bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal immune atlas of the first clinical-grade,
gene-edited pig-to-human kidney xenotransplant
Authors: Porrett Paige , Cheung Matthew , Asiimwe Rebecca , Erman Elise , Fucile Christopher , Liu Shanrun , Sun Chiao-Wang , Hanumanthu Vidya , Pal Harish , Wright Emma , Ghajar-Rahimi Gelare , Epstein Daniel , Orandi Babak , Kumar Vineeta , Anderson Douglas , Greene Morgan , Bell Markayla , Yates Stefani , Moore Kyle , Lafontaine Jennifer , Killian John , Baker Gavin , Perry Jackson , Reed Rhiannon , Little Shawn , Rosenberg Alexander , George James , Locke Jayme
Published: January 2023

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.
Blocking the CXCL1-CXCR2 axis enhances the effects of doxorubicin in HCC by remodeling the tumor microenvironment via the NF-κB/IL-1𝛽/CXCL1 signaling pathway
Authors: Zhao Huiyong , Wei Sheng , Zhou Dachen , Liu Yongfan , Guo Zicheng , Fang Chuibao , Pang Xiaoxi , Li Fei , Hou Hui , Cui Xiao
Published: January 2023

Inflammation is a core mechanism for oncogenesis. Chemokines act as important inflammation mediators in chronic inflammation and the tumor inflammatory response. However, limited information is known about chemokines in hepatocellular carcinoma (HCC), a disease that is almost entirely derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. This protumor feature was confirmed in clinical samples of human HCC. CXCL1 enhances tumorigenesis in the hepatic inflammatory microenvironment directly through tumor cells and indirectly through recruitment of macrophages. Increasing the number of macrophages in the tumor microenvironment (TME) promoted tumor cell Epithelial-mesenchymal transition (EMT) capacity and significantly elevated CXCL1 levels in the TME partly through NF-κB/IL-1𝛽 activation. To investigate the potential therapeutic value of CXCL1 in HCC with inflammatory background, blocking CXCL1 and blocking CXCL1 combined with the chemotherapy agent doxorubicin (DOX), which aimes to reshape the TME, were administered. It has been shown that blocking CXCL1-CXCR2 inhibits tumor progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to have a synchronous effect in HCC by reducing pro-tumor macrophages in the TME and suppressing tumor cell progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.
Participatory landscape sustainability assessment: where do we stand? A systematic literature review
Authors: Moreau Clémence , Blanco Julien , Randriamalala Josoa , Laques Anne-Elisabeth , Carrière Stéphanie M.
Published: January 2023

Context

In line with interdisciplinary and transdisciplinary principles of Sustainability Science, Participatory Landscape Sustainability Assessment (PLSA) studies are developing. These studies make the paradoxical promises to standardize observations to obtain robust and comparable data, while including a diversity of case studies, stakeholders and viewpoints.

Objective

The purpose of this paper is to highlight the diversity of perspectives on PLSA, arguing that the lack of coherent framing and a poor substantive theorization can limit the development of PLSA studies.

Methods

We conducted a systematic literature review on a corpus of 425 publications by combining bibliographic mapping on the full corpus and a content analysis on a sub-corpus of 138 full-texts.

Results

Our results showed that (i) this field is at the crossroads between ecology, landscape planning and sociocultural approaches, (ii) indicators combine on average 4.7 categories of sustainability, but are most applied at a local level and in a snapshot perspective, (iii) stakeholders are rarely involved in the choice of indicators (28.9% of studies) or in the assessment design (7.2%), and are mostly only asked to populate pre-identified indicators (63.9%), and (iv) viewpoint diversity is taken into consideration mainly by using indicators (67.3%) rather than by promoting deliberation (39.8%). In sum, we distinguish the participation-oriented approach, the contributive approach (anchored in positivism) and the collaborative approach (anchored in constructivism).

Conclusion

We advocate that future studies should be more explicit on the perspective they adopt in order to improve consistence between PLSA objectives, methods, and theoretical anchorages. This clarification might ultimately avoid confusion about the different regimes of participation and their respective contributions to Landscape Sustainability Science.
The protocol of DECO-MOM: a clinical trial testing the effectiveness of a mobile application for an environmental health intervention among pregnant women
Authors: Kim Hyun Kyoung
Published: January 2023

Background: Environmental toxins are particularly harmful to pregnant women and their fetuses due to the long-term effects of these toxins on children after birth. Environmental health behaviors can prevent and protect mothers and their babies’ environmental health.
Methods/Design: This study presents a protocol to examine the effect of a mobile application named “DECO-MOM” (DEep Ecology-MOM) for pregnant women. This application contains content related to environmental perceptions and behaviors according to the revised protection motivation theory. The mobile intervention will be implemented for 4 weeks for 40 pregnant women with a gestational age in the first trimester. As the control group, 40 pregnant women will be recruited at public healthcare centers in Chuncheon and Gongju cities in South Korea. The hypothesis is that the experimental group will have higher scores for environmental perceptions and behaviors than the control group. An online survey administered before and after the intervention will contain outcome parameters including depression, stress, quality of life, e-learning satisfaction, environmental perceptions, and environmental behaviors.
Discussion: This study will elaborate a guide for an intervention to enhance the effects of the mobile application on strengthening environmental health perceptions, behaviors, e-learning satisfaction, and quality of life and curtailing depression and stress among pregnant women.
Trial registration: Trial registration Number: KCT0007725
Comparison of statistical methods used to meta-analyse results from interrupted time series studies: an empirical study
Authors: Korevaar Elizabeth , Turner Simon L , Forbes Andrew B , Karahalios Amalia , Taljaard Monica , McKenzie Joanne E
Published: January 2023

Background
The Interrupted Time Series (ITS) is a robust design for evaluating public health and policy interventions or exposures when randomisation is infeasible. Several statistical methods are available for the analysis and meta-analysis of ITS studies. We sought to empirically compare available methods when applied to real-world ITS data.
Methods
We sourced ITS data from published meta-analyses to create an online data repository. Each dataset was re-analysed using two ITS estimation methods. The level- and slope-change effect estimates (and standard errors) were calculated and combined using fixed-effect and four random-effects meta-analysis methods. We examined differences in meta-analytic level- and slope-change estimates, their 95% confidence intervals, p-values, and estimates of heterogeneity across the statistical methods.
Results
Of 40 eligible meta-analyses, data from 17 meta-analyses including 283 ITS studies were obtained and analysed. We found that on average, the meta-analytic effect estimates, their standard errors and between-study variances were not sensitive to meta-analysis method choice, irrespective of the ITS analysis method. However, confidence interval widths and p-values for the meta-analytic effect estimates varied depending on the choice of confidence interval method and ITS analysis method.
Conclusions
The meta-analysis effect estimates, their standard errors and between-study variance estimates were minimally impacted by ITS analysis and meta-analysis method choice. However, the confidence interval widths and p-values could vary according to the statistical method, which may impact interpretations and conclusions of a meta-analysis. This empirical study, in conjunction with evidence from numerical simulation, allows for a more complete understanding of which methods should be used in different scenarios.
Characterization of patients with acute idiopathic pancreatitis using an administrative claims database in Japan
Authors: Imura Miki , Katada Jun
Published: January 2023

Background: Hypertriglyceridemia is one of the causes of idiopathic acute pancreatitis and atherosclerotic cardiovascular diseases. Most guidelines define fasting triglyceride levels greater than 150 mg/dL as hypertriglyceridemia; however the triglyceride level of patients with acute pancreatitis is not clear, nor is it known how much triglyceride level reduction can reduce cardiovascular events. This study aimed to characterize patients with acute idiopathic pancreatitis and especially focused on triglyceride levels, patient characteristics, pharmaceutical treatment, and prognosis.
Methods: In this retrospective analysis of an administrative claims database, patients hospitalized due to acute pancreatitis were selected, and idiopathic pancreatitis was identified using specific pre-determined ICD-10 codes. A Wilcoxon rank sum test was performed for the comparison of the means of the two cohorts, and Fisher's exact test was used to compare proportions between the cohorts. The comparison between idiopathic and non-idiopathic pancreatitis was performed using a log-rank test.
Results: Between April 1, 2008, and July 31, 2021, 44,005 patients were hospitalized for the treatment of pancreatitis; among them, 30,814 cases (70.0%) were categorized as idiopathic. The mean age of patients with idiopathic pancreatitis was 62.7±18.8 years, 68.8% of the patients were male, and the mean triglyceride levels within 3 days after hospitalization were 293.1±816.6 mg/dL. Rehospitalization due to recurrent pancreatitis and the incidence rates of cardiovascular events were 39.5% and 3.3%, respectively.
Conclusions: Patients with idiopathic pancreatitis had elevated triglyceride levels at admission. Even if triglyceride levels are not extremely high, hypertriglyceridemia might cause idiopathic pancreatitis. Therefore, there is a need for intervention in terms of triglyceride levels in patients with hypertriglyceridemia, not only to prevent cardiovascular disease, but also to prevent the onset and recurrence of acute pancreatitis.
Trial registration: Not applicable
Radio-immunotherapy by 188Re-antiCD20 and stable silencing of IGF-IR in Raji cells, new insight in treatment of lymphoma
Authors: Nasehi Leila , zadeh Baharak Abdolhossein , Rahimi Hossein , Ghahremani Mohammad hossein
Published: January 2023

Hematologic malignancies such as Non-Hodgkin’s lymphoma (NHL), remain a serious threat to human health due to their heterogeneity and complexity. The inherent genetic heterogeneity of NHL B-cells, as well as the instability of lymphoma cancer cells, results in drug resistance in lymphoma, posing a fundamental challenge to NHL treatment. Burkitt lymphoma (including Raji cell line) is a rare and highly aggressive form of B-cell NHL. Since overexpression of the insulin-like growth factor-1 receptor (IGF-1R) playing a prominent role in the development and transformation of different malignancies, especially lymphoma malignancies, we have explored the role of IGF-1R in the development and progression of Raji cells and the stable silencing of IGF-1R by lentivirus-mediated RNA interference (RNAi). We have shown that stable silencing of the IGF-1R gene in Raji cells using lentivirus-mediated-RNAi have resulted in a significant reduction in Raji cell proliferation. Moreover, the results of the cell viability assays indicated high resistance of Raji cells to rituximab. However, coupling rituximab to 188Re potentially leads to specific targeting of Raji cells by 188Re, improving the therapeutic efficacy. We found that the synergistic effect of using a gene therapy-based system in combination with radioimmunotherapy could be a promising therapeutic strategy in the future. To the best of our knowledge, this is the first study that reports the knock down of IGF-1R via lentiviral-mediated shRNA in Raji cells.
Effects of CALM intervention on neutrophil-to-lymphocyte ratio (NLR), fear of cancer recurrence and quality of life in patients with lung cancer
Authors: Zhao Jie , Wang Menglian , Huang Runze , Xu Jian , Gan Chen , Yu Sheng , Tang Lingxue , Yao Senbang , Li Wen , Cheng Huaidong
Published: January 2023

Purpose
This study aims to evaluate the effects of managing cancer and living meaningfully (CALM) intervention on the neutrophil-to-lymphocyte ratio (NLR), fear of cancer recurrence, quality of life and general distress in lung cancer patients and to explore whether there is a correlation between the NLR, fear of cancer recurrence, general distress and quality of life.
Methods
Eighty lung cancer patients with clinical range scores (≥13 points) on the FCRI severity subscale were recruited and randomly assigned to the CALM group or usual care (UC). The NLR was recorded before and after treatment. The Fear of Cancer Recurrence Inventory (FCRI), Quality of Life Questionnaire Core 30 (QLQ-C30) and Depression-Anxiety-Stress Scale (DASS-21) were used to evaluate patients at baseline (T0), immediately after treatment (T1), and at 2 (T2) and 4 (T3) months.
Results
Compared with the UC group, the NLR was significantly different before and after CALM intervention (z=-5.498; P=0.000). There were significant differences in the scores of QLQ, FCR and general distress (referring to depression and anxiety) before and after the T1, T2 and T3 interventions (F=220.30, F=315.20, F=290.10, respectively; P<0.001). The NLR in lung cancer patients was negatively correlated with QOL both before (r=-0.763; P<0.0001) and after the intervention (r=-0.810, P<0.0001). FCR and general distress were negatively correlated with the QOL scores in the CALM group (T0: r=-0.726, r=-0.776, respectively; P<0.0001; T1: r=-0.664, r=-0.647, respectively; P<0.0001; T2: r=-0.678, r=-0.695, respectively; P < 0.0001; T3: r=-0.511, P = 0.0008; r=-0.650, P<0.0001).
Conclusion
The CALM intervention can effectively reduce the NLR, alleviate the recurrence fear and general distress symptoms and improve the quality of life in lung cancer patients. Meanwhile, the NLR, fear of cancer recurrence and general distress were negatively correlated with quality of life. This indicates that the NLR can be used as a marker of the efficacy of the CALM intervention.
The discrimination of tectonic setting Using trace elements in zircons： A machine learning approach
Authors: Wang Luyuan , Zhang Chao , Geng Rui , Li Yuqi , Song Jijie , Wang Bin , Cui Fanghua
Published: January 2023

Zircon is the most important accessory mineral in geological research, and they record information on isotopes and trace elements which is of great significance in earth science research. Trace elements in Zircons can be used for analyzing the genesis of zircons, calculating the magma temperature and oxygen fugacity, and tracing the magma source. Due to the limitation of visual dimensions, the information on the zircons is mainly shown with the method of low dimensional diagrams in the present studies, so the high dimensional relationships during trace elements of the zircons are difficult to be discovered. However, with the development of machine learning, mining the high dimensional relationships during the trace elements of the zircons becomes possible. In this paper, four supervised learning algorithms including Random Forest, Support Vector Machine, Decision Tree, and eXtreme Gradient Boosting have been implemented to analyze trace elements of 3907 magmatic zircons from the GEOROC database, and a precise 13-dimensional data classifier model has been established in order to distinguish the tectonic settings of the rift, ocean island, and convergent margin. Based on the results of accuracy, precision, recall, and F1-score, the machine learning approach of eXtreme Gradient Boosting is best in the paper and the results of Accuracy, Precision, Recall, and F1-score are 0.948, 0.941, 0.922, 0.930, respectively. In summary, eXtreme Gradient Boosting in the paper could provide a high-dimensional discriminative approach to distinguish the tectonic settings.
Clinical utility of the acoustic detection of coronary stenosis as an early rule-out criterion: a blinded, prospective, monocentric study versus standard care
Authors: Birkemeyer Ralf , Wittenberg Jane , Müller Alfred , Wahler Steffen
Published: January 2023

Background:
The CADScor®System is a noninvasive and radiation-free technology that searches for stenosis induced by turbulent coronary blood flow. A CADSscore represents the acoustic detection results of coronary stenoses. We assessed consecutive patients with stable symptoms without known coronary artery disease (CAD) to define a low risk for obstructive CAD based on a low CAD score than a standard approach of clinical assessment using noninvasive and invasive diagnostic measurements.
Methods:
Overall, 214 consecutive patients aged ˃40 years in a German cardiological outpatient unit were included. Patients underwent an initial clinical assessment, a double-blinded CAD score, standard examinations, and a national guidance-based diagnostic cascade. They underwent a 6-month telephone follow-up to capture future CAD events. A CAD score of ≤20 was defined as low risk.
Results:
Overall, 196 patients completed the planned diagnostic workup after their initial visit, and 187 had a valid CAD score. All 196 patients underwent an electrocardiogram (ECG) and echocardiography, and 178 patients underwent a stress ECG. According to the initial standard evaluation, 41 patients were considered to be low-risk without further diagnosis. A CAD score of ≤20 was found in 51 patients. According to clinical standards, 85 and 77 patients underwent noninvasive testing and invasive angiography, respectively. The obstructive CAD was invasively diagnosed in 25 patients, of whom 4 had a CAD score of ≤20. No additional CAD was detected at the 6-month follow-up.
Overall, 41 of the 165 noninvasive and invasive diagnostic procedures could have been avoided with a CAD score of ≤20 as the exclusion criterion for further diagnosis after the standard initial diagnosis. Furthermore, 10 of the 52 invasive procedures without evidence of obstructive CAD could have been prevented.
Conclusions:
The obstructive CAD was confirmed in 12.8% of patients with stable symptoms and suspected CAD. Therefore, advanced noninvasive testing was mainly used for further CAD exclusion. The diagnostic yield of invasive angiography was low, and approximately a quarter of further diagnostic procedures could have been avoided with the CAD score, which showed an acceptable false-negative rate compared with the standard diagnostic tools.
Trial registration: Deutsches Register Klinischer Studien (DRKS): DRKS00016986 (22/03/2019)
Bioinformatic prediction of stage-specific transcription factor binding of Plasmopara halstedii conserved in the downy mildew and Phytophthora species
Authors: Bharti Sakshi , Thines Marco
Published: January 2023

Oomycetes, a large group of fungi-like organisms, include some destructive plant pathogens causing enormous economic damage. Phylogenetically, oomycetes belong to the kingdom Straminipila and have diverse lifestyles, including saprotrophs and both general and specialized pathogens of various eukaryotic supergroups. A rapid increase in genomic studies and next generation sequencing technologies have led to significant progress in understanding oomycete lifestyles. However, their genetics, including transcriptional regulation, have been studied to a much lesser extent. Here we provide a cross-species analysis of oomycete promoter for providing a first step towards elucidating gene regulation networks related to pathogenicity and life cycle stages. To identify conserved regulatory sequences involved in this, clustered DNA sequences of Plasmopara halstedii transcriptome time-series expression levels dataset from a preliminary study, has been used as a core reference for cross-species comparisons. Using a computational pipeline, 46 potential TFBSs motifs in 25 clusters with functionally conserved downstream genes of downy mildew and two Phytophthora species, regardless of the gene expression levels of Phytophthora transcriptomes were found. This can now be followed up by knock-out experiments in oomycete species amenable for genetic modification.
OncoVee TM -MiniPDX-guided anticancer treatment for HER2-negative intermediate-advanced gastric cancer patients: A single-arm, open-label phase I clinical study
Authors: Zhang Baonan , Li Yuzhen , Zhu Xiaodan , Chen Zhe , Huang Xiaona , Gong Tingjie , Zheng Weiwang , Bi Zhenle , Zhu Chenyang , Qian Jingyi , Li Xiaoqiang , Jin Chunhui
Published: January 2023

Background: Chemotherapy is the main treatment strategy for patients with advanced HER2-negative gastric cancer(GC); yet, many patients do not respond well to treatment. This study evaluated the sensitivity of a mini patient-derived xenograft (MiniPDX) animal model in patients with HER2-negative intermediate-advanced GC .
Methods: In this single-arm, open-label clinical study, we consecutively recruited patients with HER2-negative advanced or recurrent GC from September 2018 to July 2021. Tumor tissues were subjected to MiniPDX drug sensitivity tests for screening individualized anti-tumor drugs; appropriate drug types or combinations were selected based on drug screening results. The primary endpoints were progression-free survival (PFS) and safety, and the secondary endpoints were overall survival (OS) and objective response rate (ORR).
Results: A total of 17 patients were screened, and 14 eligible patients were included.The median follow-up time was 9 (2-34) months. The median PFS time was 14.1 (2-13) months, the median OS time was 16.9 (2-34) months, ORR was 42.9% (6/14), and DCR was 92.9% (13/14). The most common treatment-related adverse events (TRAE) were fatigue (14 (100%)), anorexia (13 (93%)) and insomnia (12 (86%)), and the most common grade 3 or worse TRAE was fatigue (6 (43%)), and anorexia (6 (43%)). The occurrence rate of myelosuppression, nausea and vomiting, abnormal liver enzymes, and other grade 3-4 chemotherapy adverse reactions were relatively low, and no grade 5 treatment-related adverse events occurred.
Conclusion: Screening of GC/GJC first-line chemotherapy regimens and targeted drugs based on the MiniPDX animal model showed relatively good tumor activity and good safety.
Breech vaginal delivery and risk of obstetric anal sphincter injuries
Authors: Leborne Perrine , de Tayrac Renaud , Zemmache Zakarya , Serrand Chris , Fabbro-Peray Pascale , Allegre Lucie , Vintejoux Emmanuelle
Published: January 2023

Introduction

Obstetric anal sphincter injuries (OASIs) at the time of childbirth can lead to serious consequences including anal incontinence, dyspareunia, pain and rectovaginal fistula. These types of lesions and their incidence have been well studied after cephalic presentation deliveries, but no publications have specifically addressed this issue in the context of vaginal breech delivery. The goal of our study was to evaluate the incidence of OASIs following breech deliveries and compare it with cephalic presentation births.

Methods

This was a retrospective cohort study involving 670 women. Of these, 224 and 446 had a vaginal birth of a fetus in the breech (breech group) and cephalic (cephalic group) presentations respectively. Both groups were matched for birthweight (± 200g), date of delivery (± 2 years) and vaginal parity. Main outcome of interest was to evaluate the incidence of OASIs following breech vaginal birth compared to cephalic vaginal births. Secondary endpoints were the incidence of intact perineum or first-degree tear, second-degree perineal tear and rates of episiotomies in each group.

Results

There was no statistically significant difference in OASIs incidence between the breech and cephalic groups (0.9% vs. 1.1%; OR 0.772 (0.133–4.479); p = 0.77). There were more episiotomies in the breech group (12.5% vs. 5.4%, p = 0.0012) and the rate of intact or first-degree perineum was similar in both groups (74.1% vs. 75.3%, p = 0.7291). A sub-analysis excluding patients with episiotomy and history of OASIs did not show any statistically significant difference either.

Conclusion

We did not demonstrate a significant difference in the incidence of obstetric anal sphincter injuries between women who had a breech vaginal birth compared to cephalic.
Seasonal variation in food security, lifestyle, nutritional status and its associated factors of the urban poor adolescents in Kuala Lumpur, Malaysia: research protocol of a prospective cohort study
Authors: Tay Janice Ee Fang , Tung Serene En Hui , Kaur Satvinder , Gan Wan Ying , Che’Ya Nik Norasma , Tan Choon Hui
Published: January 2023

Background: Climate change, obesity and undernutrition have now become a worldwide syndemic that threatens most people's health and natural systems in the 21st century. Adolescent malnutrition appears to be a matter of concern in Malaysia, and this is particularly relevant among the urban poor population. Mounting evidence points to the fact that underlying factors of malnutrition are subject to climate variability and profoundly affect nutritional outcomes. Hence, it is interesting to examine seasonal variation in nutritional status and its associated factors of urban poor adolescents in Malaysia.
Methods: This is a prospective cohort study following urban poor adolescents aged 10-17 years living in low-cost high-rise flats in Kuala Lumpur, Malaysia, across two monsoon seasons. The baseline assessment will be conducted during the onset of the Northeast Monsoon and followed up during Southwest Monsoon. Climate data will be collected by obtaining the climatological data (rainfall, temperature, and relative humidity) from Malaysia Meteorological Department. Geospatial data for food accessibility and availability, and also built (recreational facilities) environments, will be analyzed using the QGIS 3.4 Madeira software. Information on socio-demographic data, food security, lifestyle (diet and physical activity), and neighbourhood environment (food and built environment) will be collected using a self-administrative questionnaire. Anthropometric measurements, including weight, height, and waist circumference, will be conducted following WHO standardized protocol. WHO Anthro Plus was used to determine the height-for-age (HAZ) and BMI-for-age (BAZ). Anaemic status through biochemical analyses will be taken using HemoCue 201+ ® haemoglobinometer.
Discussion: The study will provide insights into the seasonal effects in nutritional status and its associated factors of urban poor adolescents. These findings can be useful for relevant stakeholders, including policymakers and the government sector, in seizing context-specific strategies and policy opportunities that are seasonally sensitive, effective, and sustainable in addressing multiple challenges to combat all forms of malnutrition, especially among urban poor communities.
Trial registration:The protocol for this review has not been registered.
The Impact of COVID-19 on Online Medical Education: A Knowledge Graph Analysis Based on Co-term Analysis
Authors: Deng Huijiao , Jiang Yi , Han Qinrong , Zhou Xingyu , Zhong Siyang , Hu Kai , Yang Lin
Published: January 2023

Background：This study aims to identify the characteristics and future directions of online medical education in the context of the novel coronavirus outbreak new through visual analytics using CiteSpace and VOSviewer bibliometric methods.
Method：From Web of Science, we searched for articles published between 2020 and 2022 using the terms online education, medical education and COVID-19, ended up with 2555 eligible papers, and the articles published between 2010 and 2019 using the terms online education, medical education and COVID-19, and we ended up with 4313 eligible papers.
Results：Before the COVID-19 outbreak, Medical students and care were the most frequent keywords and the most cited author was BRENT THOMA with 18 times. The United States is the country with the greatest involvement and research impact in the field of online medical education. The most cited journal is ACAD MED with 1326 citations. After the COVID-19 outbreak, a surge in the number of research results in related fields, and ANXIETY and four secondary keywords were identified. In addition, the concentration of authors of these publications in the USA and China is a strong indication that local epidemics and communication technologies have influenced the development of online medical education research. Regarding the centrality of research institutions, the most influential co-author network is Harvard Medical School in the United States; and regarding the centrality of references, the most representative journal to which it belongs is VACCINE.
Conclusion：This study found that hey information such as keywords, major institutions and authors, and countries differ in the papers before and after the COVID-19 outbreak. The novel coronavirus outbreak had a significant impact on the online education aspect. For non-medical and medical students, the pandemic has led to home isolation, making it difficult to offer face-to-face classes such as laboratory operations. Students have lost urgency and control over the specifics of face-to-face instruction, which has reduced the quality of teaching. Therefore, we should improve our education model according to the actual situation to ensure the quality of teaching while taking into account the physical and psychological health of students.
Clinical features and genetic analysis of Taiwanese primary immunodeficiency patients with prolonged diarrhoea and monogenetic inflammatory bowel disease
Authors: Lee Wen-I , Chen Chien-Chang , Chen Shih-Hsiang , Lai Wan-Tz , Jaing Tang-Her , Ou Liang-Shiou , Liang Chi-Jou , Kang Chen-Chen , Huang Jing-Long
Published: January 2023

Purpose: Diarrhoea lasting longer than 14 days which fails to respond to conventional management is defined as severe and protracted diarrhoea and might overlap with inflammatory bowel disease (IBD).
Methods: The prevalence, associated pathogens and prognosis of severe and protracted diarrhoea without IBD (SD) and with monogenetic IBD (mono-IBD) in primary immunodeficiency patients (PID) were investigated in Taiwan.
Results: A total of 301 patients were enrolled between 2003 and 2022, with predominantly paediatric-onset PID. Of these, 24 PID patients developed the SD phenotype before prophylactic treatment, including Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each), CVID (two) and SCID (one) without mutations. The most detectable pathogens were pseudomonas and salmonella (six each), and all patients were improved after approximately two-weeks antibiotic and/or IVIG treatment. Six (25.0%) mortalities without HSCT implement were due to respiratory failure from interstitial pneumonia (3 SCID and 1 CGD), intracranial haemorrhage (WAS), and lymphoma (HIGM). In the mono-IBD group, seventeen patients with mutant TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), LRBA (1), TTC37 (3), IL10RA (1), STAT1 (1), ZAP70 (1), PIK3CD (1), and PIK3R1 (1) genes failed to respond to aggressive treatment. Nine mono-IBD patients with TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2) and LRBA (1) mutations were fatal in the absence of HSCT. The mono-IBD group had a significantly earlier age of diarrhoea onset (1.7 vs 33.3 months, p=0.0056), a longer TPN duration (34.2 vs 7.0 months, p<0.0001), a shorter follow-up period (41.6 vs 132.6 months, p=0.007) and a higher mortality rate (58.9 vs 25.0%, p=0.012) compared with the SD group.
Conclusion: When compared to those with the SD phenotype, the mono-IBD patients had significant early-onset and poor response to empiric antibiotics, IVIG and steroids. This should be confirmed by genetic analysis or/and faecal calprotectin. Anti-inflammatory biologics and suitable HSCT still have the potential to control or even cure the mono-IBD phenotype.
A Case of Complete Recovery in a Hypereosinophilic Dermatitis Patient with Dupilumab
Authors: Jiang Xiaoyun , Ye Jun , Wu Xia , Zhu Jiang , Chen Siji , Cheng Hao
Published: January 2023

Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome (HES). Glucocorticoids are preferred for treatment but could carry a number of significant side effects. Symptoms of HED may recur after systemic glucocorticoid tapering. As a humanized monoclonal antibody targeting interleukin-4 receptor (IL-4Rα), dupilumab might be an efficacious adjuvant therapy for HED. We report a young male who suffered from erythematous papules with pruritus for over five years. He was diagnosed with HED by the presence of skin tissue with bone marrow and peripheral blood eosinophilia. Once reduction the dosage of glucocorticoid, his skin lesions relapsed. Using dupilumab, his condition significantly improved, and the glucocorticoid amount decreased successfully. In conclusion, we reported a new application of dupilumab in HED patients.
COVID-19 and Food Security among Families with Young Children in the MENA Region
Authors: Boutros Pierre , Fakih Ali
Published: January 2023

The authors have requested that this preprint be removed from Research Square.
The situation and some factors related to the health of children with autism spectrum disorder in Ninh Kieu District early childhood schools, Cantho City in 2020–2021
Authors: Duong Lam Phuc , Ho Trang Thu Thi
Published: January 2023

Autism spectrum disorder is on the rise. In a study by the National Children's Hospital, within 7 years, the number of autistic children coming to the clinic increased by 50 times, and the number of visits for treatment increased by 33 times. with a cross-sectional descriptive study design and analysis of 304 children who have been diagnosed with autism spectrum disorder and are receiving intervention in preschools and special education centers in Ninh Kieu District, Ho Chi Minh City. Can Tho 2020-2021,. Results: 53.3% of children have severe autism spectrum disorder; 86.5% of children have quality defects in social relations; 87.5% of children have communication quality defects; 85.2% of children have abnormal behavior defects; There is a relationship between sleep time, family time spent with children, children's time using technology, and the severity of children with autism spectrum disorder.
Inhibition of mild steel corrosion using Tamarind fruit fiber (TFF) extract in three different corrosive media: An experimental and quantum chemical study
Authors: Baluchamy Tamilselvi , Sethuramasamy Padmavathy , Seshian Bhuvaneshwari Durvas , Periyakaruppan Karuppasamy
Published: January 2023

The authors have requested that this preprint be removed from Research Square.
Treatment of Urticaria Caused by Severe Cryptosporidiosis in a 17-Month-Old Child – A Case Report and Review of the Literature
Authors: Azami Mehdi , Rarani Saeid Amini , Kiani Fatemeh
Published: January 2023

Background

Cryptosporidium is an intracellular protozoan that causes gastrointestinal symptoms in humans and animals. In immunocompromised patients and children under 5 years of age, the infection is severe and can be life-threatening due to severe diarrhea.

Case presentation

We report a case of urticaria associated with Cryptosporidium in a 17-month-old female Iranian child. The patient had severe diarrhea, weight loss and urticaria. Since the child's father worked in livestock farming, the hypothesis of parasite transmission from cows or calves to the house and the child was proposed. Several Cryptosporidium oocysts were detected in the modified acid-fast staining of the child's stool sample. The patient was successfully treated with nitazoxanide (100 mg twice daily) and became negative for parasites three days after treatment and one week after discharge from the hospital. Her stool pattern normalized in 1 week and she has had no recurrence after 6 months of follow up.

Conclusion

A number of parasites are associated with urticaria, but to our knowledge, there is no information on Cryptosporidium-induced urticaria. Therefore, our result may be evidence for the role of this parasite in the development of urticaria.
Uremic plasma proteins accumulate in peripheral blood mononuclear leukocytes inducing apoptosis: insights in the immuno-proteostasis response of chronic kidney disease.
Authors: Bartolini Desirée , Grignano Maria Antonietta , Piroddi Marta , Chiaradia Elisabetta , Galeazzi Gabriele , Rende Mario , Gioiello Antimo , Rampino Teresa , Libetta Carmelo , Galli Francesco
Published: January 2023

Peripheral blood mononuclear leukocytes (PBL) of uremic patients (u-PBL) prematurely die by apoptosis, thus sustaining leukopenia and immune dysfunction. Uremic retention solutes have been alleged to playing a causal role in this immune cell defect. However, both the molecular identity and pro-apoptotic mechanism of these solutes remain poorly characterized. In this study, we prepared a fraction of the uremic plasma (u-Pl) rich in these solutes (proteinaceous material with molecular weight > 50 kDa, namely the uremic-high MW fraction or u-HMW) that was used to demonstrate their pro-apoptotic activity in u-PBL. Such a detrimental activity was also confirmed in THP-1 and K562 mononuclear cells in association with increased cellular generation and secretion of H2O2, and JNK/cJun-dependent apoptotic signaling downstream of the endoplasmic reticulum stress response protein IRE1-α. The u-HMW also induced autophagy in THP-1 mononuclear leukocytes. These alterations of u-PBL proteostasis were associated with the presence in the proteome of these cells, but not of control PBL, of the main proteins and protein decoration targets (assessed by 2,4-diphenylhydrazine derivatization) of u-Pl and thus of u-HMW, namely albumin, transferrin and fibrinogen. These findings demonstrate that large solutes induce apoptosis in u-PBL leading to abnormal plasma protein endocytosis and terminal alteration of cellular proteostasis mechanisms. We define this response of PBL to large uremic solutes as the “immuno-proteostasis response” (IPR) of uremia.
Non-linear processing with a Surface Acoustic Wave reservoir computer
Authors: Meffan Robert Claude , Ijima Taiki , Banerjee Amit , Hirotani Jun , Tsuchiya Toshiyuki
Published: January 2023

Reservoir computing is a neural network algorithm that reduces the training needed for a neural network to be function. Recently, reservoir computing has been implemented using MEMs devices with prevalent non-linear dynamics to perform non-linear processing tasks. While partially explored in the past, there has been renewed interest in using Surface Acoustic Wave devices as low energy radio-frequency processors. However they have yet to be explored in the reservoir computing framework. In this work, a 39.16 MHz two-port SAW resonator on chemically reduced YZ Lithium Niobate is design and measured. The quality factor, insertion loss, linear transmission, and non-linear transmission of the devices is measured, and the relationship of these properties to reservoir computing is discussed. The SAW resonator is then configured as a time-multiplexed reservoir, and it's non-linear processing capabilities are discussed using the time-delayed parity benchmark.
Identity by descent mapping of HCV spontaneous clearance in populations of diverse ancestry
Authors: Yu Zixuan , Abdel-Azim Salma , Duggal Priya , Vergara Candelaria
Published: January 2023

Background
Acute infection with hepatitis C virus (HCV) affects millions of individuals worldwide. Host genetics plays a role in spontaneous clearance of the acute infection which occurs in approximately 30% of the individuals. Common variants in GPR158, genes in the interferon lambda (IFNL) cluster, and the MHC region have been associated with HCV clearance in populations of diverse ancestry. Fine mapping of those regions has identified some key variants and amino acids as potential causal variants but the role of rare variants in those regions and in the genome, in general, has not been explored. We aimed to detect haplotypes containing rare variants related to HCV clearance using identity-by-descent (IBD) haplotype sharing between unrelated cases/case pairs and case/controls pairs in 3,608 individuals with European and African ancestry.
Results
We detected 1,711,832 and 5,678,043 and individual pairs of IBD segments in the European and African ancestry individuals, respectively. As expected, individuals of African descent had more, and shorter segments compared to Europeans. We did not detect any significant IBD signals in the known associated gene regions.
Conclusions
IBD is based on sharing of haplotypes and is most powerful in populations with a shared founder or recent common ancestor. For the complex trait of HCV clearance, we used two outbred, global populations that limited our power to detect IBD associations. Overall, in this population-based sample we failed to detect rare variations associated with HCV clearance in individuals of European and African ancestry.
Efficacy of aqueous and methanol extracts of Euphorbia wallichii Hook. f. against larval toxocariasis
Authors: Sheikh Mohmad Muzafar , Tak Hidayatullah , Fazili Mustahson F. , Wani Ishfaq Nazir
Published: January 2023

The ever increasing anthelmintic resistance and low efficacy of conventional anthelmintics against larval toxocariasis has created an interest in evaluating plants as an effective source of anthelmintics. The aqueous and methanol extracts of Euphorbia wallichii were evaluated for efficacy against larvae of Toxocara canis both in vitro and in vivo, using an embryogenesis inhibition assay and a larval recovery assay respectively. In the in vitro study (1000) eggs were treated with 0.5, 1, and 2 mg/mL of plant extracts and the positive control was treated with same dose of albendazole. Crude methanol extract of E. wallichii (LC50 1.09 mg/mL) exhibited higher embryogenesis inhibition compared to its crude aqueous extracts (LC50 1.89 mg/mL). In the in vivo study, embryonated eggs (1000) of Toxocara canis were orally inoculated to wistar rats followed by treatment with crude methanol and aqueous extracts of Euphorbia walliachii at concentrations of 100, 200 and 400 mg/Kg and their liver and lungs were examined for the presence of T. canis larvae on the 7th day post infection (dpi). Maximum efficacy (64.75%) in larval count reduction was recorded for crude methanol extract in liver at dose of 400 mg/Kg in liver. Least efficacy (6.25%) in larval count reduction was recorded for crude aqueous extract E. wallichii at dose of 100 mg/Kg in lungs. The results reveal that Euphorbia walliachii extracts has an antitoxocaral effect and warrants further study as to suitability as an alternative anthelmintic.
Participation in Contest Programming: An Examination of Trends in U.S. ICPC Regional Contests
Authors: Blum Jeremy Joseph
Published: January 2023

A wide range of benefits have been posited from participation in programming contests. However, analysis of participation north American regional contests in the International Collegiate Programming Contest (ICPC) shows that participation in these contests is sharply declining, coinciding with the COVID-19 pandemic. Moreover, prior to the pandemic, while the number of teams participating in regional contests was increasing, the number of institutions sending teams to these contests was declining. We find several statistically significant correlations that may underscore structural reasons for this trend. Consistent participation in contests and the number of teams per institution sent to contest both are correlated with likely participation in future contests. On the other end of the spectrum, institutions sending a team to a contest for the first time in three years were much less likely to return in the next year. For this category of teams, if a team is unable to solve any problems in the contest, the institution is significantly less likely to send a team in the next year. Many of these contests have very challenging problem sets, and consequently, have many teams that fail to solve any problems. This result suggests that structuring the problem sets to increase the likelihood that most teams successfully complete problems would broaden participation in these contests.
Genetic and phenotypic parameters for sexual precocity and parasite resistance traits in Nellore cattle
Authors: de Moraes Mariana Mamedes , Gouveia Gabriela Canabrava , Ribeiro Virgínia Mara Pereira , de Araújo Andresa Eva Melo , Cardoso Eduardo Penteado , Toral Fabio Luiz Buranelo
Published: January 2023

Indicator traits of sexual precocity are widely used as selection criteria for the genetic improvement of beef cattle; however, the impact of selection for these traits on resistance to endo- and ectoparasites is unknown. Therefore, this study aimed to estimate the genetic and phenotypic parameters for indicator traits of sexual precocity and parasite resistance in Nellore cattle. The sexual precocity traits evaluated were probability of first calving (PFC) and scrotal circumference at 12 and 18 months of age (SC12 and SC18). The resistance-related traits included tick (TC), gastrointestinal nematode egg (NEC), and Eimeria spp. oocyst (EOC) counts. (Co)variance components were estimated by Bayesian inference using multitrait animal models. The mean heritabilities for PFC, SC12, SC18, TC, NEC and EOC were 0.23, 0.38, 0.42, 0.14, 0.16, 0.06, respectively, and suggest that selection will change the mean values of these traits over time. The genetic and phenotypic correlations for most pairs formed by a precocity and a resistance trait were not different from zero, suggesting that selection for sexual precocity traits will not result in changes in resistance traits. Thus, selection for indicator traits of sexual precocity does not elicit unfavorable correlated responses in resistance to endo- and ectoparasites and joint selection aimed at improving these traits can be performed using multitrait selection methods, when necessary.