bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of telemedicine workflows in nursing homes during the COVID-19 pandemic
Authors: Ford James H , Jolles Sally A , Heller Dee , Crnich Christopher 
Published: March 2023

Abstract
Background
The use of telemedicine increased dramatically in nursing homes (NHs) during the COVID-19 pandemic. However, little is known about the actual process of conducting a telemedicine encounter in NHs. The objective of this study was to identify and document the work processes associated with different types of telemedicine encounters conducted in NHs during the COVID-19 pandemic.

Methods
A mixed methods convergent study was utilized. The study was conducted in a convenience sample of two NHs that had newly adopted telemedicine during the COVID-19 pandemic. Participants included NH staff and providers involved in telemedicine encounters conducted in the study NHs. The study involved semi-structured interviews and direct observation of telemedicine encounters and post-encounter interviews with staff and providers involved in telemedicine encounters observed by research staff. The semi-structured interviews were structured using the Systems Engineering Initiative for Patient Safety (SEIPS) model to collect information about telemedicine workflows. A structured checklist was utilized to document steps performed during direct observations of telemedicine encounters. Information from interviews and observations informed the creation of a process map of the NH telemedicine encounter.

Results
A total of 17 individuals participated in semi-structured interviews. Fifteen unique telemedicine encounters were observed. A total of 18 post-encounter interviews with 7 unique providers (15 interviews in total) and three NH staff were performed. A 9-step process map of the telemedicine encounter, along with two microprocess maps related to encounter preparation and activities within the telemedicine encounter, were created. Six main processes were identified: encounter planning, family or healthcare authority notification, pre-encounter preparation, pre-encounter huddle, conducting the encounter, and post-encounter follow-up.

Conclusion
The COVID-19 pandemic changed the delivery of care in NHs and increased reliance on telemedicine services in these facilities. Workflow mapping using the SEIPS model revealed that the NH telemedicine encounter is a complex multi-step process and identified weaknesses related to scheduling, electronic health record interoperability, pre-encounter planning, and post-encounter information exchange, which represent opportunities to improve and enhance the telemedicine encounter process in NHs. Given public acceptance of telemedicine as a care delivery model, expanding the use of telemedicine beyond the COVID-19 pandemic, especially for certain NH telemedicine encounters, could improve quality of care.
Gram-negative bacteria resist antimicrobial agents by a DzrR-mediated envelope stress response
Authors: Liang Zhibin , Lin Qiqi , Wang Qingwei , Huang Luhao , Liu Huidi , Shi Zurong , Cui Zining , Zhou Xiaofan , Gao Yong-Gui , Zhou Jianuan , Zhang Lian-Hui , Deng Yizhen 
Published: March 2023

AbstractBackgroundEnvelope stress responses (ESRs) are critical for adaptive resistance of Gram-negative bacteria to envelope-targeting antimicrobial agents. However, ESRs are poorly defined in a large number of well-known plant and human pathogens.Dickeya oryzaecan withstand a high level of self-produced envelope-targeting antimicrobial agents zeamines through a zeamine-stimulated RND efflux pump DesABC. Here, we unraveled the mechanism ofD.oryzaeresponse to zeamines and determined the distribution and function of this novel ESR in a variety of important plant and human pathogens.ResultsIn this study, we documented that a two-component system regulator DzrR ofD. oryzaeEC1 mediates ESR in the presence of envelope-targeting antimicrobial agents. DzrR was found modulating bacterial response and resistance to zeamines through inducing the expression of RND efflux pump DesABC, which is likely independent on DzrR phosphorylation. In addition, DzrR could also mediate bacterial responses to structurally divergent envelope-targeting antimicrobial agents, including chlorhexidine and chlorpromazine. Significantly, the DzrR-mediated response was independent on the five canonical ESRs. We further presented evidence that the DzrR-mediated response is conserved in the bacterial species ofDickeya,Ralstonia, andBurkholderia, showing that a distantly located DzrR homolog is the previously undetermined regulator of RND-8 efflux pump for chlorhexidine resistance inB. cenocepacia.ConclusionsTaken together, the findings from this study depict a new widely distributed Gram-negative ESR mechanism and present a valid target and useful clues to combat antimicrobial resistance.
Ethnic minority representation in UK COVID-19 trials: systematic review and meta-analysis
Authors: Murali Mayur , Gumber Leher , Jethwa Hannah , Ganesh Divolka , Hartmann-Boyce Jamie , Sood Harpreet , Zaccardi Francesco , Khunti Kamlesh 
Published: March 2023

Abstract
Background
The COVID-19 pandemic has highlighted health disparities affecting ethnic minority communities. There is growing concern about the lack of diversity in clinical trials. This study aimed to assess the representation of ethnic groups in UK-based COVID-19 randomised controlled trials (RCTs).

Methods
A systematic review and meta-analysis were undertaken. A search strategy was developed for MEDLINE (Ovid) and Google Scholar (1st January 2020–4th May 2022). Prospective COVID-19 RCTs for vaccines or therapeutics that reported UK data separately with a minimum of 50 participants were eligible. Search results were independently screened, and data extracted into proforma. Percentage of ethnic groups at all trial stages was mapped against Office of National Statistics (ONS) statistics. Post hoc DerSimonian-Laird random-effects meta-analysis of percentages and a meta-regression assessing recruitment over time were conducted. Due to the nature of the review question, risk of bias was not assessed. Data analysis was conducted in Stata v17.0. A protocol was registered (PROSPERO CRD42021244185).

Results
In total, 5319 articles were identified; 30 studies were included, with 118,912 participants. Enrolment to trials was the only stage consistently reported (17 trials). Meta-analysis showed significant heterogeneity across studies, in relation to census-expected proportions at study enrolment. All ethnic groups, apart from Other (1.7% [95% CI 1.1–2.8%] vs ONS 1%) were represented to a lesser extent than ONS statistics, most marked in Black (1% [0.6–1.5%] vs 3.3%) and Asian (5.8% [4.4–7.6%] vs 7.5%) groups, but also apparent in White (84.8% [81.6–87.5%] vs 86%) and Mixed 1.6% [1.2–2.1%] vs 2.2%) groups. Meta-regression showed recruitment of Black participants increased over time (p = 0.009).

Conclusions
Asian, Black and Mixed ethnic groups are under-represented or incorrectly classified in UK COVID-19 RCTs. Reporting by ethnicity lacks consistency and transparency. Under-representation in clinical trials occurs at multiple levels and requires complex solutions, which should be considered throughout trial conduct. These findings may not apply outside of the UK setting.
The normality assumption on between-study random effects was questionable in a considerable number of Cochrane meta-analyses
Authors: Liu Ziyu , Al Amer Fahad M. , Xiao Mengli , Xu Chang , Furuya-Kanamori Luis , Hong Hwanhee , Siegel Lianne , Lin Lifeng 
Published: March 2023

Abstract
Background
Studies included in a meta-analysis are often heterogeneous. The traditional random-effects models assume their true effects to follow a normal distribution, while it is unclear if this critical assumption is practical. Violations of this between-study normality assumption could lead to problematic meta-analytical conclusions. We aimed to empirically examine if this assumption is valid in published meta-analyses.

Methods
In this cross-sectional study, we collected meta-analyses available in the Cochrane Library with at least 10 studies and with between-study variance estimates > 0. For each extracted meta-analysis, we performed the Shapiro–Wilk (SW) test to quantitatively assess the between-study normality assumption. For binary outcomes, we assessed between-study normality for odds ratios (ORs), relative risks (RRs), and risk differences (RDs). Subgroup analyses based on sample sizes and event rates were used to rule out the potential confounders. In addition, we obtained the quantile–quantile (Q–Q) plot of study-specific standardized residuals for visually assessing between-study normality.

Results
Based on 4234 eligible meta-analyses with binary outcomes and 3433 with non-binary outcomes, the proportion of meta-analyses that had statistically significant non-normality varied from 15.1 to 26.2%. RDs and non-binary outcomes led to more frequent non-normality issues than ORs and RRs. For binary outcomes, the between-study non-normality was more frequently found in meta-analyses with larger sample sizes and event rates away from 0 and 100%. The agreements of assessing the normality between two independent researchers based on Q–Q plots were fair or moderate.

Conclusions
The between-study normality assumption is commonly violated in Cochrane meta-analyses. This assumption should be routinely assessed when performing a meta-analysis. When it may not hold, alternative meta-analysis methods that do not make this assumption should be considered.
Association of the American Heart Association’s new “Life’s Essential 8” with all-cause and cardiovascular disease-specific mortality: prospective cohort study
Authors: Sun Jiahong , Li Yanzhi , Zhao Min , Yu Xiao , Zhang Cheng , Magnussen Costan G. , Xi Bo 
Published: March 2023

Abstract
Background
The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life’s Essential 8. We examined the association of total and individual CVH metrics according to Life’s Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in life.

Methods
Data were from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0–49 (low level), 50–74 (intermediate level), and 75–100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose–response analysis. The main outcomes included all-cause and CVD-specific mortality.

Results
A total of 19,951 US adults aged 30–79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51–0.71) and 58% (adjusted HR 0.42, 95% CI 0.32–0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46–0.83) and 0.36 (0.21–0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score < 75 points) CVH scores were 33.4% for all-cause mortality and 42.9% for CVD-specific mortality. Among all 8 individual CVH metrics, physical activity, nicotine exposure, and diet accounted for a large proportion of the population-attributable risks for all-cause mortality, whereas physical activity, blood pressure, and blood glucose accounted for a large proportion of CVD-specific mortality. There were approximately linear dose–response associations of total CVH score (as a continuous variable) with all-cause and CVD-specific mortality.

Conclusions
Achieving a higher CVH score according to the new Life’s Essential 8 was associated with a reduced risk of all-cause and CVD-specific mortality. Public health and healthcare efforts targeting the promotion of higher CVH scores could provide considerable benefits to reduce the mortality burden later in life.
Total portal vein replacement with peritoneal interposition graft during Whipple’s procedure for extrahepatic cholangiocarcinoma: a technical report
Authors: Marino Rebecca , Tudisco Antonella , Ratti Francesca , Pedica Federica , Aldrighetti Luca 
Published: March 2023

Abstract
Background
Aggressive surgical resection in locally advanced hepatopancreatobiliary (HPB) malignancies is frequently advocated as the only potentially curative treatment. In recent years, advances in chemotherapy regimens and surgical techniques have led to improved oncologic outcomes and overall survival, by increasing the rates of radical (R0) resections. Vascular resections are increasingly reported to further increase disease clearance rates. Within this perspective, the issue of vascular reconstruction has raised growing interest, drawing particular attention to vascular substitutes and surgical techniques for reconstruction.

Case presentation
A case of extrahepatic cholangiocarcinoma with high clinical suspicion of vascular infiltration of the portal trunk at preoperative assessment is reported. An autologous interposition graft, harvested from diaphragmatic peritoneum, was chosen as a vascular substitute leading to successful portal trunk reconstruction and overcoming all possible drawbacks associated with cadaveric and artificial grafts reconstructions.

Conclusion
This solution was strategic to ensure complete oncologic clearance averting the risk of positive margins (R1) at final pathology.
Behavioral phenotype, intestinal microbiome, and brain neuronal activity of male serotonin transporter knockout mice
Authors: Shoji Hirotaka , Ikeda Kazutaka , Miyakawa Tsuyoshi 
Published: March 2023

AbstractThe serotonin transporter (5-HTT) plays a critical role in the regulation of serotonin neurotransmission. Mice genetically deficient in 5-HTT expression have been used to study the physiological functions of 5-HTT in the brain and have been proposed as a potential animal model for neuropsychiatric and neurodevelopmental disorders. Recent studies have provided evidence for a link between the gut-brain axis and mood disorders. However, the effects of 5-HTT deficiency on gut microbiota, brain function, and behavior remain to be fully characterized. Here we investigated the effects of 5-HTT deficiency on different types of behavior, the gut microbiome, and brain c-Fos expression as a marker of neuronal activation in response to the forced swim test for assessing depression-related behavior in male 5-HTT knockout mice. Behavioral analysis using a battery of 16 different tests showed that 5-HTT−/− mice exhibited markedly reduced locomotor activity, decreased pain sensitivity, reduced motor function, increased anxiety-like and depression-related behavior, altered social behavior in novel and familiar environments, normal working memory, enhanced spatial reference memory, and impaired fear memory compared to 5-HTT+/+ mice. 5-HTT+/− mice showed slightly reduced locomotor activity and impaired social behavior compared to 5-HTT+/+ mice. Analysis of 16S rRNA gene amplicons showed that 5-HTT−/− mice had altered gut microbiota abundances, such as a decrease in Allobaculum, Bifidobacterium, Clostridium sensu stricto, and Turicibacter, compared to 5-HTT+/+ mice. This study also showed that after exposure to the forced swim test, the number of c-Fos-positive cells was higher in the paraventricular thalamus and lateral hypothalamus and was lower in the prefrontal cortical regions, nucleus accumbens shell, dorsolateral septal nucleus, hippocampal regions, and ventromedial hypothalamus in 5-HTT−/− mice than in 5-HTT+/+ mice. These phenotypes of 5-HTT−/− mice partially recapitulate clinical observations in humans with major depressive disorder. The present findings indicate that 5-HTT-deficient mice serve as a good and valid animal model to study anxiety and depression with altered gut microbial composition and abnormal neuronal activity in the brain, highlighting the importance of 5-HTT in brain function and the mechanisms underlying the regulation of anxiety and depression.
Reduced burden of antibiotic prescription in an italian pediatric primary care clinic during the first wave of COVID-19 pandemic: a shot in the arm for antimicrobial resistance?
Authors: Monzani Alice , Minelli Giulia , Rabbone Ivana 
Published: March 2023

AbstractRates of antibiotic-resistant bacteria have increased worldwide over recent years, but the Italian Institute of Health reported a disruption to this trend in 2021 compared with 2020. Children are often recipients of unnecessary antibiotic prescriptions, especially for respiratory tract infections (RTIs). During the initial phase of the COVID-19 pandemic, common RTIs substantially decreased, so it is conceivable that antibiotic prescriptions also reduced during this time. To test this hypothesis, we retrospectively collected data on all visits to a pediatric primary care clinic in Northern Italy from February 20, 2020 to June 2, 2020 and compared data with the same period in 2019. We evaluated the antibiotic prescription rate according to the diagnosis at discharge. While the total number of visits significantly decreased (1335 in 2020 vs. 4899 in 2019), there was only a slight reduction in the antibiotic prescription rate (1039 in 2019, 21.2%, vs. 272 in 2020, 20.4%). However, this corresponded to a 73.8% decrease in the total number of antibiotic prescriptions, with antibiotics for RTI accounting for 69% of the total reduction. It is possible that, at the larger scale, reduced antibiotic prescription in pediatrics during the COVID-19 pandemic resulted in a slight reduction in antimicrobial resistance.
Hearing loss: an unusual presentation of neurobrucellosis: a case report
Authors: Sah Prem Kumar , Lamichhane Hari Krishna , Tariq Ezza Fatima , Saroj K. C. , Adhikari Prabhat 
Published: March 2023

Abstract
Introduction
Brucellosis is a zoonotic disease, caused by a Gram-negative coccobacillus of Brucella genus, transmitted to humans by animals, especially cattle. It rarely involves the nervous system (neurobrucellosis); only a few cases present with hearing loss. We report a case of neurobrucellosis, that presented with bilateral sensorineural hearing loss and mild to moderate persistent headache. To the best of our knowledge, this is the first well-documented case from Nepal.

Case presentation
The patient was a 40-year-old Asian male shepherd from the western mountainous region of Nepal who came to the emergency department of Manipal Teaching Hospital, Pokhara in May, 2018 and did a follow-up for 6 months. He presented with high-grade fever, profuse sweating, headache, myalgia, and bilateral sensorineural hearing loss. His history of consuming raw milk of cattle, symptoms including persistent mild to moderate headache, bilateral hearing loss, and serological findings were suggestive of neurobrucellosis. Following treatment, the symptoms improved, including the complete recovery of hearing loss.

Conclusion
Hearing loss may be the manifestation of neurobrucellosis. Physicians should know about such presentations in brucella endemic areas.
Idiosyncratic drug-induced liver injury related to use of novel selective androgen receptor modulator RAD140 (Testalone): a case report
Authors: Ladna Michael , Taylor Kellee , Bhat Adnan , Dideban Bahram 
Published: March 2023

Abstract
Background
RAD140 (Testalone) is a novel selective androgen receptor modulator with very limited data currently available on adverse effects related to this compound. The first-in-human phase 1 trial was recently published and did report a significant proportion of elevated aspartate aminotransferase, alanine transaminase, and total bilirubin among the test subjects. RAD140 may be associated with an idiosyncratic drug-induced liver injury. It is easily purchased online as a workout supplement. Given its ease of use from being an oral formulation, and not requiring a physician’s prescription, its use among the young male population will likely rise. Clinicians should ask about the use of RAD140, and other workout supplements, in young men presenting with acute liver injury.

Case presentation
We present the case of a 26-year-old Caucasian male without any significant past medical history who presented with nausea, vomiting, severe right upper quadrant abdominal pain, and jaundice from acute liver injury. Extensive inpatient workup did not reveal a definite cause for his liver injury other than the use of a novel selective androgen receptor modulator called RAD140 (Testalone). He was treated with supportive care and discharged after short hospitalization. He was instructed to stop RAD140, which he reported compliance with, and on 2-month follow-up his liver function panel had normalized without recurrence of any symptoms.

Conclusion
Novel selective androgen receptor modulators such as RAD140 may be associated with idiosyncratic drug-induced liver injury. Workup of new liver injury in young and middle-aged males should involve asking about use of these novel compounds, for if missed and use continues, it can likely lead to fulminant liver failure or decompensated liver cirrhosis.
MiR-21-5p regulates the dynamic of mitochondria network and rejuvenates the senile phenotype of bone marrow stromal cells (BMSCs) isolated from osteoporotic SAM/P6 mice
Authors: Sikora Mateusz , Śmieszek Agnieszka , Pielok Ariadna , Marycz Krzysztof 
Published: March 2023

Abstract
Background
Progression of senile osteoporosis is associated with deteriorated regenerative potential of bone marrow-derived mesenchymal stem/stromal cells (BMSCs). According to the recent results, the senescent phenotype of osteoporotic cells strongly correlates with impaired regulation of mitochondria dynamics. Moreover, due to the ageing of population and growing osteoporosis incidence, more efficient methods concerning BMSCs rejuvenation are intensely investigated. Recently, miR-21-5p was reported to play a vital role in bone turnover, but its therapeutic mechanisms in progenitor cells delivered from senile osteoporotic patients remain unclear. Therefore, the goal of this paper was to investigate for the first time the regenerative potential of miR-21-5p in the process of mitochondrial network regulation and stemness restoration using the unique model of BMSCs isolated from senile osteoporotic SAM/P6 mice model.

Methods
BMSCs were isolated from healthy BALB/c and osteoporotic SAM/P6 mice. We analysed the impact of miR-21-5p on the expression of crucial markers related to cells’ viability, mitochondria reconstruction and autophagy progression. Further, we established the expression of markers vital for bone homeostasis, as well as defined the composition of extracellular matrix in osteogenic cultures. The regenerative potential of miR-21 in vivo was also investigated using a critical-size cranial defect model by computed microtomography and SEM–EDX imaging.

Results
MiR-21 upregulation improved cells’ viability and drove mitochondria dynamics in osteoporotic BMSCs evidenced by the intensification of fission processes. Simultaneously, miR-21 enhanced the osteogenic differentiation of BMSCs evidenced by increased expression of Runx-2 but downregulated Trap, as well as improved calcification of extracellular matrix. Importantly, the analyses using the critical-size cranial defect model indicated on a greater ratio of newly formed tissue after miR-21 application, as well as upregulated content of calcium and phosphorus within the defect site.

Conclusions
Our results demonstrate that miR-21-5p regulates the fission and fusion processes of mitochondria and facilitates the stemness restoration of senile osteoporotic BMSCs. At the same time, it enhances the expression of RUNX-2, while reduces TRAP accumulation in the cells with deteriorated phenotype. Therefore, miR-21-5p may bring a novel molecular strategy for senile osteoporosis diagnostics and treatment.