bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS‐CoV‐2 ORF3a expression in brain disrupts the autophagy–lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis
Authors: Zhu Hongling , Byrnes Colleen , Lee Y. Terry , Tuymetova Galina , Duffy Hannah B. D. , Bakir Jenna Y. , Pettit Sydney N. , Angina Jabili , Springer Danielle A. , Allende Maria L. , Kono Mari , Proia Richard L.
Published: April 2023

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes injury to multiple organ systems, including the brain. SARS‐CoV‐2's neuropathological mechanisms may include systemic inflammation and hypoxia, as well as direct cell damage resulting from viral infections of neurons and glia. How the virus directly causes injury to brain cells, acutely and over the long term, is not well understood. In order to gain insight into this process, we studied the neuropathological effects of open reading frame 3a (ORF3a), a SARS‐CoV‐2 accessory protein that is a key pathological factor of the virus. Forced ORF3a brain expression in mice caused the rapid onset of neurological impairment, neurodegeneration, and neuroinflammation—key neuropathological features found in coronavirus disease (COVID‐19, which is caused by SARS‐CoV‐2 infection). Furthermore, ORF3a expression blocked autophagy progression in the brain and caused the neuronal accumulation of α‐synuclein and glycosphingolipids, all of which are linked to neurodegenerative disease. Studies with ORF3‐expressing HeLa cells confirmed that ORF3a disrupted the autophagy–lysosomal pathway and blocked glycosphingolipid degradation, resulting in their accumulation. These findings indicate that, in the event of neuroinvasion by SARS‐CoV‐2, ORF3a expression in brain cells may drive neuropathogenesis and be an important mediator of both short‐ and long‐term neurological manifestations of COVID‐19.
Understanding and Addressing Bias in Grading: Progress at Washington University School of Medicine
Authors: Colson Eve R. , Pérez Maria , Chibueze Stanley , De Fer Thomas M. , Emke Amanda R. , Lawrence Steven J. , Wilson Sherree A. , Zehnder Nichole G. , Aagaard Eva M.
Published: April 2023

In 2020, the authors published work examining disparities in clerkship grading and found students who identify as White were more likely to receive honors grades compared with students from races/ethnicities traditionally underrepresented in medicine. Through a quality improvement approach, the authors identified the following 6 areas where improvements could mitigate grading disparities and, therefore, put processes in place to: ensure equitable access to examination preparation resources, change student assessment, develop medical student curriculum interventions, improve the learning environment, change house staff and faculty recruitment and retention practices, and provide ongoing program evaluation and continuous quality improvement processes to monitor for success. While the authors cannot yet be sure that they have achieved their goal of promoting equity in grading, they believe this evidence-based, multipronged intervention is a clear step in the right direction and encourage other schools to consider a similar approach to tackling this critically important problem at their own institutions.
Reconstructing Neurath’s Ship: A Case Study in Reevaluating Equity in a Program of Assessment
Authors: Kinnear Benjamin , Weber Danielle E. , Schumacher Daniel J. , Edje Louito , Warm Eric J. , Anderson Hannah L.
Published: April 2023

Inequity in assessment has been described as a “wicked problem”—an issue with complex roots, inherent tensions, and unclear solutions. To address inequity, health professions educators must critically examine their implicit understandings of truth and knowledge (i.e., their epistemologies) with regard to educational assessment before jumping to solutions. The authors use the analogy of a ship (program of assessment) sailing on different seas (epistemologies) to describe their journey in seeking to improve equity in assessment. Should the education community repair the ship of assessment while sailing or should the ship be scrapped and built anew? The authors share a case study of a well-developed internal medicine residency program of assessment and describe efforts to evaluate and enable equity using various epistemological lenses. They first used a postpositivist lens to evaluate if the systems and strategies aligned with best practices, but found they did not capture important nuances of what equitable assessment entails. Next, they used a constructivist approach to improve stakeholder engagement, but found they still failed to question the inequitable assumptions inherent to their systems and strategies. Finally, they describe a shift to critical epistemologies, seeking to understand who experiences inequity and harm to dismantle inequitable systems and create better ones. The authors describe how each unique sea promoted different adaptations to their ship, and challenge programs to sail through new epistemological waters as a starting point for making their own ships more equitable.
The Urgency of Now: Rethinking and Improving Assessment Practices in Medical Education Programs
Authors: Holmboe Eric S. , Osman Nora Y. , Murphy Christina M. , Kogan Jennifer R.
Published: April 2023

Assessment is essential to professional development. Assessment provides the information needed to give feedback, support coaching and the creation of individualized learning plans, inform progress decisions, determine appropriate supervision levels, and, most importantly, help ensure patients and families receive high-quality, safe care in the training environment.

While the introduction of competency-based medical education has catalyzed advances in assessment, much work remains to be done. First, becoming a physician (or other health professional) is primarily a developmental process, and assessment programs must be designed using a developmental and growth mindset. Second, medical education programs must have integrated programs of assessment that address the interconnected domains of implicit, explicit and structural bias. Third, improving programs of assessment will require a systems-thinking approach.

In this paper, the authors first address these overarching issues as key principles that must be embraced so that training programs may optimize assessment to ensure all learners achieve desired medical education outcomes. The authors then explore specific needs in assessment and provide suggestions to improve assessment practices. This paper is by no means inclusive of all medical education assessment challenges or possible solutions. However, there is a wealth of current assessment research and practice that medical education programs can use to improve educational outcomes and help reduce the harmful effects of bias. The authors’ goal is to help improve and guide innovation in assessment by catalyzing further conversations.
Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial
Authors: Jeong Hyehyun , Kim Kyu-pyo , Jeong Jae Ho , Hwang Dae Wook , Lee Jae Hoon , Kim Ki-Hun , Moon Deok-Bog , Lee Myung Ah , Park Se Jun , Chon Hong Jae , Park Jin-hong , Lee Ji Sung , Ryoo Baek-Yeol , Yoo Changhoon
Published: April 2023

Background and Aims:

The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node–positive extrahepatic cholangiocarcinoma.

Approach and Results:

Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1–14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5–35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%–47.4%) and 25.1% (17.4%–33.5%) [HR=0.96 (CI, 0.71–1.30), p=0.430], and median overall survival was 35.7 months (29.5–not estimated) and 35.7 months (30.9–not estimated) [HR=1.08 (CI, 0.71–1.64), 1-sided p=0.404], respectively. Grade 3–4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported.

Conclusions:

In resected lymph node–positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.
The prevalence and treatment of hypertension in Veterans Health Administration, assessing the impact of the updated clinical guidelines
Authors: Yamada Masaaki , Wachsmuth Jason , Sambharia Meenakshi , Griffin Benjamin R. , Swee Melissa L. , Reisinger Heather Schacht , Lund Brian C. , Girotra Saket R. , Sarrazin Mary V. , Jalal Diana I.
Published: April 2023

Objective:

Hypertension is the most common risk factor for cardiovascular disease (CVD). Several guidelines have lowered diagnostic blood pressure (BP) thresholds and treatment targets for hypertension. We evaluated the impact of the more stringent guidelines among Veterans, a population at high risk of CVD.

Methods:

We conducted a retrospective analysis of Veterans with at least two office BP measurements between January 2016 and December 2017. Prevalent hypertension was defined as diagnostic codes related to hypertension, prescribed antihypertensive drugs, or office BP values according to the BP cutoffs at least 140/90 mmHg (Joint National Committee 7 [JNC 7]), at least 130/80 mmHg [American College of Cardiology/American Heart Association (ACC/AHA)], or the 2020 Veterans Health Administration (VHA) guideline (BP ≥130/90 mmHg). Uncontrolled BP was defined per the VHA guideline as mean SBP ≥130 mmHg or DBP ≥90 mmHg.

Results:

The prevalence of hypertension increased from 71% for BP at least 140/90 to 81% for BP at least 130/90 mmHg and further to 87% for BP at least 130/80 mmHg. Among Veterans with known hypertension (n = 2 768 826), a majority [n = 1 818 951 (66%)] were considered to have uncontrolled BP per the VHA guideline. Lowering the treatment targets for SBP and DBP significantly increased the number of Veterans who would require initiation of or intensification of pharmacotherapy. The majority of Veterans with uncontrolled BP and at least one CVD risk factor remained uncontrolled after 5 years of follow-up.

Conclusion:

Lowering the BP diagnostic and treatment cutoffs increases the burden on healthcare systems significantly. Targeted interventions are needed to achieve the BP treatment goals.
Effect of sacubitril/valsartan or valsartan on ventricular remodeling and myocardial fibrosis in perimenopausal women with hypertension
Authors: Chen Jianshu , Pei Ying , Wang Qiongying , Li Caie , Liang Wei , Yu Jing
Published: April 2023

Objective:

To evaluate the impact of sacubitril/valsartan on blood pressure (BP), ventricular structure, and myocardial fibrosis compared with valsartan in perimenopausal hypertensive women.

Methods:

This prospective, randomized, actively controlled, open-label study included 292 women with perimenopausal hypertension. They were randomly divided into two groups: sacubitril/valsartan 200 mg once daily and valsartan 160 mg once daily for 24 weeks. The relevant indicators of ambulatory BP, echocardiography, and myocardial fibrosis regulation were assessed at baseline and at 24 weeks.

Results:

The 24-h mean SBP after 24 weeks of treatment was 120.08 ± 10.47 mmHg in the sacubitril/valsartan group versus 121.00 ± 9.76 mmHg in the valsartan group (P = 0.457). After 24 weeks of treatment, there was no difference in central SBP between the sacubitril/valsartan and valsartan groups (117.17 ± 11.63 versus 116.38 ± 11.58, P = 0.568). LVMI in the sacubitril/valsartan group was lower than that in the valsartan group at week 24 (P = 0.009). LVMI decreased by 7.23 g/m2 from the baseline in the sacubitril/valsartan group and 3.70 g/m2 in the valsartan group at 24 weeks (P = 0.000 versus 0.017). A statistically significant difference in LVMI between the two groups was observed at 24 weeks after adjusting for the baseline LVMI (P = 0.001). The levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CT-GF) and transforming growth factor-β (TGF-β) were reduced in the sacubitril/valsartan group compared with the baseline (P = 0.000, 0.005, and 0.000). LVMI between the two groups was statistically significant at 24 weeks after correcting for confounding factors 24-h mean SBP and 24-h mean DBP (P = 0.005). The LVMI, serum TGF-β, α-SMA, and CT-GF remained statistically significant between the two groups after further correcting the factors of age, BMI, and sex hormone levels (P < 0.05).

Conclusion:

Sacubitril/valsartan could reverse ventricular remodeling more effectively than valsartan. The different effects of these two therapies on ventricular remodeling in perimenopausal hypertensive women might be because of their different effects on the down-regulation of fibrosis-related factors.
LONG-TERM PRESERVATION OF VISUAL ACUITY AFTER RESORPTION OF ACQUIRED VITELLIFORM LESIONS IN AGE-RELATED MACULAR DEGENERATION
Authors: Ramtohul Prithvi , Freund K. Bailey
Published: April 2023

Purpose:

To report the long-term (23 years) clinical and multimodal imaging features of acquired vitelliform lesions (AVLs) associated with nonneovascular age-related macular degeneration.

Methods:

Retrospective case report. Color and red-free fundus photographs, high-resolution optical coherence tomography, fluorescein and indocyanine green angiography, and optical coherence tomography-angiography were performed.

Results:

A 58-year-old man presented with bilateral AVLs in the setting of nonneovascular age-related macular degeneration. At baseline, his best-corrected visual acuity was 20/30 in his right eye and 20/20 in his left eye. Red-free fundus photographs showed AVLs with cuticular drusen in both eyes corresponding to a “stars-in-the-sky” pattern on fluorescein. Indocyanine green angiography showed no evidence of macular neovascularization. Throughout the 23-year follow-up, the patient reported consuming 20 mg/day of lutein supplement. At the end of follow-up, his best-corrected visual acuity was 20/20 in both eyes. Color fundus photographs showed resorption of the AVLs in both eyes and High-Res optical coherence tomography showed relative preservation of the outer retinal bands in the fovea. Optical coherence tomography-angiography confirmed the absence of macular neovascularization.

Conclusion:

In nonneovascular age-related macular degeneration, spontaneous resorption of AVLs may be associated with long-term maintenance of visual acuity and relative preservation of the outer retinal morphology.
An Interdisciplinary Intervention to Reduce Gastrostomy-tube-related Pediatric Emergency Department Visits
Authors: Erlick Mariah R. , Pulhamus Marsha , Schriefer Jan , Buholtz Kimberly , DiRaddo Michelle , Foito Theresa , Hill-Sober Colleen , Levatino Elizabeth , Neumeister Samantha K. , Pizzo Angie , Sosa Tina , Ruffolo Luis I. , Verna Sarah , Wakeman Derek S. , Martin Heather A.
Published: April 2023

Introduction:

Gastrostomy tube (G-tube)-related problems, including dislodgements, are a frequent cause for emergency department (ED) visits in pediatric patients. We aimed to reduce G-tube-related ED visits at our children's hospital.

Methods:

An interprofessional team was formed including a family advisor, nurse practitioners, discharge coordinators, a pediatric surgeon, surgical residents, nurses, and quality improvement coaches. A number of interventions were put into place intended to improve caregiver preparation for G-tube placement, improved communication during the hospitalization, and postoperative interventions, including a new family education pathway and mechanical barriers to prevent tube dislodgment.

Results:

Overall, tube dislodgment accounted for 64% of G-tube-related ED visits: 14% in tubes less than 3 months from insertion and 86% in tubes older than 3 months. Our rate of ED visits for G-tube dislodgement had an initial baseline of nine visits per month. In the 3 years after the intervention, ED visits decreased from a median of 9.5 per month to 8 per month.

Discussion:

An interprofessional team implemented a quality improvement project that reduced G-tube-related ED visits in pediatric patients. Further efforts are needed to better understand the contributing drivers of G-tube-related ED visits and ways to minimize these events. Grant monies have been obtained from URMC Quality Institute and Vermont Oxford Network NICU Follow Thru Health Equity to continue our family-led quality improvement efforts.
Trocar number and placement for laparoscopic sleeve gastrectomy and comparison of single-incision and conventional laparoscopic sleeve gastrectomy: a systematic review and meta-analysis
Authors: Jiang Zhengchen , Zhang Zhao , Feng Tianyi , Cheng Yugang , Zhang Guangyong , Zhong Mingwei , Hu Sanyuan
Published: April 2023

Background:

Conventional laparoscopic sleeve gastrectomy (CLSG) has been conducted in multiple centers for treating morbid obesity, however, there are no standard criteria for (1) placing the trocar; and (2) how many trocars should be used. Single-incision laparoscopic sleeve gastrectomy (SLSG), a newly emerged technique in 2008, has been proposed as an alternative to CLSG in recent years, however, there is no definite evidence for this.

Materials and methods:

A systematic literature search was performed using the PubMed, Embase, Web of Science, and Cochrane Library databases for laparoscopic sleeve gastrectomy cases from January 2006 to October 2022. We then summarized the trocar numbers and placement patterns among these studies. A meta-analysis was conducted to compare the difference between SLSG and CLSG in the perioperative and postoperative indices.

Results:

A total of 61 studies involving 20 180 patients who underwent laparoscopic sleeve gastrectomy for treating morbid obesity were included in the systematic review, including 11 on SLSG, 35 on CLSG, and 15 studies comparing SLSG and CLSG. A systematic review showed that the trocar number varied in different CLSG studies, mainly using four or five trocars. The trocars were mainly placed in position, presenting an inverted trapezoid pattern and a left-predominant pattern. Meta-analysis showed that the operative time in the SLSG was significantly higher than that in the CLSG, and the pain Visual Analog Scale rating on postoperative day 1 in the CLSG was significantly higher than in the SLSG. There were no statistical significances in the other complications or surgical efficiency.

Conclusions:

In the CLSG, the majority of the trocars were arranged in an inverted trapezoid pattern and were of the left-predominant type. Although SLSG is a feasible technique in selected patients, there is insufficient evidence to recommend its widespread use compared with CLSG. High-quality randomized controlled trials with large study populations and long follow-up periods will be required in the future.
Pediatric Walking Speed Normal Reference Values in a Local Population
Authors: Cadieux Janette M. , Pyhala Sarah L. , Johnson Jeffrey V.
Published: April 2023

Purpose:

This study's aim was to develop a local walking speed norm using the 10-m walk test (10MWT) for 5- to 17-year-old children and youth who are developing typically.

Methods:

Healthy child and adolescent participants were recruited from schools in one rural Alaska school district. The 10MWT was performed using a 2 repetitions per speed protocol. Outcome measures were average time for the normal and fast-speed trials, separated by age and gender.

Results:

Average walking speed was established in this group of children and youth who are developing typically by age and gender.

Conclusions:

Local walking speed norms for 5- to 17-year-olds can be accurately obtained by examining students in a rural school district.
Influence of Modified Instructions on Locomotion Subtest Scores Using the Peabody Developmental Motor Scales, Second Edition
Authors: Fay Deanne , Schubbe Emily , Albrecht Andy
Published: April 2023

Purpose:

The current study assessed whether changes in verbal and visual cues used to clarify requirements of the task would result in significant score differences on the Locomotion subtest of the Peabody Developmental Motor Scales, Second Edition (PDMS-2), in children aged 2.5 to 5 years.

Methods:

The Locomotion subtest of the PDMS-2 was administered twice, 2 to 10 days apart, to 37 children. Age-matched and gender-matched groups received instructions in both standardized and modified formats, where order depended on group assignment.

Results:

Instruction type resulted in a significant change in Locomotion scores with a medium effect size and no significant interactions between instruction type and age or between instruction type and test order.

Conclusions:

Findings suggest instruction modifications using altered verbal and visual cues change PDMS-2 Locomotion subtest scores in children with typical development. These results support previous literature indicating that normative scores should not be reported if modifications were used during testing.
Endoscopy in a Pediatric Patient After Necrotizing Enterocolitis
Authors: Chang Erica , Rowe Dorothy , Patel Ashish , Pasternak Brad
Published: April 2023

Necrotizing enterocolitis (NEC) is a gastrointestinal condition usually found in premature neonates. Our case involves a full-term, 3-month-old male who was found to have pneumatosis after surgical repair of congenital cardiac defects. After cessation of enteral feeds, nasogastric tube decompression, and broad-spectrum antibiotics, breast milk was reintroduced 8 days after his procedure. Hematochezia developed, but repeat abdominal X-rays were normal with benign abdominal examinations, stable vital signs, and improved laboratory findings. Although feeds were slowly restarted with an amino acid-based formula, hematochezia persisted. Meckel’s scan was negative, and Computerized Tomography revealed diffuse bowel inflammation. Esophagogastroduodenoscopy and flexible sigmoidoscopy were performed for further evaluation which showed stricture and ulceration at the descending colon. This procedure was complicated by perforation with subsequent resection of this segment and diverting ileostomy. Due to the risk of complications, it is suggested to wait at least 6 weeks from acute events such as NEC before performing an endoscopy.
Trichobezoar: A Rare Cause of Protein-losing Enteropathy
Authors: Bashir Anam , Tejada Andrea Gosalvez , Oldham Keith T. , Thakrar Pooja D. , Lerner Diana G.
Published: April 2023

Protein-losing enteropathy (PLE) is caused by protein loss through the gastrointestinal tract which results in hypoalbuminemia. The most common causes of PLE in children include cow milk protein allergy, celiac disease, inflammatory bowel disease, hypertrophic gastritis, intestinal lymphangiectasia, and right-sided heart dysfunction. We present a case of a 12-year-old male with bilateral lower extremity edema, hypoalbuminemia, elevated stool alpha-1-antitrypsin, and microcytic anemia. He was found to have a trichobezoar in the stomach extending to the jejunum, an unusual cause of PLE. The patient underwent an open laparotomy and gastrostomy to remove the bezoar. Follow-up confirmed resolution of hypoalbuminemia.
Diabetes Self-management Education and Support Completion Before and During the COVID-19 Pandemic: Results From Local Health Departments in North Carolina
Authors: Luo Huabin , Cummings Doyle M. , Xu Lei , Watson Angie , Payton Corissa
Published: April 2023

Objective:

To assess diabetes self-management education and support (DSMES) completion rate and explore the differences in DSMES completion by different delivery models.

Methods:

We conducted a retrospective analysis of 2017-2021 DSMES data at 2 local health departments (LHDs) in Eastern North Carolina. We evaluated DSMES completion by 2 delivery models.

Results:

From 2017 to 2021, the overall DSMES completion rate was 15.3%. The delivery model of two 4-hour sessions was associated with a higher completion rate than the delivery model of four 2-hour sessions (P < .05). Patients with less than a high school education and without health insurance were less likely to have completed their DSMES training (P < .05).

Conclusion:

The DSMES completion rate at LHDs in North Carolina is very low. A delivery model consisting of 10 hours of education delivered in fewer sessions may contribute to a higher DSMES completion rate, but more research is needed. Targeted programs are needed to engage patients and improve DSMES completion.
Survival outcomes in veterans with hepatocellular carcinoma, with and without HIV infection
Authors: Sada Yvonne H. , da Costa Wilson L. , Kramer Jennifer R. , Chiao Elizabeth Y. , Zafeiropoulou Efthalia , Dong Yongquan , Chen Liang , Dang Bich N.
Published: April 2023

Background:

HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual, provider, and systems-level factors.

Methods:

We conducted a retrospective cohort study of persons with HIV (PWH) matched 1 : 1 to HIV-negative controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death.

Results:

This cohort included 200 matched pairs diagnosed with HCC between 2009 and 2016. A total of 114 PWH (57.0%) and 115 HIV-negative patients (57.5%) received guideline-concordant therapy (P = 0.92). Median survival was 13.4 months [95% confidence interval (CI) 8.7–18.1] among PWH and 19.1 months (95% CI 14.6–24.9) for HIV-negative patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment predicted risk of death. HIV status was not associated with risk of death [adjusted hazard ratio (aHR) 0.95; 95% CI 0.75–1.20; P = 0.65].

Conclusion:

HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access healthcare system. These results suggest that HIV infection alone should not exclude PWH from receiving standard therapy.
Immunogenicity, effectiveness and safety of SARS-CoV-2 vaccination in people living with HIV: A systematic review and meta-analysis
Authors: Griffin David WJ , Pai Mangalore Rekha , Hoy Jennifer F , Mcmahon James H
Published: April 2023

Objectives:

People living with HIV (PLWH) experience a greater risk of morbidity and mortality following COVID-19 infection, and poorer immunological responses to several vaccines. We explored existing evidence regarding the immunogenicity, effectiveness and safety of SARS-CoV-2 vaccines in PLWH compared with controls.

Methods:

We conducted a systematic search of electronic databases from January 2020 until June 2022, in addition to conference databases, to identify studies comparing clinical, immunogenicity and safety in PLWH and controls. We compared results between those with low (<350 cells/μL) and high (>350 cells/μL) CD4+ T-cell counts where possible. We performed a meta-analysis of seroconversion and neutralisation responses to calculate a pooled risk ratio (RR) as the measure of effect.

Results

We identified thirty studies, including four reporting clinical effectiveness, 27 immunogenicity, and 12 reporting safety outcomes. PLWH were 3% (RR 0.97, 95% CI 0.95–0.99) less likely to seroconvert and 5% less likely to demonstrate neutralisation responses (RR 0.95, 95% CI 0.91–0.99) following a primary vaccine schedule. Having a CD4+ T-cell count <350 cells/μL (RR 0.91, 95% CI 0.83–0.99) compared with a CD4+ T-cell count >350 cells/μL, and receipt of a non-mRNA vaccine in PLWH compared to controls (RR 0.86, 95% CI 0.77–0.96) were associated with reduced seroconversion. Two studies reported worse clinical outcomes in PLWH.

Conclusions

While vaccines appear safe in PLWH, this group experience poorer immunological responses following vaccination than controls, particularly with non-mRNA vaccines and low CD4+ T-cell counts. PLWH should be prioritized for mRNA COVID-19 vaccines, especially PLWH with more advanced immunodeficiency.
The state of the pediatric HIV epidemic in Lesotho: results from a population-based survey
Authors: Frederix Koen , Schwitters Amee , Chung Grace , Mccracken Stephen , Kupamundi Takura , Patel Hetal K. , Arpadi Stephen , Domaoal Robert A. , Ntene-Sealiete Keletso , Thin Kyaw , Wiesner Lubbe , Low Andrea
Published: April 2023

Objective:

Lesotho does not have reliable data on HIV prevalence in children, relying on estimates generated from program data. The 2016 Lesotho Population-based HIV Impact Assessment (LePHIA) aimed to determine HIV prevalence among children 0-14 years to assess the effectiveness of the prevention of mother to child transmission (PMTCT) program and guide future policy.

Methods:

A nationally representative sample of children under 15 years underwent household-based, two-stage HIV testing from November 2016-May 2017. Children <18 months with a reactive screening test were tested for HIV infection using total nucleic acid (TNA) PCR. Parents (61.1%) or legal guardians (38.9%) provided information on children's clinical history. Children aged 10–14 years also answered a questionnaire on knowledge and behaviors.

Results:

HIV prevalence was 2.1% (95% CI: 1.5–2.6%). Prevalence in 10–14 year olds (3.2%; 95% CI: 2.1%, 4.2%) was significantly greater compared to 0–4 year olds (1.0%; 95% CI: 0.5%, 1.6%). HIV prevalence in girls and boys was 2.6% (95% CI: 1.8% – 3.3%) and 1.5% (95% CI: 1.0% – 2.1%), respectively. Based on reported status and/or the presence of detectable antiretrovirals, 81.1% (95% CI: 71.7–90.4%) of HIV-positive children were aware of their status, 98.2% (95% CI: 90.7 – 100.0%) of those aware were on ART and 73.9% (95% CI: 62.1–85.8%) of those on ART were virally suppressed.

Conclusions:

Despite the roll-out of Option B+ in Lesotho in 2013, pediatric HIV prevalence remains high. Further research is required to understand the greater prevalence among girls, barriers to PMTCT, and how to better achieve viral suppression in children living with HIV.
EFFECTS OF M101—AN EXTRACELLULAR HEMOGLOBIN—APPLIED DURING CARDIOPULMONARY RESUSCITATION: AN EXPERIMENTAL RODENT STUDY
Authors: Iten Manuela , Glas Michael , Kindler Manuel , Ostini Alessandro , Nansoz Sandra , Haenggi Matthias
Published: April 2023

During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina, applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions (P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation (P < 0.001) and acidosis decreased (P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.
Why the Treatment Sequence Matters
Authors: Wu Victoria S. , Elshami Mohamedraed , Stitzel Henry J. , Lee Jonathan J. , Hue Jonathan J. , Kyasaram Ravi K. , Hardacre Jeffrey M. , Ammori John B. , Winter Jordan M. , Selfridge Jennifer Eva , Mohamed Amr , Chakrabarti Sakti , Bajor David , Mahipal Amit , Ocuin Lee M.
Published: April 2023

Objective:

To define the optimal threshold of perioperative chemotherapy completion and relative dose intensity (RDI) for patients with resected pancreatic ductal adenocarcinoma (PDAC).

Background:

Many patients who undergo pancreatectomy for PDAC fail to initiate or complete recommended perioperative chemotherapy. The association between the amount of perioperative chemotherapy received and overall survival (OS) is not well-defined.

Methods:

Single-institution analysis of 225 patients who underwent pancreatectomy for stage I/II PDAC (2010–2021). Associations between OS, chemotherapy cycles completed, and RDI were analyzed.

Results:

Regardless of treatment sequence, completion of ≥67% of recommended cycles was associated with improved OS compared with no chemotherapy [median OS: 34.5 vs 18.1 months; hazard ratio (HR): 0.43; 95% CI: 0.25–0.74] and <67% of cycles (median OS: 17.9 months; HR: 0.39; 95% CI: 0.24–0.64). A near-linear relationship existed between cycles completed and the RDI received (β = 0.82). A median RDI of 56% corresponded to the completion of 67% of cycles. Receipt of ≥56% RDI was associated with improved OS compared with no chemotherapy (median OS: 35.5 vs 18.1 months; HR: 0.44; 95% CI: 0.23–0.84) and <56% RDI (median OS: 27.2 months; HR: 0.44; 95% CI: 0.20–0.96). Neoadjuvant chemotherapy is associated with increased odds of receiving ≥67% of recommended cycles (odds ratio: 2.94; 95% CI: 1.45–6.26) and ≥56% RDI (odds ratio: 4.47; 95% CI: 1.72–12.50).

Conclusions:

Patients with PDAC who received ≥67% of recommended chemotherapy cycles or ≥56% cumulative RDI had improved OS. Neoadjuvant therapy was associated with increased odds of receiving ≥67% of cycles and ≥56% cumulative RDI and should be considered in all patients with resectable PDAC.
Understanding how and under what circumstances integrated knowledge translation works for people engaged in collaborative research: metasynthesis of IKTRN casebooks
Authors: Dunn Sandra I. , Bhati Divya Kanwar , Reszel Jessica , Kothari Anita , McCutcheon Chris , Graham Ian D.
Published: April 2023

Introduction and aims:

Interaction and collaboration between researchers, patients/public, clinicians, managers and policy-makers are necessary to enhance the relevance and use of research, improve planning, and optimize healthcare delivery and outcomes. The Integrated Knowledge Translation Research Network (IKTRN) published four casebooks from 2019 to 2021, describing varied approaches to research co-production. Our aim was to examine the case studies to extend existing theoretical and empirical perspectives about how co-production works.

Methods:

We used metasynthesis, a qualitative research design that includes seven iterative steps (clarify the purpose, delineate the case studies included, extract and code the data, derive themes from the coded data, determine the relationships of the themes to research co-production, synthesize the concepts, and build theory).

Results:

A total of 35 cases was reviewed. The aggregate findings of this metasynthesis identified multiple contextual and process factors, barriers, and facilitators that influence integrated knowledge translation (IKT), and a range of IKT activities that increased the likelihood of success of co-production during research. In comparing the findings from the metasynthesis with existing literature, we found a number of consistencies, but also new information about barriers, facilitators, IKT activities and outcomes, thereby adding to our understanding about factors that influence co-production.

Conclusions:

This metasynthesis provided concrete examples to optimize co-produced clinical and health system research. More research is needed to fully understand how to overcome some challenging modifiable barriers, establish relationships, facilitate communication, overcome power differentials and create processes for knowledge-users working across boundaries (clinical practice and research) to stay engaged and participate fully in research endeavours.
Internal cues for optimizing reproduction in a varying environment
Authors: Law Leo , Xue BingKan
Published: April 2023

In varying environments, it is beneficial for organisms to utilize available cues to infer the conditions they may encounter and express potentially favourable traits. However, external cues can be unreliable or too costly to use. We consider an alternative strategy where organisms exploit internal sources of information. Even without sensing environmental cues, their internal states may become correlated with the environment as a result of selection, which then form a memory that helps predict future conditions. To demonstrate the adaptive value of such internal cues in varying environments, we revisit the classic example of seed dormancy in annual plants. Previous studies have considered the germination fraction of seeds and its dependence on environmental cues. In contrast, we consider a model of germination fraction that depends on the seed age, which is an internal state that can serve as a memory. We show that, if the environmental variation has temporal structure, then age-dependent germination fractions will allow the population to have an increased long-term growth rate. The more the organisms can remember through their internal states, the higher the growth rate a population can potentially achieve. Our results suggest experimental ways to infer internal memory and its benefit for adaptation in varying environments.
Transmission dynamics of lyssavirus in
Myotis myotis
: mechanistic modelling study based on longitudinal seroprevalence data
Authors: Kim Younjung , Leopardi Stefania , Scaravelli Dino , Zecchin Barbara , Priori Pamela , Festa Francesca , Drzewnioková Petra , De Benedictis Paola , Nouvellet Pierre
Published: April 2023

We investigated the transmission dynamics of lyssavirus in
Myotis myotis
and
Myotis blythii
, using serological, virological, demographic and ecological data collected between 2015 and 2022 from two maternity colonies in northern Italian churches. Despite no lyssavirus detection in 556 bats sampled over 11 events by reverse transcription-polymerase chain reaction (RT-PCR), 36.3% of 837 bats sampled over 27 events showed neutralizing antibodies to
European bat lyssavirus 1
, with a significant increase in summers. By fitting sets of mechanistic models to seroprevalence data, we investigated factors that influenced lyssavirus transmission within and between years. Five models were selected as a group of final models: in one model, a proportion of exposed bats (median model estimate: 5.8%) became infectious and died while the other exposed bats recovered with immunity without becoming infectious; in the other four models, all exposed bats became infectious and recovered with immunity. The final models supported that the two colonies experienced seasonal outbreaks driven by: (i) immunity loss particularly during hibernation, (ii) density-dependent transmission, and (iii) a high transmission rate after synchronous birthing. These findings highlight the importance of understanding ecological factors, including colony size and synchronous birthing timing, and potential infection heterogeneities to enable more robust assessments of lyssavirus spillover risk.
The human placenta: new perspectives on its formation and function during early pregnancy
Authors: Burton Graham J. , Jauniaux Eric
Published: April 2023

The placenta has evolved to support the development of the embryo and fetus during the different intrauterine periods of life. By necessity, its development must precede that of the embryo. There is now evidence that during embryogenesis and organogenesis, the development of the human placenta is supported by histotrophic nutrition secreted from endometrial glands rather than maternal blood. These secretions provide a plentiful supply of glucose, lipids, glycoproteins and growth factors that stimulate rapid proliferation and differentiation of the villous trophoblast. Furthermore, evidence from endometrial gland organoids indicates that expression and secretion of these products are upregulated following sequential exposure to oestrogen, progesterone and trophoblastic and decidual hormones, in particular prolactin. Hence, a feed-forward signalling dialogue is proposed among the trophoblast, decidua and glands that enables the placenta to stimulate its own development, independent of that of the embryo. Many common complications of pregnancy represent a spectrum of disorders associated with deficient trophoblast proliferation. Increasing evidence suggests that this spectrum is mirrored by one of impaired decidualization, potentially compromising histotroph secretion through diminished prolactin secretion and reduced gland function. Optimizing endometrial wellbeing prior to conception may therefore help to prevent common pregnancy complications, such as miscarriage, growth restriction and pre-eclampsia.
Metabolic perturbations and key pathways associated with the antibacterial activity of Clitoria ternatea flower anthocyanin fraction against Escherichia coli
Authors: Jeyaraj Ethel Jeyaseela , Han Mei-Ling , Li Jian , Choo Wee Sim
Published: April 2023

Clitoria ternatea flowers are rich in anthocyanins and possess various biological activities. Specifically, the antibacterial mechanism of action of C. ternatea anthocyanins remains unknown and was investigated in Escherichia coli. Time-kill assay was used to assess the antibacterial activity and the metabolic perturbations in E. coli were investigated utilising LC-MS-based metabolomics. Pathway analyses were carried out for metabolites showing ≥ 2-fold changes. The anthocyanin fraction remarkably reduced the growth of E. coli at 4 h by 95.8 and 99.9% at minimum inhibitory concentration (MIC) and 2 × MIC, respectively. The antibacterial activity of the anthocyanin fraction (MIC) was shown to have perturbed glycerophospholipids (1-Acyl-sn-glycero-3-phosphoethanolamine, phosphatidylglycerol, diacylglycerol and cardiolipin), amino acids (valine, tyrosine and isoleucine) and energy (ubiquinone and NAD) metabolites at 1 and 4 h. This study demonstrated significant metabolic perturbations of the glycerophospholipid, amino acid and energy metabolism being the key pathways involved in the antibacterial activity of anthocyanins from C. ternatea and has promising potential as antibacterial agents for E. coli-related infections.
An insight into seroepidemiology and dynamics of circulating serotypes of Dengue virus over a four year period from western Uttar Pradesh, India
Authors: Mustafa Zeeshan , Khan Haris Manzoor , Azam Mohd , Sami Hiba , Ali Syed Ghazanfar , Ahmad Islam , Raza Adil , Khan Mohammad Azam
Published: April 2023

An important public health problem in India is dengue infection, and every year there is an increase in dengue cases. Dengue affects all individuals irrespective of their gender and age, but still, the infection rate was higher among males and younger ones. Despite low severity in general, the dengue virus can cause severe health conditions in some individuals. Genetic characterization of the circulating endemic dengue virus (DENV) serotypes plays a significant role in establishing epidemiological knowledge and subsequent vaccine development. In the present study, over a 4-yr period, we tried to figure out the dengue virus transmission dynamics in major regions of western Uttar Pradesh in North India. ELISA tests were used to diagnose dengue, and PCRs were used to determine the circulating serotype. We found that dengue infection peaks after the rainy season and affects all sexes and ages. A total of 1277 individuals were found positive for dengue; among them, 61.7% were males, and 38.3% were females. DEN-1 was found in 23.12%, DEN-2 in 45%, DEN-3 in 29.06%, and DEN-4 in 1.5% of the dengue-infected individuals. All four dengue virus serotypes are circulating in the study area, and dengue virus serotype-2 (DEN-2) is the most prevalent serotype.
A context-based chatbot surpasses trained radiologists and generic ChatGPT in following the ACR appropriateness guidelines
Authors: Rau A , Rau S , Fink A , Tran H , Wilpert C , Nattenmueller J , Neubauer J , Bamberg F , Reisert M , Russe MF
Published: April 2023

Background

Radiological imaging guidelines are crucial for accurate diagnosis and optimal patient care as they result in standardized procedures and thus reduce inappropriate imaging studies. In the present study, we investigated the potential to support clinical decision-making using an interactive chatbot designed to provide personalized imaging recommendations based on indexed and vectorized American College of Radiology (ACR) appropriateness criteria documents.

Methods

We utilized 209 ACR appropriateness criteria documents as specialized knowledge base and employed LlamaIndex and the ChatGPT 3.5-Turbo to create an appropriateness criteria contexted chatbot (accGPT). Fifty clinical case files were used to compare the accGPT’s performance against radiologists at varying experience levels and to generic ChatGPT 3.5 and 4.0.

Results

All chatbots reached at least human performance level. For the 50 case files, the accGPT provided a median of 83% (95% CI 82-84) ‘usually appropriate’ recommendations, while radiologists provided a median of 66% (95% CI 62-70). GPT 3.5-Turbo 70% (95% CI 67-73) and GPT 4 79% (95% CI 76-81) correct answers. Consistency was highest for the accGPT with almost perfect Fleiss’ Kappa of 0.82. Further, the chatbots provided substantial time and cost savings, with an average decision time of 5 minutes and a cost of 0.19 Euro for all cases, compared to 50 minutes and 29.99 Euro for radiologists (both p < 0.01).

Conclusion

ChatGPT-based algorithms have the potential to substantially improve the decision-making for clinical imaging studies in accordance with ACR guidelines. Specifically, a context-based algorithm performed superior to its generic counterpart, demonstrating the value of tailoring AI solutions to specific healthcare applications.