bluuebunny/crossref_metadata_2025 huggingface dataset:
Escalating combinations of enhanced infectivity and immune escape define SARS-CoV-2 Omicron lineage replacement
Authors: Chen Nicholas F.G. , Pham Kien , Chaguza Chrispin , Lopes Rafael , Klaassen Fayette , Weinberger Daniel M. , Pitzer Virginia E. , Warren Joshua L. , Grubaugh Nathan D. , Hahn Anne M.
Published: January 2024

In 2022, consecutive sweeps of the highly transmissible SARS-CoV-2 Omicron-family maintained high viral transmission levels despite extensive antigen exposure on the population level resulting from both vaccinations and infections. To better understand variant fitness in the context of the highly dynamic immunity landscape of 2022, we aimed to dissect the interplay between immunity and fitness advantages of emerging SARS-CoV-2 Omicron lineages on the population-level. We evaluated the relative contribution of higher intrinsic transmissibility or immune escape on the fitness of emerging lineages by analyzing data collected through our local genomic surveillance program from Connecticut, USA. We compared growth rates, estimated infections, effective reproductive rates, average viral copy numbers, and likelihood for causing vaccine break-through infections. Using these population-level data, we find that newly emerging Omicron lineages reach dominance through a specific combination of enhanced intrinsic transmissibility and immune escape that varies over time depending on the state of the host-population. Using similar frameworks that integrate whole genome sequencing together with clinical, laboratory, and epidemiological data can advance our knowledge on host-pathogen dynamics in the post-emergence phase that can be applied to other communicable diseases beyond SARS-CoV-2.
SCIseg: Automatic Segmentation of T2-weighted Intramedullary Lesions in Spinal Cord Injury
Authors: Naga Karthik Enamundram , Valosek Jan , Smith Andrew C. , Pfyffer Dario , Schading-Sassenhausen Simon , Farner Lynn , Weber Kenneth A. , Freund Patrick , Cohen-Adad Julien
Published: January 2024

Purpose

To develop a deep learning tool for the automatic segmentation of T2-weighted intramedullary lesions in spinal cord injury (SCI).

Material and Methods

This retrospective study included a cohort of SCI patients from three sites enrolled between July 2002 and February 2023. A deep learning model,SCIseg, was trained in a three-phase process involving active learning for the automatic segmentation of intramedullary SCI lesions and the spinal cord. The data consisted of T2-weighted MRI acquired using different scanner manufacturers with heterogeneous image resolutions (isotropic/anisotropic), orientations (axial/sagittal), lesion etiologies (traumatic/ischemic/hemorrhagic) and lesions spread across the cervical, thoracic and lumbar spine. The segmentations from the proposed model were visually and quantitatively compared with other open-source baselines. Wilcoxon signed-rank test was used to compare quantitative MRI biomarkers (lesion volume, lesion length, and maximal axial damage ratio) computed from manual lesion masks and those obtained automatically withSCIsegpredictions.

Results

MRI data from 191 SCI patients (mean age, 48.1 years ± 17.9 [SD]; 142 males) were used for model training and evaluation. SCIseg achieved the best segmentation performance for both the cord and lesions. There was no statistically significant difference between lesion length and maximal axial damage ratio computed from manually annotated lesions and those obtained usingSCIseg.

Conclusion

Automatic segmentation of intramedullary lesions commonly seen in SCI replaces the tedious manual annotation process and enables the extraction of relevant lesion morphometrics in large cohorts. The proposed model segments lesions across different etiologies, scanner manufacturers, and heterogeneous image resolutions.SCIsegis open-source and accessible through the Spinal Cord Toolbox.

Automatic segmentation of the spinal cord and T2-weighted lesions in spinal cord injury on MRI scans across different treatment strategies, lesion etiologies, sites, scanner manufacturers, and heterogeneous image resolutions.

Key Results

An open-source, automatic method,SCIseg, was trained and evaluated on a dataset of 191 spinal cord injury patients from three sites for the segmentation of the spinal cord and T2-weighted lesions.

SCIseggeneralizes across traumatic and non-traumatic lesions, scanner manufacturers, and heterogeneous image resolutions, enabling the automatic extraction of lesion morphometrics in large multi-site cohorts.

Quantitative MRI biomarkers, namely, lesion length and maximal axial damage ratio derived from the automatic predictions showed no statistically significant difference when compared with manual ground truth, implying reliability inSCIseg’spredictions.
Accuracy, Utility and Applicability of the WHOOP Wearable Monitoring Device in Health, Wellness and Performance - a systematic review
Authors: Khodr Riham , Kamal Latifah , Minerbi Amir , Gupta Gaurav
Published: January 2024

Introduction

The WHOOP wearable device is gaining popularity in clinical and performance applications with the ability to track sleep and heart rate parameters and provide feedback on recovery and strain. With the claims on potential benefits, a critical evaluation of the underlying scientific literature and the accuracy of these devices is imperative.

Methods

Authors systematically reviewed studies examining the accuracy and clinical applications of the WHOOP device.

Results

The WHOOP appears to have acceptable accuracy for two-stage sleep and heart rate metrics, but depending on the study, room for improvement for four-stage sleep and heart rate variability identification. There are numerous preliminary studies looking at the WHOOP’s ability to track and/or influence sleep and exercise behaviours at the cohort and/or population level. The impact of athletic performance and/or objective sleep is limited based on existing studies.

Discussion

The clinical application for the WHOOP, given the acceptable accuracy levels, continues to expand. Uses have included impact on sports performance, correlation with medical conditions (i.e. cognitive dysfunction), sleep and health behaviours in various populations. Limitations of existing accuracy trials include variable design and reporting metrics, while results from non-accuracy trials require further clinical validation for response rate and effect size.

Conclusion

The WHOOP wearable device has acceptable accuracy for sleep and cardiac variables to be used in clinical studies where a baseline can be established and, ideally, other clinical outcomes and gold standard tools can be employed.
Perspectives of young people, family carers and voluntary sector staff on help-seeking for mental health difficulties in a rural region of the United Kingdom - a qualitative study
Authors: Oduola Sheri , Coombes Emma , Hodgekins Jo , Jones Andy
Published: January 2024

Purpose

To explore key stakeholders from rural communities’ perspectives of help-seeking for mental health difficulties.

Methods/design

Semi-structured interviews and a focus group were conducted with participants living in the East of England, UK. Thematic analysis was used to organise and analyse the data.

Results

Nine participants were recruited. Participants described barriers and facilitators of help-seeking. Barriers included: lengthy waiting times, socioeconomic means, poor therapeutic relationships, insufficient treatment duration, poor transition between services, high staff turnover, and limited investment. Facilitators included: family involvement/support, school nurses, shorter delays in accessing specialist services such as eating disorder services, and the offer of family therapy. Suggestions for improving future help-seeking and pathways to care, included: peer-support for young people, enhanced support for carers, early intervention and raising awareness of mental health.

Originality

Our qualitative approach meant we were able to explore in detail the existence and mechanisms underlying varied barriers and facilitators of care pathways amongst our sample. This allowed us to report rich findings and recommendations for clinical practice and future research work.

Practical implications

Training young people to support other young people, and identifying mental health champions in rural communities could reduce distress and ameliorate pressures on the health service.
A Healthcare Service Delivery and Epidemiological Model for Investigating Resource Allocation for Health: TheThanzi La OnseModel
Authors: Hallett Timothy B. , Mangal Tara D. , Tamuri Asif U. , Arinaminpathy Nimalan , Cambiano Valentina , Chalkley Martin , Collins Joseph H. , Cooper Jonathan , Gillman Matthew S. , Giordano Mosè , Graham Matthew M. , Graham William , Janoušková Eva , Jewell Britta L. , Lin Ines Li , Smith Robert Manning , Manthalu Gerald , Mnjowe Emmanuel , Mohan Sakshi , Molaro Margherita , Ng’ambi Wingston , Nkhoma Dominic , Piatek Stefan , Revill Paul , Rodger Alison , Salmanidou Dimitra , She Bingling , Smit Mikaela , Twea Pakwanja D. , Colbourn Tim , Mfutso-Bengo Joseph , Phillips Andrew N.
Published: January 2024

Background

Decisions need to be made in all healthcare systems about the allocation of available resources with the aim of improving population health. Evidence is needed for these decisions, which can have enormous consequences for population health, especially in lower-income settings.

Methods

We address this need using an individual-based simulation model of healthcare need and service delivery that we have developed for Malawi, drawing on demographic, epidemiological and routine healthcare system data (on facilities, staff, and consumables). We compare the model’s simulated outputs with available data and estimate the impact that the healthcare system is having currently. We analyse the effects of improvements in healthcare access, clinician performance and consumables availability.

Findings

Malawi’s healthcare system averted 40 million Disability-Adjusted Life-Years (DALYs) in the five-year period to end-2019, which is half of the total DALYS that the population (total size: 19 million in 2020) would otherwise incur. This impact is strongly focussed on young children (mediated largely by programmes addressing respiratory infections, HIV/AIDS and malaria) and also by the HIV/AIDS and TB programmes (among adults). More services seem to be delivered than would be expected based on the number of staff and expected time needed for services. Nevertheless, the additional services that are provided (through service times being reduced or additional HCW hours worked) account for half the impact of the healthcare system (i.e., ∼20 million DALYS averted). If system improvements gave ill persons immediate access to healthcare, led to optimal referral and diagnosis accuracy, and eliminated consumable stock-outs, the overall impact of the healthcare system could increase by up to ∼30% (12 million more DALYS averted).

Conclusions

The healthcare system in Malawi generates substantial health gains to the population with very limited resources. Strengthening interventions could potentially increase these gains considerably and so should be a priority for investigation and investment. A detailed individual-based simulation model of healthcare service delivery is a valuable tool for healthcare system planning and for evaluating proposals for healthcare system strengthening.
Lower probability of viral suppression in people living with HIV who are parents in Lima, Peru
Authors: Navarro-Galarza Valeria , González-Lagos Elsa , Robledo Jorge , Graña Ana , Gotuzzo Eduardo
Published: January 2024

Introduction

Parenting can be a detriment for selfcare among people living with HIV (PLWH) out of concern for their children’s futures and responsibilities that may limit attendance to health services. We explored the association between having children <20 years-old and viral suppression in PLWH.

Methods

Retrospective cohort study from secondary data of PLWH enrolled at the largest HIV program in Lima between 2012-2018. We established parenthood by participant self-report children <20 years-old at enrollment, with additional data gathered for PLWH who reported a child born during the first year after enrollment. The main outcome was viral suppression (<400 copies/mL) by the end of follow-up. We conducted Cox regression analyses for repeated events, censoring at time of death or lost to follow-up. We built the final model by backward stepwise regression including potentially important variables and those with p-value ≤ 0.20 in bivariate analyses, presenting hazard ratios (HR), adjusted HR (aHR), and 95% confidence intervals (CIs).

Results

In 3170 PLWH, median age at enrollment was 31.6 years (range 17.9-76.1), 79.8% were men and 27.2% reported having children <20 years-old (median=2). At end of follow-up (8766.6 person-years), 534 (62.0%) were virally suppressed. In our final multivariate model, having children <20 years-old (aHR 3.53; [95% CI] 1.88 - 6.62) and the birth of a child during the first year after enrollment in the program (HR 1.81; [95% CI] 1.30 – 2.50) were independently associated with lack of viral suppression by end of follow-up. Based on health status of the PLWH, we estimated 70% and 69% of children to be at risk of maternal and paternal orphanhood, respectively.

Conclusion

In our setting, being a parent was associated with lower probability of viral suppression, creating a risk of orphanhood for children of PLWH. Family support services may facilitate HIV care and help PLWH maximize viral suppression.
Interprofessional Care Team, Staffing, and Setting Characteristics that Impact Patient Outcomes: A Review of Reviews
Authors: Pletcher Alix , Woodward Kyla , Hoge Natalie , Blair-Stahn Nathaniel , Lindstedt Paulina , Gohari Zahra , Flaxman Abraham , Iribarren Sarah
Published: January 2024

Background

The purpose of this study was to identify research methods and evidence pertaining to the relationship of interprofessional acute care teams and hospital characteristics on patient outcomes in hospital-based acute care.

Methods

A review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews guidelines. The search strategy was executed across PubMed, CINAHL, and Embase. The review included 12 systematic reviews from 2012 to 2023 that examine the impact of acute care staffing characteristics on patient outcomes.

Results

Workforce characteristics primarily focused on nurse staffing, with a limited number of studies assessing the impact of interprofessional teams or non-clinical workers on care quality. There is limited data describing the context of care delivery via potential relationships between hospital characteristics, interprofessional team staffing levels, and patient outcomes.

Conclusions

To promote comparability across studies, future workforce research should include a comprehensive analytic approach that includes clearly defined variables representing interprofessional care teams, community factors, and staffing and patient characteristics.
Clarifying the anatomy of tetralogy of Fallot with S-shaped ascending aorta
Authors: Gupta Saurabh Kumar , Mukharjee Aprateem , Pandey Niraj Nirmal , Ramakrishnan Sivasubramanian , Kothari Shyam Sunder , Saxena Anita , Anderson Robert H
Published: January 2024

Background

We have recently encountered several cases of tetralogy of Fallot with an abnormally oriented S-shaped ascending aorta. In this retrospective study, we sought to clarify the morphology of this unusual under-recognized variant of tetralogy of Fallot.

Methods

We reviewed our databases to identify all patients with tetralogy of Fallot having an S-shaped ascending aorta. We then used computed tomographic angiography to make a detailed assessment of the cardiac morphology.

Results

Out of the 21 patients we identified, 18 (86%) had a right aortic arch, 2 (9%) had a left aortic arch, and the remaining patient (5%) had a double aortic arch. Patients with right aortic arch, compared to those with the normally oriented ascending aorta, had lesser aortic override (29.3±14% vs 54.8±13.2%; p=0.0001) and a wider ascending aorta (2.52±0.7 cm vs 1.80±0.32; p=0.0003). Overall, compared to normal cases, the ascending aorta was located posteriorly, with a higher sterno-aortic distance (2.55±0.8 cm vs 0.99±0.45 cm; p=0.0001). The ascending aorta was longer (4.12±1.7 vs 3.07±0.82, p=0.03) although the tortuosity index (1.22±0.19 vs 1.15±0.17, p=0.23) was not different. Of the cases with right aortic arch and S-shaped ascending aorta, 16 (89%) had extrinsic compression of the right pulmonary artery (p = 0.0001), while 7 (39%) had crossed pulmonaryarteries(p = 0.008), with no such findings in those with normally oriented ascending aorta or those with left aortic arch and S-shaped ascending aorta.

Conclusion

Tetralogy of Fallot with an S-shaped ascending aorta is a variant with lesser aortic override and a more posterior location of the aorta. Compression of the right pulmonary artery and crossed pulmonary arteries are frequent when the arrangement is associated with a right-sided aortic arch. These findings may have important implications for surgical management.
The genetics and epidemiology ofN-andO-IgA glycomics
Authors: Visconti Alessia , Rossi Niccolò , Bondt Albert , Hipgrave Ederveen Agnes , Thareja Gaurav , Koeleman Carolien A. M. , Stephan Nisha , Halama Anna , Lomax-Browne Hannah J. , Pickering Matthew C. , Zhou Xu-jie , Wuhrer Manfred , Suhre Karsten , Falchi Mario
Published: January 2024

Immunoglobulin (Ig) glycosylation modulates the immune response, and plays a critical role in ageing and diseases. Studies have mainly focused on IgG glycosylation, and little is known about the genetics and epidemiology of IgA glycosylation. Here, we generated, using a novel LC-MS method, the first large-scale IgA glycomics dataset in serum from 2,423 twins, encompassing 71N-andO-glycan species. We showed that, despite the lack of a direct genetic template, glycosylation is highly heritable, and that glycopeptide structures are sex-specific, and undergo substantial changes with ageing. We observe extensive correlations between the IgA and IgG glycomes, and, exploiting the twin design, show that they are predominantly influenced by shared genetic factors. A genome-wide association study identified eight loci associated with both the IgA and IgG glycomes (ST6GAL1,ELL2,B4GALT1,ABCF2,TMEM121,SLC38A10,SMARCB1,MGAT3), and two novel loci specifically modulating IgAO-glycosylation (C1GALT1andST3GAL1). Validation of our findings in an independent cohort of 320 individuals from Qatar showed that the underlying genetic architecture is conserved across ethnicities. Our study delineates the genetic landscape of IgA glycosylation and provides novel potential functional links with the aetiology of complex immune diseases, including genetic factors involved in IgA nephropathy risk.
Exploring athlete pain assessment experiences and priorities; A two-part qualitative series of athlete and physiotherapist interactions. Part One. “Gauging and discerning” - Athlete & physiotherapist pain assessment experiences and interactions
Authors: Purcell Ciarán , Walsh Caoimhe Barry , Van Oirschot Garett , Fullen Brona M , Ward Tomás , Caulfield Brian M
Published: January 2024

Objectives

To explore the content (subjective questions, objective tools and outcome measures) and discuss the nature (qualitative elements and wider considerations) of the athlete pain assessment by facilitating shared understandings of athlete and sports physiotherapists.

Design

Qualitative Research using a hermeneutic phenomenological approach.

Methods

We carried out focus groups comprising a deliberate criterion sample using a constructivist perspective. We developed a topic guide and used reflexive thematic analysis. We developed codes, candidate themes and finalised themes iteratively, and employed a critical friend to add depth to our analysis. Our paper follows the consolidated criteria for reporting qualitative research (COREQ) guidelines.

Results

We completed five focus groups comprising twelve athletes (five female, seven male) and four sports physiotherapists (four male). Three final themes (and eight subthemes) were created; (i) Measures, Scales and Dimensions (value and limitations of tools and scales, multidimensional methods, making sense and interpreting), (ii) Connect, Listen and Learn (the pain interview and athlete’s story, forging the athlete-clinician connection), (iii) Lighthouse in the Storm: providing direction for athletes in pain. (information overload and indecision, a beacon of direction; the role of the physiotherapist, the burden of expectation; challenges for physiotherapists)

Conclusion

We described and explored the phenomena of pain assessment in sport including current pain assessment strategies. Comprehensive multidimensional assessment methods that preserve the athlete-clinician therapeutic relationship and facilitate optimal communication are priorities for future research and practice.
Testing federated analytics across secure data environments using differing statistical approaches on cross-disciplinary data
Authors: Gallier S. , Topham A. , Hodson J. , McNulty D. , Giles T. , Cox S. , Chaganty J. , Cooper L. , Perks S. , Quinlan P. , Sapey E.
Published: January 2024

BACKGROUND

Introducing data-driven technologies into health systems can enhance population health and streamline care delivery. The use of diverse and geographically varied data is key for tackling health and societal challenges, despite associated technical, ethical, and governance complexities. This study explored the efficacy of federated analytics using general linear models (GLMs) and machine learning (ML) models, comparing outcomes with non-federated data analysis.

METHODS

A Conditional Transformation Generative Adversarial Network was used to create two synthetic datasets (training set: N=10,000; test set: N=1,000), using real-world data from 381 asthma patients. To simulate a federated environment, the resulting data were distributed across nodes in a Microsoft Azure Trusted Research Environment (TRE). GLMs (one-way ANOVA) and ML models (gradient boosted decision trees) where then produced, using both federated and non-federated approaches. The consistency of predictions produced by the ML models were then compared between approaches, with predictive accuracy of the models quantified by the area under the receiver operating characteristic curve (AUROC).

FINDINGS

GLMs produced from federated data distributed between two TREs were identical to those produced using a non-federated approach. However, ML models produced by federated and non-federated approaches, and using different data distributions between TREs, were non-identical. Despite this, when applied to the test set, the classifications made by the federated models were consistent with the non-federated model in 84.7-90.4% of cases, which was similar to the consistency of repeated non-federated models (90.9-91.5%). Consequently, overall predictive accuracies for federated and non-federated models were similar (AUROC: 0.663-0.669).

INTERPRETATION

This study confirmed the robustness of GLMs utilising ANOVA within a federated framework, yielding consistent outcomes. Moreover, federated ML models demonstrated a high degree of classification agreement, with comparable accuracy to traditional non-federated models. These results highlight the viability of federated approaches for reliable and accurate data analysis in sensitive domains.
Delayed effects of cigarette graphic warning labels on smoking behavior
Authors: Shi Zhenhao , Wang An-Li , Liu Jiaying , Audrain-McGovern Janet , Lynch Kevin G. , Loughead James , Langleben Daniel D.
Published: January 2024

Introduction

Graphic warning labels (GWLs) are widely employed to communicate smoking-related health risks; however, their implementation in the US has been held back by concerns about their efficacy. Most GWLs elicit a high level of emotional reaction (ER). The extent to which ER contributes to GWLs efficacy in improving smoking outcomes is a subject of debate. Our recent study showed poorer efficacy of the high-ER GWLs versus the low-ER ones during a month-long naturalistic exposure. Whether GWL effects persist after discontinuing the exposure remains unclear.

Methods

We conducted a secondary analysis to investigate the delayed effects of GWLs on smoking severity in adult smokers. The number of cigarettes smoked per day (CPD) was measured immediately as well as 4 weeks after the end of a month-long exposure to high-ER versus low-ER GWLs. Participants indicated their subjective feeling of being relieved from having to see the GWLs.

Results

We found a significant reduction in CPD from the immediate to the 4-week post-exposure timepoint. There was no difference in CPD reduction between the high-ER and low-ER groups.

Subjective sense of relief from GWL exposure was associated with greater CPD reduction in the high-ER group, but not the low-ER group.

Conclusions

Our study suggests lasting impact of GWLs on smoking behavior. The findings may be particularly important to high-arousal GWLs, which appear less effective in reducing smoking during active exposure.

Implications

Whether GWLs that evoke higher ER are more effective remains inconclusive. We recently showed that high-ER GWLs are less effective than low-ER ones in reducing smoking during continuous exposure. Here, we found evidence of delayed GWL effects such that smoking decreased from immediately to four weeks after the end of GWL exposure. Feeling of relief from GWL exposure was associated greater smoking reduction in the high-ER group. We suggest that continuously exposing smokers to high-ER GWLs that have been well remembered may be unnecessary and counterproductive.
Symptoms of children and adolescents infected with SARS-CoV-2 variants alpha, delta or omicron
Authors: Schulze Hansjörg , Bayer Wibke
Published: January 2024

Symptoms experienced by children and adolescents with SARS-CoV-2 infections in the alpha, delta and omicron variant dominated phases were investigated using an online survey, and the frequencies of reported symptoms and changes over time were analyzed. The most prevalent symptoms were fever above 38 °C, tiredness, headache, runny or blocked nose, sneezing and dry cough. Lethargy and nausea were reported significantly more frequently in the omicron variant dominated phase than in the earlier phases of the pandemic. Compared to symptoms reported by adults, fever and gastrointestinal symptoms were reported more frequently for children, especially in the omicron variant dominated phase, whereas the frequency of loss of smell and loss of taste was significantly lower in children than in adults.
Sex Differences in People with Tourette Syndrome and Persistent Motor or Vocal Tic Disorder in the Tourette Association of America International Consortium for Genetics Database
Authors: Dy-Hollins Marisela E. , Chibnik Lori B. , Tracy Natasha A. , Osiecki Lisa , Budman Cathy L. , Cath Danielle C. , Grados Marco A. , King Robert A. , Gholson Lyon , Rouleau Guy A. , Sandor Paul , Singer Harvey S. , Sharma Nutan , Mathews Carol A. , Scharf Jeremiah
Published: January 2024

Background and Objective

Tourette Syndrome (TS) and Persistent Motor or Vocal Tic Disorders (PMVT) are more prevalent in males (vs. females). Females with TS may have a delay in diagnosis, and more complex tic features (vs. males). With respect to comorbidities, obsessive-compulsive disorder (OCD) is more prevalent in females; attention-deficit hyperactivity disorder (ADHD) is more prevalent in males. Less is known about sex differences in PMVT. This study analyzes sex differences in outcomes among individuals with TS and PMVT in the Tourette Association of America International Consortium for Genetics dataset (TAAICG).

Design/Methods

Data from 2403 individuals (N=2109 TS; N=294 PMVT) from the TAAICG were analyzed to explore the relationship between sex and TS or PMVT outcomes: age at tic onset; age at diagnosis; time-to-diagnosis; tic severity; and comorbidity rates. Regression models were adjusted for age and family relationships to examine the impact of sex on outcomes.

Results

Females with TS (25.5% of the sample) had a later age of symptom onset (6.5±2.8 vs. 6.0±2.7; p=0.001), later age at diagnosis (13.3±11.2 vs. 10.7±8.1; p=0.0001), and a longer time-to-diagnosis [3 (1,7) vs. 2 (1,5), p=0.01] than males. The total Yale-Global Tic Severity Scale (YGTSS) was lower in females with TS (28.4±9.1 vs. 30.7±8.7); p<0.0001); OCD was slightly more prevalent in females (55% vs. 48.7%; p=0.01) although OCD severity did not differ by sex; ADHD was more prevalent in males (55.7% vs 38.9%; p<0.001). Females with TS had 0.46 lower odds of being diagnosed with TS (p<0.00001). Females with PMVT (42.9% of the sample) had an earlier age of symptom onset (7.9±3.3 vs. 8.9±3.7; p=0.05). Motor or vocal tic severity (YGTSS) was not significantly different. OCD, but not ADHD, was more prevalent in females (OCD: 41.9% vs. 22.2%; p<0.001: ADHD:16.5% vs 21.0%; p=0.4).

Conclusion

Females with TS are less likely to be formally diagnosed and have a later age of symptom onset, later age at diagnosis, longer time-to-diagnosis, higher prevalence of OCD, and lower prevalence of ADHD (vs. males). Females with PMVT have an earlier age of symptom onset, higher prevalence of OCD, but similar ADHD prevalence rates (vs. males). Females with TS and PMVT may be clinically different than males with TS. Future research is needed to understand differences longitudinally in TS and PMVT.
Predictors of upper respiratoryStreptococcus pneumoniaecolonization among working-age adults with prevalent exposure to overcrowding
Authors: Parker Anna M. , Jackson Nicole , Awasthi Shevya , Kim Hanna , Alwan Tess , Wyllie Anne L. , Kogut Katherine , Holland Nina , Mora Ana M. , Eskenazi Brenda , Riley Lee W. , Lewnard Joseph A.
Published: January 2024

Background

The epidemiology of adult pneumococcal carriage remains poorly understood. We assessed risk factors for pneumococcal carriage among adults in socioeconomically-disadvantaged farmworker communities with prevalent overcrowding.

Methods

From July-November 2020, we administered surveys and collected saliva from working-age adults within clinical and community settings throughout Monterey County, California. We detected pneumococci via qPCR assays targetinglytAandpiaBgenes. We evaluated predictors of pneumococcal carriage detection via conditional logistic regression.

Results

Among 1,283 participants, 117 (9.1%) had any detectable pneumococcal carriage and 53 (4.1%) carried pneumococci at a higher density threshold (lytAandpiaBcT<35). Pneumococcal carriage was more common among individuals of lower socioeconomic status, as signified by indigenous background (odds ratio [OR]=3.94 [95% confidence interval: 2.36-6.60]), engagement in fieldwork (OR=2.01 [1.12-3.63]), and lacking high school-level education (OR=0.48 [0.26-0.90]). Within the household, carriers were more likely than non-carriers to be exposed to children aged <5 years (OR=1.45 [0.95-2.20]), and to be exposed to crowding (OR=1.48 [0.96-2.30] and 2.84 [1.20-6.73], respectively, for participants living in households with >2-4 and >4 persons per bedroom vs. ≤2 persons per bedroom). Household crowding was independently associated with increased risk of carriage among participants not exposed to children aged <5 years (OR=2.05 [1.18-3.59] for participants living in households with >2 vs. ≤2 persons per bedroom). Exposure to children aged <5 years and exposure to household crowding were each associated with increased pneumococcal density among carriers (piaBcTdifference of 2.04 [0.36-3.73] and 2.44 [0.80-4.11], respectively).

Conclusions

While exposure to young children was an important risk factor for pneumococcal carriage, the association of crowding with increased risk of carriage in households without young children suggests transmission among adults may also occur in crowded congregate settings.
Customization and acceptability of the WHO Labor care guide to improve labor monitoring among health workers in Uganda. An Iterative Development Study
Authors: Godfrey Mugyenyi R , Josaphat Byamugisha K , Wilson Tumuhimbise , Esther Atukunda C , Fajardo Yarine T
Published: January 2024

Background

Cognisant of the persistent maternal and perinatal mortality rates, the WHO has called for adoption and evaluation of new adaptable and context-specific health solutions to improve labor monitoring and health outcomes. We aimed at customizing and refining the new WHO labour care guide (LCG) to suite health care provider (HCP) needs in monitoring labour in Southwestern Uganda.

Methods

We used an iterative approach to customize and refine the new WHO LCG. Between 1stJuly 2023 and 30thNovember 2023, we conducted; 1)30 stakeholder interviews to identify user needs and challenges, and inform the first LCG modifications; 2)10 HCP exit interviews to obtain feedback and modify LCG prototype one; 3)Two focus group discussions following use of prototype two to identify any further user needs; 4)Exit expert panel interviews involving HCPs to refine LCG components; 5)Pilot testing of final prototype among 40 HCPs; 6)Final panel reviews from two expert conferences, the National Safe Motherhood Conference, and Association of Obstetricians and Gynaecologists of Uganda to refine/consolidate modifications of final prototype for Uganda, ready for evaluation.

Results

A total of 120 HCPs and MOH officials previously exposed to the new WHO LCG, with median age of 36 years (IQR;26-48) were interviewed. Over 53 modifications were made to tailor the WHO LCG into the modified LCG prototype for Uganda including; 1)Adjusting observation ordering to improve flow, clarity, and facilitate an easy user interface; 2)Inclusion of vital socio-demographic data compatible with existing programs in Uganda to prompt risk identification; 3)Modification of medications, baby-mother parameters/observations to suit local context; and 4)Inclusion of key cues to action, clinical notes and labour outcome data to facilitate auditing, accountability, reference, utilization and immediate postpartum care. All HCPs found the modified LCG useful, easy to use, appropriate, comprehensive, inclusive and would recommend it to others for use. Over 80% HCPs reported they took <2 minutes to plot/fill all observations on the LCG after assessment.

Conclusions

Active involvement of targeted end-users in customizing the LCG was observed to improve inclusiveness, ownership, comprehensiveness, acceptability, engagement and uptake. The modified LCG prototype was found to be simple, appropriate and easy-to-use. Further research to evaluate this LCG prototype feasibility and effectiveness is needed.
Frequency of ocular manifestations in rheumatic autoimmune diseases (ARDs); a cross-sectional study
Authors: Sohail Usama
Published: January 2024

Autoimmune disorders involve diverse symptomatic manifestations constituting an abnormal or exaggerated immune function and serve to attack self-antigens and result in tissue destruction. This study aims to comprehensively analyse the prevalence, type, associative factors, and the resultant impact of ocular symptoms on patients presented to rheumatology departments of multi-center tertiary care hospitals in Lahore. Methods. A total of 300 patients were studied during the time frame of Jan 2021-Dec 2022. Results. Rheumatoid Arthritis comprised 45.7 % (n=137) of patients, Systemic Lupus Erythematosus (SLE) was present in 34.3% (N=103) patients. Spondylarthritis 8.3%, Granulomatous Polyangiitis 3.3%, Juvenile idiopathic arthritis 0.7%, and Bechet Disease 2.3% were present. The total number of patients who developed eye manifestations was 18%. Keratoconjunctivitis Sicca was observed in 4 females and 2 males with overall frequency of 11.1%. Conclusions. Our study showed a surge in the cases of SLE diagnosed and witnessed during the period of 2022, but our study showed an overall decrease in the incidence of eye complications.
Prevalence of diabetes among Indigenous women in Guatemala: A retrospective chart review study of 13 643 patients between 2015-2022
Authors: Alajajian Stephen , Bartolimin Jenny , Martin Yolanda Juarez , Scott Caitlin , Rohloff Peter , Flood David
Published: January 2024

There are limited data on diabetes among Indigenous populations in Guatemala. In a retrospective chart review of a clinical program serving more than 13 000 primarily Indigenous women in Guatemala, age-adjusted diabetes prevalence was 7.9% (95% CI: 7.3 to 8.5), and 37.9% (95% CI: 35.1 to 40.8%) of women were undiagnosed.
Assessing the impact of interventions on the major Omicron BA.2 outbreak in spring 2022 in Shanghai
Authors: Liu Hengcong , Cai Jun , Zhou Jiaxin , Xu Xiangyanyu , Ajelli Marco , Yu Hongjie
Published: January 2024

Background

Shanghai experienced a significant surge in Omicron BA.2 infections from March to June 2022. In addition to the standard interventions in place at that time, additional interventions were implemented in response to the outbreak. However, the impact of these interventions on BA.2 transmission remains unclear.

Methods

We systematically collected data on the daily number of newly reported infections during this wave and utilized a Bayesian approach to estimate the daily effective reproduction number. Data on public health responses were retrieved from the Oxford COVID-19 Government Response Tracker and served as a proxy for the interventions implemented during this outbreak. Using a log-linear regression model, we assessed the impact of these interventions on the reproduction number. Furthermore, we developed a mathematical model of BA.2 transmission. By combining the estimated effect of the interventions from the regression model and the transmission model, we estimated the number of infections and deaths averted by the implemented interventions.

Results

We found a negative association (-0.0069, 95% CI: -0.0096 to -0.0045) between the level of interventions and the number of infections. If interventions did not ramp up during the outbreak, we estimated that the number of infections and deaths would have increased by 22.6% (95% CI: 22.4-22.8%), leading to a total of 768,576 (95% CI: 768,021-769,107) infections and 722 (95% CI: 722-723) deaths. If no interventions were deployed during the outbreak, we estimated that the number of infections and deaths would have increased by 46.0% (95% CI: 45.8-46.2%), leading to a total of 915,099 (95% CI: 914,639-915,518) infections and 860 (95% CI: 860-861) deaths.

Conclusion

Our findings suggest that the interventions adopted during the Omicron BA.2 outbreak in spring 2022 in Shanghai were effective in reducing SARS-CoV-2 transmission and disease burden. Our findings emphasize the importance of non-pharmacological interventions in controlling quick surges of cases during epidemic outbreaks.
Priorities and barriers for research related to primary ciliary dyskinesia
Authors: Goutaki Myrofora , Lam Yin Ting , Rubbo Bruna , Chalmers James D , Kouis Panayiotis , Marsh Gemma , Papon Jean-François , Raidt Johanna , Robinson Phil , Behan Laura , Lucas Jane S
Published: January 2024

Background

Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research.

Methods

To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with PCD specialists selected using purposive sampling. We transcribed, coded, and analysed interview data using thematic analysis. Based on interview themes we identified, we developed an anonymous survey and circulated it widely through the BEAT-PCD network.

Results

We interviewed 28 participants from 15 countries across different disciplines and expertise levels. The main themes identified as priorities for PCD research were improving diagnosis, understanding prevalence, and disease course; phenotypic variability; disease monitoring; treatment strategies; clinical trial endpoints; and neglected research areas. In total, 136 participants (49% paediatric pulmonologists) from 36 countries completed the survey. Most commonly reported barriers for research were low awareness about PCD and difficulties securing funding—in more than one-third of cases, participants reported undertaking predominantly unfunded research. Research questions ranked highest included priorities related to further improving diagnosis, treating PCD, managing upper and lower airway problems, and studying clinical variability and disease prognosis.

Conclusion

We need to overcome barriers of limited funding and low awareness and promote collaborations between centres, disciplines, experts, and patients to address PCD priorities effectively. Our results contribute to the ongoing efforts of guiding the use of existing limited research resources and setting up a roadmap for future research activities.

Take home message

Our study defined PCD research priorities including improving diagnosis, treatments, managing upper and lower airway disease, and understanding prognosis. Key barriers identified include low disease awareness and limited funding opportunities.
Immunotherapy Time of Infusion Impacts Survival in Head and Neck Cancer: A Propensity Score Matched Analysis
Authors: Ruiz-Torres Daniel A. , Naegele Saskia , Podury Archana , Wirth Lori , Shalhout Sophia Z. , Faden Daniel L.
Published: January 2024

The adaptive immune response is physiologically regulated by the circadian rhythm. Data in lung and melanoma malignancies suggests immunotherapy infusions earlier in the day may be associated with improved response; however, the optimal time of administration for patients with HNSCC is not known. We aimed to evaluate the association of immunotherapy infusion time with overall survival (OS) and progression free survival (PFS) in patients with HNSCC in an Institutional Review Board-approved, retrospective cohort study. 113 patients met study inclusion criteria and 98 patients were included in a propensity score-matched cohort. In the full unmatched cohort (N=113), each additional 20% of infusions received after 1500h conferred an OS hazard ratio (HR) of 1.35 (95% C.I.1.2-1.6; p-value=0.0003) and a PFS HR of 1.34 (95% C.I.1.2-1.6; p-value <0.0001). A propensity score-matched analysis of patients who did or did not receive ≥ 20% of infusions after 1500h showed that those who were administered ≥20% of infusions after 1500h trended towards a shorter OS (HR=1.35; p-value=0.26) and a shorter PFS (HR=1.57, 95% C.I. 1.02-2.42, p-value=0.04). Each additional 20% of infusions received after 1500h remained robust in the matched cohort multivariable analysis and was associated with shorter OS (adjusted HR=1.4 (95% C.I.1.2-1.8), p-value<0.001). Patients with advanced HNSCC who received more of their infusions in the afternoon were associated with shorter OS and PFS and scheduling immunotherapy infusions earlier in the day may be warranted.

Conflict of Interest Statement

Dr. Wirth reports receiving advisory board fees from Ayala Pharmaceuticals, Blueprint Medicines, Cue Biopharma, Cullinan Oncology, Genentech USA, Loxo Oncology, Merck, NewLink Genetics, Novartis, and Rakuten Medical, consulting fees and advisory board fees from Bayer HealthCare Pharmaceuticals and Eisai, advisory board fees and fees for serving on a steering committee from Eli Lilly, and fees for serving on a data and safety monitoring board from Iovance Biotherapeutics. Dr. Faden has received research funding from Bristol Myers Squibb and Foundation Medicine, holds equity in Illumina and receives consulting fees from Noetic and Focus on Boston. The remaining authors have no conflicts to report.

Research Highlights

Immunotherapy early in the day may result in improved response rates in HNSCC, consistent with data in other solid malignancies.
Probiotic effect of trichloroacetic acid on cervicovaginal microbiota in cervical intraepithelial neoplasia: A pilot study
Authors: Shibata Takeo , Ohno Ayumu , Murakami Isao , Takakura Masahiro , Sasagawa Toshiyuki , Imanishi Tadashi , Mikami Mikio
Published: January 2024

Symbiosis of bacteria and human papillomavirus (HPV) in the cervicovaginal environment influences cervical intraepithelial neoplasia (CIN) progression or regression. In this case series, we enrolled all 10 patients who had resolved CIN after a cervical local treatment using trichloroacetic acid (TCA). Prominent changes in the cervicovaginal microbiota, such as an enrichment of the genusBifidobacteriumand genusLactobacillus, were observed in seven of 10 patients. A decrease in cervicovaginal bacterial alpha diversity was observed in 4 patients with high-risk HPV clearance. Differential abundance analysis revealed that genusBifidobacteriumincreased significantly after TCA. The dominance of a single bacteria can be characteristic of CIN cures after TCA. These results highlight the potential link of cervicovaginal bacteria such as genusBifidobacteriumand genusLactobacillusin the clearance of CIN and high-risk HPV. This pilot study guides future research questions that specific cervicovaginal bacteria may be promising candidates for probiotic therapy to treat CIN and HPV infections.
Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development
Authors: Courreges Christina J.F. , Davenport Elizabeth C.M. , Bilanges Benoit , Rebollo-Gomez Elena , Hukelmann Jens , Schoenfelder Priya , Edgar James R. , Sansom David , Scudamore Cheryl , Roychudhuri Rahul , Garden Oliver A. , Vanhaesebroeck Bart , Okkenhaug Klaus
Published: January 2024

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cellsin vitro.

Our data suggest that VPS34 is required for the maturation of Treg cells or that mature Treg cells depend on VPS34 for survival. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy contributes to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells.
Pregnancy affects flight behavior in big brown bats (Eptesicus fuscus)
Authors: Calistri-Yeh Adrienne , Hilliard Young Vanessa K , Klingerman Michaele , Kloepper Laura N.
Published: January 2024

Pregnancy involves increased body mass and decreased locomotor performance in many species and can be especially impactful on volant animals. To test the hypothesis that bats modify flight behavior to adjust for pregnancy-related increases in mass, we recorded thermal video from a maternity colony of big brown bats (Eptesicus fuscus) as they emerged from a roost, during periods associated with pregnancy and post-pregnancy. From video tracking, we calculated the vertical drop distance before upward motion (UM), time from emergence until UM, average speeds before and after UM, and average wingbeat rate per second (WBR). Bats recorded during the pregnancy period had a significantly larger drop distance, longer time until UM, faster flight speed before UM, and higher WBR compared to bats recorded during the non-pregnancy period. Our results suggest that pregnancy has a significant effect on flight in female bats, with a particularly strong impact on achieving UM after emergence. However, the higher WBR recorded from bats flying during the pregnancy period implies that bats acclimate to such changes in body mass by altering their flight behaviors to sustain UM while pregnant.