bluuebunny/crossref_metadata_2025 huggingface dataset:
To err is human; to be perfect is AI: embracing mistakes as a catalyst for human formation development
Authors: Deguma Melona C
Published: September 2023

In a culture overwhelmed by the quest for perfection, thereby committing acts like intellectual dishonesty, erring is left to be a valuable human experience. Recent articles in the Oxford Journal of Public Health explore the impact of artificial intelligence (AI) technology on human relationships in different settings. It is crucial to acknowledge the potential benefits of AI while also being mindful of its possible misuse. As AI technology becomes more integrated into our daily lives, pursuing perfection propels its advancement. However, using AI technology to pursue perfection may adversely affect people’s mental health. In this paper, I argue that pursuing perfection can harm one’s well-being. Instead, it is crucial to acknowledge and embrace one’s mistakes to foster personal growth and development.
Atopic manifestations of inborn errors of immunity
Authors: Sams Laura , Wijetilleka Sonali , Ponsford Mark , Gennery Andrew , Jolles Stephen
Published: September 2023

Purpose of review

Allergy and atopic features are now well recognized manifestations of many inborn errors of immunity (IEI), and indeed may be the hallmark in some, such as DOCK8 deficiency. In this review, we describe the current IEI associated with atopy, using a comprehensive literature search and updates from the IUIS highlighting clinical clues for underlying IEI such as very early onset of atopic disease or treatment resistance to enable early and accurate genetic diagnosis.

Recent findings

We focus on recently described genes, their categories of pathogenic mechanisms and the expanding range of potential therapies.

We highlight in this review that patients with very early onset or treatment resistant atopic disorders should be investigated for an IEI, as targeted and effective therapies exist. Early and accurate genetic diagnosis is crucial in this cohort to reduce the burden of disease and mortality.
Neighborhood Deprivation and Neural Tube Defects
Authors: Pruitt Evans Shannon , Ailes Elizabeth C. , Kramer Michael R. , Shumate Charles J. , Reefhuis Jennita , Insaf Tabassum Z. , Yazdy Mahsa M. , Carmichael Suzan L. , Romitti Paul A. , Feldkamp Marcia L. , Neo Dayna T. , Nembhard Wendy N. , Shaw Gary M. , Palmi Elizabeth , Gilboa Suzanne M. ,   National Birth Defects Prevention Study
Published: September 2023

Background:

Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk.

Methods:

The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race–ethnicity, maternal education, and maternal age at delivery.

Results:

Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race–ethnicity.

Conclusions:

Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.
Transportability Without Positivity: A Synthesis of Statistical and Simulation Modeling
Authors: Zivich Paul N. , Edwards Jessie K. , Lofgren Eric T. , Cole Stephen R. , Shook-Sa Bonnie E. , Lessler Justin
Published: September 2023

Studies designed to estimate the effect of an action in a randomized or observational setting often do not represent a random sample of the desired target population. Instead, estimates from that study can be transported to the target population. However, transportability methods generally rely on a positivity assumption, such that all relevant covariate patterns in the target population are also observed in the study sample. Strict eligibility criteria, particularly in the context of randomized trials, may lead to violations of this assumption. Two common approaches to address positivity violations are restricting the target population and restricting the relevant covariate set. As neither of these restrictions is ideal, we instead propose a synthesis of statistical and simulation models to address positivity violations. We propose corresponding g-computation and inverse probability weighting estimators. The restriction and synthesis approaches to addressing positivity violations are contrasted with a simulation experiment and an illustrative example in the context of sexually transmitted infection testing uptake. In both cases, the proposed synthesis approach accurately addressed the original research question when paired with a thoughtfully selected simulation model. Neither of the restriction approaches was able to accurately address the motivating question. As public health decisions must often be made with imperfect target population information, model synthesis is a viable approach given a combination of empirical data and external information based on the best available knowledge.
The Relationships Between Blood Pb Levels and Blood Pressure Among Lead-Exposed Workers in China: A Repeated-Measure Study
Authors: Han Zhiyuan , Gong Shiyang , Tu Yuting , Lang Chunyan , Tang Jiachun , Wang Tuanwei , Xia Zhao-lin
Published: September 2023

Objectives

To explore the differences in the increase of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in 3 consecutive years among lead (Pb) workers.

Methods

Four hundred forty-eight Pb workers were enrolled in this repeated-measure study. Blood Pb, SBP, and DBP were measured in 2015 to 2017. Repeated measure of analysis of variance was used to compare the differences in the increase of SBP and DBP.

Results

The mean SBP values were 124.0/125.5/126.9 mm Hg, and the mean DBP values were 75.4/77.4/77.8 mm Hg from 2015 to 2017. The differences in the increase of SBP and DBP were 2.94/2.42 mm Hg during the 3-year period. The average annual increase of SBP or DBP showed an upward trend in different Pb dose groups (F = 4.904, P = 0.002; F = 3.612, P = 0.013).

Conclusions

Lead exposure caused average annual increases in SBP and DBP with 0.98 and 0.81 mm Hg, which provided basic data for health surveillance.
Portrait of COVID-19 Outbreaks in the Workplaces of the Monteregie Region
Authors: Bastien Marc-Étienne , Guay Maryse , Cambron-Goulet Évelyne , Lajoie Élisabeth , Berbiche Djamal , Kadaoui Nabila
Published: September 2023

Objectives: The aims of the studies are to describe COVID-19 outbreaks in the workplaces of the Monteregie Region, Quebec, Canada, and to evaluate potential risk factors for identifying at least one COVID-19 outbreak in these workplaces. Methods: An ecological retrospective cohort study was conducted using deidentified databases of COVID-19 outbreaks that occurred in workplaces from February 27, 2020, to June 30, 2021. Results: Among 30,489 workplaces studied, 897 workplaces with at least one COVID-19 outbreak were identified. These outbreaks were associated with a sizeable number of workers in the workplace (adjusted odds ratio [aOR] = 6.78; 95% CI: 5.43–8.47), the presence of temporary foreign workers (aOR = 2.26; 95% CI: 1.53–3.33), contacts with clients (aOR = 1.93; 95% CI: 1.68–2.21), and being localized in the Montreal Metropolitan Area (aOR = 1.26; 95% CI: 1.09–1.45). Conclusions: These results enable the identification of potential risk factors for COVID-19 outbreaks in workplaces, with the aim of targeting workplaces where infection control and prevention measures might be enhanced or adapted to improve workers’ health.
Determining Unmet Needs Among Workers’ Compensation Stakeholders to Prevent Work Disability in the State of Vermont
Authors: Peterik Kara , Kennedy Deborah , Bentley Mary Helen , Guyette Mary , David Dent , McDonough Christine , Ulack Christopher , Wallace Scott , Huyck Karen
Published: September 2023

Purpose

Vermont has high rates of young people receiving federal disability benefits leading to substantial gaps in the workforce. The purpose of this project was to determine the unmet needs of interested parties in the workers’ compensation (WC) process.

Methods

A type of focus group, experience groups, was used to elicit key parties’ experiences in the WC system. Facilitators used open-ended prompts to encourage discussion among participants about their experience with the WC system. Data were analyzed using thematic coding procedures to identify common motifs.

Results

Common themes emerged including challenges in navigating the WC system, lack of communication among stakeholders, and providing and receiving appropriate health care to facilitate RTW.

Conclusions

Understanding unmet needs of interested parties in the WC process allows for the creation of targeted, high-value, early intervention strategies to reduce long-term work disability.
Use of artificial intelligence to identify patients to be assessed in a breast clinic on 2-week wait: a retrospective cohort study
Authors: Rao Ahsan , Manley Lara , Smith Simon
Published: September 2023

Background:

The number of urgent referrals from primary care to specialist one stop breast clinics continues to rise beyond the capacity of the 2-week wait service. This study aims to use artificial intelligence (AI) to identify patients with new breast symptoms requiring a biopsy to identify those who should be prioritised for urgent breast clinic assessment.

Methods:

Data were collected retrospectively for patients attending one stop triple assessment breast clinic at Broomfield hospital between 1 June and 1 October 2021. PHP machine learning software was used to run AI on the data to identify patients who had a core biopsy in clinic.

Results:

A total of 794 cases were referred to one stop breast clinic for new breast symptoms—37 male (4.6%) and 757 female (95.3%). The average age of the patients included was 43.2 years. Five hundred thirty-six patients (67.5%) presented with a breast lump, 180 (22.7%) with breast pain, 61 (7.7%) with changes to shape or skin and 13 (1.6%) with a lump identified by their general practitioner. The patients who had a biopsy were of increased age [52.8 (SD 17.9) vs. 44.1 (SD 16.8), P<0.001], and had previous mammogram [n=21, (31.8%) vs. n=148 (20.3%), P 0.03], previous benign breast disease [n=9 (13.6%) vs. n=23 (3.1%), P<0.001], and increased use of HRT [n=13 (19.7%) vs. n=53 (6.4%), P<0.001]. The sensitivity and specificity of AI with neural network algorithms were 84% and 90%, respectively.

Conclusion:

AI was very effective at predicting the presenting symptoms that are likely to result in biopsy and can therefore be used to identify patients who need to be seen urgently in breast clinic.
The Presence of an Arteria Lusoria Should Be Checked When Reporting 18F-FCH PET/CT Performed to Localize Hyperfunctioning Parathyroid Glands
Authors: Talbot Jean-Noël , Périé Sophie , Tassart Marc , Safa Jean-Baptiste , Montravers Françoise , Balogova Sona
Published: September 2023

Nonrecurrent inferior laryngeal nerve (NRILN) is a rare anatomical variant, which significantly increases the risk of nerve injury during neck surgery, for example, thyroidectomy or parathyroidectomy (PTX). The absence of the brachiocephalic trunk and presence of arteria lusoria (AL) are strong predictors of NRILN in the right neck. FCH PET/CT is now a recognized imaging modality in hyperparathyroidism (HPT). We report 2 patients with primary or renal HPT in whom FCH PET detected right HFPTs and low-dose noncontrast CT evidenced AL. The NRILN was thus preserved during PTX. We recommend searching for AL on FCH PET/CT (even low-dose) in HPT before PTX.
Impact of 18F-FDG PET on the Management in Patients With Recurrent Gynecologic cancer
Authors: Pak Kyoungjune , Yoon Hai-Jeon
Published: September 2023

Purpose

Gynecological cancer is the most prevalent cancer among women worldwide. We performed a meta-analysis to assess the impact of 18F-FDG PET on the management of patients with recurrent gynecological cancers, including cervical, uterine, and ovarian cancers.

Methods

We systematically searched MEDLINE and EMBASE databases for English-language publications. All published studies on the impact of PET scans on the management of patients with recurrent gynecological cancers were reviewed. The proportion of management change (%), defined as the percentage of patients whose management changed after FDG PET to those who underwent FDG PET, was calculated. The data from each study were analyzed using MedCalc Statistical Software version 14.12.0 (MedCalc Software, Ostend, Belgium).

Results

Nineteen studies including 6191 patients were eligible for inclusion. The impact of FDG PET scan for detecting recurrence/metastasis in patients with gynecologic cancer was evaluated using management change rates, ranging from 9.4% to 60.7% with a pooled effect of 42.0% (95% confidence interval [CI], 34.5%–49.6%; I
2 = 92.9%). In the subtype analysis, FDG PET scanning resulted in changes in the management in 48.5% (95% CI, 37.8%–59.3%; I
2 = 67.8%) of cervical cancer, 34.7% (95% CI, 33.4%–36.0%; I
2 = 0%) of uterine cancer, and 40.3% (95% CI, 26.7%–54.7%; I
2 = 95.2%) of ovarian cancer cases.

Conclusions

FDG PET has a significant impact on the restaging of patients with gynecological cancer. These findings suggest that FDG PET should be performed, especially in cases of suspected recurrence/metastasis in the main gynecologic cancer types, including cervical, ovarian, and uterine cancers.
Metastatic Esophageal Adenocarcinoma Showing 68Ga-DOTATATE Uptake
Authors: Fılızoglu Nuh , Ozguven Salih
Published: September 2023

The role of 68Ga-DOTATATE PET/CT in the evaluation of neuroendocrine tumors is well defined. Nevertheless, 68Ga-DOTATATE uptake may be seen in some tumors other than neuroendocrine tumors as a reflection of tumor blood supply and somatostatin receptor expression. Although 68Ga-DOTATATE uptake has been described in a number of nonneuroendocrine tumors, no case of 68Ga-DOTATATE uptake in esophagus adenocarcinoma has been reported. We present the case of a 52-year-old man who had a metastatic esophageal adenocarcinoma showing 68Ga-DOTATATE uptake.
68Ga-PSMA–Avid Liver Metastases From Colon Cancer, Not Visualized on FDG PET Scan
Authors: Doroudinia Abtin , Chekuri Satyanarayana
Published: September 2023

18F-FDG PET/CT scan is a well-known modality to assess distant metastases and treatment response in the patients with primary colon cancer. We are presenting an interesting case of 68Ga-PSMA–avid liver metastases in a 74-year-old man with colon cancer and recently diagnosed prostate cancer. The liver metastases were positive on initial FDG PET but lost FDG avidity on subsequent posttreatment FDG PET scans. Biopsy from the PSMA-avid liver lesions confirmed metastasis from colon origin. PSMA is expressed in various forms of tumor neovasculature other than prostate cancer with potential new applications as a theranostic agent in the future.
Steroids May Be Associated With Extensive Skeletal Muscle Uptake of 18F-FDG
Authors: Kawabata Kazuna , Hosono Makoto , Mori Yukiko , Tsukamoto Suzune , Ito Shunsuke , Ando Saya , Kanagaki Mitsunori
Published: September 2023

Purpose

The possibility of steroid administration inducing the extensive skeletal muscle uptake (ESMU) of FDG in PET scans was investigated.

Methods

From 8923 consecutive 18F-FDG PET/CT scans taken at our hospital, 23 scans (15 patients) met adult age and ESMU-positive inclusion criteria. Among the 15 patients, 13 with both ESMU-positive and -negative scans were examined for association with steroid administration.

Results

Extensive skeletal muscle uptake was associated with a history of steroid administration (χ
2 test: P = 0.001). Notably, 20 ESMU-positive scans and 11 ESMU-negative scans were significantly different, with 0 to 95 days (median, 18.5 days) and 0 to 708 days (median, 319.0 days) since the last steroid administration, respectively (Mann-Whitney U test, P = 0.003). A significant correlation was observed between mean skeletal muscle SUVmax and the number of days since the last steroid administration (Spearman rank correlation coefficient, ρ = −0.501, P = 0.004). Specifically, the degree of ESMU tended to decrease over time, after steroid administration. From multiple regression analysis, the number of days since the last steroid administration was significantly associated with mean SUVmax (P = 0.007), but the blood glucose level was not significant (P = 0.204), revealing that the number of days since the last steroid administration was an independent risk factor. Multicollinearity was low (the variance inflation factor was 1.007 for both the number of days since the last steroid administration and blood glucose levels).

Conclusions

Steroid administration within months before PET may be one cause of ESMU.
Variability in tibia-fibular geometry is associated with increased tibial strain from running loads
Authors: Keast Meghan , Bonacci Jason , Fox Aaron
Published: September 2023

Variation in tibial geometry may alter strain magnitude and distribution during locomotion. We investigated the effect of tibia-fibula geometric variations on tibial strain with running loads applied at various speeds. Participant-specific three-dimensional models of the tibia-fibula were created using lower limb computed tomography scans from 30 cadavers. Finite-element models were developed in FEBio, and running loads from 3, 4 and 5 m s
−1
were applied to extract effective strain from the tibial shaft. Linear regression models evaluated the relationship between geometric characteristics and effective strain along the tibial shaft. We found a statistically significant positive relationship between: (i) increased thickness of the midshaft to upper tibia with increased condyle prominence and effective strain at points along the distal anterolateral and proximal posterior regions of the tibial shaft; and (ii) increased midshaft cortical thickness and effective strain at points along the medial aspect of the distal tibial shaft. It is possible that increased thickness in the more proximal region of the tibia causes strain to redistribute to areas that are more susceptible to the applied loads. A thickness imbalance between the upper and distal portions of the tibial shaft could have a negative impact on tibial stress injury risk.
Plasticity and seasonality of the vertical migration behaviour of Antarctic krill using acoustic data from fishing vessels
Authors: Bahlburg Dominik , Hüppe Lukas , Böhrer Thomas , Thorpe Sally E. , Murphy Eugene J. , Berger Uta , Meyer Bettina
Published: September 2023

Understanding the vertical migration behaviour of Antarctic krill is important for understanding spatial distribution, ecophysiology, trophic interactions and carbon fluxes of this Southern Ocean key species. In this study, we analysed an eight-month continuous dataset recorded with an ES80 echosounder on board a commercial krill fishing vessel in the southwest Atlantic sector of the Southern Ocean. Our analysis supports the existing hypothesis that krill swarms migrate into deeper waters during winter but also reveals a high degree of variability in vertical migration behaviour within seasons, even at small spatial scales. During summer, we found that behaviour associated with prolonged surface presence primarily occurred at low surface chlorophyll a concentrations whereas multiple ascent–descent cycles per day occurred when surface chlorophyll a concentrations were elevated. The high plasticity, with some krill swarms behaving differently in the same location at the same time, suggests that krill behaviour is not a purely environmentally driven process. Differences in life stage, physiology and type of predator are likely other important drivers. Finally, our study demonstrates new ways of using data from krill fishing vessels, and with the routine collection of additional information in potential future projects, they have great potential to significantly advance our understanding of krill ecology.
New Middle to ?Late Jurassic dinosaur tracksites in the Central High Atlas Mountains, Morocco
Authors: Oussou Ahmed , Falkingham Peter L. , Butler Richard J. , Boumir Khadija , Ouarhache Driss , Ech-charay Kawtar , Charrière André , Maidment Susannah C. R.
Published: September 2023

Besides bones, fossil tracks and trackways are important sources of knowledge about dinosaur palaeobiology. Here, we report three new tracksites from two different synclines in the Imilchil area, Central High Atlas, Morocco. The tracks and trackways are preserved in fluvial deposits in different levels of the Isli Formation (Early Bathonian–?Upper Jurassic), and contain impressions made by sauropods, theropods and ornithopods, as well as tracks that might represent bird-like non-avian theropod dinosaurs. In addition to traditional field measurements, three-dimensional digital models of the track sites were created using photogrammetry. These new tracksites add to the rich faunal ichnoassemblage already recorded from the High Atlas Mountains and North Africa, which is considerably richer than the contemporaneous body fossil record, and also provide new data on dinosaurs–substrate interactions.
Parasedimentitalea psychrophila sp. nov., a psychrophilic bacterium isolated from deep-sea sediment
Authors: Li An-Qi , Zhang Chan , Li Deng-Hui , Qi Xiao-Qing , Meng Liang , Wu Long-Fei , Li Xue-Gong , Zhang Wei-Jia
Published: September 2023

A novel bacterium, strain QS115T, was isolated from deep-sea sediment collected from the South China Sea at a depth of 1151 m. Phylogenetic analyses based on 16S rRNA gene sequences indicated that QS115T was most closely related to

Parasedimentitalea marina

W43T, with similarity of 98.21 %. Strain QS115T shared 82.39 % average nucleotide identity, 26.3 % digital DNA–DNA hybridization and 85.32 % average amino acid identity with

P. marina

W43T. Cells of strain QS115T were Gram-stain-negative, rod-shaped and grew optimally at 10 °C, pH 7.5 and 2 % (w/v) NaCl. The principal fatty acids were summed feature 8 (C18 : 1
 ω7c/ω6c), the major respiratory quinone was ubiquinone-10 and predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, glycophospholipid, phosphatidylglycerol and phosphatidylcholine. Polyphasic analyses of physiological and phenotypic characteristics and genomic studies suggested that strain QS115T represents a novel species of the genus

Parasedimentitalea

, for which the name Parasedimentitalea psychrophila sp. nov. is proposed (type strain QS115T=MCCC 1K04395T=JCM 34219T).
Functional genomics implicates natural killer cells in the pathogenesis of ankylosing spondylitis
Authors: Chiñas Marcos , Fernandez-Salinas Daniela , Aguiar Vitor R. C. , Nieto-Caballero Victor E. , Lefton Micah , Nigrovic Peter A. , Ermann Joerg , Gutierrez-Arcelus Maria
Published: September 2023

Objective

Multiple lines of evidence indicate that ankylosing spondylitis (AS) is a lymphocyte-driven disease. However, which lymphocyte populations are critical in AS pathogenesis is not known. In this study, we aimed to identify the key cell types mediating the genetic risk in AS using an unbiased functional genomics approach.

Methods

We integrated genome-wide association study (GWAS) data with epigenomic and transcriptomic datasets of human immune cells. To quantify enrichment of cell type-specific open chromatin or gene expression in AS risk loci, we used three published methods that have successfully identified relevant cell types in other diseases. We performed co-localization analyses between GWAS risk loci and genetic variants associated with gene expression (eQTL) to find putative target genes.

Results

Natural killer (NK) cell-specific open chromatin regions are significantly enriched in heritability for AS, compared to other immune cell types such as T cells, B cells, and monocytes. This finding was consistent between two AS GWAS. Using RNA-seq data, we validated that genes in AS risk loci are enriched in NK cell-specific gene expression. Using the human Space-Time Gut Cell Atlas, we also found significant upregulation of AS-associated genes predominantly in NK cells. Co-localization analysis revealed four AS risk loci affecting regulation of candidate target genes in NK cells: two known loci,ERAP1 and TNFRSF1A, and two under-studied loci,ENTR1(akaSDCCAG3) andB3GNT2.

Conclusion

Our findings suggest that NK cells may play a crucial role in AS development and highlight four putative target genes for functional follow-up in NK cells.
Muscle cell atrophy induced by miR-155-5p reveals molecular targets in skeletal muscle disorders
Authors: Lopes Letícia , Cury Sarah Santiloni , de Moraes Diogo , Oliveira Jakeline Santos , de Oliveira Grasieli , Cabral-Marques Otavio , Fernandez Geysson Javier , Hirata Mario Hiroyuki , Wang Da-Zhi , Dal-Pai-Silva Maeli , Carvalho Robson Francisco , Freire Paula Paccielli
Published: September 2023

MicroRNAs are small regulatory molecules that control gene expression. An emerging property of muscle miRNAs is the cooperative regulation of transcriptional and epitranscriptional events controlling muscle phenotype. miR-155 has been related to muscular dystrophy and muscle cell atrophy. However, the function of miR-155 and its molecular targets in muscular dystrophies remain poorly understood. Throughin silicoandin vitroapproaches we identify distinct transcriptional profile of muscle cell atrophy induced by miR-155-5p. The atrophic myotubes changed the expression of 359 genes (166 up-regulated and 193 down-regulated). We reanalyzed muscle transcriptomic data from dystrophin-deficient patients and detected overlap with gene expression patterns in miR-155-treated myotubes. Our analysis indicated that miR-155 regulates a set of transcripts, including Aldh1l, Nek2, Bub1b, Ramp3, Slc16a4, Plce1, Dync1i1, and Nr1h3. Enrichment analysis demonstrates 20 targets involved in metabolism, cell cycle regulation, muscle cell maintenance, and immune system. Moreover, digital cytometry confirmed a significant increase in M2 macrophages, indicating miR-155 effects on immune response in dystrophic muscles. We highlight a critical miR-155 associated with disease-related pathways in skeletal muscle disorders.
Attendance at remote versus face-to-face outpatient appointments in an NHS Trust
Authors: Kerr Gabriele , Greenfield Geva , Hayhoe Benedict , Gaughran Fiona , Halvorsrud Kristoffer , da Costa Mariana Pinto , Rehill Nirandeep , Raine Rosalind , Majeed Azeem , Costelloe Ceire , Neves Ana Luisa , Beaney Thomas
Published: September 2023

Introduction

With the growing use of remote appointments within the National Health Service, there is a need to understand potential barriers of access to care for some patients. In this observational study we examined missed appointments rates, comparing remote and face-to-face appointments among different patient groups.

Methods

We analysed adult outpatient appointments at Imperial College Healthcare NHS Trust in Northwest London in 2021. Rates of missed appointments per patient were compared between remote vs. face-to-face appointments using negative binomial regression models. Models were stratified by appointment type (first or a follow-up).

Results

There were 874,659 outpatient appointments for 189,882 patients, 29.5% of whom missed at least one appointment. Missed rates were 12.5% for remote first appointments and 9.2% for face-to-face first appointment. Remote and face-to-face follow-up appointments were missed at similar rates (10.4% and 10.7%, respectively). For remote and face-to-face appointments, younger patients, residents of more deprived areas, and patients of Black, Mixed, and ‘other’ ethnicities missed more appointments. Male patients missed more face-to-face appointments, particularly at younger ages, but gender differences were minimal for remote appointments. Patients with long-term conditions (LTCs) missed more first appointments, whether face-to-face or remote. In follow-up appointments, patients with LTCs missed more face-to-face appointments but fewer remote appointments.

Discussion

Remote face-to-face appointments were missed more often than face-to-face first appointments, follow-ups appointments had similar attendance rates for both modalities. Sociodemographic differences in outpatient appointment attendance were largely similar between face-to-face and remote appointments, indicating no widening of inequalities in attendance due to appointment modality.
RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variants Monitoring, and Risk Pre-warning
Authors: Li Cuiping , Ma Lina , Zou Dong , Zhang Rongqin , Bai Xue , Li Lun , Wu Gangao , Huang Tianhao , Zhao Wei , Jin Enhui , Bao Yiming , Song Shuhui
Published: September 2023

The Resource for Coronavirus 2019 (RCoV19,https://ngdc.cncb.ac.cn/ncov/) is an open-access information resource dedicated to providing valuable data on the genomes, mutations, and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this updated implementation of RCoV19, we have made significant improvements and advancements over the previous version. Firstly, we have implemented a highly refined genome data curation model. This model now features an automated integration pipeline and optimized curation rules, enabling efficient daily updates of data in RCoV19. Secondly, we have developed a global and regional lineage evolution monitoring platform, alongside an outbreak risk pre-warning system. These additions provide a comprehensive understanding of SARS-CoV-2 evolution and transmission patterns, enabling better preparedness and response strategies. Thirdly, we have developed a powerful interactive mutation spectrum comparison module. This module allows users to compare and analyze mutation patterns, assisting in the detection of potential new lineages. Furthermore, we have incorporated a comprehensive knowledgebase on mutation effects. This knowledgebase serves as a valuable resource for retrieving information on the functional implications of specific mutations. In summary, RCoV19 serves as a vital scientific resource, providing access to valuable data, relevant information, and technical support in the global fight against COVID-19.
Metabolic Phenotypes of Overweight/Obesity and Risk of Cardiovascular Diseases in Postmenopausal Women: Findings from the China PEACE Million Persons Project
Authors: Deng Danying , Nie Zhiqiang , Wang Jiabin , Chen Chaolei , Wang Wenbin , Zhu Yanchen , Guan Qingyu , Ou Yanqiu , Feng Yingqing
Published: September 2023

BACKGROUND

Obesity and metabolic abnormalities were associated with increased risk of cardiovascular diseases (CVD). However, much remains unknown about which metabolic weight phenotypes and how relate to CVD, especially in postmenopausal women.

METHODS AND RESULTS

We included 15,575 postmenopausal women aged 35 to 75 years (median age, 60.6 [IQR: 55.0-65.7]) free of CVD at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project between 1 January 2016 and 31 December 2020 in Guangdong Province at 8 sites. Cox regression models were used to investigate the associations of metabolic and overweight/obese status with the risk of developing CVD. Over a median follow-up period of 3.32 years, a total of 1354 CVD events occurred. Overall, 30.3% were metabolically heathy among the 9404 overweight/obese participants, while 49.2% were metabolically unhealthy among the 6171 normal weight subjects. Compared with the metabolically healthy normal weight group, the remaining three groups of participants were all at higher risk of combined CVD, with multivariate-adjusted hazard ratios and 95% confidence intervals of 1.41 (1.16–1.71) for metabolically unhealthy normal weight, 1.42 (1.16–1.73) for metabolically healthy overweight/obesity, and 1.75 (1.47–2.07) for metabolically unhealthy overweight/obesity. When subdividing overweight/obesity separately into overweight and obesity, combined CVD risk was only greater in metabolically unhealthy individuals across different weight categories.

CONCLUSIONS

Postmenopausal women with metabolically healthy overweight/obesity and metabolically unhealthy normal weight had a higher risk of cardiovascular disease than those with metabolically healthy normal weight, and the association of metabolically unhealthy overweight/obesity was greatest among four categories, suggesting that metabolic abnormalities and overweight/obesity should be monitored and controlled.

CLINICAL PERSPECTIVE

What Is New?

Postmenopausal women with metabolic abnormalities combined with overweight/obesity and even normal weight had a higher risk of cardiovascular disease (CVD) than those with metabolically healthy normal weight.

Metabolically healthy overweight/obesity were associated with greater risk of CVD, indicating that overweight/obesity alone may contribute to CVD risk in postmenopausal women.

What Are the Clinical Implications?

Individuals who are metabolically unhealthy and overweight/obese warrant close clinical supervision, while those of normal weight should not be ignored.
Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain
Authors: Small Gabriel I. , Fedorova Olga , Olinares Paul Dominic B. , Chandanani Joshua , Banerjee Anoosha , Choi Young Joo , Molina Henrik , Chait Brian , Darst Seth A. , Campbell Elizabeth A.
Published: September 2023

The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N-terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5’-cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated. Here we determine high-resolution cryo-electron microscopy structures of catalytic intermediates for the NMPylation and deRNAylation/capping reactions, revealing diverse nucleotide binding poses and divalent metal ion coordination sites to promote its repertoire of activities. The deRNAylation/capping structure explains why GDP is a preferred substrate for the capping reaction over GTP. Altogether, these findings enhance our understanding of the promiscuous coronaviral NiRAN domain, a therapeutic target, and provide an accurate structural platform for drug development.
Cost-effectiveness and budget impact of decentralising childhood tuberculosis diagnosis: a mathematical modelling study in six high tuberculosis incidence countries
Authors: d’Elbée Marc , Harker Martin , Mafirakureva Nyashadzaishe , Nanfuka Mastula , Huyen Ton Nu Nguyet Minh , Taguebue Jean-Voisin , Moh Raoul , Khosa Celso , Mustapha Ayeshatu , Mwanga-Amumpere Juliet , Borand Laurence , Kwedi Nolna Sylvie , Komena Eric , Cumbe Saniata , Mugisha Jacob , Natukunda Naome , Eang Mao Tan , Wittwer Jérôme , Bénard Antoine , Bernard Tanguy , Sohn Hojoon , Bonnet Maryline , Wobudeya Eric , Marcy Olivier , Dodd Peter J. ,   TB-Speed Health Economics Study Group
Published: September 2023

Background

The burden of childhood tuberculosis remains high globally, largely due to under-diagnosis. Decentralising childhood tuberculosis diagnosis services to lower health system levels could improve case detection, but there is little empirically based evidence on cost-effectiveness or budget impact.

Methods

We assessed the cost-effectiveness and budget impact of decentralising a comprehensive diagnosis package for childhood tuberculosis to district hospitals (DH-focused) or primary health centres (PHC-focused) compared to standard of care (SOC) in Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone, and Uganda (NCT04038632). A mathematical model was developed to assess the health and economic outcomes of the intervention from a health system perspective. Estimated outcomes were tuberculosis cases, deaths, disability- adjusted life years and incremental cost-effectiveness ratios (ICERs). We also calculated the budget impact of nationwide implementation.

Findings

For the DH-focused strategy versus SOC, ICERs ranged between $263 (Cambodia) and $342 (Côte d’Ivoire) per disability-adjusted life-year (DALY) averted. For the PHC-focused strategy versus SOC, ICERs ranged between $477 (Cambodia) and $599 (Côte d’Ivoire) per DALY averted. Results were sensitive to TB prevalence and the discount rate used. The additional costs of implementing the DH-focused strategy ranged between $13M (Cambodia) and $50M (Mozambique), and between $14M (Sierra Leone) and $135M (Uganda) for the PHC-focused strategy.

Interpretation

The DH-focused strategy may be cost-effective in some countries, depending on the cost- effectiveness threshold used for policy making. Either intervention would require substantial early investment.

Funding

Unitaid
High-flow nasal cannula vs non-invasive ventilation in acute hypoxia: Propensity score matched study
Authors: Munroe Elizabeth S , Prevalska Ina , Hyer Madison , Meurer William J , Mosier Jarrod M , Tidswell Mark A. , Prescott Hallie C , Wei Lai , Wang Henry , Fung Christopher M
Published: September 2023

RATIONALE

The optimal treatment for early hypoxemic respiratory failure is unclear, and both high-flow nasal cannula and non-invasive ventilation are used. Determining clinically relevant outcomes for evaluating non-invasive respiratory support modalities remains a challenge.

OBJECTIVES

To compare the effectiveness of initial treatment with high-flow nasal cannula versus non-invasive ventilation for acute hypoxemic respiratory failure.

METHODS

We conducted a retrospective cohort study of patients with acute hypoxemic respiratory failure treated with high-flow nasal cannula or non-invasive ventilation within 24 hours of Emergency Department arrival (1/2018-12/2022). We matched patients 1:1 using a propensity score for odds of receiving non-invasive ventilation. The primary outcome was major adverse pulmonary events (28-day mortality, ventilator-free days, non-invasive respiratory support hours) calculated using a Win Ratio.

MEASUREMENTS AND MAIN RESULTS

1,265 patients met inclusion criteria. 795 (62.8%) received high-flow oxygen and 470 (37.2%) received non-invasive ventilation. We propensity score matched 736/1,265 (58.2%) patients. There was no difference between non-invasive ventilation vs high-flow nasal cannula in 28-day mortality (17.7% vs 23.1%, p=0.08) or ventilator-free days (median [Interquartile Range]: 28 [25, 28] vs 28 [13, 28], p=0.50), but patients on non-invasive ventilation required treatment for fewer hours (median 7 vs 13, p< 0.001). Win Ratio for composite major adverse pulmonary events favored non-invasive ventilation (1.26, 95%CI 1.06-1.49, p< 0.001).

CONCLUSIONS

In this observational study of patients with acute hypoxemic respiratory failure, initial treatment with non-invasive ventilation was superior to high-flow nasal cannula for major pulmonary adverse events. Evaluation of composite outcomes is important in the assessment of respiratory support modalities.
Indicators of Co-occurrence of Mood Disorder with Chronic Medical Conditions: Evidence from an Administrative Claims Data Analysis
Authors: Chhabria Karishma , Krause Trudy Millard , Hamden Randa , Jabbi Mbemba
Published: September 2023

Objective

Mood disorder (including major depression and bipolar disorder) prevalence is over 10% and accounts for a significant share of global disease burden. Mental and physical illness are related, however, the association between mood disorders and acute/chronic disease subclasses remains poorly understood.

Methods

This observational cross-sectional study used administrative claims data from 6,709,258 adult enrollees with a full-year enrollment in the 2018 OPTUM Clinformatics® database. Data of enrollees with/without diagnoses of a mood disorder co-occurring with chronic comorbid conditions (defined by the Elixhauser Comorbidity Index) using the International Classification of Diseases (ICD-10) were analyzed by accounting for age, race, and ethnicity.

Results

Overall, the sample was predominantly non-Hispanic Caucasians (64.56%), with 48.59% females and a mean age of 43.54 years±12.46 years. The prevalence of mood disorders was 3.71% (248,890), of which 0.61% (n=40,616) had bipolar disorders and 3.10% (n=208,274) had Major Depressive Disorder (MDD). Logistic regression odds ratios revealed a strong association between mood disorder diagnoses and peptic ulcers (2.11; CI=2.01-2.21), weight loss (2.53; CI, 2.46-2.61), renal failure (2.37, CI = 2.31-2.42), peripheral vascular disease (2.24; CI=2.19-2.30), and pulmonary circulation disorder (1.77; CI=1.70-1.84).

Conclusions

Overall, mood disorders were associated with vascular and cardiac chronic medical conditions, suggesting a possible pathophysiological link between these conditions. The results highlight the importance of understanding the prevalence of co-occurring mood and medical conditions and may inform novel biological diagnostics and future identification of mechanisms for multimorbidity.
Organizing the coactivity structure of the hippocampus from robust to flexible memory
Authors: Gava Giuseppe P. , Lefèvre Laura , Broadbelt Tabitha , McHugh Stephen B. , Vítor Lopes-dos-Santos , Brizee Demi , Hartwich Katja , Sjoberg Hanna , Perestenko Pavel V. , Toth Robert , Sharott Andrew , Dupret David
Published: September 2023

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons of the superficial CA1pyramidalesublayer to whole population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to successfully meet memory demands.
Macroevolutionary dynamics in micro-organisms: generalists give rise to specialists across biomes in the ubiquitous bacterial phylumMyxococcota
Authors: Padfield Daniel , Kay Suzanne , Vos Rutger , Quince Christopher , Vos Michiel
Published: September 2023

Prokaryotes dominate the Tree of Life, but our understanding of the macroevolutionary processes generating this diversity is still limited. Habitat transitions are thought to be a key driver of prokaryote diversity, but we still know relatively little about how prokaryotes successfully transition and persist across environments, and how this varies between biomes and lineages. Here, we investigate biome transitions and specialisation in natural populations of a focal bacterial phylum, theMyxococcota, sampled across a range of replicated soils and freshwater and marine sediments in Cornwall (UK). By targeted deep sequencing of the protein-coding generpoB, we found >2000 uniqueMyxococcotalineages, with the majority (77%) being biome specialists and <5% able to live across the salt barrier. Discrete character evolution models revealed that biome specialists very rarely transitioned to specialising in another biome. Instead, generalists mediated transitions between biome specialists. Multistate hidden-state speciation and extinction models found variation in speciation rate across the tree, but this variation was independent of biome association and specialisation. Overall, our results help explain how microbes transition between biomes and are consistent with “the jack-of-all-trades” trade-off, where generalists suffer a cost in any individual environment, resulting in rapid evolution of niche specialists.
RNA-based sensitive fungal pathogen detection
Authors: Micheel Julia , Aron Franziska , Kelani Abdulrahman A. , Girbardt Christian , Blango Matthew G. , Walther Grit , Wollny Damian
Published: September 2023

Detecting fungal pathogens, a major cause of severe systemic infections, remains challenging due to the difficulty and time-consuming nature of diagnostic methods. This delay in identification hinders targeted treatment decisions and may lead to unnecessary use of broad-spectrum antibiotics. To expedite treatment initiation, one promising approach is to directly detect pathogen nucleic acids such as DNA, which is often preferred to RNA because of its inherent stability. However, a higher number of RNA molecules per cell makes RNA a more promising diagnostic target which is particularly prominent for highly expressed genes such as rRNA. Here, we investigated the utility of a minimal input-specialized reverse transcription protocol to increase diagnostic sensitivity. This proof-of-concept study demonstrates that fungal rRNA detection by the minimal input protocol is drastically more sensitive compared to detection of genomic DNA even with high levels of human RNA background. This approach can detect several of the most relevant human pathogenic fungal genera, such asAspergillus, Candida, andFusariumand thus represents a powerful, cheap, and easily adaptable addition to currently available diagnostic assays.
LanTERN: a fluorescent sensor that specifically binds lanthanides
Authors: Jones Ethan , Su Yang , Sander Chris , Justman Quincey A. , Springer Michael , Silver Pamela A.
Published: September 2023

Lanthanides, a series of fifteen f-block elements, are crucial in modern technology, and their purification by conventional chemical means comes at a significant environmental cost. Synthetic biology offers promising solutions. However, the lack of biochemical tools to measure lanthanide binding is a bottleneck to progress. Here, we introduce LanTERN, a lanthanide-responsive fluorescent protein rationally engineered from the lanmodulin-binding protein, LanM. LanTERN was designed based on GCaMP, a genetically encoded calcium indicator that couples the ion binding of four EF hand motifs to increased GFP fluorescence. We engineered seven mutations across the parent construct’s four EF hand motifs to switch specificity from calcium to lanthanides. The resulting protein, LanTERN, directly converts the binding of 10 measured lanthanides to 14-fold or greater increased fluorescence. LanTERN development opens new avenues for creating improved lanthanide-binding proteins and bio-sensing systems.