bluuebunny/crossref_metadata_2025 huggingface dataset:
A practical evaluation of online self-assisted previewing architecture on rain classroom for biochemistry lab courses
Authors: Ben Songbin , Liu Chenshu , Yang Pinyi , Gong Jiayi , He Yin
Published: March 2024

In the aftermath of the COVID pandemic, we have been promoting online learning as a new learning tool. This study investigated the design of the optimal structure of online self-assisting coursework for laboratory courses that can assist students to better prepare for hands-on experiments. Undergraduate students from Liaoning University, who took the “Biochemistry Experiments” laboratory class, were asked to evaluate a self-learning segment offered on the Rain Classroom, an online platform that was provided to students before each in-person lab session as a preparation. Survey questions consisting of both multiple-choice and free-response questions were carefully designed to help evaluate students' sentiment toward the online previewing platform. Cramér's V correlation was used to determine the correlation between multiple choice answers, WordCloud and topic modeling analysis were conducted after textmining to analyze the emotions students express through the free response questions, and an analysis of variance (ANOVA) was conducted to evaluate the relationship between students' usage of the online interface and overall performance in class. The majority of students believe the previewing of the content on Rain Classroom to be helpful for their upcoming hands-on practice in the in-person laboratory course. At the same time, helpful insights were drawn from students' feedback through sentiment analysis from their entries in free-response questions in the survey. We showed that having online tools to pre-expose students to the laboratory-related material is helpful in preparing the students for hands-on laboratory courses. At the same time, we also offer a few suggestions that may guide the design of future online resources for laboratory classes such as involving multi-modality media to improve engagement and perfecting the interactive feature to increase its usage by students.
The effect of exercise on flow-mediated dilation in people with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Qiu Bopeng , Zhou Yilun , Tao Xifeng , Hou Xiao , Du Liwen , Lv Yuanyuan , Yu Laikang
Published: March 2024

Introduction

An increasing number of studies have investigated the effect of exercise on flow-mediated dilation (FMD) in people with type 2 diabetes mellitus (T2DM), while the findings were controversial. The primary aim of this systematic review and meta-analysis was to investigate the effect of exercise on FMD in T2DM patients, and the secondary aim was to investigate the optimal type, frequency, session duration, and weekly time of exercise for T2DM patients.

Methods

Searches were conducted in PubMed, Cochrane Library, Scopus, Web of Science, Embase and EBSCO databases. The Cochrane risk of bias tool (RoB2) in randomized trial and Physiotherapy Evidence Database (PEDro) scale were used to assess the methodological quality of the included studies.

Results

From the 3636 search records initially retrieved, 13 studies met the inclusion criteria. Our meta-analysis revealed that exercise had a significant effect on improving FMD in T2DM patients [WMD, 2.18 (95% CI, 1.78-2.58), p < 0.00001, I2 = 38%], with high-intensity interval training (HIIT) being the most effective intervention type [HIIT, 2.62 (1.42-3.82); p < 0.0001; aerobic exercise, 2.20 (1.29-3.11), p < 0.00001; resistance exercise, 1.91 (0.01-3.82), p = 0.05; multicomponent training, 1.49 (0.15-2.83), p = 0.03]. In addition, a higher frequency [> 3 times, 3.06 (1.94-4.19), p < 0.00001; ≤ 3 times, 2.02 (1.59-2.45), p < 0.00001], a shorter session duration [< 60 min, 3.39 (2.07-4.71), p < 0.00001; ≥ 60 min, 1.86 (1.32-2.40), p < 0.00001], and a shorter weekly time [≤ 180 min, 2.40 (1.63-3.17), p < 0.00001; > 180 min, 2.11 (0.82-3.40), p = 0.001] were associated with larger improvements in FMD.

Conclusion

This meta-analysis provides clinicians with evidence to recommended that T2DM patients participate in exercise, especially HIIT, more than 3 times per week for less than 60 min, with a target of 180 min per week being reached by increasing the frequency of exercise.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42023466575.
Research on performance of jet refrigeration cycle driven by waste heat of refrigerated vehicle
Authors: Jiang Shujun , Pan Xiubin , Zhang Song , Huang Yanmei , Que Wenshuai , Sang Hailang , Guan Wei
Published: March 2024

Nowadays, refrigerated food storage and transport vehicles are very common. However, with regard to the engine of vehicles, a significant amount of heat is discharged into the environment in the form of exhaust gas and jacket water. If the cooling system is used to convert this waste heat into cooling capacity, the thermal efficiency of the engine will be improved to a certain extent. Therefore, this paper uses two waste heat recovery jet refrigeration systems to recover heat from the exhaust gas and jacket water of the refrigerated vehicle. One is a conventional jet refrigeration system that uses only engine exhaust as the heat source, and the other is a system that adds a preheater upstream of the generator based on the conventional system, using engine jacket water to preheat the working fluid. This paper presents the results of comparing the impact of R141b/R123, R141b/R245fa, R142b/R134a, and R142b/R152a working fluids on system performance, and considers the effects of operating temperature and secondary flow pressure drop in the ejector receiving chamber on the system performance. The research results indicate that of the four selected working fluids, the R141b/R245fa (0.4/0.6) blend has the best overall performance. After the addition of a preheater, the system using R142b/R134a (0.6/0.4) hybrid working fluid achieves the maximum cooling capacity of 16.0994 kW and the maximum thermal efficiency of 5.45%, and the exergy loss in the generator is 1 kW lower than without the preheater.
Experiences of young mothers with the uptake of Sulfadoxine-Pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a cross-sectional study in the Lake endemic region, Kenya
Authors: Matanda Dennis Juma , Zulu Tchaiwe , Odwe George , Okoth Oscar , Nakuya Zoe
Published: March 2024

Background

A substantial proportion of the world population is affected by malaria with 241 million malaria cases reported globally. Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine-Pyrimethamine (SP) is an effective chemotherapy but its utilisation has not been optimised. Few studies focus on young mothers and their experiences regarding the optimal uptake of IPTp-SP.

Methods

The study design was cross-sectional with data derived from six focus group discussions with mothers aged 15–24 years who had a pregnancy and gave birth to a live baby within the last two years in Kisumu and Migori counties, Kenya. Inductive analysis was used to identify themes and patterns.

Results

Young mothers were motivated to take IPTp-SP during pregnancy if they had prior knowledge about SP and its associated benefits and if they were knowledgeable about the consequences of malaria infection during pregnancy. Perceived side effects of SP, lack of awareness of SP as a malaria prevention therapy, lack of knowledge on the benefits of SP, dosage and frequency of uptake, poor communication by health providers towards young mothers, and inconsistent supply of SP at health facilities inhibited young mothers from attaining the recommended 3+ doses of IPTp-SP.

Conclusions

There is a need for health literacy programmes that focus on increasing knowledge of IPTp-SP dosage, timing and benefits for both the young pregnant mother and her foetus. Community engagement through dialogue with mentor mothers and male partners will be an important complementary approach in establishing a support system for young women for positive health outcomes including attaining the recommended 3+ doses of IPTp-SP.
Investigating peripheral blood monocyte and T-cell subsets as non-invasive biomarkers for asymptomatic hepatic steatosis: results from the Multi-Ethnic Study of Atherosclerosis
Authors: Niedecker Rhys W. , Delaney Joseph A. , Doyle Margaret F. , Sparks Andrew D. , Sitlani Colleen M. , Buzkova Petra , Zeb Irfan , Tracy Russell P. , Psaty Bruce M. , Budoff Matthew J. , Olson Nels C.
Published: March 2024

Background

Circulating immune cells have gained interest as biomarkers of hepatic steatosis. Data on the relationships between immune cell subsets and early-stage steatosis in population-based cohorts are limited.

Methods

This study included 1,944 asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with immune cell phenotyping and computed tomography measures of liver fat. Participants with heavy alcohol use were excluded. A liver-to-spleen ratio Hounsfield units (HU) <1.0 and liver attenuation <40 HU were used to diagnose liver fat presence and >30% liver fat content, respectively. Logistic regression estimated cross-sectional associations of immune cell subsets with liver fat parameters adjusted for risk factors. We hypothesized that higher proportions of non-classical monocytes, Th1, Th17, and memory CD4+ T cells, and lower proportions of classical monocytes and naive CD4+ T cells, were associated with liver fat. Exploratory analyses evaluated additional immune cell phenotypes (n = 19).

Results

None of the hypothesized cells were associated with presence of liver fat. Higher memory CD4+ T cells were associated with >30% liver fat content, but this was not significant after correction for multiple hypothesis testing (odds ratio (OR): 1.31, 95% confidence interval (CI): 1.03, 1.66). In exploratory analyses unadjusted for multiple testing, higher proportions of CD8+CD57+ T cells were associated with liver fat presence (OR: 1.21, 95% CI: 1.02, 1.44) and >30% liver fat content (OR: 1.34, 95% CI: 1.07, 1.69).

Conclusions

Higher circulating memory CD4+ T cells may reflect liver fat severity. CD8+CD57+ cells were associated with liver fat presence and severity, but replication of findings is required.
Dysfunctional mitochondria, disrupted levels of reactive oxygen species, and autophagy in B cells from common variable immunodeficiency patients
Authors: Berman-Riu Maria , Cunill Vanesa , Clemente Antonio , López-Gómez Antonio , Pons Jaime , Ferrer Joana M.
Published: March 2024

Introduction

Common Variable Immunodeficiency (CVID) patients are characterized by hypogammaglobulinemia and poor response to vaccination due to deficient generation of memory and antibody-secreting B cells. B lymphocytes are essential for the development of humoral immune responses, and mitochondrial function, hreactive oxygen species (ROS) production and autophagy are crucial for determining B-cell fate. However, the role of those basic cell functions in the differentiation of human B cells remains poorly investigated.

Methods

We used flow cytometry to evaluate mitochondrial function, ROS production and autophagy processes in human naïve and memory B-cell subpopulations in unstimulated and stimulated PBMCs cultures. We aimed to determine whether any alterations in these processes could impact B-cell fate and contribute to the lack of B-cell differentiation observed in CVID patients.

Results

We described that naïve CD19+CD27- and memory CD19+CD27+ B cells subpopulations from healthy controls differ in terms of their dependence on these processes for their homeostasis, and demonstrated that different stimuli exert a preferential cell type dependent effect. The evaluation of mitochondrial function, ROS production and autophagy in naïve and memory B cells from CVID patients disclosed subpopulation specific alterations. Dysfunctional mitochondria and autophagy were more prominent in unstimulated CVID CD19+CD27- and CD19+CD27+ B cells than in their healthy counterparts. Although naïve CD19+CD27- B cells from CVID patients had higher basal ROS levels than controls, their ROS increase after stimulation was lower, suggesting a disruption in ROS homeostasis. On the other hand, memory CD19+CD27+ B cells from CVID patients had both lower ROS basal levels and a diminished ROS production after stimulation with anti-B cell receptor (BCR) and IL-21.

Conclusion

The failure in ROS cell signalling could impair CVID naïve B cell activation and differentiation to memory B cells. Decreased levels of ROS in CVID memory CD19+CD27+ B cells, which negatively correlate with their in vitro cell death and autophagy, could be detrimental and lead to their previously demonstrated premature death. The final consequence would be the failure to generate a functional B cell compartment in CVID patients.
Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells
Authors: Zhang Han , Zhang Pengpeng , Lin Xuefeng , Tan Lin , Wang Yuhang , Jia Xiaoteng , Wang Kai , Li Xin , Sun Daqiang
Published: March 2024

Background

The tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD.

Method

Utilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2.

Results

Our study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD’s microenvironment. We underscored pDCs’ role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2’s function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment.

Conclusion

The creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.
Biology of neurofibrosis with focus on multiple sclerosis
Authors: Lozinski Brian M. , Ghorbani Samira , Yong V. Wee
Published: March 2024

Tissue damage elicits a wound healing response of inflammation and remodeling aimed at restoring homeostasis. Dysregulation of wound healing leads to accumulation of effector cells and extracellular matrix (ECM) components, collectively termed fibrosis, which impairs organ functions. Fibrosis of the central nervous system, neurofibrosis, is a major contributor to the lack of neural regeneration and it involves fibroblasts, microglia/macrophages and astrocytes, and their deposited ECM. Neurofibrosis occurs commonly across neurological conditions. This review describes processes of wound healing and fibrosis in tissues in general, and in multiple sclerosis in particular, and considers approaches to ameliorate neurofibrosis to enhance neural recovery.
Eliminating invisible deaths: the woeful state of global rabies data and its impact on progress towards 2030 sustainable development goals for neglected tropical diseases
Authors: Swedberg Catherine , Bote Katrin , Gamble Luke , Fénelon Natael , King Alasdair , Wallace Ryan M.
Published: March 2024

Like other neglected diseases, surveillance data for rabies is insufficient and incompatible with the need to accurately describe the burden of disease. Multiple modeling studies central to estimating global human rabies deaths have been conducted in the last two decades, with results ranging from 14,000 to 74,000 deaths annually. Yet, uncertainty in model parameters, inconsistency in modeling approaches, and discrepancies in data quality per country included in global burden studies have led to recent skepticism about the magnitude of rabies mortality. Lack of data not only limits the efficiency and monitoring of rabies elimination strategies but also severely diminishes abilities to advocate for support from international funding agencies. Meanwhile, the most vulnerable communities continue to suffer from deaths that could have been prevented through more robust reporting. The Zero by 30 global strategy to eliminate dog-mediated human rabies by 2030 recommends endemic countries adopt the intersectoral approach, Integrated Bite Case Management (IBCM), as a cost-effective method to enhance surveillance. However, effective implementation of IBCM is impeded by challenges such as limited capacity, resources, knowledge, skills, and attitudes toward compliance. To address this, the World Health Organization and United Against Rabies Forum have developed several open-access tools to guide national control programs in strong data collection practices, and online data repositories to pragmatically streamline reporting and encourage data sharing. Here, we discuss how current and future initiatives can be best employed to improve the implementation of existing surveillance tools and prioritization of effective data reporting/sharing to optimize progress toward 2030 elimination.
Charting and analyzing the catch distribution of Japan’s coastal fisheries resources based on centennial statistics
Authors: Watari Shingo , Takemura Shion , Oyaizu Hitomi
Published: March 2024

Spatiotemporal changes in catches and transition of fishing grounds have been observed in various coastal fishery resources in Japanese waters in recent years. Are these changes part of cyclical fluctuations on a centennial timescale? Are these changes situations that have never been observed prior to this? Are common factors included in the long-term fluctuations among coastal fisheries resources? A total of 12 important Japanese coastal fisheries resources including fishes, shells, invertebrates, and algae were analyzed using fisheries statistics on the geographical center of catch compiled since 1894. The time series of the geographical center of catch showed a cyclical fluctuation trend over time rather than changing monotonically. The geographic center of catch in recent years (2019–2021) was located at the northeastern margin of the distribution, compared to its location since the end of the 19th century for many fishery resources. For coastal fishery resources, the situation in terms of fluctuations in the geographical center of catch is more extreme than in the past 100 years. The results of the dynamic factor analysis suggested that the state of these resources may be affected by the global ocean environment and other factors including human activities. Examining how fisheries have responded to past cyclical fluctuations may provide insight into adapting to the current rapid changes caused by climate change.
Temperature-induced variations in dulse (Devaleraea mollis) nutrition provide indirect benefits on juvenile red abalone (Haliotis rufescens) Growth
Authors: Rizzo Natalie R. , Beckert Samantha B. , Boles Sara E. , Gross Jackson A.
Published: March 2024

Changes in climate conditions can have cascading repercussions for organismal performance and survival, altering the productivity of aquatic systems. While numerous studies have examined the direct effects of temperature on species fitness, fewer studies have analyzed how individual impacts may translate to downstream primary consumers. Temperature-induced changes in the nutritional quality of seaweed may cause critical shifts in energy and nutrient availability for these consumers. A multifaceted experiment was conducted to assess the indirect impacts of California’s coastal climate conditions on abalone growth. This experiment fed juvenile red abalone (Haliotis rufescens) of two different size classes in ambient water conditions with the seaweed dulse (Devaleraea mollis), conditioned at 13°C, 15°C, and 17°C for 92 days. Nutritional analyses revealed significantly higher protein and nitrogen content in the 17°C dulse culture than in the 15°C and 13°C cultures, and no significant differences in carbohydrates. Furthermore, analyses on body weight ratio and condition factor indicate that juvenile red abalone of smaller size display significantly better growth and condition when fed dulse cultured at higher temperatures. Differences between size classes suggest that temperature changes, and subsequent shifts in the nutritional composition of dulse, may have greater impacts on smaller, younger red abalone.
Carbonate system variability in the Mediterranean Sea: a modelling study
Authors: Tsiaras Kostas , Frangoulis Constantin , Stamataki Natalia
Published: March 2024

A basin-scale Mediterranean carbonate system model has been setup, building on the POSEIDON operational biogeochemical model. The spatial variability of carbonate system variables from a 13-year simulation (2010-2022) was validated against CARIMED in situ data (DIC, TA, pCO2), showing reasonable agreement in reproducing the observed patterns and preserving the dynamics in different areas, except a slight overestimation (~15 µmol/kg) of TA in the Eastern Levantine. The time-variability of model outputs (DIC, TA, pCO2, pH) was validated, against available time-series from Western (DYFAMED, Villefranche-PointB) and Eastern Mediterranean (HCB) sites, showing good agreement with the data, particularly for pCO2, pH and DIC. The model failed to reproduce the observed late summer peak of TA at DYFAMED/PointB sites, which may be partly attributed to the advection of lower alkalinity Atlantic water in the area. The seasonal variability of DIC and pCO2@20°C was found to be mainly controlled by winter mixing and the subsequent increase of primary production and net CO2 biological uptake, which appeared overestimated at HCB. Along with the reference simulation, three sensitivity simulations were performed, de-activating the effect of biology, evaporation and CO2 air-sea fluxes on DIC and TA, in order to gain insight on the processes regulating the simulated carbonate system variability. The effect of biological processes on DIC was found more significant (peak during spring) in the more productive North Western Mediterranean, while evaporation had a stronger impact (peak during late summer) in the Levantine basin. CO2 air-sea flux was higher in the Western Mediterranean, particularly the Gulf of Lions and Alboran Sea, as well as in river influenced areas, such as the N. Adriatic and along the pathway of the Black Sea Water in the Aegean. A weak release of CO2 was found in the Eastern Levantine and Libyan Sea. Its basin average (+2.1 mmol/m2/day) and positive trend (+0.1 mmol/m2/day/year) indicates a gradually increasing net CO2 ocean uptake. The simulated positive trends of DIC (0.77 μmol/kg/year) and TA (0.53 μmol/kg/year) in the North Western Mediterranean were consistent with observational and modelling studies, in constrast with the Levantine basin, where no significant trends were found for TA.
Identification and genomic analysis of a novel temperate bacteriophage infecting Labrenzia aggregata isolated from the Mariana Trench
Authors: Gu Bingyu , Wang Haowen , Lv Jiayi , Zheng Yanfen , Zhang Xiao-Hua , Zhan Yuanchao
Published: March 2024

In marine environments, viruses play a pivotal role, yet deep-sea bacteriophages remains largely uncharacterized. The bacterium Labrenzia aggregata RF14, isolated from the Mariana Trench at a depth of 4,000 meters, harbors prophage regions based on a previous study. In this study, we induced a temperate bacteriophage from it using mitomycin C. The bacteriophage exhibited an icosahedral structure with a non-extendable tail and was named vB_LagS-V1. The genome size of it is 39,329 bps with a 59.46% G+C content, encoding 60 putative open reading frames. Genomic and phylogenetic analyses demonstrated that vB_LagS-V1 along with many bacteriophages infecting Hyphomicrobiales, constituted a newly unclassified family, which we designated as Hyphoviridae. Within this novel family, vB_LagS-V1 is distinct with isolated phages and clustered with two uncultured prophages within Labrenzia, forming an unclassified new genus, given a name of Labrenmarinevirus. The codon usage correlation and absence of tRNAs found in vB_LagS-V1, also prevail in some deep-sea bacteriophages, highlighting their adaptations to the deep-sea prokaryotic hosts. Moreover, vB_LagS-V1 encoded two auxiliary metabolic genes, cysteine dioxygenase and phosphoadenosine phosphosulfate reductase, which might help the phage and its host adapt to high hydrostatic pressure in the deep-sea environments. Our study will significantly contribute to the understanding of deep-sea bacteriophages and their interactions with hosts in extreme environments.
The competency index for clinical research professionals: a potential tool for competency-based clinical research academic program evaluation
Authors: Jones Carolynn Thomas , Liu Xin , Hornung Carlton A. , Fritter Jessica , Neidecker Marjorie V.
Published: March 2024

Background

Accreditation of graduate academic programs in clinical research requires demonstration of program achievement of Joint Task Force for Clinical Trial Competence-based standards. Evaluation of graduate programs include enrollment, student grades, skills-based outcomes, and completion rates, in addition to other measures. Standardized measures of competence would be useful.

Methods

We used the Competency Index for Clinical Research Professionals (CICRP), in a separate-sample pretest-posttest study to measure self-confidence or self-efficacy in clinical research competency comparing cohorts of students entering and completing a master’s degree program in clinical research across three semesters (summer 2021 – spring 2022). CICRP is a 20-item Likert scale questionnaire (0 = Not at all confident; 10 = extremely confident).

Results

The study sample of 110 students (54 in the entry course, 56 in the exit course) showed overall 80.9% entered the program with only a baccalaureate degree and 55.5% had no prior experience in managing clinical trial research. Cronbach alpha for the instrument showed a high level of content validity (range 0.93–0.98). Median CICRP item rating range at entry was [1, 6] and at exit [7, 10]. Mean CICRP total score (sum of 20 items) at entry was 72.7 (SD 41.9) vs. 167.0 (SD 21.1) at exit (p < 0.001). Mean total score at program entry increased with increasing years of clinical trial management experience but attenuated at program exit.

Conclusion

This is the first use of the CICRP for academic program evaluation. The CICRP may be a useful tool for competency-based academic program evaluation, in addition to other measures of program excellence.
Case report: A novel COL3A1 variant in a Colombian patient with isolated cerebrovascular involvement in vascular Ehlers–Danlos syndrome
Authors: Valencia-Cifuentes Valeria , Sinisterra-Díaz Stiven Ernesto , Quintana-Peña Valentina , Folleco Edgar , Nastasi-Catanese José A. , Pachajoa Harry , Fernández-Cubillos Juan P.
Published: March 2024

Introduction

To date, approximately 600 unique pathogenic variants have been reported in COL3A1 associated with vascular Ehlers–Danlos syndrome (vEDS). The objective of this study was to describe a patient with a novel variant in COL3A1 associated with vEDS.

Case report

We describe the clinical history and thorough phenotyping of a patient with brain aneurysms and identified a novel pathogenic variant in COL3A1. This male patient reported transient focal neurologic symptoms. Physical examination showed abnormal atrophic scarring, horizontal stretch marks under the arms, and an acrogeric appearance of the skin of the hands and feet. Brain imaging revealed extensive dilation of both internal carotids and the vertebrobasilar system. Molecular analysis identified a variant in COL3A1 (NM_000090.4):c.3058G>T p.(Gly1020Cys), which was classified as likely pathogenic. Currently, the patient has never had an event concerning dissection/rupture of tissues that could be affected in this condition.

Conclusion

This report demonstrates that exhaustive evaluation with clinical and genetic approaches should be considered in patients with vascular abnormalities. vEDS has a variable clinical presentation and often goes unrecognized, even though it is related to life-threatening complications and a shortened life expectancy. Diagnosis confirmed by genetic testing is crucial to determining appropriate surveillance, prevention, treatment, and genetic counseling.
Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study
Authors: Gai Xiaoyan , Yan Changjian , Wu Chaoling , Duan Zhonghui , Fan Jiarun , Yuan Shengren , Yang Ping , Bao Fang , Jing Hongmei , Cai Chao , Ma Yingmin , Zhang Weilong , Sun Yongchang
Published: March 2024

Background

Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context.

Methods

We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset.

Results

The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations.

Conclusion

No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW’s efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.
Burnout among diabetes specialist registrars across the United Kingdom in the post-pandemic era
Authors: Agha Adnan , Basu Ansu , Anwar Eram , Hanif Wasim
Published: March 2024

Introduction

Burnout syndrome is a condition resulting from chronic work-related stress exposure and can be identified by the presence of one or more of the three classic dimensions of burnout, i.e., emotional exhaustion, depersonalization, and lack of personal accomplishment, which negatively impact physician health and productivity.

Objective

This study aimed to identify burnout among Diabetes and Endocrinology Specialty Training Registrars (DStRs) across the United Kingdom.

Design/setting

It was a Cross-sectional observational study after ethical approval ERSC_2022_1166, utilizing the gold standard Maslach Burnout Inventory to measure burnout syndrome, and to determine self-reported stressors and compare them with the results of our previous survey in 2018.

Participants

Over 430 DStRs across the United Kingdom were invited electronically through their deanery representatives and specialty training bodies.

Results

Using Google Forms™ to gather data, we were able to collect 104 completed surveys. Results revealed that 62.5% (n = 65) of participants have burnout (5% increase from the previous survey in 2018), 38.6% (n = 40) have high emotional exhaustion, and 44.2% (n = 46) feel a lack of personal accomplishment. “General Internal Medicine specific workload” was the most common self-reported stressor reported by 87.5% (n = 91) of participants, whereas bullying/harassment and discrimination at work were reported by 35.6% (n = 37) and 30.77% (n = 32) of participants, respectively. Using multivariable logistic regression model, personal stress (OR, 4.00; 95% CI, 1.48–10.86; p = 0.006) had significant, while Bullying/harassment (OR, 3.75; 95% CI, 0.93–15.12; p = 0.063) had marginal impact on the presence of burnout.

Conclusion

Diabetes and Endocrinology Specialty Training Registrars frequently experience burnout syndrome, which has increased over the last 4 years. However, organizational changes can help identify, prevent, and treat physician burnout.

Trial registration

NCT05481021 available at https://ichgcp.net/clinical-trials-registry/NCT05481021.
Common mycorrhizal network: the predominant socialist and capitalist responses of possible plant–plant and plant–microbe interactions for sustainable agriculture
Authors: Ullah Asad , Gao Danmei , Wu Fengzhi
Published: March 2024

Plants engage in a variety of interactions, including sharing nutrients through common mycorrhizal networks (CMNs), which are facilitated by arbuscular mycorrhizal fungi (AMF). These networks can promote the establishment, growth, and distribution of limited nutrients that are important for plant growth, which in turn benefits the entire network of plants. Interactions between plants and microbes in the rhizosphere are complex and can either be socialist or capitalist in nature, and the knowledge of these interactions is equally important for the progress of sustainable agricultural practice. In the socialist network, resources are distributed more evenly, providing benefits for all connected plants, such as symbiosis. For example, direct or indirect transfer of nutrients to plants, direct stimulation of growth through phytohormones, antagonism toward pathogenic microorganisms, and mitigation of stresses. For the capitalist network, AMF would be privately controlled for the profit of certain groups of plants, hence increasing competition between connected plants. Such plant interactions invading by microbes act as saprophytic and cause necrotrophy in the colonizing plants. In the first case, an excess of the nutritional resources may be donated to the receiver plants by direct transfer. In the second case, an unequal distribution of resources occurs, which certainly favor individual groups and increases competition between interactions. This largely depends on which of these responses is predominant (“socialist” or “capitalist”) at the moment plants are connected. Therefore, some plant species might benefit from CMNs more than others, depending on the fungal species and plant species involved in the association. Nevertheless, benefits and disadvantages from the interactions between the connected plants are hard to distinguish in nature once most of the plants are colonized simultaneously by multiple fungal species, each with its own cost-benefits. Classifying plant–microbe interactions based on their habitat specificity, such as their presence on leaf surfaces (phyllospheric), within plant tissues (endophytic), on root surfaces (rhizospheric), or as surface-dwelling organisms (epiphytic), helps to highlight the dense and intricate connections between plants and microbes that occur both above and below ground. In these complex relationships, microbes often engage in mutualistic interactions where both parties derive mutual benefits, exemplifying the socialistic or capitalistic nature of these interactions. This review discusses the ubiquity, functioning, and management interventions of different types of plant–plant and plant–microbe interactions in CMNs, and how they promote plant growth and address environmental challenges for sustainable agriculture.
Genomic and biological control of Sclerotinia sclerotiorum using an extracellular extract from Bacillus velezensis 20507
Authors: Cheng Yunqing , Lou Hanxiao , He Hongli , He Xinyi , Wang Zicheng , Gao Xin , Liu Jianfeng
Published: March 2024

Introduction

Sclerotinia sclerotiorum is a known pathogen that harms crops and vegetables. Unfortunately, there is a lack of effective biological control measures for this pathogen. Bacillus velezensis 20507 has a strong antagonistic effect on S. Sclerotiorum; however, the biological basis of its antifungal effect is not fully understood.

Methods

In this study, the broad-spectrum antagonistic microorganisms of B. velezensis 20507 were investigated, and the active antifungal ingredients in this strain were isolated, purified, identified and thermal stability experiments were carried out to explore its antifungal mechanism.

Results

The B. velezensis 20507 genome comprised one circular chromosome with a length of 4,043,341 bp, including 3,879 genes, 185 tandem repeats, 87 tRNAs, and 27 rRNAs. Comparative genomic analysis revealed that our sequenced strain had the closest genetic relationship with Bacillus velezensis (GenBank ID: NC 009725.2); however, there were significant differences in the positions of genes within the two genomes. It is predicted that B. velezensis 20507 encode 12 secondary metabolites, including difficidin, macrolactin H, fengycin, surfactin, bacillibactin, bacillothiazole A-N, butirosin a/b, and bacillaene. Results showed that B. velezensis 20507 produced various antagonistic effects on six plant pathogen strains: Exserohilum turcicum, Pyricularia oryzae, Fusarium graminearum, Sclerotinia sclerotiorum, Fusarium oxysporum, and Fusarium verticillioides. Acid precipitation followed by 80% methanol leaching is an effective method for isolating the antifungal component ME80 in B. velezensis 20507, which can damage the membranes of S. sclerotiorum hyphae and has good heat resistance. Using high-performance liquid chromatography, and Mass Spectrometry analysis, it is believed that fengycin C72H110N12O20 is the main active antifungal substance.

Discussion

This study provides new resources for the biological control of S. Sclerotiorum in soybeans and a theoretical basis for further clarification of the mechanism of action of B. velezensis 20507.
Digital biomarkers from gaze tests for classification of central and peripheral lesions in acute vestibular syndrome
Authors: Duvieusart Benjamin , Leung Terence S. , Koohi Nehzat , Kaski Diego
Published: March 2024

Acute vestibular syndrome (AVS) is characterised by a sudden vertigo, gait instability, nausea and nystagmus. Accurate and rapid triage of patients with AVS to differentiate central (potentially sinister) from peripheral (usually benign) root causes is a challenge faced across emergency medicine settings. While there exist bedside exams which can reliably differentiate serious cases, they are underused due to clinicians’ general unfamiliarity and low confidence interpreting results. Nystagmus is a fundamental part of AVS and can facilitate triaging, but identification of relevant characteristics requires expertise. This work presents two quantitative digital biomarkers from nystagmus analysis, which capture diagnostically-relevant information. The directionality biomarker evaluates changes in direction to differentiate spontaneous and gaze-evoked (direction-changing) nystagmus, while the intensity differential biomarker describes changes in intensity across eccentric gaze tests. In order to evaluate biomarkers, 24 sets of three gaze tests (left, right, and primary) are analysed. Both novel biomarkers were found to perform well, particularly directionality which was a perfect classifier. Generally, the biomarkers matched or eclipsed the performance of quantitative nystagmus features found in the literature. They also surpassed the performance of a support vector machine classifier trained on the same dataset, which achieved an accuracy of 75%. In conclusion, these biomarkers simplify the diagnostic process for non-specialist clinicians, bridging the gap between emergency care and specialist evaluation, ultimately benefiting patients with AVS.
Adaptive fuzzy control for tendon-sheath actuated bending-tip system with unknown friction for robotic flexible endoscope
Authors: Ren Fan , Wang Xiangyu , Yu Ningbo , Han Jianda
Published: March 2024

Introduction

The tendon-sheath actuated bending-tip system (TAB) has been widely applied to long-distance transmission scenes due to its high maneuverability, safety, and compliance, such as in exoskeleton robots, rescue robots, and surgical robots design. Due to the suitability of operation in a narrow or tortuous environment, TAB has demonstrated great application potential in the area of minimally invasive surgery. However, TAB involves highly non-linear behavior due to hysteresis, creepage, and non-linear friction existing on the tendon routing, which is an enormous challenge for accurate control.

Methods

Considering the difficulties in the precise modeling of non-linearity friction, this paper proposes a novel fuzzy control scheme for the Euler-Lagrange dynamics model of TAB for achieving tracking performance and providing accurate friction compensation. Finally, the asymptotic stability of the closed-loop system is proved theoretically and the effectiveness of the controller is verified by numerical simulation carried out in MATLAB/Simulink.

Results

The desired angle can be reached quickly within 3 s by adopting the proposed controller without overshoot or oscillation in Tracking Experiment, demonstrating the regulation performance of the proposed control scheme. The proposed method still achieves the desired trajectory rapidly and accurately without steady-state errors in Varying-friction Experiment. The angle errors generated by external disturbances are < 1 deg under the proposed controller, which returns to zero in 2 s in Anti-disturbance Experiment. In contrast, comparative controllers take more time to be steady and are accompanied by oscillating and residual errors in all experiments.

Discussion

The proposed method is model-free control and has no strict requirement for the dynamics model and friction model. It is proved that advanced tracking performance and real-time response can be guaranteed under the presence of unknown bounded non-linear friction and time-varying non-linear dynamics.
The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance
Authors: Xu Jinyuan , Zhu Lilin , Xu Jie , Lin Kailong , Wang Juan , Bi Yan-long , Xu Guo-Tong , Tian Haibin , Gao Furong , Jin Caixia , Lu Lixia
Published: March 2024

Background

To identify key and shared insulin resistance (IR) molecular signatures across all insulin-sensitive tissues (ISTs), and their potential targeted drugs.

Methods

Three datasets from Gene Expression Omnibus (GEO) were acquired, in which the ISTs (fat, muscle, and liver) were from the same individual with obese mice. Integrated bioinformatics analysis was performed to obtain the differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was carried out to determine the “most significant trait-related genes” (MSTRGs). Enrichment analysis and PPI network were performed to find common features and novel hub genes in ISTs. The shared genes of DEGs and genes between DEGs and MSTRGs across four ISTs were identified as key IR therapeutic target. The Attie Lab diabetes database and obese rats were used to verify candidate genes. A medical drug-gene interaction network was conducted by using the Comparative Toxicogenomics Database (CTD) to find potential targeted drugs. The candidate drug was validated in Hepa1-6 cells.

Results

Lipid metabolic process, mitochondrion, and oxidoreductase activity as common features were enriched from ISTs under an obese context. Thirteen shared genes (Ubd, Lbp, Hp, Arntl, Cfd, Npas2, Thrsp., Tpx2, Pkp1, Sftpd, Mthfd2, Tnfaip2, and Vnn3) of DEGs across ISTs were obtained and confirmed. Among them, Ubd was the only shared gene between DEGs and MSTRGs across four ISTs. The expression of Ubd was significantly upregulated across four ISTs in obese rats, especially in the liver. The IR Hepa1-6 cell models treated with dexamethasone (Dex), palmitic acid (PA), and 2-deoxy-D-ribose (dRib) had elevated expression of Ubd. Knockdown of Ubd increased the level of p-Akt. A lowing Ubd expression drug, promethazine (PMZ) from CTD analysis rescued the decreased p-Akt level in IR Hepa1-6 cells.

Conclusion

This study revealed Ubd, a novel and shared IR molecular signature across four ISTs, as an effective biomarker and provided new insight into the mechanisms of IR. PMZ was a candidate drug for IR which increased p-Akt level and thus improved IR by targeting Ubd and downregulation of Ubd expression. Both Ubd and PMZ merit further clinical translational investigation to improve IR.
The utility of liquid biopsy-based methylation biomarkers for colorectal cancer detection
Authors: Loomans-Kropp Holli A.
Published: March 2024

Colorectal cancer (CRC) is one of the most prevalent cancers and the second leading cause of cancer-related deaths in the United States. It is also one of the few cancers with established screening guidelines, however these methods have significant patient burden (e.g., time, invasive). In recent years, the development of liquid biopsy-based screening methods for biomarker detection have emerged as alternatives to traditional screening. Methylation biomarkers are of particular interest, and these markers can be identified and measured on circulating tumor and cell-free DNA. This perspective summarizes the current state of CRC screening and the potential integration of DNA methylation markers into liquid biopsy-based techniques. Finally, I discuss limitations to these methods and strategies for improvement. The continued development and implementation of liquid biopsy-based cancer screening approaches may provide an acceptable alternative to individuals unwilling to be screened by traditional methods.