bluuebunny/crossref_metadata_2025 huggingface dataset:
NanoSquiggleVar: A method for direct analysis of targeted variants based on nanopore sequencing signals
Authors: Lang Jidong
Published: March 2023

Background

Nanopore sequencing is a fourth-generation sequencing technology that has developed rapidly in recent years. It has long sequencing read lengths and does not require the polymerase chain reaction to be performed. These characteristics give it unique advantages over the next-generation sequencing technology under certain usage scenarios. The number of bioinformatics analysis algorithms and/or tools developed with nanopore sequencing has increased sharply during the past years, undoubtedly providing great help and support for the application of nanopore sequencing in scientific research and practical scenarios.

Results

We developed NanoSquiggleVar, a method for direct analysis of targeted variants based on nanopore sequencing signals. It first establishes a set of wild-type and mutant-type target signals within the same experimental and sequencing system, named wild squiggle set and variant squiggle set, respectively. In each sequencing iteration, the signal is sliced into fragments by a moving window of 1-unit step size. Then, dynamic time warping is used to compare the signal squiggles to the detected variants. Point mutations, insertions and deletions (indels), and homopolymer sequences were simulated and generated by Scrappie and then analyzed and evaluated with NanoSquiggleVar. We found that all of these variants were efficiently detected and discriminated, and the results were consistent with the expectations.

Conclusions

NanoSquiggleVar can directly identify targeted variants from the nanopore sequencing electrical signal without the requirement of base calling, sequence alignment, or variant detection with downstream analysis. We hope that this method can complement targeted variant detection using nanopore sequencing and potentially serve as a reference for real-time sequencing and analysis.
Design and Mathematical Analysis of Activating Amplifiers that Enable Modular Temporal Control in Synthetic Circuits
Authors: Lam Calvin
Published: March 2023

The ability to control mammalian cells such that they self-organize or enact therapeutic effects as desired has incredible implications. Not only would it further our understanding of native processes such as development and the immune response, but it would also have powerful applications in medical fields such as regenerative medicine and immunotherapy. This control is typically obtained by synthetic circuits that use synthetic receptors, but control remains incomplete. For example, the synthetic juxtacrine receptors (SJRs) are widely used as they are fully modular and enable spatial control, but they have limited gene expression amplification and temporal control. I therefore designed transcription factor based amplifiers that amplify gene expression and enable unidirectional temporal control by prolonging duration of target gene expression. Using anin silicoframework for SJR signaling, I combined these amplifiers with SJRs and show that these SJR amplifier circuits can improve the quality of self-organization and direct different spatiotemporal patterning. I then show that these circuits can improve chimeric antigen receptor (CAR) T cell tumor killing against heterogenous and homogenous antigen expression tumors. These amplifiers are flexible tools that improve control over SJR based circuits and have both basic and therapeutic applications.

Graphical Abstract
Improving inversion of model parameters from action potential recordings with kernel methods
Authors: Oslandsbotn Andreas , Cloninger Alexander , Forsch Nickolas
Published: March 2023

Abstract

Current methods for solving inverse problems in cardiac electrophysiology are limited by their accuracy, scalability, practicality, or a combination of these. In this proof-of-concept study we demonstrate the feasibility of using kernel methods to solve the inverse problem of estimating the parameters of ionic membrane currents from observations of corresponding action potential (AP) traces. In particular, we consider AP traces generated by a cardiac cell action potential model, which mimics those obtained experimentally in measurablein vitrocardiac systems. Using synthetic training data from the 1977 Beeler-Reuter AP model of mammalian ventricular cardiomyocytes, we demonstrate our recently proposed boosted kernel ridge regression (KRR) solver StreaMRAK, which is particularly robust and well-adapted for high-complexity functions. We show that this method is less memory demanding, estimates the model parameters with higher accuracy, and is less exposed to parameter sensitivity issues than existing methods, such as standard KRR solvers and loss-minimization schemes based on nearest-neighbor heuristics.
Multiple sequence-alignment-based RNA language model and its application to structural inference
Authors: Zhang Yikun , Lang Mei , Jiang Jiuhong , Gao Zhiqiang , Xu Fan , Litfin Thomas , Chen Ke , Singh Jaswinder , Huang Xiansong , Song Guoli , Tian Yonghong , Zhan Jian , Chen Jie , Zhou Yaoqi
Published: March 2023

Compared to proteins, DNA and RNA are more difficult languages to interpret because 4-letter-coded DNA/RNA sequences have less information content than 20-letter-coded protein sequences. While BERT (Bidirectional Encoder Representations from Transformers)-like language models have been developed for RNA, they are ineffective at capturing the evolutionary information from homologous sequences because unlike proteins, RNA sequences are less conserved. Here, we have developed an unsupervised Multiple sequence-alignment-based RNA language model (RNA-MSM) by utilizing homologous sequences from an automatic pipeline, RNAcmap. The resulting unsupervised, two-dimensional attention maps and one-dimensional embeddings from RNA-MSM can be directly mapped with high accuracy to 2D base pairing probabilities and 1D solvent accessibilities, respectively. Further fine-tuning led to significantly improved performance on these two downstream tasks over existing state-of-the-art techniques. We anticipate that the pre-trained RNA-MSM model can be fine-tuned on many other tasks related to RNA structure and function.
Discovery of a Novel 3site State as the Multi-Substrate Bound State of P450cam
Authors: Sahil Mohammad , Singh Tejender , Ghosh Soumya , Mondal Jagannath
Published: March 2023

Archetypal metalloenzyme Cytochrome P450cam (CYP101A1) catalyzes regioselective hydroxylation of its native substrate camphor in heme active site. However, the proposal of potential existence of additional substrate binding modes distal from the active site in P450cam and their concomitant roles in regulating recognition at active site have remained a matter of recurring discourse. Herein we report the discovery of a novel3sitestate in P450cam, where three substrate molecules were observed to simultaneously bind to P450cam at three distinct sites including the heme active site. These three binding modes, hereby referred ascatalytic,waitingandallostericbinding modes in3sitestate, are allosterically inter-linked and function in mutually synergistic fashion. The3sitestate possesses regio-selective conformations of substrate essential for catalysis and establishes substrate-ingress and product exit process to and from the active site via two distinct channels. The ensemble of three-state binding modes are found to be self-consistent with NMR pseudo-contact shift data obtained from TROSY-HSQC measurements and DEER based predictions. Binding of redox partner Putidaredoxin with3sitemodel retains closed conformation of 3site state, siding with NMR based hypothesis that the catalysis would take place in closed insulation of P450cam even in presence of its redox partner.

Statement of Significance

Ubiquitous superfamily of mono-oxygenases cytochrome P450s are involved in broad range of metabolic process in all domains of life and are also important drug targets. Apart from the well known and established binding mode in heme active site, the substrate bindings at additional distal sites have been postulated in multitude of P450s. Using the archetypal bacterial cytochrome P450 i.e., P450cam, a novel3sitestate of cytochrome P450 is elucidated in this work. The novel 3site state has two additional binding modes namelywaitingandallosteric(also postulated previously), apart from known binding modecatalyticin the active site. The known functions of P450cam are found to be most optimally explained by this 3site state, instead of single substrate bound catalytic state. This state can be of critical importance for CYP superfamily at large and potentially be useful in understanding the non-Michaelis behaviour, observed in many P450s.
Uncovering the Hidden Gems of Psoriasis Literature: An Neural Language Model-Assisted Interactive Web Tool
Authors: Wu Sunsi , Gu Xinpei , Xiao Ruiheng , Gao Hongzhi , Yang Bo , Kang Yanlan
Published: March 2023

BACKGROUND

The comprehensive data on psoriasis research are numerous and complex, making it difficult to retrieve and classify manually. The ability to quickly mine literature based on various fine topics using deep learning natural language processing technology to assess research topics and trends in the field of psoriasis disease will have a significant impact on doctors’ research and patients’ health education

METHOD

A neural topic model is used to identify fine topics of psoriasis literature published in the PubMed database from 2000 to 2021. Dermatologists evaluate the algorithm-modeled topics, summarize the categories into the most effective topics, and perform linear trend model analysis. The accurate classified topics are presented on an interactive web page to identify research hotspots and trends.

RESULTS

At the categorical level, after review by clinicians, 158 out of 160 generated topics were found effective and categorized into 8 groups: Therapeutic methods (34.34%), pathological mechanisms (23.46%), comorbidity (20.04%), Clinical manifestations and differential diagnosis (12.77%), experimental modalities and methods (3.22%), diagnostic tools (2.99%), epidemiology (1.75%), and meetings/guidelines (1.43%). A linear regression model had good accuracy (MSE=0.252602, SSE=42.1845) and strong correlation (R-Squared=0.898009). ANOVA results showed that categories significantly impacted the model (p<=0.05), with experimental modalities and methods having the strongest relationship with year, and clinical manifestations and differential diagnosis having the weakest. An interactive web tool (https://psknlr.github.io) facilitates quick retrieval of titles, journals, and abstracts in different categories, as well as browsing literature information under specific topics and accessing corresponding article pages for professional knowledge on psoriasis.

CONCLUSIONS

The neural topic model and interactive web tool can effectively identify the research hotspots and trends in psoriasis literature, assisting clinicians and patients in retrieving and comparing pertinent topics and research accomplishments of various years.
Adaptive-learning physics-aware light-field microscopy enables day-long and millisecond-scale super-resolution imaging of 3D subcellular dynamics
Authors: Zhu Lanxin , Sun Jiahao , Yi Chengqiang , Zhang Meng , Huang Yihang , Wu Sicen , He Mian , Chen Liting , Zhang Yicheng , Zheng Chunhong , Chen Hao , Zhang Yuhui , Li Dongyu , Fei Peng
Published: March 2023

Long-term and high-spatiotemporal-resolution 3D imaging of living cells remains an unmet challenge for super-resolution microscopy, owing to the noticeable phototoxicity and limited scanning speed. While emerging light-field microscopy can mitigate this issue through three-dimensionally capturing biological dynamics with merely single snapshot, it suffers from suboptimal resolution insufficient for resolving subcellular structures. Here we propose an Adaptive Learning PHysics-Aware Light-Field Microscopy (Alpha-LFM) with a physics-aware deep learning framework and adaptive-tuning strategies capable for highly-generalizable light-field reconstruction of diverse subcellular dynamics. Alpha-LFM delivers sub-diffraction-limit spatial resolution (∼120 nm) while maintaining high temporal resolution and low phototoxicity. It enables rapid (at hundreds of volumes per second), long-term (up to 60 hours) 3D super-resolution imaging of diverse intracellular dynamics with exceptional details. Using Alpha-LFM approach, we finely resolve the lysosome-mitochondrial interactions, capture rapid motion of peroxisome and the endoplasmic reticulum, and reveal the variations in mitochondrial fission activity throughout two complete cell cycles.
Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse
Authors: Hsu Caroline M. , Weiner Daniel E. , Manley Harold J. , Miskulin Dana , Ladik Vladimir , Frament Jill , Argyropoulos Christos , Abreo Kenneth , Chin Andrew , Gladish Reginald , Salman Loay , Johnson Doug , Lacson Eduardo K.
Published: March 2023

Rationale & Objective

SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses.

Study Design

Retrospective observational study

Setting & Participants

SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination.

Exposure(s)

Two and three doses of SARS-CoV-2 vaccine

Outcome(s)

Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time

Analytical Approach

“Undiagnosed” SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥ 100 BAU/mL, not associated with receipt of vaccine or “diagnosed” SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time.

Results

Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥ 500 BAU/mL in the first month, with 23% maintaining a titer ≥ 500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥ 500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥ 500 BAU/mL at six months.

Limitations

Assays used had upper limits.

Conclusions

Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population’s vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.
Real-world effectiveness of mpox (monkeypox) vaccines: a systematic review
Authors: Xu Mingda , Liu Caifen , Du Zhanwei , Bai Yuan , Wang Zhen , Gao Chao
Published: March 2023

Understanding the effectiveness of smallpox vaccines against mpox in humans can inform public health preparedness for mpox prophylaxis during the 2022 outbreak. However, the efficacy of current vaccines against mpox has been inferred from animal and immunogenicity studies and has barely been demonstrated in human clinical trials. Thus, we conducted a systematic literature review to estimate the real-world effectiveness of mpox vaccines. The study showed a pooled estimate of 0.89 (95% CI: 0.86-0.91) for the third-generation smallpox vaccine (MVA-BN) effectiveness during the 2022 outbreak. The results showed that the incidence of mpox was significantly lower in the vaccinated group than in the unvaccinated group. Considering the potential mutations, side effects, and breakthrough infections, it is recommended to develop a next-generation vaccine that is more effective and safer for future mpox outbreaks.
ChatGPT Goes to Operating Room: Evaluating GPT-4 Performance and Its Potential in Surgical Education and Training in the Era of Large Language Models
Authors: Oh Namkee , Choi Gyu-Seong , Lee Woo Yong
Published: March 2023

Purpose

This study aimed to assess the performance of ChatGPT, specifically the GPT-3.5 and GPT-4 models, in understanding complex surgical clinical information and its potential implications for surgical education and training.

Methods

The dataset comprised 280 questions from the Korean general surgery board exams conducted between 2020 and 2022. Both GPT-3.5 and GPT-4 models were evaluated, and their performances were compared using McNemar’s test.

Results

GPT-3.5 achieved an overall accuracy of 46.8%, while GPT-4 demonstrated a significant improvement with an overall accuracy of 76.4%, indicating a notable difference in performance between the models (P < 0.001). GPT-4 also exhibited consistent performance across all subspecialties, with accuracy rates ranging from 63.6% to 83.3%.

Conclusion

ChatGPT, particularly GPT-4, demonstrates a remarkable ability to understand complex surgical clinical information, achieving an accuracy rate of 76.4% on the Korean general surgery board exam. However, it is important to recognize the limitations of LLMs and ensure that they are used in conjunction with human expertise and judgment.
Trade-offs between water use and greenhouse gas emissions related to food systems: an optimization study in French adults
Authors: Kesse-Guyot Emmanuelle , Pointereau Philippe , Brunin Joséphine , Perraud Elie , Toujgani Hafsa , Berthy Florine , Allès Benjamin , Touvier Mathilde , Lairon Denis , Mariotti François , Baudry Julia , Fouillet Hélène
Published: March 2023

Water use (WU) and greenhouse gas emissions (GHGe) are two main issues facing food systems. Still, they have rarely been studied together even though they are potentially conflicting because their levers for improvement are not necessarily the same. Data on food-related environmental pressures suggest that GHGe and WU can be improved jointly, but their potential conflicts and trade-offs have not been explored. This is what we studied here by a compromise programming approach, using multi-criteria non-linear optimization under a set of nutritional and epidemiological constraints. We used food consumption data of adults aged 18-64 years (n=1,456) from the French representative study INCA 3 (2014-2015) coupled with food environmental impact data from the Agribalyse ® database. A full range of scenarios was identified by prioritizing the two objectives differently, giving weight from 0% to 100%, by 5-% steps, to GHGe improvement over WU improvement.

Overall, we showed that it is possible to achieve significant joint reductions in WU and GHGe relative to their observed values: across the prioritization scenarios, WU reduction ranged from -36% to -14% as its prioritization decreased, while GHGe reduction varied less, from -44 to -52% as its prioritization increased. These joint important reductions in GHGe and WU required the removal of meat consumption (beef, pork, poultry and processed meat), while the consumptions of offal and dairy products remained moderate in order to meet nutrient reference values. However, the consumption of some foods varied according to the priority given to WU over GHGe reductions (namely, vegetables, fruit juice, dairy products, eggs, refined cereal, substitutes, offal and potatoes). Fish, whole grains, and fruit remained more constant due to the epidemiological constraints used. Whatever the scenario, the modeled diets were more plant-based than the observed diet from which they differed significantly (only 23-31% of common food consumptions), and were therefore healthier (63-76% reduction in distance to theoretical minimum risk of chronic disease).

To conclude, while focusing solely on WU reduction induces a joint GHGe reduction that is near-maximal, the reverse is not true, showing that there is good alignment but also some divergence between these objectives. This suggests that food systems WU should be better considered in dietary guidelines for healthy and sustainable diet.
Use of pharmacy services in community-dwelling middle-aged and older adults; findings from The Irish Longitudinal Study on Ageing (TILDA)
Authors: Murry Logan T. , Flood Michelle , Holton Alice , Kenny Rose Anne , Moriarty Frank
Published: March 2023

Introduction

The role of community pharmacists has evolved in recent years with expansion in pharmacy services offered. This study aims to assess pharmacy services use among adults aged ≥50 years in Ireland, and determine the demographic and clinical factors associated with pharmacy services use.

Methods

This cross-sectional study included community-dwelling participants in wave 4 of The Irish Longitudinal Study on Ageing (TILDA), aged ≥56 years who were self-respondents. TILDA is a nationally representative cohort study, with wave 4 data collected during 2016. TILDA collects participant demographics and health data, in addition to information on the use of several services when visiting the pharmacy in the last 12 months. Characteristics and pharmacy services use were summarised. Multivariate logistic regression was used to examine the association of demographic and health factors with reporting (i) any pharmacy service use and (ii) requesting medicines advice.

Results

Among 5,782 participants (55.5% female, mean age 68 years), 96.6% (5,587) reported visiting a pharmacy in the previous 12 months, and almost one fifth of these (1,094) availed of at least one specified pharmacy service. The most common non-dispensing services reported were requesting advice about medications (786, 13.6%), blood pressure monitoring (184, 3.2%), and vaccination (166, 2.9%). Controlling for other factors, female sex (odds ratio (OR) 1.32, 95%CI 1.14-1.52), third-level education (OR 1.85, 95%CI 1.51-2.27), higher rates of GP visits, private health insurance (OR 1.29, 95%CI 1.07-1.56), higher number of medications, loneliness, and respiratory condition diagnosis (OR 1.42, 95%CI 1.14-1.74) were associated with higher likelihood of availing of pharmacy services. The relationship between these factors and requesting medicines advice were similar.

Conclusion

A high proportion of middle-aged and older adults visit community pharmacy and a fifth avail of specified pharmacy services. Despite advances in the services offered in pharmacies, medicines advice remains at the core of pharmacists’ practice.
What risk doBrucellavaccines pose to humans? A systematic review of the scientific literature on occupational exposure
Authors: Vives-Soto Manuel , Puerta-García Amparo , Pereira José-Luis , Rodríguez-Sánchez Esteban , Solera Javier
Published: March 2023

Introduction

Vaccination of cattle, sheep and goats with attenuated strains ofBrucellais an effective measure for controlling brucellosis, although the vaccines pose risks to humans during the manufacturing process and throughout their distribution and administration to animals.

Objective

The aim of this study was to review the risk posed to humans by occupational exposure to vaccine strains and the measures that should be implemented to minimize this risk.

Materials and methods

This article reviewed the scientific literature indexed in PubMed up to January 31, 2023, following “the PRISMA guidelines”; special emphasis was placed on the vaccine strain used and the route of exposure.

Results

Twelve primary reports were found: six included the Rev-1 strain, three the S19, and four the RB-51 strain. Rev-1 seemed to be the most virulent. The most frequent type of exposure was needle injury during administration, while exposure accidents during vaccine manufacturing were exceptional. Prolonged contact with the pathogen, lack of information and a low adherence to personal protective equipment (PPE) use in the work environment were determining factors for becoming infected. Despite strict protection measures, a percentage of vaccine manufacturing workers developed a positive serology to the vaccine strain, which may have conferred immunity.

Conclusions

Brucellavaccines pose risk of contagion to humans from their production to their administration to cattle; therefore, protection measures should be extreme, and active surveillance of exposed workers should be implemented.
Longitudinal population-level HIV epidemiologic and genomic surveillance highlights growing gender disparity of HIV transmission in Uganda
Authors: Monod Mélodie , Brizzi Andrea , Galiwango Ronald M , Ssekubugu Robert , Chen Yu , Xi Xiaoyue , Kankaka Edward Nelson , Ssempijja Victor , Dörner Lucie Abeler , Akullian Adam , Blenkinsop Alexandra , Bonsall David , Chang Larry W , Dan Shozen , Fraser Christophe , Golubchik Tanya , Gray Ronald H , Hall Matthew , Jackson Jade C , Kigozi Godfrey , Laeyendecker Oliver , Mills Lisa A. , Quinn Thomas C , Reynolds Steven J. , Santelli John , Sewankambo Nelson K. , Spencer Simon EF , Ssekasanvu Joseph , Thomson Laura , Wawer Maria J , Serwadda David , Godfrey-Faussett Peter , Kagaayi Joseph , Grabowski M Kate , Ratmann Oliver ,   Rakai Health Sciences Program,   PANGEA-HIV consortium
Published: March 2023

HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15-24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. Here, we integrated population-based surveillance of 38,749 participants in the Rakai Community Cohort Study and longitudinal deep sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted, while HIV transmission to girls and women (aged 15-24 years) from older men declined by about one third, transmission to women (aged 25-34 years) from men that were 0-6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programs to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa.
Relative vaccine effectiveness (rVE) of mRNA COVID-19 boosters in people aged at least 75 years in the UK vaccination programme, during the Spring-Summer (monovalent vaccine) and Autumn-Winter 2022 (bivalent vaccine) booster campaigns: a prospective test negative case-control study
Authors: Chatzilena Anastasia , Hyams Catherine , Challen Rob , Marlow Robin , King Jade , Adegbite David , Kinney Jane , Clout Madeleine , Maskell Nick , Oliver Jennifer , Finn Adam , Danon Leon ,   The Avon CAP Research Group
Published: March 2023

Background

Understanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is an urgent public health priority. A precise analysis of the rVE of monovalent and bivalent boosters given during the 2022 Spring-Summer and Autumn-Winter campaigns, respectively, in a defined population has not been reported.

Aim

We therefore assessed rVE against hospitalisation for the Spring-Summer (fourth vs third monovalent mRNA vaccine doses) and Autumn-Winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters.

Methods

A prospective single-centre test-negative design case-control study of ≥75 year-olds hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, sex, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation.

Results

682 controls and 182 cases were included in the Spring-Summer booster analysis; 572 controls and 152 cases for the Autumn-Winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed rVE 46·6% (95% confidence interval [CI] 13·9-67·1) versus those not fully boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had rVE 46·7% (95%CI 18-65·1), compared to a fourth monovalent mRNA COVID-19 vaccine dose.

Conclusions

Both fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offer similar protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support immunisation programmes in several European countries that advised the use of BA.1/ancestral bivalent booster doses.
Altered Amygdala Volumes and Microstructure in Focal Epilepsy Patients with Tonic-Clonic Seizures, Ictal and Post-Ictal Central Apnea
Authors: Zeicu Claudia , Legouhy Antoine , Scott Catherine A. , Oliveira Joana F. A. , Winston Gavin , Duncan John S , Vos Sjoerd B. , Thom Maria , Lhatoo Samden , Zhang Hui , Harper Ronald M. , Diehl Beate
Published: March 2023

Abstract and key words

Objectives

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death for patients with epilepsy; however, the pathophysiology remains unclear. Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further. Here, we determined volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by presence or absence of FBTCS, ictal central apnea (ICA) and post-ictal central apnea (PICA).

Methods

73 patients with only-focal seizures and 30 with FBTCS recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. We acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between healthy subjects, and patients with only-focal seizures or FBTCS The FBTCS group was further subdivided by presence of ICA and PICA, verified by VEEG.

Results

Bilateral amygdala volumes were significantly increased in the FBTCS cohort compared to healthy controls and the focal cohort. Patients with recorded PICA had the highest increase in bilateral amygdala volume of the FBTCS cohort.

Amygdala neurite density index (NDI) values were significantly decreased in both the focal and FBTCS groups relative to healthy controls, with values in the FBTCS group being the lowest of the two. The presence of PICA was associated with significantly lower NDI valuesvsthe non-apnea FBTCS group (p=0.004).

Significance

Individuals with FBTCS and PICA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk.
Individualized epidemic spreading models predict epilepsy surgery outcomes: a pseudo-prospective study
Authors: Millán Ana. P. , van Straaten Elisabeth C.W. , Stam Cornelis J. , Nissen Ida A. , Idema Sander , Van Mieghem Piet , Hillebrand Arjan
Published: March 2023

Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but up to 50% of patients continue to have seizures one year after the resection. In order to aid presurgical planning and predict postsurgical outcome in a patient-by-patient basis, we developed a framework of individualized computational models that combine epidemic spreading with patient-specific connectivity and epileptogeneity maps: the Epidemic Spreading Seizure and Epilepsy Surgery framework (ESSES). The ESSES parameters were fitted in a retrospective study (N= 15) to reproduce invasive electroencephalography (iEEG)-recorded seizures. ESSES could not only reproduce the iEEG-recorded seizures, but significantly better so for patients with good (seizure-free, SF) than bad (non-seizure-free, NSF) outcome (area under the curveAUC= 0.73). Once the model parameters were set in the retrospective study, ESSES can be applied also to patients without iEEG data. We illustrate here the clinical applicability of ESSES with apseudo-prospective study(N= 34) with a blind setting (to the resection strategy and surgical outcome) that emulated the presurgical conditions. ESSES could predict the chances of good outcome afteranyresection by finding patient-specific optimal resection strategies, which we found to be smaller for SF than NSF patients, suggesting an intrinsic difference in the network organization or presurgical evaluation results of NSF patients. The actual surgical plan also overlapped more with the optimal resection, and had a larger effect in decreasing modeled seizure propagation, for SF patients than for NSF patients. Overall, ESSES could correctly predict 75% of NSF and 80.8% of SF cases pseudo-prospectively. Our results show that individualised computational models may inform surgical planning by suggesting optimal resections and providing information on the likelihood of a good outcome after a proposed resection. This is the first time that such a model is validated on a fully independent cohort without the need for iEEG recordings.
Pandemic telehealth flexibilities for buprenorphine treatment: A synthesis of evidence and policy implications for expanding opioid use disorder care in the U.S
Authors: Krawczyk Noa , Rivera Bianca D. , King Carla , Dooling Bridget C.E.
Published: March 2023

Buprenorphine is a highly effective treatment for opioid use disorder and a critical tool for addressing the worsening U.S. overdose crisis. However, multiple barriers to treatment - including stringent federal regulations - have historically made this medication hard to reach for many who need it. In 2020, under the COVID-19 Public Health Emergency, federal regulators substantially changed access to buprenorphine by allowing prescribers to initiate patients on buprenorphine via telehealth without first evaluating them in person. As the Public Health Emergency is set to expire in May of 2023, Congress and federal agencies can leverage extensive evidence from studies conducted during the wake of the pandemic to make evidencebased decisions on the regulation of buprenorphine going forward. To aid policy makers, this review synthesizes and interprets peer-reviewed research on the effect of buprenorphine flexibilities on uptake and implementation of telehealth, and its impact on OUD patient and prescriber experiences, access to treatment and health outcomes. Overall, our review finds that many prescribers and patients took advantage of telehealth, including the audio-only option, with a wide range of benefits and few downsides. As a result, federal regulators—including agencies and Congress—should continue non-restricted use of telehealth for buprenorphine initiation.
Childhood Hepatitis B Immunization Coverage and Barriers in Sierra Leone, Liberia, and Guinea: Analysis of National Surveys (2018-2020)
Authors: Yendewa George A. , James Peter B. , Mohareb Amir M. , Barrie Umaru , Massaquoi Samuel P.E. , Yendewa Sahr A. , Ghazzawi Manal , Bockarie Tahir , Cumming Peterlyn E. , Diallo Ibrahima S. , Johnson Ambulai , Vohnm Benjamin , Babawo Lawrence S. , Deen Gibrilla F. , Kabba Mustapha , Sahr Foday , Lakoh Sulaiman , Salata Robert A.
Published: March 2023

Vaccination against hepatitis B virus (HBV) is effective at preventing mother-to-child transmission. Sierra Leone, Liberia and Guinea are hyperendemic West African countries; yet childhood immunization coverage is suboptimal and barriers to immunization are poorly understood. We analyzed national survey data (2018-2020) of children aged 4-35 months to assess full HBV immunization (receiving 3 doses of the pentavalent vaccine) and incomplete immunization (receiving < 3 doses). Statistical analysis was conducted using the complex sample command in SPSS (version 28). Multivariate logistic regression was used to identify determinants of incomplete immunization. Overall, 11181 mothers were analyzed (4846 from Sierra Leone, 2788 from Liberia and 3547 from Guinea). Sierra Leone had the highest HBV childhood immunization coverage (70.3%), followed by Liberia (64.5%) and Guinea (40.0%). Within countries, immunization coverage varied by sociodemographic characteristics (education, religion, household wealth index, access to mass media) and healthcare access (antenatal visits, place of delivery and health facility proximity). In multivariate regression analysis, Muslim mothers, lower household wealth index, < 4 antenatal visits, home delivery and distance to health facility were predictors of incomplete immunization (all p < 0.05). Addressing these socioeconomic and healthcare access barriers will be essential to help achieve the 2030 viral hepatitis elimination goals.
Understanding the Lived Experience of Chronic Pain: A Systematic Review and Synthesis of Qualitative Evidence Syntheses
Authors: van Rysewyk S , Blomkvist R , Crighton R , Hodson F , Roomes D , Shea E , Smith BH , Toye F
Published: March 2023

Background

Although multiple measures of the causes and consequences of chronic non-cancer pain (CNCP) are available and can inform pain management, no quantitative summary of these measures can describe the meaning of pain for a patient. The lived experience of pain tends to be a blind spot in pain management. This study aimed to: (1) integrate qualitative research investigating the lived experience of a range of CNCP conditions; (2) establish common qualitative themes in CNCP experience; and (3) evaluate the relevance of our results through a survey questionnaire based on these themes, administered across the United Kingdom.

Methods

Six bibliographic databases were searched from inception to February 2021 to identify Qualitative Evidence Syntheses (QES) that investigated the lived experience of CNCP and its impact on everyday life and activities. Themes and trends were derived by thematic qualitative analysis in collaboration with two patient and public involvement representatives through two workshops. The output from these workshops helped inform the creation of twenty survey statements.

Results

The research team identified and screened 1,323 titles, and considered 86 abstracts, including 20 in the final review. Eight themes were developed from the study findings: (1) my pain gives rise to negative emotions; (2) changes to my life and to my self; (3) adapting to my new normal; (4) effects of my pain management strategies; (5) hiding and showing my pain; (6) medically explaining my pain; (7) relationships to those around me; and (8) working while in pain. Each theme gave rise to one or two survey questions. The survey was shared with members of the UK pain community over a two-week period in November 2021, and was completed by 1,219 people, largely confirming the above themes.

Conclusion/implications

This study provides a validated summary of the lived experience of CNCP. It highlights the adverse nature, complications, and consequences of living with CNCP in the UK, and the multiple shortcomings in the ways in which pain is addressed by others in the UK. Our findings are consistent with published meta-ethnographies on chronic non-malignant musculoskeletal pain, and chronic low-back pain. Despite the underrepresentation of qualitative research in the pain literature compared to quantitative approaches, for understanding the complexity of the lived experience of pain, qualitative research is an essential tool.
Childhood trauma is prevalent and associated with co-occurring depression, anxiety, mania and psychosis in young people attending Australian youth mental health services
Authors: Bendall Sarah , Eastwood Oliver , Spelman Tim , McGorry Patrick , Hickie Ian , Yung Alison R. , Amminger Paul , Wood Stephen J. , Pantelis Christos , Purcell Rosemary , Phillips Lisa
Published: March 2023

Objectives

Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorder groups, there is evidence that trauma is associated with an admixture of affective, anxiety, and psychotic symptoms in adults. Given that both early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people.

Methods

We used data from the Transitions Study, a longitudinal investigation of young people attending one of four headspace youth mental health services in Melbourne and Sydney, Australia between January 2011 and August 2012. Participants were 775 young people aged 12 to 25 (65.9% female; mean age = 18.3, SD = 3.2). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania, and psychosis symptoms than with any one in isolation.

Results

Approximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%) during childhood or adolescence. Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain (depression, mania, anxiety and psychosis). Childhood trauma was more strongly associated with the co-occurrence of these symptoms than with any one of these domains in isolation, such that trauma-exposed young people were more likely to experience increased symptom clustering than their non-exposed counterparts.

Conclusions

Childhood trauma is pervasive in youth mental health services and associated with a heterogeneous symptom profile that cuts across traditional diagnostic boundaries.
Mortality Associated with Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: MFIRE Registry
Authors: Duggal Neal , Engoren Milo , Chadderdon Scott M , Rodriguez Evelio , Morse M. Andrew , Vannan Mani A , Yadav Pradeep , Morcos Michael , Li Flora , Reisman Mark , Garcia-Sayan Enrique , Raghunathan Deepa , Sodhi Nishtha , Sorajja Paul , chen lily , Rogers Jason H , Calfon Press Marcella , Kovach Christopher , Gill Edward A , Zahr Firas , Chetcuti Stanley , Yuan Yuan , Mentz Graciela , Lim D. Scott , Ailawadi Gorav
Published: March 2023

BACKGROUND The association, if any, between the effective regurgitant orifice (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients undergoing mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip™ system. The objective is to determine the association between EROA/LVEDV and 1-year mortality among patients undergoing m-TEER with MitraClip™. METHODS In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. RESULTS We studied 525 patients with secondary MR who underwent m-TEER in 11 centers. Most patients were male (63%) and were NYHA class III (61%) or IV (21%). MR was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely with median=0.19 mm2/mL, interquartile range [0.12,0.28] mm2/mL, and 187 (36%) patients had values <0.15 mm2/mL. Post-procedural MR severity improved substantially, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%. 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation of EROA/LVEDV was associated with 1-year mortality (odds ratio=0.600, 95% confidence interval [0.386,0.933], p=0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. CONCLUSIONS Lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in a multi-center registry. The slope of the association is steep at low values, but gradually becomes flatter as Ln(EROA/LVEDV) increases.
Peripheral and Cerebral Vascular Reactivity in Black and White Women: Examining the Impact of Psychosocial Stress Exposure Versus Internalization and Coping
Authors: Martin Zachary T. , Al-daas Iman O. , Cardenas Natalia , Kolade John O. , Merlau Emily R. , Vu Joshua K. , Brown Kyrah K. , Brothers R. Matthew
Published: March 2023

Black women have the highest rates of cardiovascular and cerebrovascular disease prevalence and mortality in part due to blunted vascular function. Psychosocial stress likely also contributes but its relationship to vascular function remains incompletely understood. Recent studies suggest that internalization and coping strategies are more important than stress exposure alone. We hypothesized that Black women have blunted peripheral and cerebral vascular function and that, among Black women, this would be inversely related with psychosocial stress internalization/coping but not stress exposures. Healthy Black (n= 21; 20 ± 2 yr) and White (n= 16; 25 ± 7 yr) women underwent testing for forearm reactive hyperemia (RH), brachial artery flow-mediated dilation (FMD), and cerebrovascular reactivity (CVR). Psychosocial stress exposure (adverse childhood experiences, ACEs; past week discrimination, PWD) and internalization/coping techniques (John Henryism Active Coping Scale, JHAC12; Giscombe Superwoman Schema Questionnaire, G-SWS-Q) were assessed. RH and CVR (p> 0.05) were not different between groups whereas FMD was lower in Black women (p= 0.007). Neither ACEs nor PWD were associated with FMD in either group (p> 0.05 for all). JHAC12 scores were negatively associated with FMD in Black women (p= 0.014) but positively associated with FMD in White women (p= 0.042). SWS-Succeed was negatively associated (p= 0.044) and SWS-Vulnerable tended to be negatively associated (p= 0.057) with FMD in Black women. These findings indicate that blunted FMD in Black women may be due more to internalization and maladaptive coping than stress exposure alone.