuseppe , Canada Justin M. , Arena Ross , Abbate Antonio 
Published: June 2022

Abstract
Background
Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF.

Method
We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes.

Discussion
The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF.
Trial registration: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.
Neoadjuvant immunotherapy across cancers: meeting report from the Immunotherapy Bridge—December 1st–2nd, 2021
Authors: Burton Elizabeth M. , Amaria Rodabe N. , Cascone Tina , Chalabi Myriam , Gross Neil D. , Mittendorf Elizabeth A. , Scolyer Richard A. , Sharma Padmanee , Ascierto Paolo A. 
Published: June 2022

AbstractAfter the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply interrogate longitudinal tissue in order to gain translatable, pan-malignancy insights into response and mechanisms of resistance to immunotherapy. Neoadjuvant immunotherapy across cancers was a focus of discussion at the virtual Immunotherapy Bridge meeting (December 1–2, 2021). Clinical, biomarker, and pathologic insights from prostate, breast, colon, and non-small-cell lung cancers, melanoma and non-melanoma skin cancers were discussed and are summarized in this report.
Microglial amyloid beta clearance is driven by PIEZO1 channels
Authors: Jäntti Henna , Sitnikova Valeriia , Ishchenko Yevheniia , Shakirzyanova Anastasia , Giudice Luca , Ugidos Irene F. , Gómez-Budia Mireia , Korvenlaita Nea , Ohtonen Sohvi , Belaya Irina , Fazaludeen Feroze , Mikhailov Nikita , Gotkiewicz Maria , Ketola Kirsi , Lehtonen Šárka , Koistinaho Jari , Kanninen Katja M. , Hernández Damian , Pébay Alice , Giugno Rosalba , Korhonen Paula , Giniatullin Rashid , Malm Tarja 
Published: June 2022

Abstract
Background
Microglia are the endogenous immune cells of the brain and act as sensors of pathology to maintain brain homeostasis and eliminate potential threats. In Alzheimer's disease (AD), toxic amyloid beta (Aβ) accumulates in the brain and forms stiff plaques. In late-onset AD accounting for 95% of all cases, this is thought to be due to reduced clearance of Aβ. Human genome-wide association studies and animal models suggest that reduced clearance results from aberrant function of microglia. While the impact of neurochemical pathways on microglia had been broadly studied, mechanical receptors regulating microglial functions remain largely unexplored.

Methods
Here we showed that a mechanotransduction ion channel, PIEZO1, is expressed and functional in human and mouse microglia. We used a small molecule agonist, Yoda1, to study how activation of PIEZO1 affects AD-related functions in human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGL) under controlled laboratory experiments. Cell survival, metabolism, phagocytosis and lysosomal activity were assessed using real-time functional assays. To evaluate the effect of activation of PIEZO1 in vivo, 5-month-old 5xFAD male mice were infused daily with Yoda1 for two weeks through intracranial cannulas. Microglial Iba1 expression and Aβ pathology were quantified with immunohistochemistry and confocal microscopy. Published human and mouse AD datasets were used for in-depth analysis of PIEZO1 gene expression and related pathways in microglial subpopulations.

Results
We show that PIEZO1 orchestrates Aβ clearance by enhancing microglial survival, phagocytosis, and lysosomal activity. Aβ inhibited PIEZO1-mediated calcium transients, whereas activation of PIEZO1 with a selective agonist, Yoda1, improved microglial phagocytosis resulting in Aβ clearance both in human and mouse models of AD. Moreover, PIEZO1 expression was associated with a unique microglial transcriptional phenotype in AD as indicated by assessment of cellular metabolism, and human and mouse single-cell datasets.

Conclusion
These results indicate that the compromised function of microglia in AD could be improved by controlled activation of PIEZO1 channels resulting in alleviated Aβ burden. Pharmacological regulation of these mechanoreceptors in microglia could represent a novel therapeutic paradigm for AD.