bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges and chances coexist: A visualized analysis and bibliometric study of research on bioresorbable vascular scaffolds from 2000 to 2022
Authors: Zhang Xiaohan , Guo Zezhen , Zhu Lihong , Liu Yao , Wang Huan , Jiang Yuchen , Du Bai , Hu Yuanhui
Published: June 2023

Background:

Bioresorbable scaffolds (BVS) provide a transient supporting force for blocked vessels and allow them to return to previous physiological characteristics. After verification with twists and turns, it has been acknowledged as an emerging revolution in percutaneous coronary intervention that expresses the current concept of intervention without placement. Through this bibliometric study, we organized the knowledge structure of bioresorbable scaffolds and attempted to predict future research hotspots in this field.

Methods:

seven thousand sixty-three articles were retrieved from the web of science core collection database from 2000 to 2022. Then, we utilize CiteSpace 6.1.R2, Biblioshiny and VOS viewer 1.6.18 to analyze the data visually.

Results:

First, according to the spatial analysis, the number of annual publications has shown an approximately increasing trend over the past 2 decades. The USA, the People’s Republic of China, and GERMANY published the most articles on bioresorbable scaffolds. Second, SERRUYS P ranked first for his most prolific work and highest cited frequency in this domain. Third, the hotspots in this field can be inferred from the keyword distribution; they were the fabrication technique based on tissue engineering; the factors to be optimized for bioresorbable scaffolds, such as mechanical property, degradation, and implantation; and the common adverse effects of bioresorbable scaffolds, such as thrombosis. Most importantly, in terms of burst detection, we could speculate that cutting-edge technology for manufacturing scaffolds represented by 3D printing constitutes the future hotspots in bioresorbable scaffold development.

Conclusion:

In the first visualized bibliometric analysis of BVS, we attempt to provide a panoramic view. By enrolling extensive literature, we review the growing trend of BVSs. Since its first introduction, it has been through periods of early prosperity, questioned safety subsequently and the resultantly advanced techniques in recent years. In future, the research should focus on utilizing novel techniques to consummate the manufacturing quality and assure the safety of BVSs.
Effects of physical activity interventions on anthropometric indicators and health indices in Chilean children and adolescents: A protocol for systematic review and/or meta-analysis
Authors: Godoy-Cumillaf Andrés , Farías-Valenzuela Claudio , Duclos-Bastías Daniel , Giakoni-Ramírez Frano , Vásquez-Gómez Jaime , Bruneau-Chávez José , Bizzozero-Peroni Bruno
Published: June 2023

Introduction:

Physical activity interventions have been a proven effective means of preventing or treating overweight and obesity in children and adolescents. The results of these interventions in many cases are based on the determination of the effect they produce on anthropometric evaluations, which allow the calculation of health indices. However, the effects of physical activity interventions on anthropometric assessments in Chilean children and adolescents have not been systematized. The objective of this study is to provide a detailed protocol for a systematic review with meta-analysis that synthesizes the available evidence on the effect of physical activity interventions on anthropometric indicators and health indices in Chilean children and adolescents and identifies the field-based methods and health indices most used for body composition estimation.

Methods:

This protocol was performed according to the PRISMA declaration. MEDLINE (PubMed), Web of Science, Scopus, and Scielo databases will be systematically searched. Eligible studies will include randomized controlled trials (RCTs), non-RCTs and pre-post studies.

Conclusion:

This systematic review and meta-analysis protocol is designed to provide up-to-date evidence that could significantly assist public health policy makers and implementers of physical activity interventions through evidence-based guidance and recommendations.
Dorsal pancreatic agenesis: a case report
Authors: Dhakal Binaya , Pant Sujit , Choudhary Saroj , Basnet Bina , Neupane Shanta
Published: June 2023

Introduction and importance:

The pancreas develops from a small ventral bud and a larger dorsal bud. During the rotation of the foregut, the ventral pancreas rotates toward the dorsal pancreas and joins together to form a complete pancreas with ducts. Among the various developmental congenital anomalies, dorsal pancreatic agenesis is one of the rare entities, with less than a hundred cases reported so far. It involves the absence of the dorsal bud derivatives (head, body, and tail).

Case presentation:

Herein, we present a case of a 50-year-old woman who presented to general outpatient department with a complaint of abdominal pain. The patient was diagnosed with cholelithiasis with a contrast-enhanced computed tomography finding of dorsal pancreatic agenesis on a detailed workup. However, the patient did not have any other associated anomalies or symptoms associated with dorsal pancreatic agenesis. The patient was managed for cholelithiasis with laparoscopic cholecystectomy.

Clinical discussion:

Failure in development due to aberrant embryogenesis may cause partial or complete agenesis of the dorsal pancreas. The minor papilla, the accessory pancreatic duct, the body, and the tail of the pancreas are not present in the case of complete dorsal agenesis. Most cases of dorsal pancreatic agenesis are asymptomatic and diagnosed incidentally, whereas some of the cases may present with other associated abnormalities. It is almost always diagnosed via imaging modalities.

Conclusion:

Dorsal pancreatic agenesis is a very rare congenital anomaly of the pancreas. It can be diagnosed via various imaging modalities and almost always remains a radiological diagnosis with incidental findings.
An institutional experience of hydatidosis and cysticercosis in Nepal: a retrospective chart review
Authors: Sharma Nisha , Tiwari Sansar B. , Gaire Prabin , Manandhar Usha , Bohara Sujan , Nepal Gaurav
Published: June 2023

Background:

This study aimed to investigate the demographic characteristics, anatomical distribution, and histopathological features of hydatidosis and cysticercosis in a Nepalese population presenting to a tertiary care hospital. The study also aimed to provide a better understanding of the clinical and pathological aspects of these diseases in the local context.

Methods:

This retrospective study analyzed all cases of hydatidosis and cysticercosis reported in the Department of Pathology at Tribhuvan University Teaching Hospital between January 2013 and December 2019. Demographic, clinical, radiological, and histopathological data were collected and analyzed from hospital charts.

Results:

During the 7-year study period, the authors identified 112 cases of hydatid cysts and 26 cases of cysticercosis. The mean age of patients with hydatidosis was 33.86 years (range: 5–74 years), while the mean age of patients with cysticercosis was 25.39 years (range: 4–63 years). Females were more commonly affected with hydatidosis (68, 61.7%) than males (44, 39.3%), resulting in a male-to-female ratio of 0.6:1. In contrast, there was no significant sex difference in cysticercosis cases, with 14 (53.85%) males and 12 (46.15%) females affected. The most commonly affected site for hydatid cysts was the lung (47 cases, 42%), followed by the liver (41 cases, 36.6%). The study identified three cases of neurocysticercosis. The average diameter of hydatid cysts and cysticercosis was 8.7 cm and 1.7 cm, respectively.

Conclusion:

In conclusion, our study provides important insights into the clinical and pathological features of hydatidosis and cysticercosis in a Nepalese population. These zoonotic diseases pose a significant health burden, particularly among the poor and marginalized populations. Our findings highlight the need to integrate prevention and control measures into the healthcare system to decrease the overall burden of these diseases.
Malignant cerebral edema after cranioplasty, a rare complication: case series and literature review
Authors: Bui Manh Huy , Dong He Van , Duong Ha Dai , VAN Hanh Duc , Dong Son Van , Bui Cuong Xuan , Chu Hung Thanh
Published: June 2023

Objective:

Cranioplasty is standard neurosurgery performed after decompressive craniectomy. Fatal malignant cerebral oedema complications associated with this procedure are rare and clinically distinct, although unpredictable. It is thought that the pressure difference from removing atmospheric pressure had a long-term effect on the brain. This combined with the negative pressure applied by intraoperative pressure drainage may impact the perfusion brain. Here, the authors report four cases of cerebral oedema after cranioplasty and review similar cases in the literature.

Case presentation:

The authors report on four cases of patients who underwent cranioplasty following decompressive craniotomy and subsequently died after surgery. Three of the patients had undergone craniotomy following trauma, while one patient had skull resorption. All four patients developed cerebral oedema immediately after surgery and exhibited significant craniofacial depression (also known as sunk flap syndrome). A negative pressure drainage system was utilized in all cases. One patient remained intubated, while the remaining three developed postoperative epilepsy and subsequently fell into a coma. Dilated and fixed pupils were observed in all patients, and computed tomography scans revealed diffuse cerebral oedema. Despite intensive resuscitation efforts and attempts at decompression, all four patients ultimately succumbed to their conditions.

Conclusion:

Fatal post-cranioplasty malignant cerebral oedema is a rare but very dangerous complication. Despite being rare, neurosurgeons should be aware that this fatal complication can occur after cranioplasty.
The Faculty Nurse Attending Model at the Mount Sinai Hospital
Authors: Cartwright Frances , Oliver Beth , Ambrosia Todd , Fulmer Terry
Published: June 2023

The ongoing nursing shortage and the ravages of the COVID-19 pandemic have further challenged nursing staff with devastating shortages. This article describes the Faculty Nurse Attending Model, an innovative approach incorporating nursing faculty into staffing and the ongoing interdisciplinary rounds at the Mount Sinai Hospital in New York City. The Mount Sinai Phillips School of Nursing faculty actively participates in the pilot unit to support nursing practice and ensure that the curricula address contemporary practice.
Using Two Statewide Medical Operations Coordination Centers to Load Balance in Pediatric Hospitals During a Severe Respiratory Surge in the United States
Authors: Mitchell Steven H. , Merkel Matthias J. , Eriksson Carl O. , Sakata Vicki L. , King Mary A.
Published: June 2023

OBJECTIVES:

Report on the use of two statewide Medical Operations Coordination Centers (MOCCs) to manage a rapid surge in pediatric acute and critical care patient needs.

DESIGN:

Brief report.

SETTING:

The states of Washington and Oregon during the pediatric respiratory surge in November 2022/December 2022 which overwhelmed existing pediatric acute and critical care hospital capacity.

PATIENTS:

Pediatric patients requiring hospitalization in Washington and Oregon.

INTERVENTIONS:

Adaptations to the use of two existing statewide MOCCs to provide pediatric patient load balancing through surveillance, modifications of existing referral agreements, coordinated expansion of resources, activation of regional crisis standards of care, and integration of pediatric critical care physicians from Harborview Medical Center as subject matter experts (SMEs).

MEASUREMENTS AND MAIN RESULTS:

The Washington and Oregon MOCCs managed 183 pediatric requests from hospitals unable to transfer pediatric patients between November 1, 2022, and December 14, 2022. Sixteen percent of requests were for children younger than 3 months and 37% were for children between 3 months and 1 year; most had acute viral respiratory disease. Requests for children older than 13 years old were primarily intentional drug ingestions. Fifty-eight percent were for critically ill children and 17% originated from critical access hospitals. Washington’s SMEs were utilized in nearly a quarter of cases with the disposition changing in 38% of these.

CONCLUSIONS:

Washington and Oregon statewide MOCCs have leveraged centralized coordination to effectively load balance a surge in pediatric patients which has overwhelmed existing pediatric hospital resources. Centralized coordination and surveillance informed pediatric hospitals and policy makers of unmet clinical needs and facilitated rapid expansion of clinical capacity and modifications to referral processes. Integration of pediatric SMEs enabled efficient triage of these resources. MOCCs provide an adaptable centralized resource for addressing surge and have been effective in managing overwhelmed pediatric hospital resources in Washington and Oregon.
Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector functions magnitude but not durability
Authors: Shubin Zhanna , Stanfield-Oakley Sherry , Puangkaew Jiraporn , Pitisutthithum Punnee , Nitayaphan Sorachai , Gurunathan Sanjay , Sinangil Faruk , Chariyalertsak Suwat , Phanuphak Nittaya , Ake Julie A. , O’connell Robert J. , Vasan Sandhya , Akapirat Siriwat , Eller Michael A. , Ferrari Guido , Paquin-Proulx Dominic
Published: June 2023

Objective(s):

The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a non-neutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability.

Design:

RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai Adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (Group 1) or were boosted with ALVAC-HIV and AIDSVAX Group 2) or only AIDSVAX alone (Group 3) 24 weeks after completing the RV144 series.

Methods:

Plasma samples from RV306 study participants were used to measure antibody dependent cellular phagocytosis (ADCP), antibody dependent neutrophil phagocytosis (ADNP), antibody dependent complement deposition (ADCD), antibody dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses.

Results:

Additional boosting increased the magnitude of all Fc mediated effector functions two weeks following the additional boost compared to two weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24 to 26 weeks after the last vaccination for the study participants receiving an additional boost compared to those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared to two weeks after completing the RV144 regimen.

Conclusions:

Additional boosting of RV144 improved the magnitude but not the durability of some Fc mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.
Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use: a single arm trial
Authors: Hahn Judith A. , Ngabirano Christine , Fatch Robin , Emenyonu Nneka I. , Cheng Debbie M. , Adong Julian , Tumwegamire Adah , Terrault Norah A. , Linas Benjamin P. , Jacobson Karen R. , Muyindike Winnie R.
Published: June 2023

Objective:

Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption.

Design:

Prospective study of PWH receiving INH.

Methods:

We included PWH in southwest Uganda with recent (prior three months) (n = 200) or no (prior year) self-reported alcohol consumption (n = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2x the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST ≥5x the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2-5x the ULN or moderate symptoms.

Results:

The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% (95% CI: 5.7–12.0); all resolved after INH cessation. Incidence was 6.0% (95% CI: 3.1–10.2) among those reporting recent alcohol use and 12.9% (95% CI: 7.0–21.0) of those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI: 17.2–27.0); 25.0% (95% CI: 19.0–31.8) among those with recent alcohol use and 14.8% (95% CI: 8.1–23.9) among those with no prior year alcohol use.

Conclusions:

Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN).
Respiratory protection: what SARS-CoV-2 has taught us
Authors: Loeb Mark
Published: June 2023

Purpose of review

This review summarizes the epidemiological evidence for respiratory personal protective equipment for SARA-CoV-2, a topic of considerable controversy.

Recent findings

The main findings are that the observational studies and non-coronavirus disease 2019 (COVID-19) randomized trials do not provide clear evidence that the N95 respirators offer superior protection over surgical masks. A randomized controlled trial on COVID-19 provides evidence that the absolute risk to healthcare workers over time using surgical masks is similar to N95 respirators.

The implications of the findings are that surgical masks and N95 respirators can be considered for respiratory protection in healthcare workers.
BactoBattle: A game-based learning companion for medical bacteriology
Authors: Imwattana Korakrit , Methawirune Areeya , Voralakkulchai Isara , Ngamskulrungroj Popchai
Published: June 2023

A card game called “BactoBattle” was developed to help medical students who have just started learning medical bacteriology improve their learning efficacy and learning satisfaction, especially on the topic of antimicrobial resistance. Copies of the game were placed in the students’ study room (approximately 1 set per 12 students) and made available to the students throughout the study period so that students could choose to play the game during their free time if desired. After the study period had ended, the students were asked to complete a questionnaire and a post-test. In total, 33 students completed the questionnaire, and were split into two groups: the player group, comprising 12 (36.4%) students who had played the game, and the non-player group. The player group perceived that they could memorize more knowledge compared to the non-player group and indeed recorded higher post-test scores than the non-player group (10.4 vs. 8.3 [out of 15 points], p = 0.031). However, there was no difference in the learning motivation (p = 0.441) nor enjoyment (p = 0.562) between the two groups. A majority of the players said they would continue playing the game after the study period and would recommend the game to other students. In short, the BactoBattle game can be a useful tool to improve the learning efficacy of students, but its effect on learning satisfaction remains unclear.
Brain Tuberculoma: CSF CBNAAT for Mycobacterium tuberculosis negative but Biopsy Culture positive - OLD is still GOLD: a case report
Authors: Shankar Gokul S , Nair Sreeja , Jacob Teena , Idikula Mercy John
Published: June 2023

Tuberculoma of the brain is one of the most severe extrapulmonary forms that affect patients less than 40 years of age. They are space-occupying masses of granulomatous tissue that result from haematogenous spread from a distant focus of tuberculous infection by Mycobacterium tuberculosis. Symptoms and radiologic features being nonspecific usually leads to misdiagnosis and mimics a variety of other infectious diseases. Anti- Tubercular drugs are essential for the successful treatment of cerebral tuberculomas. A 52-year-old woman with known co-morbidities and chronic kidney disease presented with complaints of disoriented talk, vomiting, fever, and decreased response since 1 day. The initial radiological imaging showed ring-enhancing lesions and a differential diagnosis of septic emboli, vasculitis, and tuberculosis was considered. A repeat MRI suggested Tuberculoma. CSF studies showed predominant lymphocytes with elevated protein. CBNAAT & AFB smears of CSF were negative. The patient was started on anti-tuberculous drugs and steroids. But did not respond to the treatment and twelve days later, a brain biopsy was taken and sent for cultures. She deteriorated progressively and died 14 days after admission. Twelve days after her demise, the Mycobacterial culture of the brain biopsy specimen grew Mycobacterium tuberculosis.
Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings
Authors: Minor Nicholas R. , Ramuta Mitchell D. , Stauss Miranda R. , Harwood Olivia E. , Brakefield Savannah F. , Alberts Alexandra , Vuyk William C. , Bobholz Max J. , Rosinski Jenna R. , Wolf Sydney , Lund Madelyn , Mussa Madison , Beversdorf Lucas J. , Aliota Matthew T. , O’Connor Shelby L. , O’Connor David H.
Published: June 2023

Innovative methods for evaluating virus risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been used alongside widespread individual-based SARS-CoV-2 testing programs to provide population-level data. These environmental surveillance strategies have predominantly relied on pathogen-specific detection methods to monitor viruses through space and time. However, this provides a limited picture of the virome present in an environmental sample, leaving us blind to most circulating viruses. In this study, we explore whether pathogen-agnostic deep sequencing can expand the utility of air sampling to detect many human viruses. We show that sequence-independent single-primer amplification sequencing of nucleic acids from air samples can detect common and unexpected human respiratory and enteric viruses, including influenza virus type A and C, respiratory syncytial virus, human coronaviruses, rhinovirus, SARS-CoV-2, rotavirus, mamastrovirus, and astrovirus.
Identification of Key Biomarkers for Early Warning of Diabetic Retinopathy Using BP Neural Network Algorithm and Hierarchical Clustering Analysis
Authors: Li Peiyu , Wang Hui , Fan Zhihui , Tian Guo
Published: June 2023

Background

Diabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence.

Methods

In this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through BP neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease.

Results

The key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation.

Conclusions

The key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.
The effect of a video intervention on knowledge, awareness and perception of Natural Procreative Technology (NaProTechnology) among pharmacy undergraduate students in Nigeria
Authors: Mosanya Adaobi Uchenna , Ezenkwele Eziamaka Pauline , Jacinta Emegoakor Fausta Chioma , Okeh Mmaduabuchi , Isah Abdulmuminu
Published: June 2023

Background

Natural Procreative Technology (NaProTechnology) is a system of management of infertility and other reproductive health issues which requires the application of a woman’s observation and record of key events throughout her menstrual cycle.

Objectives

The study assessed the knowledge, awareness, and perception of NaProTechnology as well as the effect of an educational intervention among pharmacy undergraduate students at University of Nigeria, Nsukka.

Methods

It was a cross-sectional, questionnaire-based study. The ethical approval was obtained from the research ethics committee of the Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka. At baseline, the knowledge, awareness and perception of the students were assessed. Followed by the administration of an educational video on NaProTechnology. Then a post intervention survey was done to assess the effect of the educational intervention.

Key findings

There were 410 and 350 students in the pre- and post-intervention surveys respectively with relatively equal number of males and females. Majority were between 18 and 29 years old. Less than 5% were married while the highest proportion of the respondents were from 300 level The knowledge, awareness, and positive perception of NaProTechnology among the pharmacy students prior to intervention were poor but improved markedly post intervention (P < 0.001).

Conclusion

A video intervention was effective in improving the short-term knowledge, awareness and positive perception of NaProTechnology among pharmacy students.

Key messages

What is already known on this topic?

Natural Procreative Technology (NaProTechnology) is a system of management of infertility based on the observation and record of fertility biomarkers by a woman.

What this study adds?

The level of knowledge, awareness, and positive perception of NaProTechnology among the pharmacy undergraduates students were poor prior to a video intervention but improved markedly afterwards

How this study might affect research, practice or policy?

This study would lead to the public health system approach of informing, educating and communicating NaProTechnology to pharmacy students to achieve long-term effects by using well-designed courses and curriculum implementation.
Low-usage splice junctions underpin immune-mediated disease risk
Authors: El Garwany Omar , Panousis Nikolaos I , Knights Andrew , Kumasaka Natsuhiko , Imaz Maria , Vilarino Lorena Boquete , Tsingene Anthi , Barnett Alice , Gomez Celine , Gaffney Daniel J , Anderson Carl A.
Published: June 2023

The majority of immune-mediated disease (IMD) risk loci are located in non-coding regions of the genome, making it difficult to decipher their functional effects. To assess the extent to which alternative splicing contributes to IMD risk, we mapped genetic variants associated with alternative splicing (splicing quantitative trait loci or sQTL) in macrophages exposed to 24 cellular conditions. We found that genes involved in innate immune response pathways undergo extensive differential splicing in response to stimulation and detected significant sQTL effects for 5,734 genes across all conditions. We colocalised sQTL signals for over 700 genes with IMD-associated risk loci from 21 IMDs with high confidence (PP4 ≥ 0.75). Approximately half of the colocalisations implicate lowly-used splice junctions (mean usage ratio < 0.1). Finally, we demonstrate how an inflammatory bowel disease (IBD) risk allele increases the usage of a lowly-used isoform of PTPN2, a negative regulator of inflammation. Together, our findings highlight the role alternative splicing plays in IMD risk, and suggest that lowly-used splicing events significantly contribute to complex disease risk.
Biomechanical Strain Responses in the Optic Nerve Head Region in Glaucoma Patients After Intraocular Pressure Lowering
Authors: Yuan Zhuochen , Czerpak Cameron A. , Kashaf Michael Saheb , Quigley Harry A. , Nguyen Thao D.
Published: June 2023

Objective

To measure strain values and their association with intraocular pressure (IOP) change across five posterior eye regions in glaucoma patients.

Design

Cohort study.

Participants

Glaucoma patients who were imaged with optical coherence tomography (OCT) prior to and after laser suturelysis following trabeculectomy surgery (29 image pairs, 26 persons)

Intervention

Noninvasive imaging of the eye.

Main Outcomes

Strain values in eye regions.

Results

Mean strains were lowest in the retina and highest in the prelaminar neural tissue (PLNT) forEmax,Γmax, andEzz. The values ofEmaxin the anterior lamina cribrosa (ALC) and sclera were significantly related (P=0.0094, linear regression). Higher axial strain (Ezz) was significantly associated with greater IOP decrease in the ALC, PLNT, and retina (P<0.05). HigherΓmaxandEmaxstrains were significantly associated with greater IOP decreases across all 5 eye regions. ALC and PLNT had negative median radial (Err) compliance, while sclera had positiveErrcompliance (P=0.017).EmaxandΓmaxstrains of the ALC were significantly and positively associated with these strains in the other 4 regions (P<0.005). Likewise, theEzzof ALC had a significant positive relationship with the other 4 regions (P<0.05).

Conclusions

Regional strains in the optic nerve head zone can be effectively measured using OCT and are related to the magnitude of IOP change. Strains were largest in PLNT and ALC and were smallest in retina. The sclera and choroid on average expand radially and circumferentially indicating a volume increase with IOP lowering.
sPreserved recognition of basic visual features despite lack of awareness of shape: evidence from a case of neglect
Authors: Karakose-Akbiyik Seda , Schubert Teresa , Caramazza Alfonso
Published: June 2023

Human visual experience of objects comprises a combination of different visual features, such as their color, position, and shape. Spatial attention is thought to play a role in creating a coherent perceptual experience, integrating visual information coming from a given location, but the mechanisms underlying this process are not entirely understood. Deficits of spatial attention in which this integration process does not occur normally, such as neglect, can provide insights regarding the mechanisms of spatial attention in visual object recognition. In this study, we describe a series of experiments conducted with an individual with neglect, XX. XX presents characteristic lack of awareness of the left side of individual objects, evidenced by poor object and face recognition, and impaired word reading. However, he exhibits intact recognition of color within the boundaries of the same objects he fails to recognize. Furthermore, he can also report the orientation and location of a colored region on the neglected left side despite lack of awareness of the shape of the region. To our knowledge, selective lack of awareness of shape despite intact processing of basic visual features in the same spatial location has not been reported previously. XX’s performance raises intriguing questions and challenges about the role of spatial attention in the formation of coherent object percepts and visual awareness.
Tuning methylation-dependent silencing dynamics by synthetic modulation of CpG density
Authors: Ma Yitong , Budde Mark W. , Zhu Junqin , Elowitz Michael B.
Published: June 2023

Methylation of cytosines in CG dinucleotides (CpGs) within promoters has been shown to lead to gene silencing in mammals in natural contexts. Recently, engineered recruitment of methyltransferases (DNMTs) at specific loci was shown to be sufficient to silence synthetic and endogenous gene expression through this mechanism. A critical parameter for DNA methylation-based silencing is the distribution of CpGs within the target promoter. However, how the number or density of CpGs in the target promoter affects the dynamics of silencing by DNMT recruitment has remained unclear. Here we constructed a library of promoters with systematically varying CpG content, and analyzed the rate of silencing in response to recruitment of DNMT. We observed a tight correlation between silencing rate and CpG content. Further, methylation-specific analysis revealed a constant accumulation rate of methylation at the promoter after DNMT recruitment. We identified a single CpG site between TATA box and transcription start site (TSS) that accounted for a substantial part of the difference in silencing rates between promoters with differing CpG content, indicating that certain residues play disproportionate roles in controlling silencing. Together, these results provide a library of promoters for synthetic epigenetic and gene regulation applications, as well as insights into the regulatory link between CpG content and silencing rate.
COBRA improves the quality of viral genomes assembled from metagenomes
Authors: Chen LinXing , Banfield Jillian F.
Published: June 2023

Microbial and viral diversity, distribution, and ecological impacts are often studied using metagenome-assembled sequences, but genome incompleteness hampers comprehensive and accurate analyses. Here we introduce COBRA (ContigOverlapBasedRe-Assembly), a tool that resolvesde Bruijngraph based assembly breakpoints and joins contigs. While applicable to any short-read assembled DNA sequences, we benchmarked COBRA by using a dataset of published complete viral genomes from the ocean. COBRA accurately joined contigs assembled by metaSPAdes, IDBA_UD, and MEGAHIT, outcompeting several existing binning tools and achieving significantly higher genome accuracy (96.6% vs 19.8-59.6%). We applied COBRA to viral contigs that we assembled from 231 published freshwater metagenomes and obtained 7,334 high-quality or complete species-level genomes (clusters with 95% average nucleotide identity) for viruses of bacteria (phages), ∼83% of which represent new phage species. Notably, ∼70% of the 7,334 species genomes were circular, compared to 34% before COBRA analyses. We expanded genomic sampling of ≥ 200 kbp phages (i.e., huge phages), the largest of which was curated to completion (717 kbp in length). The improved phage genomes from Rotsee Lake provided context for metatranscriptomic data and indicatedin situactivity of huge phages, WhiB andcysC/cysHencoding phages from this site. In conclusion, COBRA improves the assembly contiguity and completeness of microbial and viral genomes and thus, the accuracy and reliability of analyses of gene content, diversity, and evolution.
Invasion of spontaneous germinal centers by naive B cells is rapid and persistent
Authors: van den Broek T. , Oleinika K. , Rahmayanti S. , Castrillon C. , van der Poel C.E. , Carroll M.C.
Published: June 2023

In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a novel tool for identifying early events in the breaking of B cell tolerance in autoimmunity.

One Sentence Summary

The autoreactive germinal center is an open structure that is susceptible to rapid and persistent naive B cell invasion, with clonal expansion and auto-antibody induction and diversification.
Detecting Regime Shifts: Neurocomputational Substrates for Over- and Underreactions to Change
Authors: Wang Mu-Chen , Wu George , Wu Shih-Wei
Published: June 2023

Abstract

The world constantly changes, with the underlying state of the world shifting from one regime to another. The ability to detect a regime shift, such as the onset of a pandemic or the end of a recession, significantly impacts individual decisions as well as governmental policies. However, determining whether a regime has changed is usually not obvious, as signals are noisy and reflective of the volatility of the environment. We designed an fMRI paradigm that examines a stylized regime-shift detection task. Human participants showed systematic over- and underreaction: Overreaction was most commonly seen when signals were noisy but when environments were stable and change is possible but unlikely. By contrast, underreaction was observed when signals were precise but when environments were unstable and hence change was more likely. These behavioral signatures are consistent with thesystem-neglectcomputational hypothesis, which posits that sensitivity or lack thereof to system parameters (noise and volatility) is central to these behavioral biases. Guided by this computational framework, we found that individual subjects’ sensitivity to system parameters were represented by two distinct brain networks. Whereas a frontoparietal network selectively represented individuals’ sensitivity to signal noise but not environment volatility, the ventromedial prefrontal cortex (vmPFC) showed the opposite pattern. Further, these two networks were involved in different aspects of regime-shift computations: while vmPFC correlated with subjects’ beliefs about change, the frontoparietal network represented the strength of evidence in favor of regime shifts. Together, these results suggest that regime-shift detection recruits belief-updating and evidence-evaluation networks and that under- and overreactions arise from how sensitive these networks are to the system parameters.

Significance statement

Judging whether the world has changed, from the onset of a market boom to the end of a pandemic, is ubiquitous. The ability to detect regime shifts not only impacts individual decisions but also governmental policies. However, these judgments are hard to make because the signals we receive are noisy and reflective of the volatility of the environment. We find that people overreact to changes when they receive noisy signals in stable environments, but underreact when facing precise signals in unstable environments. Under- and overreactions can be read out by distinct brain networks according to their sensitivity in responding to different environmental parameters that impact regime changes. This suggests that parameter selectivity at the network level guides regime-shift detection.
Closed ecosystems extract energy through self-organized nutrient cycles
Authors: Goyal Akshit , Flamholz Avi I. , Petroff Alexander P. , Murugan Arvind
Published: June 2023

Our planet is a self-sustaining ecosystem powered by light energy from the sun, but roughly closed to matter. Many ecosystems on Earth are also approximately closed to matter and recycle nutrients by self-organizing stable nutrient cycles, e.g., microbial mats, lakes, open ocean gyres. However, existing ecological models do not exhibit the self-organization and dynamical stability widely observed in such planetary-scale ecosystems. Here, we advance a new conceptual model that explains the self-organization, stability and emergent features of closed microbial ecosystems. Our model incorporates the bioenergetics of metabolism into an ecological framework. By studying this model, we uncover a crucial thermodynamic feedback loop that enables metabolically diverse communities to almost always stabilize nutrient cycles. Surprisingly, highly diverse communities self-organize to extract≈10% of the maximum extractable energy, or≈100 fold more than randomized communities. Further, with increasing diversity, distinct ecosystems show strongly correlated fluxes through nutrient cycles. However, as the driving force from light increases, the fluxes of nutrient cycles become more variable and species-dependent. Our results highlight that self-organization promotes the efficiency and stability of complex ecosystems at extracting energy from the environment, even in the absence of any centralized coordination.
Ocular Manifestations in a Cohort of 43 Patients with KBG Syndrome
Authors: Carter Drake C. , Kierzkowska Ola , Sarino Kathleen , Guo Lily , Marchi Elaine , Lyon Gholson J
Published: June 2023

Ophthalmological conditions are underreported in patients with KBG syndrome, which is classically described as presenting with dental, developmental, intellectual, skeletal, and craniofacial abnormalities. This study analyzed the prevalence of four ophthalmological conditions (strabismus, astigmatism, myopia, hyperopia) in 43 patients with KBG syndrome carrying pathogenic variants inANKRD11or deletions in 16q24.3 and compared it to the literature. 43 patients were recruited via self-referral or a private Facebook group hosted by the KBG Foundation. Virtual interviews were conducted to collect a comprehensive medical history verified by medical records. From these records, data analysis was performed to calculate the prevalence of ophthalmological conditions. Strabismus was reported in 10 (23.3%) participants, while astigmatism, myopia, and hyperopia were reported in 12 (27.9%), 7 (16.3%), and 9 (20.9%) participants, respectively. Other reported conditions include anisometropia, amblyopia, and nystagmus. When compared to the literature, the prevalence of strabismus and refractive errors is higher than other studies. However, more research is needed to determine if mutations inANKRD11play a role in abnormal development of the visual system. In patients with established KBG syndrome, screening for misalignment or refractive errors should be done, as interventions in patients with these conditions can improve functioning and quality of life.
Zero-shot Interpretable Phenotyping of Postpartum Hemorrhage Using Large Language Models
Authors: Alsentzer Emily , Rasmussen Matthew J , Fontoura Romy , Cull Alexis L , Beaulieu-Jones Brett , Gray Kathryn J , Bates David W , Kovacheva Vesela P
Published: June 2023

Many areas of medicine would benefit from deeper, more accurate phenotyping, but there are limited approaches for phenotyping using clinical notes without substantial annotated data. Large language models (LLMs) have demonstrated immense potential to adapt to novel tasks with no additional training by specifying task-specific i nstructions. We investigated the per-formance of a publicly available LLM, Flan-T5, in phenotyping patients with postpartum hemorrhage (PPH) using discharge notes from electronic health records (n=271,081). The language model achieved strong performance in extracting 24 granular concepts associated with PPH. Identifying these granular concepts accurately allowed the development of inter-pretable, complex phenotypes and subtypes. The Flan-T5 model achieved high fidelity in phenotyping PPH (positive predictive value of 0.95), identifying 47% more patients with this complication compared to the current standard of using claims codes. This LLM pipeline can be used reliably for subtyping PPH and outperformed a claims-based approach on the three most common PPH subtypes associated with uterine atony, abnormal placentation, and obstetric trauma. The advantage of this approach to subtyping is its interpretability, as each concept contributing to the subtype determination can be evaluated. Moreover, as definitions may change over time due to new guidelines, using granular concepts to create complex phenotypes enables prompt and efficient updating of the algorithm. Using this lan-guage modelling approach enables rapid phenotyping without the need for any manually annotated training data across multiple clinical use cases.
A comprehensive evolutionary scenario for the origin and neofunctionalization of theDrosophilaspeciation geneOdysseus(OdsH)
Authors: Vilas Boas Nunes William , Siqueira de Oliveira Daniel , de Rezende Dias Guilherme , Carvalho Antonio Bernardo , Putinhon Ícaro Caruso , Matos Biselli Joice , Guegen Nathalie , Akkouche Abdou , Burlet Nelly , Vieira Cristina , Carareto Claudia M. A.
Published: June 2023

Odysseus(OdsH) was the first gene described inDrosophilarelated to speciation and hybrid sterility. This gene was first described in themelanogastersubgroup and more specifically in the sterile hybrids from crosses betweenD. mauritianaandD. simulans. Its origin is attributed to the duplication of the geneunc-4, which would have occurred in the ancestor of the subgenusSophophora. By using a much larger sample ofDrosophilaspecies, we showed that contrary to what has been previously proposed,OdsHorigin occurred approximately 62 million years ago (Mya). Then,OdsHhave experienced rapid neofunctionalization in male reproductive tracts, evidenced by its evolutionary rates, expression and transcription factor binding sites. Furthermore, the analysis of the OdsH peptide sequence allowed the identification of mutations in the DNA- and protein-binding domains ofD. mauritianathat could result in incompatibility with genomes from other species. We then explored the expression ofOdsHin the spermatocytes ofD. arizonaeandD. mojavensis, a pair of recently diverged sister species with incomplete reproductive isolation and expected to find the involvement ofOdsHin hybrid sterility. Our data indicated thatOdsHexpression is not atypical in male-sterile hybrids from these species. In conclusion, we have demonstrated that the origin ofOdsHoccurred earlier than previously proposed and that its neofunctionalization in male sexual functions occurred rapidly after its origin. Our results also suggested that its role as a speciation gene, as in themelanogastersubgroup of species, may be restricted to this specific taxon.