bluuebunny/crossref_metadata_2025 huggingface dataset:
Infertility and Identity: A Closer Look Into Experiences of Emerging Young Adult Childhood Cancer Survivors
Authors: Sira Natalia , McNeil Sarah , Hegde Archana , Geistman Kayla , Schwartz Abby
Published: October 2023

Objective: While medical advances are enabling more children with cancer to live into adulthood, a large majority of them suffer from the late effects of treatment and about 30% experience infertility. Infertility impacts both male and female survivors complicating typical development for emerging young adults (EYAs) who typically spend this developmental period actively constructing their identities related to family and gender roles, attaining professional skills, and establishing social views. As literature is limited on identity formation and coping with infertility in young survivors, this study aimed to understand the experiences of childhood cancer survivors who are faced with infertility as a late treatment effect while reconstructing their identity. Method: A qualitative descriptive approach was used to explore the experiences and effects of childhood cancer complications on the identity development of six emerging adults (ages 18–29). Guided by the theoretical framework of identity development data were collected using semistructured interviews. Results: Four distinct themes emerged after the data analyses: restricted exploration and uncertain future, challenges to intimacy and communication, restructuring identity through redefining roles, and coping through familial support. Conclusions: Findings indicate that developmental processes of identity formation are complicated by the challenges stemming from infertility and require specific efforts to reconstruct core identity and redefine desired parental roles. Experimentation and self-discovery may be restricted for EYA cancer survivors as they reevaluate their views on intimate relationships, communication, potential professional roles, and family composition. Practical recommendations for multidisciplinary team members to support this growing population are discussed.
Construction of Human Digital Twin Model Based on Multimodal Data and Its Application in Locomotion Mode Identification
Authors: Zhong Ruirui , Hu Bingtao , Feng Yixiong , Zheng Hao , Hong Zhaoxi , Lou Shanhe , Tan Jianrong
Published: October 2023

With the increasing attention to the state and role of people in intelligent manufacturing, there is a strong demand for human-cyber-physical systems (HCPS) that focus on human-robot interaction. The existing intelligent manufacturing system cannot satisfy efficient human-robot collaborative work. However, unlike machines equipped with sensors, human characteristic information is difficult to be perceived and digitized instantly. In view of the high complexity and uncertainty of the human body, this paper proposes a framework for building a human digital twin (HDT) model based on multimodal data and expounds on the key technologies. Data acquisition system is built to dynamically acquire and update the body state data and physiological data of the human body and realize the digital expression of multi-source heterogeneous human body information. A bidirectional long short-term memory and convolutional neural network (BiLSTM-CNN) based network is devised to fuse multimodal human data and extract the spatiotemporal features, and the human locomotion mode identification is taken as an application case. A series of optimization experiments are carried out to improve the performance of the proposed BiLSTM-CNN-based network model. The proposed model is compared with traditional locomotion mode identification models. The experimental results proved the superiority of the HDT framework for human locomotion mode identification.
A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells
Authors: Zhang Xiuyan , Wang Yu , Lu Jinchang , Xiao Lun , Chen Hui , Li Quanxue , Li Yuan-Yuan , Xu Peng , Ruan Changgeng , Zhou Haixia , Zhao Yun
Published: October 2023

Background

Zinc finger protein X-linked (ZFX) has been shown to promote the growth of tumor cells, including leukemic cells. However, the role of ZFX in the growth and drug response of chronic myeloid leukemia (CML) stem/progenitor cells remains unclear.

Methods

Real-time quantitative PCR (RT–qPCR) and immunofluorescence were used to analyze the expression of ZFX and WNT3 in CML CD34+ cells compared with normal control cells. Short hairpin RNAs (shRNAs) and clustered regularly interspaced short palindromic repeats/dead CRISPR-associated protein 9 (CRISPR/dCas9) technologies were used to study the role of ZFX in growth and drug response of CML cells. Microarray data were generated to compare ZFX-silenced CML CD34+ cells with their controls. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to study the molecular mechanisms of ZFX to regulate WNT3 expression. RT–qPCR and western blotting were used to study the effect of ZFX on β-catenin signaling.

Results

We showed that ZFX expression was significantly higher in CML CD34+ cells than in control cells. Overexpression and gene silencing experiments indicated that ZFX promoted the in vitro growth of CML cells, conferred imatinib mesylate (IM) resistance to these cells, and enhanced BCR/ABL-induced malignant transformation. Microarray data and subsequent validation revealed that WNT3 transcription was conservatively regulated by ZFX. WNT3 was highly expressed in CML CD34+ cells, and WNT3 regulated the growth and IM response of these cells similarly to ZFX. Moreover, WNT3 overexpression partially rescued ZFX silencing-induced growth inhibition and IM hypersensitivity. ZFX silencing decreased WNT3/β-catenin signaling, including c-MYC and CCND1 expression.

Conclusion

The present study identified a novel ZFX/WNT3 axis that modulates the growth and IM response of CML stem/progenitor cells.
Rational probe design for efficient rRNA depletion and improved metatranscriptomic analysis of human microbiomes
Authors: Tan Asako , Murugapiran Senthil , Mikalauskas Alaya , Koble Jeff , Kennedy Drew , Hyde Fred , Ruotti Victor , Law Emily , Jensen Jordan , Schroth Gary P. , Macklaim Jean M. , Kuersten Scott , LeFrançois Brice , Gohl Daryl M.
Published: October 2023

The microbiota that colonize the human gut and other tissues are dynamic, varying both in composition and functional state between individuals and over time. Gene expression measurements can provide insights into microbiome composition and function. However, efficient and unbiased removal of microbial ribosomal RNA (rRNA) presents a barrier to acquiring metatranscriptomic data. Here we describe a probe set that achieves efficient enzymatic rRNA removal of complex human-associated microbial communities. We demonstrate that the custom probe set can be further refined through an iterative design process to efficiently deplete rRNA from a range of human microbiome samples. Using synthetic nucleic acid spike-ins, we show that the rRNA depletion process does not introduce substantial quantitative error in gene expression profiles. Successful rRNA depletion allows for efficient characterization of taxonomic and functional profiles, including during the development of the human gut microbiome. The pan-human microbiome enzymatic rRNA depletion probes described here provide a powerful tool for studying the transcriptional dynamics and function of the human microbiome.
Non-targeted metabolomics analysis of metabolite changes in two quinoa genotypes under drought stress
Authors: Zhu Xiaolin , Zhang Mingjun , Wang Baoqiang , Song Xinrong , Wang Xian , Wei Xiaohong
Published: October 2023

Background

Quinoa is an important economic crop, drought is one of the key factors affecting quinoa yield. Clarifying the adaptation strategy of quinoa to drought is conducive to cultivating drought-tolerant varieties. At present, the study of quinoa on drought stress-related metabolism and the identification of related metabolites are still unknown. As a direct feature of biochemical functions, metabolites can reveal the biochemical pathways involved in drought response.

Result

Here, we studied the physiological and metabolic responses of drought-tolerant genotype L1 and sensitive genotype HZ1. Under drought conditions, L1 had higher osmotic adjustment ability and stronger root activity than HZ1, and the relative water content of L1 was also higher than that of HZ1. In addition, the barrier-to- sea ratio of L1 is significantly higher than that of HZ1. Using untargeted metabolic analysis, a total of 523, 406, 301 and 272 differential metabolites were identified in L1 and HZ1 on day 3 and day 9 of drought stress. The key metabolites (amino acids, nucleotides, peptides, organic acids, lipids and carbohydrates) accumulated differently in quinoa leaves. and HZ1 had the most DEMs in Glycerophospholipid metabolism (ko00564) and ABC transporters (ko02010) pathways.

Conclusion

These results provide a reference for characterizing the response mechanism of quinoa to drought and improving the drought tolerance of quinoa.
Pathogens in PICU before and during the SARS-CoV-2 pandemic in China: a multicenter retrospective study
Authors: Ni Jingwen , Zhao Zhe , Wang Chun , Jin Youpeng , Wang Yi , Liang Zhenhua , Li Shujun , Chen Jie , Du Yanqiang , Li Yipei , Huang Hanwu , Guo Yuxiong , Zhong Yujie , Feng Zhichun , Fang Kenan , Hong Xiaoyang
Published: October 2023

Background

Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics.

Methods

This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021.

Results

In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05).

Conclusion

After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population’s behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.
At-home computerized executive-function training to improve cognition and mobility in normal-hearing adults and older hearing aid users: a multi-centre, single-blinded randomized controlled trial
Authors: Downey Rachel , Gagné Nathan , Mohanathas Niroshica , Campos Jennifer L. , Pichora-Fuller Kathleen M. , Bherer Louis , Lussier Maxime , Phillips Natalie A. , Wittich Walter , St-Onge Nancy , Gagné Jean-Pierre , Li Karen
Published: October 2023

Background

Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults.

Methods

A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45–60 years old) and older adults (65–80 years old), as well as older hearing aid users (65–80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE’s StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia’s PERFORM Centre.

Discussion

This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss.

Trial registration

Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998
The value of elevated cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis
Authors: Wang Qin , Wang YongFang , Yang Yan , Kong YanXi , Peng Yuan
Published: October 2023

Bacterial meningitis is a serious complication after neurosurgery and has a high mortality rate. Early diagnosis and timely treatment are crucial or will have disastrous consequences. The classic triad of bacterial meningitis lacks sensitivity and specificity. Therefore, the diagnosis of post-neurosurgical bacterial meningitis relies on cerebrospinal fluid. But traditional cerebrospinal fluid parameters are not completely reliable in diagnosing post-neurosurgical bacterial meningitis. Previous studies have found that CSF lactate concentration is related to bacterial meningitis. But, after the craniocerebral operation, the cerebrospinal fluid of most patients is bloody. Whether red blood cells interfere with diagnosing PNBM based on lactate concentration is limited. In the current study, we further analysis on whether red blood cells interfere with diagnosing PNBM based on lactate concentration. This study aimed to investigate the value of cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis. A prospective observational study was performed on 62 patients at Kunshan First People’s Hospital’s intensive care unit affiliated with Jiangsu University. We found that erythrocytes do not affect cerebrospinal fluid lactate, and elevated lactate concentrations can be used as a marker for postoperative bacterial meningitis.
Tracking tumor alteration in glioma through serum fibroblast activation protein combined with image
Authors: Yang Xiao-song , zhu Peng , Xie Rong-Xing , Chen Peng-fei , Liu Hong , Cheng Xiao-Man , Zhu Zheng-Quan , Peng Xiao-min , Liu Hai-bin , Yang Qun-Ying , Li Jun-Qi , Zhang Ji
Published: October 2023

Purpose

Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker.

Methods

We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies.

Results

A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed.

Conclusions

The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.
The effect of smoking on latent hazard classes of metabolic syndrome using latent class causal analysis method in the Iranian population
Authors: Khodamoradi Farzad , Nazemipour Maryam , Mansournia Nasrin , Yazdani Kamran , khalili Davood , Arshadi Maedeh , Etminan Mahyar , Mansournia Mohammad Ali
Published: October 2023

Background

The prevalence of metabolic syndrome is increasing worldwide. Clinical guidelines consider metabolic syndrome as an all or none medical condition. One proposed method for classifying metabolic syndrome is latent class analysis (LCA). One approach to causal inference in LCA is using propensity score (PS) methods. The aim of this study was to investigate the causal effect of smoking on latent hazard classes of metabolic syndrome using the method of latent class causal analysis.

Methods

In this study, we used data from the Tehran Lipid and Glucose Cohort Study (TLGS). 4857 participants aged over 20 years with complete information on exposure (smoking) and confounders in the third phase (2005–2008) were included. Metabolic syndrome was evaluated as outcome and latent variable in LCA in the data of the fifth phase (2014–2015). The step-by-step procedure for conducting causal inference in LCA included: (1) PS estimation and evaluation of overlap, (2) calculation of inverse probability-of-treatment weighting (IPTW), (3) PS matching, (4) evaluating balance of confounding variables between exposure groups, and (5) conducting LCA using the weighted or matched data set.

Results

Based on the results of IPTW which compared the low, medium and high risk classes of metabolic syndrome (compared to a class without metabolic syndrome), no association was found between smoking and the metabolic syndrome latent classes. PS matching which compared low and moderate risk classes compared to class without metabolic syndrome, showed that smoking increases the probability of being in the low-risk class of metabolic syndrome (OR: 2.19; 95% CI: 1.32, 3.63). In the unadjusted analysis, smoking increased the chances of being in the low-risk (OR: 1.45; 95% CI: 1.01, 2.08) and moderate-risk (OR: 1.68; 95% CI: 1.18, 2.40) classes of metabolic syndrome compared to the class without metabolic syndrome.

Conclusions

Based on the results, the causal effect of smoking on latent hazard classes of metabolic syndrome can be different based on the type of PS method. In adjusted analysis, no relationship was observed between smoking and moderate-risk and high-risk classes of metabolic syndrome.
Maternal weight trajectories and associations with infant growth in South African women
Authors: Madlala Hlengiwe P. , Bengtson Angela M. , Hannan Luke , Malaba Thokozile R. , Kalk Emma , Nyemba Dorothy , Boulle Andrew , Myer Landon
Published: October 2023

Background

Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months.

Methods

Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression.

Results

Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium–high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium–high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01–1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97–2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68–6.41), haemoglobin levels (OR 1.39, 95% CI 1.11–1.74) and parity (OR 1.39, 95% CI 1.15–1.67); living with HIV (OR 0.47, 95% CI 0.30–0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59–1.83) with increased infant WAZ at 12 months of age.

Conclusion

Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes.
Conditional diagnostic accuracy according to inflammation status and age for diagnosing tuberculous effusion
Authors: Jeon Da Som , Kim Sung-Hoon , Lee Jang Ho , Choi Chang-Min , Park Hyung Jun
Published: October 2023

Background

Tuberculous effusion varies from lymphocyte-dominant to neutrophilic effusion according to inflammation status. The criteria of adenosine deaminase (ADA) and lymphocyte/neutrophil (L/N) ratio have yet not been evaluated across different disease conditions.

Methods

Patients who conducted pleural fluid analysis from 2009 to 2019 at Asan Medical Center were included. Criteria (ADA of 50 and L/N ratio of 0.75) were evaluated by quantile subgroups according to age, C-reactive protein (CRP), white blood cell (WBC), and lactate dehydrogenase (LD) by the Monte Carlo simulation method to diagnose tuberculosis. The model for the ADA and L/N ratio was evaluated by AUROC.

Results

Among the 2,918 reviewed cases, 2034 were included with 229 (11.26%) tuberculosis cases. The mean baseline ADA AUROC was 0.88 across all patients. Increased CRP and WBC showed high proportions of neutrophilic tuberculous effusion, with low sensitivity of approximately 45% and 33% in the fifth WBC and CRP groups, respectively. The AUROC of the models decreased with the increase in WBC and CRP groups (ADA model: 0.69 [the top quantile WBC group], 0.74 [the top quantile CRP group]). The AUROC of the models did not show a trend according to the increase in LD and age.

Conclusion

Inflammatory status affects the diagnostic metrics for tuberculous effusion due to the progression of tuberculous effusion. Clinicians should consider the low accuracy of tuberculous effusion criteria in high-inflammatory conditions when diagnosing tuberculosis.
Dietary caffeine intake is associated with favorable metabolic profile among apparently healthy overweight and obese individuals
Authors: Alshahrani Shadia Hamoud , Atia Yasir A. , Badir Raheem Atiya , Almalki Sami G. , Tayyib Nahla A , Shahab Sana , Romero-Parra Rosario Mireya , Abid Mohammed Kadhem , Hussien Beneen M. , Ramaiah Pushpamala
Published: October 2023

Background

Recent studies have revealed some conflicting results about the health effects of caffeine. These studies are inconsistent in terms of design and population and source of consumed caffeine. In the current study, we aimed to evaluate the possible health effects of dietary caffeine intake among overweight and obese individuals.

Methods

In this cross-sectional study, 488 apparently healthy individuals with overweight and obesity were participated. Dietary intake was assessed by a Food Frequency Questionnaire (FFQ) and the amount of dietary caffeine was calculated. Body composition was determined by bioelectrical impedance analysis (BIA). Enzymatic methods were used to evaluate serum lipid, glucose, and insulin concentrations.

Results

Those at the highest tertile of dietary caffeine intake had lower percentage of fat mass, higher fat free mass and appetite score (P < 0.05). Also, lower total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) was observed in higher tertiles of dietary caffeine intake compared with lower tertiles. In multinomial adjusted models, those at the second tertile of dietary caffeine intake were more likely to have higher serum insulin (P = 0.04) and lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared with first tertile (P = 0.03) in crude model. While, in the age, body mass index (BMI), sex, physical activity, socio-economic status (SES) and energy intake –adjusted model (Model III), those at the third tertile of dietary caffeine intake were more likely to have low serum LDL concentrations [odds ratio (OR) = 0.957; CI = 0.918–0.997; P = 0.04]. With further adjustment to dietary vegetable, fiber and grain intake, those at the third tertile of dietary caffeine intake were more likely to have low systolic blood pressure (SBP), LDL and high HDL levels compared with those at the first tertile (P < 0.05).

Conclusion

High intakes of dietary caffeine was associated with lower LDL, SBP, insulin resistance and higher HDL concentrations among overweight and obese individuals. However, due to observational design of the study, causal inference is impossible and further studies are warranted to confirm our findings.
The impact and the challenges of implementing a faculty development program on health professions education in a Brazilian Medical School: a case study with mixed methods
Authors: Cintra Karine Angélica , Borges Marcos Carvalho , Panúncio-Pinto Maria Paula , de Almeida Troncon Luiz Ernesto , Bollela Valdes Roberto
Published: October 2023

Purpose

Faculty development in health professions education is still challenging in developing countries like Brazil. Work overload and the lack of financial support hinder faculty members' participation. Ribeirão Preto Medical School founded its Center for Faculty Development in 2016. Since then, an essential skills module (ESMo) on health professions education (HPE) has been offered regularly to faculty members and preceptors of seven undergraduate programs. This case study aims to evaluate the impact of this Essential Skills Module on the educational practices of participants two years after attending the module and the challenges faced during the process.

Method

The study used a mixed-method approach with a description of the demographic and professional profile data of the ESMo participants. Immediate post-ESMo perceptions (satisfaction and learning) of the participants were determined with structured instruments. Two years later, a semi-structured interview was conducted and recorded to determine the long-term effects (application of learning and behavior changing as an educator). NVIVO® software was used to store and systematize the thematic discourse analysis with a socio-constructivist theoretical framework interpretation.

Results

One hundred forty-six participants were included: 86 (59%) tenured faculty members, 49 (33,5%) clinical preceptors, and 11 (7,5%) invited teachers. Most were female (66%), and 56% had teaching experience shorter than ten years. 52 (69%) out of 75 eligible participants were interviewed. The immediate reaction to participating in the module was quite positive and 80% have already implemented an educational intervention in their daily activities. Discourses thematic analysis showed five emerging themes appearing in different frequencies: Changes in teaching activities (98%); Lack of previous pedagogical training (92.3%); Commitment and enthusiasm towards teaching (46.15%); Overlapping functions inside the institution (34.6%) and Challenges for student assessment (23%).

Conclusion

This first in-depth evaluation of the long-term effects of a faculty development intervention in a Brazilian Health Profession Education school showed that participation positively changed participants' teaching & learning practices. These interventions consistently fostered a community of practice and valued faculty development processes in local and national scenarios.
Impact of clinical decision support on controlled substance prescribing
Authors: Seymour Rachel B. , Wally Meghan K. , Hsu Joseph R. ,   PRIMUM Group, Beuhler Michael , Bosse Michael J. , Gibbs Michael , Griggs Christopher , Jarrett Steven , Leas Daniel , Odum Susan , Roomian Tamar , Runyon Michael , Saha Animita , Schiro Sharon , Sullivan D. Matthew , Watling Brad , Wyatt Stephen , Yu Ziqing
Published: October 2023

Background

Prescription drug overdose and misuse has reached alarming numbers. A persistent problem in clinical care is lack of easy, immediate access to all relevant information at the actionable time. Prescribers must digest an overwhelming amount of information from each patient’s record as well as remain up-to-date with current evidence to provide optimal care. This study aimed to describe prescriber response to a prospective clinical decision support intervention designed to identify patients at risk of adverse events associated with misuse of prescription opioids/benzodiazepines and promote adherence to clinical practice guidelines.

Methods

This study was conducted at a large multi-center healthcare system, using data from the electronic health record. A prospective observational study was performed as clinical decision support (CDS) interventions were sequentially launched (January 2016–July 2019). All data were captured from the medical record prospectively via the CDS tools implemented. A consecutive series of all patient encounters including an opioid/benzodiazepine prescription were included in this study (n = 61,124,172 encounters; n = 674,785 patients). Physician response to the CDS interventions was the primary outcome, and it was assessed over time using control charts.

Results

An alert was triggered in 23.5% of encounters with a prescription (n = 555,626). The prescriber decision was influenced in 18.1% of these encounters (n = 100,301). As the number of risk factors increased, the rate of decision being influenced also increased (p = 0.0001). The effect of the alert differed by drug, risk factor, specialty, and facility.

Conclusion

The delivery of evidence-based, patient-specific information had an influence on the final prescription in nearly 1 in 5 encounters. Our intervention was sustained with minimal prescriber fatigue over many years in a large and diverse health system.
Versatile generation of precise gene edits in bovines using SEGCPN
Authors: Wang Ming , Ding Fangrong , Wang Haiping , Li Ling , Dai Yunping , Sun ZhaoLin , Li Ning
Published: October 2023

Background

Gene knockout and knock-in have been widely performed in large farm animals based on genome editing systems. However, many types of precise gene editing, including targeted deletion, gene tagging, and large gene fragment replacement, remain a challenge in large farm animals.

Results

Here, we established versatile self-excising gene-targeting technology in combination with programmable nucleases (SEGCPN) to efficiently generate various types of precise gene editing in bovine. First, we used this versatile method to successfully generate bovine embryos with point mutations and 11-bp deletions at the MSTN locus. Second, we successfully generated bulls with EGFP labeling at the SRY locus. Finally, we successfully generated humanized cows in which the endogenous 18-kb α-casein gene was replaced with a 2.6-kb human α-lactalbumin gene.

Conclusions

In summary, our new SEGCPN method offers unlimited possibilities for various types of precise gene editing in large animals for application both in agriculture and disease models.
Circulating chemerin levels in preeclampsia: a systematic review and meta-analysis
Authors: Yin Yangxue , Xie Shuangshuang , Xu Qin , Liao Lingyun , Chen Hongqin , Zhou Rong
Published: October 2023

Background

Preeclampsia (PE) is a new-onset pregnancy-specific disorder with a high prevalence that leads to over 70 000 maternal and 500 000 foetal fatalities worldwide each year. The level of chemerin, a newly identified adipokine, is increased in diabetic and obese patients. Currently, there are several studies describing the relationship between maternal circulating chemerin levels and PE. Therefore, this study aimed to assess their association in pooled samples.

Methods

Four databases were systematically searched to identify potential studies that reported circulating chemerin levels in PE and normal pregnancy groups. Standardized mean differences (SMDs), 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated using a random-effects meta-analysis. The probability of heterogeneity was also investigated by sensitivity analysis, subgroup analysis, and meta-regression.

Results

Thirteen studies in 11 articles with a total of 860 PE patients and 1309 women with normal pregnancies met the inclusion criteria. The results of the meta-analysis revealed that circulating chemerin, which levels in PE patients were considerably higher than those in controls (SMD = 1.39, 95% CI: 1.02, 1.77, 95% PI: -0.07, 2.86). Moreover, sensitivity analysis determined that the outcomes of the overall pooled results were not affected after the elimination of any study. Notably, subgroup analysis demonstrated a similar expression pattern irrespective of geographic location, severity, timing of sampling, and sample size. Last, there were no factors that significantly impacted the overall estimate, according to meta-regression.

Conclusions

This meta-analysis is the first to assess circulating chemerin levels in PE patients. The findings indicate that circulating chemerin levels may be a potential marker to diagnose PE.
IgG immune complex-induced acute lung injury is ameliorated by cAMP via down-regulation of C/EBP- and AP-1-mediated transcriptions
Authors: Yan Chunguang , Chen Jing , Tang Huifang , Deng Chunmin , Zhang Qi , Wang Ximo
Published: October 2023

Background

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are life threatening pulmonary diseases, and we are now lack of effective therapeutic methods. Inflammatory responses are essential for initiating ALI/ARDS. Thus, ameliorating inflammatory reaction might be beneficial for treatment of the disease. There are increasing data that phosphodiesterase-4 (PDE4)-selective inhibitors, which may elevate cellular cyclic adenosine 3′, 5′-monophosphate (cAMP) level, could suppress inflammation. However, whether they could be used to treat IgG immune complex (IgG-IC)-associated ALI has not been determined.

Methods

ALI is induced by treating mice with airway deposition of IgG immune complexes. Cellular cAMP concentrations are elevated by treating mice or macrophages with Rolipram/Roflumilast. The degree of pulmonary injury is reflected by lung permeability, leukocyte accumulation, histological change and expressions of pro-inflammatory mediators. 6-Bnz-cAMP and H-89 are used to regulate protein kinase A (PKA) activity, and 8-pCPT-2′-O-Me-cAMP is applied to activate exchange proteins directly activated by cAMP (Epac). Gene expressions are analyzed by real-time PCR, ELISA or Western blot. CCAAT/enhancer binding protein (C/EBP) and activation protein 1 (AP-1) transcription activities are estimated by measuring the luciferase productions.

Results

IgG-IC-induced ALI is attenuated by the PDE4-selective inhibitor, which is due to reduced expressions of cytokine and chemokines. Interestingly, we find that cAMP downstream effector molecule PKA but not Epac is involved in negative regulation of IgG-IC-mediated pro-inflammatory mediators’ productions. Mechanistically, activation of cAMP-PKA signal axis leads to inactivation of MAPK pathway, resulting in a decrease in C/EBP- and AP-1-mediated transcriptions of pro-inflammatory mediators.

Conclusions

Our data demonstrate, for the first time, that cAMP-PKA signal is involved in down-regulation of IgG-IC-associated inflammatory responses via down-regulating MAPK activation, which is critical for transcriptional activities of C/EBP and AP-1. Collectively, our experiments provide theoretical base for the potential application of PDE4-selective inhibitor to clinic for treatment of IgG-IC-related acute lung injury.
Insights from the scale-up and implementation of the Deadly Liver Mob program across nine sites in New South Wales, Australia, according to the RE-AIM framework
Authors: Cama Elena , Beadman Kim , Beadman Mitch , Walker Melinda , Treloar Carla
Published: October 2023

Background

The Deadly Liver Mob (DLM) program is a peer-led health promotion program that aims to improve access to screening and treatment for blood borne viruses and sexually transmissible infections for Aboriginal and Torres Strait Islander Australians. In this paper, we used client and staff insights to explore the successes and challenges of implementing the DLM program according to the RE-AIM framework, which explores real-world implementation of interventions according to reach, effectiveness, adoption, implementation, and maintenance.

Methods

Clients and staff were recruited through the DLM program. Semi-structured interviews were conducted with four Aboriginal and Torres Strait Islander and 11 non-Aboriginal or Torres Strait Islander health workers, as well as 33 Aboriginal and Torres Strait Islander clients of the program.

Results

Findings show the positive effects of the DLM program, in creating a culturally safe and sensitive environment for Aboriginal and Torres Strait Islander clients to access care. In particular, the employment of frontline Aboriginal and Torres Strait Islander workers to deliver the education was touted as one of the primary successes of the program, in enabling workers to build trust between clients and mainstream health systems, which has the flow on effect of encouraging clients to go through to screening. The use of the RE-AIM framework illustrates the challenges of implementing real-world interventions across various locations, such as the difficulties in delivering DLM in regional and remote areas due to covering large geographic areas with minimal public transport available.

Conclusions

The data emphasise the need for interventions to be adaptable and flexible, altering elements of the program to suit local and community needs, such as by offering mobile and outreach services to enable access across regional and rural areas. The findings of this evaluation have been used to develop tools so that the learnings from DLM can be shared with others who may be hoping to implement DLM or other similar programs.
Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice
Authors: Schmid Anna Marlene , Razim Agnieszka , Wysmołek Magdalena , Kerekes Daniela , Haunstetter Melissa , Kohl Paul , Brazhnikov Georgii , Geissler Nora , Thaler Michael , Krčmářová Eliška , Šindelář Martin , Weinmayer Tamara , Hrdý Jiří , Schmidt Katy , Nejsum Peter , Whitehead Bradley , Palmfeldt Johan , Schild Stefan , Inić-Kanada Aleksandra , Wiedermann Ursula , Schabussova Irma
Published: October 2023

Background

E. coli O83 (Colinfant Newborn) is a Gram-negative (G-) probiotic bacterium used in the clinic. When administered orally, it reduces allergic sensitisation but not allergic asthma. Intranasal administration offers a non-invasive and convenient delivery method. This route bypasses the gastrointestinal tract and provides direct access to the airways, which are the target of asthma prevention. G- bacteria such as E. coli O83 release outer membrane vesicles (OMVs) to communicate with the environment. Here we investigate whether intranasally administered E. coli O83 OMVs (EcO83-OMVs) can reduce allergic airway inflammation in mice.

Methods

EcO83-OMVs were isolated by ultracentrifugation and characterised their number, morphology (shape and size), composition (proteins and lipopolysaccharide; LPS), recognition by innate receptors (using transfected HEK293 cells) and immunomodulatory potential (in naïve splenocytes and bone marrow-derived dendritic cells; BMDCs). Their allergy-preventive effect was investigated in a mouse model of ovalbumin-induced allergic airway inflammation.

Results

EcO83-OMVs are spherical nanoparticles with a size of about 110 nm. They contain LPS and protein cargo. We identified a total of 1120 proteins, 136 of which were enriched in OMVs compared to parent bacteria. Proteins from the flagellum dominated. OMVs activated the pattern recognition receptors TLR2/4/5 as well as NOD1 and NOD2. EcO83-OMVs induced the production of pro- and anti-inflammatory cytokines in splenocytes and BMDCs. Intranasal administration of EcO83-OMVs inhibited airway hyperresponsiveness, and decreased airway eosinophilia, Th2 cytokine production and mucus secretion.

Conclusions

We demonstrate for the first time that intranasally administered OMVs from probiotic G- bacteria have an anti-allergic effect. Our study highlights the advantages of OMVs as a safe platform for the prophylactic treatment of allergy.

Graphical Abstract
Peroxiredoxin II regulates exosome secretion from dermal mesenchymal stem cells through the ISGylation signaling pathway
Authors: Han Ying-Hao , Mao Ying-Ying , Lee Kyung Ho , Cho Hee Jun , Yu Nan-Nan , Xing Xiao-Ya , Wang Ai-Guo , Jin Mei-Hua , Hong Kwan Soo , Sun Hu-Nan , Kwon Taeho
Published: October 2023

Background

Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood.

Results

In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway.

Conclusions

Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine.
Sarcopenia and myosteatosis diagnostic tool for gastrointestinal cancer: creatinine to cystatin C ratio as evaluation marker
Authors: Liu Hao , Wang Junjie , Tan Shanjun , Zhang Zhige , Yan Mingyue , Han Jun , Sui Xiangyu , Yang Fan , Wu Guohao
Published: October 2023

Objective

This study aimed to develop a simplified diagnostic tool for assessing sarcopenia and myosteatosis in gastrointestinal cancer patients, focusing on the creatinine to cystatin C ratio (CCR) as an evaluation marker.

Methods

955 patients were split into training (n = 671) and validation (n = 284) cohorts. Using logistic regression, risk factors for sarcopenia and myosteatosis were identified. The predictive capacity of the developed model was examined. The association between CCR and muscle imaging parameters, along with its impact on clinical outcomes, was analyzed.

Results

No significant differences were observed in baseline traits between cohorts. CCR emerged as a significant risk factor for both sarcopenia and myosteatosis. Nomograms for diagnosing these conditions demonstrated strong predictive ability, with AUC values indicating high accuracy (sarcopenia AUC: 0.865–0.872; myosteatosis AUC: 0.848–0.849). The clinical utility of the nomograms was confirmed through decision curve analysis. CCR showed significant association with muscle imaging parameters and was a reliable indicator for assessing the risk of sarcopenia, myosteatosis, and cachexia. Moreover, CCR was able to differentiate between patient survival and disease progression rates.

Conclusion

A diagnostic tool for sarcopenia and myosteatosis in gastrointestinal cancer patients was developed, with CCR being a pivotal biomarker for disease diagnosis and prognosis prediction.

Graphical Abstract
Circulating prolactin level in Juvenile Systemic Lupus Erythematosus and its correlation with disease activity: a case control study
Authors: Soliman Hend Mehawed , Fahmy Balsam Sherif , Ali Moataz Gamal , Shafie Eman Shafik
Published: October 2023

Background

The linkage between prolactin (PRL) and systemic lupus erythematosus (SLE) is still vague. Determination of serum levels of prolactin to reveal its role in patients with SLE is the aim of the study.

Methods

This is a case-control study performed on 40 children with SLE and 40 age- and sex-matched controls. Cases were further subdivided according to disease activity into mild, moderate, and severe groups using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score. Serum prolactin levels were assayed by ELISA (enzyme-linked immunosorbent assay).

Results

prolactin level was significantly higher in SLE patients (17.3 ± 6.6 µg/L) than in controls (13.5 ± 5.3 µg/L) (P value = 0.005). Although the prolactin level was highest in severe cases (19.3 ± 7.7 µg/L), followed by moderate cases (17.0 ± 5.3 µg/L), and lowest in mild cases (14.0 ± 6.2 µg/L), the variance between the 3 groups was not statistically significant (P value = 0.212). A significant positive correlation between prolactin level and SLEDAI score was detected (r = 0.368) (P value = 0.019). Hyperprolactinemia was found in 8 patients (20%) but not in controls; 4 out of 8 patients with hyperprolactinemia (50%) showed neurological manifestations compared to only 3 out of 32 patients with a normal prolactin level (9.4%) (P value = 0.007).

Conclusion

A relationship between serum prolactin levels and juvenile SLE disease was detected. Neurological manifestations were more prevalent among SLE patients with hyperprolactinemia.