bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot of rapid implementation of the advanced practice provider in the workflow of an existing tele-critical care program
Authors: Laudanski Krzysztof , Huffenberger Ann Marie , Scott Michael J. , Wain Justin , Ghani Danyal , Hanson C. William 
Published: July 2022

AbstractIncorporating the advanced practice provider (APP) in the delivery of tele critical care medicine (teleCCM) addresses the critical care provider shortage. However, the current literature lacks details of potential workflows, deployment difficulties and implementation outcomes while suggesting that expanding teleCCM service may be difficult. Here, we demonstrate the implementation of a telemedicine APP (eAPP) pilot service within an existing teleCCM program with the objective of determining the feasibility and ease of deployment. The goal is to augment an existing tele-ICU system with a balanced APP service to assess the feasibility and potential impact on the ICU performance in several hospitals affiliated within a large academic center. A REDCap survey was used to assess eAPP workflows, expediency of interventions, duration of tasks, and types of assignments within different service locations. Between 02/01/2021 and 08/31/2021, 204 interventions (across 133 12-h shift) were recorded by eAPP (nroutine = 109 (53.4%); nurgent = 82 (40.2%); nemergent = 13 (6.4%). The average task duration was 10.9 ± 6.22 min, but there was a significant difference based on the expediency of the task (F [2; 202] = 3.89; p < 0.022) and type of tasks (F [7; 220] = 6.69; p < 0.001). Furthermore, the eAPP task type and expediency varied depending upon the unit engaged and timeframe since implementation. The eAPP interventions were effectively communicated with bedside staff with only 0.5% of suggestions rejected. Only in 2% cases did the eAPP report distress. In summary, the eAPP can be rapidly deployed in existing teleCCM settings, providing adaptable and valuable care that addresses the specific needs of different ICUs while simultaneously enhancing the delivery of ICU care. Further studies are needed to quantify the input more robustly.
Managing innovation: a qualitative study on the implementation of telehealth services in rural emergency departments
Authors: Nataliansyah Mochamad Muska , Merchant Kimberly A. S. , Croker James A. , Zhu Xi , Mohr Nicholas M. , Marcin James P. , Rahmouni Hicham , Ward Marcia M. 
Published: July 2022

Abstract
Background
Telehealth studies have highlighted the positive benefits of having the service in rural areas. However, there is evidence of limited adoption and utilization. Our objective was to evaluate this gap by exploring U.S. healthcare systems’ experience in implementing telehealth services in rural hospital emergency departments (TeleED) and by analyzing factors influencing its implementation and sustainability.

Methods
We conducted semi-structured interviews with 18 key informants from six U.S. healthcare systems (hub sites) that provided TeleED services to 65 rural emergency departments (spoke sites). All used synchronous high-definition video to provide the service. We applied an inductive qualitative analysis approach to identify relevant quotes and themes related to TeleED service uptake facilitators and barriers.

Results
We identified three stages of implementation: 1) the start-up stage; 2) the utilization stage; and 3) the sustainment stage. At each stage, we identified emerging factors that can facilitate or impede the process. We categorized these factors into eight domains: 1) strategies; 2) capability; 3) relationships; 4) financials; 5) protocols; 6) environment; 7) service characteristics; and 8) accountability.

Conclusions
The implementation of healthcare innovation can be influenced by multiple factors. Our study contributes to the field by highlighting key factors and domains that play roles in specific stages of telehealth operation in rural hospitals. By appreciating and responding to these domains, healthcare systems may achieve more predictable and favorable implementation outcomes. Moreover, we recommend strategies to motivate the diffusion of promising innovations such as telehealth.
Reduced frequencies of Foxp3+GARP+ regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype
Authors: Hou Jia , Wang Xia , Su Chunxia , Ma Weirong , Zheng Xiwei , Ge Xiahui , Duan Xiangguo 
Published: July 2022

Abstract
Background
Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism.

Objective
To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD.

Methods
GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed.

Results
Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3+GARP+ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3+GARP− Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood.

Conclusion
Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage.
Association of circulating vaspin levels and patients with metabolic-associated fatty liver disease: a systematic review and meta-analysis
Authors: Zhu Yuqing , Ke Yani , Hu Yijie , Wu Kaihan , Liu Shan , Hu Jie 
Published: July 2022

Abstract
Background
The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals.

Methods
Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen’s kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies.

Results
The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [− 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis.

Conclusion
In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD.
Long-term cancer risk in heterozygous familial hypercholesterolemia relatives: a 25-year cohort study
Authors: Kjærgaard Kasper Aalbæk , Harborg Sixten , Jensen Henrik Kjærulf , Borgquist Signe 
Published: July 2022

Abstract
Background
Heterozygous familial hypercholesterolemia (HeFH) due to low-density lipoprotein receptor (LDLR) mutations predisposes patients to highly elevated levels of cholesterol, and patients are at increased risk of adverse cardiovascular events and other morbidities. Whether the LDLR mutation and high cholesterol levels affect the risk of cancer remains unknown. The purpose of the present study was to assess the long-term cancer risk in HeFH relatives.

Methods
Study participants were identified by cascade screening during 1992–1994. A comparison cohort was matched 10:1 to the relatives from the Danish general population based on birth year, gender and address. All participants were followed until a cancer diagnosis, migration, death, or end of follow-up as of December 31, 2019. The primary endpoint was any incident cancer diagnosis.

Results
In total, we included 221 relatives with a median age of 37 years (interquartile range: 27–53 years). A total of 117 (53%) of the relatives carried a LDLR gene mutation. The crude hazard ratio of our primary endpoint did not reveal any differences in cancer incidence in mutation-carrying relatives compared with the general population cohort (1.18; 95% CI, 0.81–1.71). Nonmutation-carrying relatives however had a lower cancer incidence than the general population (0.45: 95% CI, 0.26–0.80). Thus, the risk among mutation-carrying HeFH relatives compared with nonmutation-carrying HeFH relatives was increased (HR: 2.39; 95% CI, 1.24–4.61).

Conclusion
In Denmark, LDLR mutation-carrying HeFH relatives did not have a different cancer risk than the general population. In contrast, nonmutation-carrying relatives had a lower risk of cancer.
A longitudinal study of naloxone opioid overdose awareness and reversal training for first-year medical students: specific elements require reinforcement
Authors: Sandhu Reena K. , Heller Michael V. , Buckanavage Jack , Haslund-Gourley Benjamin , Leckron Joshua , Kupersmith Brady , Goss Nathaniel C. , Samson Kyle , Gadegbeku Annette B. 
Published: July 2022

Abstract
Background
The opioid epidemic is a progressively worsening public health crisis that continues to impact healthcare system strategies such as overdose reversal and destigmatization. Even among healthcare professionals, there remains a lack of confidence in naloxone administration and a prevalence of stigma. While training can play a major impact in reducing these shortcomings, the long-term effectiveness has yet to be characterized in training healthcare professionals. This study examined the long-term retention of opioid overdose awareness and reversal training (OOART) by evaluating performance at two-time intervals, immediately post-training and at a 3-month follow-up.

Methods
Voluntary training was offered to first-year (M1) medical students at the Drexel University College of Medicine in 2021. At this training, 118 students completed training, 95 completed the post-training survey, and 42 completed the 3-month follow-up.

Results
Opioid reversal knowledge questions assessed significantly increased scores post-training and at the 3-month follow-up. In three of the attitude questions, scores were improved at both follow-up timepoints. In addition, three attitude questions indicating a participant’s confidence to respond to an opioid overdose situation increased directly after the training, but regressed at the 3-month follow-up. The remaining questions did not show any statistical difference across the survey intervals.

Conclusions
This study establishes that while OOART provides participants with the knowledge of how to respond to an opioid overdose, the retention of this knowledge at a 3-month interval is reduced. The results were mixed for longitudinal assessment of participant’s attitudes toward people with opioid use disorder. Some positive increases in attitudes were retained at the 3-month interval, while others trended back toward pre-training levels. These results support the effectiveness of the training but also provide evidence that OOART must be reinforced often.
Follicle-stimulating hormone signaling in Sertoli cells: a licence to the early stages of spermatogenesis
Authors: Wang Jia-Ming , Li Zhen-Fang , Yang Wan-Xi , Tan Fu-Qing 
Published: July 2022

AbstractFollicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively expressed in Sertoli cells. As the only type of somatic cell in the seminiferous tubule, Sertoli cells regulate spermatogenesis not only by controlling their own number and function but also through paracrine actions to nourish germ cells surrounded by Sertoli cells. After follicle-stimulating hormone binds to its receptor and activates the follicle-stimulating hormone signaling pathway, follicle-stimulating hormone signaling will establish a normal Sertoli cell number and promote their differentiation. Spermatogonia pool maintenance, spermatogonia differentiation and their entry into meiosis are also positively regulated by follicle-stimulating hormone signaling. In addition, follicle-stimulating hormone signaling regulates germ cell survival and limits their apoptosis. Our review summarizes the aforementioned functions of follicle-stimulating hormone signaling in Sertoli cells. We also describe the clinical potential of follicle-stimulating hormone treatment in male patients with infertility. Furthermore, our review may be helpful for developing better therapies for treating patients with dysfunctional follicle-stimulating hormone signaling in Sertoli cells.
Repopulated microglia induce expression of Cxcl13 with differential changes in Tau phosphorylation but do not impact amyloid pathology
Authors: Karaahmet Berke , Le Linh , Mendes Monique S. , Majewska Ania K. , O’Banion M. Kerry 
Published: July 2022

AbstractBackgroundAdult microglia rely on self-renewal through division to repopulate and sustain their numbers. However, with aging, microglia display morphological and transcriptional changes that reflect a heightened state of neuroinflammation. This state threatens aging neurons and other cells and can influence the progression of Alzheimer’s disease (AD). In this study, we sought to determine whether renewing microglia through a forced partial depletion/repopulation method could attenuate AD pathology in the 3xTg and APP/PS1 mouse models.MethodsWe pharmacologically depleted the microglia of two cohorts of 21- to 22-month-old 3xTg mice and one cohort of 14-month-old APP/PS1 mice using PLX5622 formulated in chow for 2 weeks. Following depletion, we returned the mice to standard chow diet for 1 month to allow microglial repopulation. We assessed the effect of depletion and repopulation on AD pathology, microglial gene expression, and surface levels of homeostatic markers on microglia using immunohistochemistry, single-cell RNAseq and flow cytometry.ResultsAlthough we did not identify a significant impact of microglial repopulation on amyloid pathology in either of the AD models, we observed differential changes in phosphorylated-Tau epitopes after repopulation in the 3xTg mice. We provide evidence that repopulated microglia in the hippocampal formation exhibited changes in the levels of homeostatic microglial markers. Lastly, we identified novel subpopulations of microglia by performing single-cell RNAseq analysis on CD45int/+cells from hippocampi of control and repopulated 3xTg mice. In particular, one subpopulation induced after repopulation is characterized by heightened expression ofCxcl13.ConclusionOverall, we found that depleting and repopulating microglia causes overexpression of microglialCxcl13with disparate effects on Tau and amyloid pathologies.
A retrospective analysis of serous effusions based on the newly proposed international system for reporting serous fluid cytopathology: a report of 3633 cases in an oncological center
Authors: Zhu Yan-li , Ren Wen-hao , Wang Qian , Jin Hai-zhu , Guo Yi-yi , Lin Dong-mei 
Published: July 2022

AbstractBackgroundThe International System for Reporting Serous Fluid Cytopathology (TIS) was recently proposed. We retrospectively applied TIS recommendations for reporting the cytological diagnosis of serous effusions and reported our experience.MethodsAll the serous effusions from January 2018 to September 2021 were retrieved from the database. Recategorization was performed using the TIS classification, the risk of malignancy (ROM) was calculated for each TIS category. In addition, on the basis of the original TIS classification, we further subdivided the TIS category IV (suspicious for malignancy, SFM) into 2 groups (IVa and IVb) according to cytological characteristics (quality and quantity) to explore the necessity of SFM subclassification. The performance evaluation was carried out using different samples (pleural, peritoneal and pericardial effusions) and preparation methods (conventional smears, liquid-based preparations and cell blocks).ResultsA total of 3633 cases were studied: 17 (0.5%) were diagnosed as ‘nondiagnostic’ (I, ND), 1100 (30.3%) as ‘negative for malignancy’ (II, NFM), 101 (2.8%) as ‘atypia of undetermined significance’ (III, AUS), 677 (18.6%) as ‘suspicious for malignancy’ (IV, SFM), and 1738 (47.8%) as ‘malignant’ (V, MAL). The ROMs for the categories were 38.5%, 28.6%, 52.1%, 99.4% and 100%, respectively. The ROM for SFM was significantly higher than that for AUS (P < 0.001), while the difference between the ROMs for IVa and IVb was insignificant. The sensitivity, negative predictive value (NPV) and diagnostic accuracy of liquid-based preparations were all superior to those of conventional smears and cell blocks in detecting abnormalities. Using the three preparation methods simultaneously had the highest sensitivity, NPV and diagnostic accuracy.ConclusionSerous effusion cytology has a high specificity and positive predictive value (PPV), and TIS is a user-friendly reporting system. Liquid-based preparations could improve the sensitivity of diagnosis, and it is best to use three different preparation methods simultaneously for serous effusion cytologic examination.
Increased spine PIP3 is sequestered from dendritic shafts
Authors: Ueda Yoshibumi , Sugimoto Naotoshi , Ozawa Takeaki 
Published: July 2022

AbstractPhosphatidylinositol 3,4,5-trisphosphate (PIP3) is a lipid second messenger that is crucial for the synaptic plasticity underlying learning and memory in pyramidal neurons in the brain. Our previous study uncovered PIP3 enrichment in the dendritic spines of hippocampal pyramidal neurons in the static state using a fluorescence lifetime-based PIP3 probe. However, the extent to which PIP3 enrichment is preserved in different states has not been fully investigated. Here, we revealed that PIP3 accumulation in dendritic spines is strictly controlled even in an active state in which PIP3 is increased by glutamate stimulation and high potassium-induced membrane depolarization. Time-course PIP3 analysis clarified the gradual PIP3 accumulation in dendritic spines over days during neuronal development. Collectively, these results deepen our understanding of PIP3 dynamics in dendritic spines, and the dysregulation of the PIP3 gradient between dendritic spines and shafts could cause neuronal diseases and mental disorders, such as autism spectrum disorder.
Genetic diversity of drug-resistant Mycobacterium tuberculosis clinical isolates from Khuzestan province, Iran
Authors: Bakhtiyariniya Pejman , Khosravi Azar Dokht , Hashemzadeh Mohammad , Savari Mohammad 
Published: July 2022

AbstractThe emergence of drug-resistant strains of the Mycobacterium tuberculosis (MTB) has challenged tuberculosis control programs. So far, few studies using the 24-locus mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTR) have investigated the genetic diversity of MTB in Iran. This study aimed to determine the genetic diversity of MTB isolates resistant to first-line anti-tuberculosis drugs using 24-locus MIRU-VNTR in southwestern Iran. Out of 6620 MTB clinical isolates, 29 resistant isolates to one or more isoniazid, rifampin, and ethambutol were detected using drug susceptibility testing by the proportional method. The manual 24-locus MIRU-VNTR was used to determine the MTB resistant isolates’ phylogenetic relationship. MIRU-VNTRplus web application tools were applied to analyze the associated data. Using 24-locus MIRU-VNTR, 13.8% of isolates (n = 4) were distributed in two clusters, and the remaining 86.2% (n = 25) showed a unique pattern. Four clonal complexes were observed in the minimum spanning tree based on the double-locus variant. Most isolates belonged to Delhi/CAS (34.5%, 10/29) and NEW-1 (24.1%, 7/29) sub-lineages, followed by EAI and LAM with a frequency of 6.9% (2/29) and 3.5% (1/29), respectively. Eight isolates (27.6%) did not match any genotype in the database. The 24-locus MIRU-VNTR showed a high discriminatory power; however, the 15-locus and 12-locus set analyses were more discriminative. Our study revealed a high degree of genetic diversity among drug-resistant MTB isolates, which could be interpreted as the low rate of person-to-person transmission in this region. The 15-locus MIRU-VNTR would be recommended for preliminary genotyping of drug-resistant MTB.