bluuebunny/crossref_metadata_2025 huggingface dataset:
Surrogate selection oversamples expanded T cell clonotypes
Authors: Yu Peng , Lian Yumin , Zuleger Cindy L. , Albertini Richard J. , Albertini Mark R. , Newton Michael A.
Published: July 2023

Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects of surrogate selection assays, which we confirm may lead to an enrichment for amplified, potentially disease-relevant T cell clones. Our specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires.

Funding

This research was supported in part by the National Science Foundation (grant 2023239-DMS), and by grants from the National Institutes of Health: R01 GM102756, P01 CA022443, P01 CA250972, P50 CA278595, UL1 TR002373, P50 CA269011, and P30 CA014520. This work was also supported by resources at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA, and the UW Carbone Comprehensive Cancer Center. Additional support was provided by Ann’s Hope Foundation, Taking on Melanoma, the Tim Eagle Memorial, and the Jay Van Sloan Memorial from the Steve Leuthold Family Foundation, philanthropic support in the USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the views of the Dept. of Veterans Affairs or the United States Government.
Insight into the structural hierarchy of the protease cascade that regulates the mosquito melanization response
Authors: Saab Sally A. , Zhang Xiufeng , Zeineddine Suheir , Morejon Bianca , Michel Kristin , Osta Mike A.
Published: July 2023

Serine protease cascades regulate important insect immune responses, including melanization and Toll pathway activation. In the context of melanization, central components of these cascades are clip domain serine proteases (CLIPs) including the catalytic,clip domainserineproteases (cSPs) and their non-catalytichomologs (cSPHs). Here, we define partially the structural hierarchy ofAn. gambiaecSPs of the CLIPB family, central players in melanization, and characterize their relative contributions to bacterial melanization and to mosquito susceptibility to bacterial infections. Usingin vivogenetic analysis we show that the protease cascade branches downstream of the cSPs CLIPB4 and CLIPB17 into two branches one converging on CLIPB10 and the second on CLIPB8. We also show that the contribution of key cSPHs to melanizationin vivoin response to diverse microbial challenges is more significant than any of the individual cSPs, possibly due to partial functional redundancy among the latter. Interestingly, we show that the key cSPH CLIPA8 which is essential for the efficient activation cleavage of CLIPBsin vivois efficiently cleaved itself by several CLIPBsin vitro, suggesting that cSPs and cSPHs regulate signal amplification and propagation in melanization cascades by providing positive reinforcement upstream and downstream of each other.
Diffusion-weighted magnetic resonance imaging for the diagnosis of giant cell arteritis – a comparison with T1-weighted black-blood imaging
Authors: Seitz Luca , Bucher Susana , Bütikofer Lukas , Maurer Britta , Bonel Harald M. , Wagner Franca , Lötscher Fabian , Seitz Pascal
Published: July 2023

Objectives

To investigate the diagnostic performance of diffusion-weighted imaging (DWI) of the superficial cranial arteries in the diagnosis of giant cell arteritis (GCA).

Methods

Retrospectively, 156 patients with clinically suspected GCA were included. A new 4-point ordinal DWI rating scale was developed. A post-contrast, fat-suppressed, T1-weighted “black-blood” sequence (T1-BB) was rated for comparison. Ten arterial segments were assessed: common superficial temporal arteries, temporal and parietal branches, occipital and posterior auricular arteries bilaterally. The expert clinical diagnosis after ≥ 6 months of follow-up was the diagnostic reference standard. Diagnostic accuracy was evaluated for different rating methods.

Results

The study cohort consisted of 87 patients with and 69 without GCA. For DWI, the area under the curve was 0.90. For a cut-off of ≥ 2 consecutive pathological slices, DWI showed a sensitivity of 75.9%, a specificity of 94.2% and a positive likelihood ratio of 13.09. With a cut-off of ≥ 3 consecutive pathological slices, sensitivity was 70.1%, specificity was 98.6%, and the positive likelihood ratio was 48.38. For the T1-BB, values were 88.5%, 88.4% and 7.63, respectively. The inter-rater analysis for DWI with a cut-off of ≥ 2 pathological slices showed a kappa of 1.00 on the patient level and 0.85 on the arterial segment level. For the T1-BB the kappa was 0.78 and 0.79, respectively.

Conclusion

DWI of the superficial cranial arteries demonstrates a good diagnostic accuracy and reliability for the diagnosis of GCA. DWI is widely available and can be used immediately in clinical practice for patients with suspected GCA.
ChatGPT may free time needed by the interventional radiologist for administration / documentation: A study on the RSNA PICC line reporting template
Authors: Senge Jan F. , McMurray Matthew T. , Haupt Fabian , Breiding Philipe S. , Beisbart Claus , Daneshvar Keivan , Komarek Alois , Nöldge Gerd , Mosler Frank , Bosbach Wolfram A.
Published: July 2023

Motive

Documentation and administration, unpleasant necessities, take a substantial part of the working time in the subspecialty of interventional radiology. With increasing future demand for clinical radiology predicted, time savings from use of text drafting technologies could be a valuable contribution towards our field.

Method

Three cases of peripherally inserted central catheter (PICC) line insertion were defined for the present study. The current version of ChatGPT was tasked with drafting reports, following the Radiological Society of North America (RSNA) template.

Key results

Score card evaluation by human radiologists indicates that time savings in documentation / administration can be expected without loss of quality from using ChatGPT. Further, automatically generated texts were not assessed to be clearly identifiable as AI-produced.

Conclusions

Patients, doctors, and hospital administrators would welcome a reduction of the time that interventional radiologists need for documentation and administration these days. If AI-tools as tested in the present study are brought into clinical application, questions about trust into those systems eg with regard to medical complications will have to be addressed.
Honey Experiment on LeProsy Ulcer (HELP) Study Protocol: A Randomised Control Trial of Raw, Unadulterated African Honey for Ulcer Healing in Leprosy: A Study Protocol
Authors: Udo Sunday Odihiri , Sunday Pius Ogbu , Tsaku Paul Alumbugu , Oladejo Israel Olaoluwa , Meka Anthony , Ugwu Linda , Ajisola Motunrayo , Akinyemi Joshua , Omigbodun Akinyinka , Choudhury Sopna , Sartori Jo , Ilozumba Onaedo , Watson Samuel I. , Lilford Richard J
Published: July 2023

Background

As in diabetes, ulcers in leprosy occur as a result of nerve damage and loss of sensation due to neuropathy. The aim of this study is to evaluate the healing properties of raw, undiluted African honey in comparison with normal saline dressing of leprosy ulcers.

Methods

This is a multi-centre, comparative, prospective, single-blinded, parallel-group, 1:1 individually randomised controlled trial to be conducted at The Leprosy Referral Hospital, Chanchaga, Niger state in central Nigeria and St. Benedict Hospital, Ogoja, Cross River state, South-south Nigeria. Raw, unadulterated honey will be used in the ulcer dressing of the eligible consenting participants in the intervention group while those in the control group will be treated by dressing with normal saline. The main outcomes will be the proportion of complete healing and the rate of healing up to 84 days post-randomisation. Follow-up will be for 6 months from randomisation. We aim to enter 90-130 participants into the study. Observations will be made by blinded observers examining photographs of ulcers.

Discussion

Our study will provide an unbiased estimate of the effect of honey on the healing of neuropathic ulcers.

Trial registration

ISRCTN10093277. Registered on 22 December 2021.
The principal component-based clinical aging clock (PCAge) identifies signatures of healthy aging and provides normative targets for clinical intervention
Authors: Fong Sheng , Pabis Kamil , Latumalea Djakim , Dugersuren Nomuundari , Unfried Maximilian , Tolwinski Nicholas , Kennedy Brian , Gruber Jan
Published: July 2023

Clinical healthy aging recommendations are disease-centric and reactive rather than focusing on holistic, organismal aging. In contrast, biological age (BA) estimation informs risk stratification by predicting all-cause mortality, however current BA clocks do not pinpoint aging mechanisms making it difficult to intervene clinically. To generate actionable BA clocks, we developed and validated a principal component (PC)-based clinical aging clock (PCAge) that identifies signatures (PCs) associated with healthy and unhealthy aging trajectories. We observed that by intervening in PC-specific space, angiotensin-converting-enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) normalize several modifiable clinical parameters, involved in renal and cardiac function as well as inflammation. Proactive treatment with ACE-I/ARBs appeared to significantly reduce future mortality risk and prevented BA acceleration. Finally, we developed a reduced BA clock (PC_mAge), based directly on PCAge, which has equivalent predictive power, but is optimized for immediate application in clinical practice. Our Geroscience approach points to mechanisms associated with BA providing targets for preventative medicine to modulate biological process(es) that drive the shift from healthy functioning toward aging and the eventual manifestations of age-related disease(s).
Extended Hematology-Oncology Fellowships in Bone Marrow Transplantation, Leukemia, Lymphoma, and Myeloma: What Proportion of Trainees Train and Remain at these Centers?
Authors: Prasad Vinay
Published: July 2023

Introduction

A number of extra fellowships after traditional hematology oncology training have started in recent years, including training in lymphoma, myeloma, bone marrow transplantation, and leukemia. The benefit of this additional training is disputed.

Methods and Materials

We sought to quantify, from publicly reported data, what percentage of trainees either performed the extra year at the same location as they performed their fellowship– raising the question why they did not gain this training during the regular fellowship years– and what fraction stayed on at the same institution–raising the question of why the training was not performed on the job. Google and LinkedIn searches were performed to assemble the dataset.

Results

We examined 6 programs that made their graduate information public. We found 30% (17/56) of fellows either trained at the same institution or remained at the same institution as their extra fellowship.

Conclusion

Nearly 1 in 3 trainees that forgo an extra year do so in a context where they had opportunity to work at that center before or afterwards, raising the question as to whether the extra year was needed or could have been built into existing professional obligations.
Alternations in gut microbiota and host transcriptome of patients with coronary artery disease
Authors: Chen Liuying , Mou Xuanting , Li Jingjing , Li Miaofu , Ye Caijie , Gao Xiaofei , Liu Xiaohua , Ma Yunlong , Xu Yizhou , Zhong Yigang
Published: July 2023

Background

Coronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.

Results

Herein, we collected 54 fecal and 54 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that 10 bacteria biomarkers can distinguish CAD patients from health controls with a high performance (AUC = 0.939). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbegenus Fusicatenibacterwas associated with expression of CAD-risk genes, such asGBP2,MLKL, andCPR65. In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genusBlautia,Eubacterium,Fusicatenibacter, andMonoglobus.

Conclusions

Our results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.
Label-free cell detection of acute leukemia using ghost cytometry
Authors: Kawamura Yoko , Nakanishi Kayoko , Murata Yuri , Teranishi Kazuki , Miyazaki Ryusuke , Toda Keisuke , Imai Toru , Kajiwara Yasuhiro , Nakagawa Keiji , Matsuo Hidemasa , Adachi Souichi , Ota Sadao , Hiramatsu Hidefumi
Published: July 2023

Early diagnosis and prompt initiation of appropriate treatment are critical for improving the prognosis of acute leukemia. Currently, acute leukemia is diagnosed by microscopic morphological examination of bone marrow smears and flow cytometric immunophenotyping of bone marrow cells stained with fluorophore-conjugated antibodies. However, these diagnostic processes require trained professionals and are time and resource-intensive. Here, we present a novel diagnostic approach using ghost cytometry, a recently developed high-content flow cytometric approach, which enables machine vision-based, stain-free, high-speed analysis of cells, leveraging their detailed morphological information. We demonstrate that ghost cytometry can detect leukemic cells from the bone marrow cells of patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), without relying on biological staining. The method presented here holds promise as a precise, simple, swift, and cost-effective method for the diagnosis of acute leukemia in clinical practice.
The PREVENT Dementia programme: Baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia
Authors: Ritchie Craig W. , Wells Katie , Gregory Sarah , Carriere Isabelle , Danso Samuel O. , Driscoll David , Dounavi Maria-Eleni , Hillary Robert , Koychev Ivan , Lawlor Brian , Li Su , Low Audrey , Mak Elijah , Malhotra Paresh , Manson Jean , Marioni Riccardo , Murphy Lee , Naci Lorina , O’Brien John T , Stewart William , Muniz-Terrera Graciela , Ritchie Karen
Published: July 2023

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine mid-life risk factors for dementia, identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort.

Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery, and are imaged using multi-modal 3T magnetic resonance imaging (MRI) scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies which supplement the main PREVENT cohort are also described.

The PREVENT cohort baseline data includes 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ±5.47), with the majority female (n=433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% vs 48.6%) and a relatively high prevalence ofAPOE⍰4carriers (n=264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n=672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (ACE-III) (Total score 95.6 ±4.06). Mean white matter hyperintensity (WMH) volume at recruitment was 2.26 ± 2.77 ml (median = 1.39ml), with hippocampal volume 8.15 ± 0.79ml. There was good representation of known dementia risk factors in the cohort.

The PREVENT cohort offers a novel dataset to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer’s Disease Data Initiative (ADDI) platform and Dementia Platforms UK (DPUK) platform pending approval of the data access request from the PREVENT steering group committee.
Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Lu Scott , Peluso Michael J. , Glidden David V. , Davidson Michelle C. , Lugtu Kara , Pineda-Ramirez Jesus , Tassetto Michel , Garcia-Knight Miguel , Zhang Amethyst , Goldberg Sarah A. , Chen Jessica Y. , Fortes-Cobby Maya , Park Sara , Martinez Ana , So Matthew , Donovan Aidan , Viswanathan Badri , Hoh Rebecca , Donohue Kevin , McIlwain David R. , Gaudiliere Brice , Anglin Khamal , Yee Brandon C. , Chenna Ahmed , Winslow John W. , Petropoulos Christos , Deeks Steven G. , Briggs-Hagen Melissa , Andino Raul , Midgley Claire M. , Martin Jeffrey N. , Saydah Sharon , Kelly J. Daniel
Published: July 2023

To understand the roles of acute phase viral dynamics and host immune responses in PASC, we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR. Participants self-collected nasal specimens up to 21 times within the first 28 days after symptom onset; Interviewer-administered clinical questionnaires and blood samples were collected at enrollment and days 9, 14, 21, 28, and month 4 and 8 post-symptom. Defining PASC as the presence of any symptom new or worse since infection reported at their 4-month visit, we compared viral markers (quantity and duration of viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. In comparison to those who fully recovered, those who developed PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA, infectious virus, and N-antigen, longer duration of viral shedding, and lower Spike-specific IgG levels within the first 10 days of the acute phase of illness. No significant differences were identified among a panel of host immune markers, though there was a trend toward higher initial levels of certain markers (e.g., MCP-1, IFN-α, and IFN-γ) in those who went on to develop PASC. Early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC. These findings highlight the importance of understanding the early biological markers from acute SARS-CoV-2 infection in the natural history of PASC.

Onset Sentence Summary

Early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC.
Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s disease
Authors: Salvadó Gemma , Horie Kanta , Barthélemy Nicolas R. , Vogel Jacob W. , Binette Alexa Pichet , Chen Charles D. , Aschenbrenner Andrew J , Gordon Brian A. , Benzinger Tammie L.S. , Holtzman David M. , Morris John C. , Palmqvist Sebastian , Stomrud Erik , Janelidze Shorena , Ossenkoppele Rik , Schindler Suzanne E. , Bateman Randall J. , Hansson Oskar
Published: July 2023

Biological staging of individuals with Alzheimer’s disease (AD) may improve diagnostic and prognostic work-up of dementia in clinical practice and the design of clinical trials. Here, we created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm by evaluating cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau biomarkers in 426 participants from BioFINDER-2, that represent the entire spectrum of AD. The model composition and main analyses were replicated in 222 participants from the Knight ADRC cohort. SuStaIn revealed in the two cohorts that the data was best explained by a single biomarker sequence (one subtype), and that five CSF biomarkers (ordered: Aβ42/40, tau phosphorylation occupancies at the residues 217 and 205 [pT217/T217 and pT205/T205], microtubule-binding region of tau containing the residue 243 [MTBR-tau243], and total tau) were sufficient to create an accurate disease staging model. Increasing CSF stages (0-5) were associated with increased abnormality in other AD-related biomarkers, such as Aβ- and tau-PET, and aligned with different phases of longitudinal biomarker changes consistent with current models of AD progression. Higher CSF stages at baseline were associated with higher hazard ratio of clinical decline. Our findings indicate that a common pathophysiologic molecular pathway develops across all AD patients, and that a single CSF collection is sufficient to reliably indicate the presence of both AD pathologies and the degree and stage of disease progression.
Risk of severe outcomes among Omicron sub-lineages BA.4.6, BA.2.75 and BQ.1 compared to BA.5 in England
Authors: Seghezzo Giulia , Nash Sophie G , Aziz Nurin Abdul , Hope Russel , Bernal Jamie Lopez , Gallagher Eileen , Dabrera Gavin , Thelwall Simon
Published: July 2023

Since the emergence of Omicron variant of SARS-CoV-2 in late 2021, a number of sub-lineages have arisen and circulated internationally. Little is known about the relative severity of Omicron sub-lineages BA.2.75, BA.4.6 and BQ.1. We undertook a case-control analysis to determine the clinical severity of these lineages relative to BA.5, using whole genome sequenced, PCR-confirmed infections, between 1 August 2022 to 27 November 2022, among those who presented to emergency care in England 14 days after and up to one day prior to the positive specimen. A total of 10,375 episodes were included in the analysis, of which 5,207 (50.2%) were admitted to hospital or died. Multivariable conditional regression analyses found no evidence for greater odds of hospital admission or death among those with BA.2.75 (OR= 0.96, 95% CI: 0.84 to 1.09), and BA.4.6 (OR= 1.02, 95% CI: 0.88 to 1.17) or BQ.1 (OR= 1.03, 95 % CI: 0.94 to 1.13) compared to BA.5. Future lineages may not follow the same trend and there remains a need for continued surveillance of COVID-19 variants and their clinical outcomes to inform the public health response.
Factors associated with therapeutic inertia in individuals with type 2 diabetes mellitus started on basal insulin
Authors: Shabnam Sharmin , Gillies Clare L , Davies Melanie J , Dex Terry , Melson Eka , Khunti Kamlesh , Webb David R , Zaccardi Francesco , Seidu Samuel
Published: July 2023

Aim

In this study we aim to identify the risk factors for treatment inertia in patients with type 2 diabetes mellitus (T2DM) who have been recently started on basal insulin (BI).

Methods

Using UK CPRD GOLD, we identified adults with T2DM with suboptimal glycaemia (HbA1c within 12 months of BI ≥7% (≥53 mmol/mol)). We used multivariable Cox regression model to describe the association between patient characteristics and the time to treatment intensification.

Results

A total of 12,556 patients were analysed. Compared to individuals aged <65 years, those aged ≥65 years had lower risk of treatment intensification (HR: 0.69; 95% CI: 0.64-0.73). Other risk factors included being female (0.93, 0.89-0.99), longer T2DM duration (0.99, 0.98-0.99), living in the most deprived areas (0.90, 0.83-0.98), being a current smoker (0.91, 0.84-0.98), having one (0.91, 0.85- 0.97) or more than one comorbidity (0.88, 0.82-0.94), and patients who were on metformin (0.71, 0.63-0.80), or 2nd generation sulphonylureas (0.85; 0.79-0.92) or DPP4 inhibitors (0.87, 0.82-0.93) compared to those who were not.

Conclusion

Therapeutic inertia still remains a major barrier, with multiple factors associated with delay in intensification. Interventions to overcome therapeutic inertia need to be implemented at both patient and health care professional level.
Assessment of compliance of baby friendly hospital initiative in tertiary care hospital, South India
Authors: ruban A.charles pon , S Nair Lekshmy , Maria David Linta , V Mahalakshmi , Jerin Grace Manorita , Prithvi K Manoj , K S Jyodhish
Published: July 2023

Objectives

To assess the compliance of a tertiary care hospital, South India with the ten steps of the Baby Friendly Hospital Initiative following the UNICEF/WHO global criteria.

Design

Cross-sectional study

Setting

Tertiary care hospital, South India

Participants

Staff nurses who are posted in in the obstetrics and gynaecology department and the mothers admitted antenatal, postnatal, and labour wards.

Results

Only 35% of the staff nurses interviewed received formal training in breastfeeding techniques. Written information about breastfeeding was given to all prenatal mothers (100%) yet, only 75% knew the importance of breastfeeding soon after delivery. Only 62.5% of babies were exclusively breastfed and 51.3% of the babies were breastfed within one hour of birth. Compliance with the Ten Steps of baby friendly initiative was 66.63%, signifying a moderate compliance overall.

Conclusion

The compliance to Ten steps of BFHI in low resource setting shows an overall moderate compliance. The Ten Steps of BFHI may be implemented more effectively in all medical facilities through the mother’s absolute affection Programme (MAA). More focused approaches are needed to improve the breastfeeding practices even in tertiary care settings in India.

Keypoint

What is already known on this topic

Good breast-feeding practices are essential for reducing infant mortality. The effect of interventions by the Government on breast feeding practices especially in a tertiary care hospital setting, South India is poorly studied.

What this study adds

Practice of exclusive breast feeding is low. Compliance with the Ten Steps of baby friendly initiative was low even in a tertiary care setup in south India.

How this study might affect research, practice and/or policy

Good breast-feeding practices should be promoted in all health facilities. More focused interventions are needed to fill this gap.
The genetic diversity of Nipah virus across spatial scales
Authors: Azuero Oscar Cortés , Lefrancq Noémie , Nikolay Birgit , McKee Clifton , Cappelle Julien , Hul Vibol , Ou Tey Putita , Hoem Thavry , Lemey Philippe , Rahman Mohammed Ziaur , Islam Ausraful , Gurley Emily S. , Duong Veasna , Salje Henrik
Published: July 2023

Nipah virus (NiV), a highly lethal virus in humans, circulates silently inPteropusbats throughout South and Southeast Asia. Difficulty in obtaining genomes from bats means we have a poor understanding of NiV diversity, including how many lineages circulate within a roost and the spread of NiV over increasing spatial scales. Here we develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N=257, 175 from bats, 73 from humans) from six countries over 22 years (1999–2020). In Bangladesh, where most human infections occur, we find evidence of increased spillover risk from one of the two co-circulating sublineages. We divide the four major NiV sublineages into 15 genetic clusters (emerged 20-44 years ago). Within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1,500-2,000 km2. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate that each genetic cluster occupies an average area of 1.3 million km2(95%CI: 0.6-2.3 million), with 14 clusters in an area of 100,000 km2(95%CI: 6-24). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most of the genetic clusters have been identified, but only ∼15% of overall NiV diversity has been uncovered. Our findings are consistent with entrenched co-circulation of distinct lineages, even within individual roosts, coupled with slow migration over larger spatial scales.
Leveraging Large Language Models for Generating Responses to Patient Messages
Authors: Liu Siru , McCoy Allison B. , Wright Aileen P. , Carew Babatunde , Genkins Julian Z. , Huang Sean S. , Peterson Josh F. , Steitz Bryan , Wright Adam
Published: July 2023

Objective

This study aimed to develop and assess the performance of fine-tuned large language models for generating responses to patient messages sent via an electronic health record patient portal.

Methods

Utilizing a dataset of messages and responses extracted from the patient portal at a large academic medical center, we developed a model (CLAIR-Short) based on a pre-trained large language model (LLaMA-65B). In addition, we used the OpenAI API to update physician responses from an open-source dataset into a format with informative paragraphs that offered patient education while emphasizing empathy and professionalism. By combining with this dataset, we further fine-tuned our model (CLAIR-Long). To evaluate the fine-tuned models, we used ten representative patient portal questions in primary care to generate responses. We asked primary care physicians to review generated responses from our models and ChatGPT and rated them for empathy, responsiveness, accuracy, and usefulness.

Results

The dataset consisted of a total of 499,794 pairs of patient messages and corresponding responses from the patient portal, with 5,000 patient messages and ChatGPT-updated responses from an online platform. Four primary care physicians participated in the survey. CLAIR-Short exhibited the ability to generate concise responses similar to provider’s responses. CLAIR-Long responses provided increased patient educational content compared to CLAIR-Short and were rated similarly to ChatGPT’s responses, receiving positive evaluations for responsiveness, empathy, and accuracy, while receiving a neutral rating for usefulness.

Conclusion

Leveraging large language models to generate responses to patient messages demonstrates significant potential in facilitating communication between patients and primary care providers.
Contextual and psychological factors of mask-wearing among secondary school students: A cross-sectional survey from Toronto
Authors: Liang Thomas , Kraguljac Alan , Science Michelle
Published: July 2023

Introduction

After the Ontario government withdrew masking regulations, mask-wearing became a personal choice. Many studies have investigated the factors associated with public mask-wearing, but few have explored the knowledge, attitudes, and psychological factors of masking in high school students. Our study aims to fill this gap.

Methods

In February 2023, a cross-sectional survey was distributed online to Grade 9-12 students in a school located in Toronto. Descriptive statistics, correlation analysis, and logistic regression were performed on the quantitative data, while thematic analysis was used to evaluate the qualitative responses.

Results

Most of the 62 participants were male with the median age of 16. Approximately half of the respondents reported some frequency of mask-wearing over the past month. Almost all participants claimed to be knowledgeable about COVID-19’s modes of transmission and preventative measures. More participants supported voluntary masking in schools rather than mandated masking. Demographic variables, existing COVID-19 knowledge, and perceived medical benefits were not significantly correlated with masking behaviour. Students who supported voluntary masking were ∼22 times more likely to wear a mask compared to those who held negative attitudes. Participants who felt a high level of perceived barriers were ∼30 times less likely to wear a mask. Mask-wearing individuals cited protection and aesthetic reasons, while the opposition raised arguments about the reduced concern of COVID-19 and downsides of masks.

Conclusion

Adolescent mask-wearing is significantly impacted by pre-existing attitudes towards masks, while perceived barriers strongly discourage students from wearing masks. Future research should investigate how to best promote positive beliefs regarding mask-wearing to youth.
Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes
Authors: Wang Jingxuan , Hill-Jarrett Tanisha , Buto Peter , Pederson Annie , Sims Kendra D. , Zimmerman Scott C. , DeVost Michelle A , Ferguson Erin , Lacar Benjamin , Yang Yulin , Choi Minhyuk , Caunca Michelle R. , La Joie Renaud , Chen Ruijia , Glymour M. Maria , Ackley Sarah F.
Published: July 2023

Background

Consistent methods for evaluating the link between brain structure and cognition are essential for understanding determinants of neurologic outcomes. Studies examining associations between brain volumetric measures and cognition use various statistical approaches to account for variation in intracranial volume (ICV). It is unclear if commonly used approaches yield consistent results.

Methods

Using a brain-wide association approach in the MRI substudy of UK Biobank (N=41,964; mean age=64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and five ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV, with and without further adjustment for ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2,784 regression models.

Findings

The adjustment and residual approaches typically produced similar estimates, which were inconsistent with results from the crude and proportional approaches. Inconsistencies across approaches were largest when estimates from the adjustment and residual approaches were further from the null. That is, the approach used was least important when the association between brain volume and cognitive performance was close to null; in this case, all approaches tend to estimate a null association.

Interpretation

Commonly used methods to correct for ICV yield inconsistent results and the proportional method diverges from other methods. Adjustment methods are the simplest to implement while producing biologically plausible associations.
Predicting nutrition and environmental factors associated with female reproductive disorders using a knowledge graph and random forests
Authors: Chan Lauren E , Casiraghi Elena , Putman Tim , Reese Justin , Harmon Quaker E. , Schaper Kevin , Hedge Harshad , Valentini Giorgio , Schmitt Charles , Motsinger-Reif Alison , Hall Janet E , Mungall Christopher J , Robinson Peter N , Haendel Melissa A
Published: July 2023

Objective

Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (e.g., endometriosis, ovarian cyst, and uterine fibroids).

Materials and Methods

We harmonized survey data from the Personalized Environment and Genes Study on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and applying a random forest for edge prediction to identify variables potentially associated with FRDs. We also conducted logistic regression analysis for comparison.

Results

Across 9765 PEGS respondents, the KG analysis resulted in 8535 significant predicted links between FRDs and chemicals, phenotypes, and diseases. Amongst these links, 32 were exact matches when compared with the logistic regression results, including comorbidities, medications, foods, and occupational exposures.

Discussion

Mechanistic underpinnings of predicted links documented in the literature may support some of our findings. Our KG methods are useful for predicting possible associations in large, survey-based datasets with added information on directionality and magnitude of effect from logistic regression. These results should not be construed as causal, but can support hypothesis generation.

Conclusion

This investigation enabled the generation of hypotheses on a variety of potential links between FRDs and exposures. Future investigations should prospectively evaluate the variables hypothesized to impact FRDs.
Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US
Authors: Park Sang Woo , Messacar Kevin , Douek Daniel C. , Spaulding Alicen B. , E. Metcalf C. Jessica , Grenfell Bryan T.
Published: July 2023

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although there are large uncertainties in our predictions, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to narrow uncertainties in future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.
The Contribution of Commonly Diagnosed Genetic Disorders to Small for Gestational Age Birth and Subsequent Morbidity and Mortality in Preterm Infants
Authors: Bomback Miles , Everett Selin , Lyford Alex , Sahni Rakesh , Kim Faith , Baptiste Caitlin , Motelow Joshua E. , Tolia Veeral , Clark Reese , Hays Thomas
Published: July 2023

Objective

Preterm infants born small, vs. appropriate for gestational age (SGA, AGA) are at greater risk for morbidity and mortality. The contribution of genetic disorders to preterm SGA birth, morbidity, and mortality is unknown. We sought to determine the association between genetic disorders and preterm SGA birth, and the association between genetic disorders and morbidity or mortality within preterm SGA infants. We hypothesized that genetic disorders were significantly associated with both.

Study Design

This was a retrospective multicenter cohort study of 409 339 infants, born 23–33 weeks’ gestation between 2000 and 2020. The odds of preterm SGA (vs AGA) birth, and the odds of severe morbidity or mortality within SGA preterm infants were determined for infants with genetic disorders, after adjusting for known risk factors.

Results

Genetic disorders were present in 3.0 and 1.3% of SGA and AGA preterm infants respectively; genetic disorders conferred an aOR (95% CI) of 2.06 (1.92, 2.21) of SGA birth. Genetic disorders were present in 4.3 of preterm SGA infants with morbidity or mortality and 2.1% of preterm SGA infants that did not experience morbidity or mortality. Genetic disorders conferred an aOR (95% CI) of 2.12 (2.66, 3.08) of morbidity or mortality.

Conclusions

Genetic disorders are strongly associated with preterm SGA birth, morbidity, and mortality. Clinicians should consider genetic testing of preterm SGA infants, particularly in the setting of other comorbidities or anomalies. Prospective, genomic research is needed to clarify the contribution of genetic disorders to disease in this population.
Experiences and attitudes towards Menstrual Suppression among Women with Bacterial vaginosis Randomised to Continuous Use of NuvaRing in Kenya
Authors: Casmir Edinah , Wairimu Njeri , Kiptinness Catherine , Oluoch Lynda , Maina Stephen Gakuo , Walker Kristina Wilbekin , Mugo Nelly , Marrazzo Jeanne , Ngure Kenneth
Published: July 2023

Background

The contraceptive vaginal ring (NuvaRing), one of the Multipurpose Prevention Technologies (MPT) products, is effective in preventing unintended pregnancies and may contribute to reducing the frequency of Bacterial Vaginosis (BV), which is a risk factor for HIV acquisition, transmission, and shedding among women. NuvaRing may cause irregular menstruation, including menstrual suppression, which may influence women’s decision on product choice, use, and acceptability. In this prospective cohort study, we assessed women’s experiences with menstruation suppression following continued NuvaRing use.

Methods

A total of 18 in-depth interviews were conducted using a semi-structured interview guide among purposively selected women with BV in Thika, Kenya, aged 18-40 years, who used NuvaRing continuously. All women received counseling on possibility of menstrual suppression following continuous NuvaRing use. Audio recordings were transcribed verbatim and thematically analyzed.

Results

Participants who expected and were aware that menstrual suppression was a possible side effect of Nuvaring accepted its benefits, and expressed acceptance and desire to continue using NuvaRing. Participants who had not anticipated menstrual suppression expressed anxiety and fear, with some expressing desire to continue using NuvaRing but worried about unintended negative consequences. The ability to perform daily activities uninterrupted, reduced expenses on sanitary supplies, enhanced sexual pleasure and relationships, and absence of menstrual pain were benefits of menstrual suppression. Although all participants received counseling on menstrual suppression, some expressed anxiety over the possibility of unintended pregnancy. As a result, they frequented medical facilities for health check-ups and pregnancy tests, and some used combined oral contraceptives to induce menses.

Conclusion

Understanding perceptions regarding menstrual suppression is crucial in offering targeted and comprehensive counseling to improve women’s understanding of menstruation suppression to influence acceptance and use of NuvaRing. Additionally, improved male involvement in reproductive health concerns and women’s autonomy in discussing reproductive health issues with partners is essential.
Association between relative income and mental health in adults during the COVID-19 pandemic in Korea: Insights from a community health survey
Authors: Moon Min Hui , Choi Min Hyeok
Published: July 2023

People of lower socioeconomic status are much more likely to be vulnerable to COVID-19. This study aimed to compare the associations between mental health according to relative national and community income levels during the COVID-19 pandemic. Mental health inequalities according to income level during the COVID-19 pandemic were assessed using the Korea Community Health Survey before (2019) and after the COVID-19 pandemic (2021). Univariate analyses were used to calculate the perceived stress and depression rates according to the risk factor categories. A multivariate logistic regression analysis was performed to identify the association between two types of income levels (Korean or community) and perceived stress and depression. In addition, we investigated the effect of relative income levels by subgroup (gender and region) on perceived stress and the experience of depression. During COVID-19, although depression crude rates increased (from 6.24% to 7.2%), perceived stress crude rates remained similar. In addition, as for mental health inequality according to community income level, even after adjusting for each independent variable, perceived stress [Odds Ratio (OR): 1.31, 95% Confidence Interval (CI):1.31–1.32] and experience of depression (OR: 1.63, 95% CI: 1.62–1.63) increased as the income level decreased. The effect of relative income level on perceived stress rate was found to be more pronounced in urban areas than in rural areas in terms of community income levels. Contrarily, the effect of relative income level on the depression rate was found to be weaker. Our findings demonstrated that mental health inequalities based on income level were more likely to occur during the COVID-19 pandemic and that disparities in community income levels may better reflect mental health inequalities.