bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying potential effects of relative age in school year: an instrumental variable phenome-wide association study in the UK Biobank
Authors: de Lange Melanie A , Davies Neil M , Millard Louise AC , Tilling Kate
Published: June 2023

Background

Observational research shows that a child’s relative age within their school year (‘relative age’) is associated with educational attainment and mental health. However, previous studies have only examined a small number of outcomes and evidence of the persistence of effects into adulthood is mixed. We conducted a hypothesis-free investigation of the effects of relative age.

Method

We used a regression discontinuity design and an instrumental variable (IV)-pheWAS in the UK Biobank (participants aged 40-69 years at baseline), using the PHESANT software package. We created two IVs for relative age: being born in September vs. August (n=64 075) and week of birth (n=383 309). Outcomes passing the Bonferroni-correctedPvalue threshold for either instrument were plotted to identify those displaying a discontinuity at the school year transition.

Results

We found 21 traits associated with at least one of the instruments (Pvalue below the Bonferroni threshold). Of these, 13 showed a discontinuity at the school year transition. These included previously identified effects including those with a younger relative age being less likely to have educational qualifications and more likely to have started smoking at an earlier age. We also identified a novel potential effect of a younger relative age in school year causing a better lung function as adults.

Conclusion

Educational policy should address educational inequality due to relative age. Further research should seek to replicate our identified effect on lung function in different populations, and investigate the mechanisms through which this effect may act.

Key Messages

Children’s relative age within their school year has been associated with mental health in childhood and educational attainment.

Our results supported previously identified effects, with those who were younger in their school year being less likely to have educational qualifications and more likely to report starting smoking at an earlier age.

We also found a potential beneficial effect of a younger relative age in school year on lung function in adulthood.
The impact of a hybrid hospital at home program in reducing subacute rehabilitation referrals
Authors: Yadav Ravi R , Mahyoub Mohammed A , Capriotti Michael W , Berio-Dorta Raul L , Dougherty Kacie , Shukla Ajit
Published: June 2023

Purpose

The purpose of this study was to validate Hospital at Home as an appropriate care option for patients of certain diagnostic-related groups and acuity levels.

Patients and methods

We compared outcomes for patients in a Hospital at Home program at Virtua Health in 2022 (N = 272) to traditional inpatients at Virtua hospitals during the same year who did not participate in the Hospital at Home program (N = 13879). We defined outcomes as recommendations for subacute rehabilitation (SAR) and final disposition upon inpatient discharge. Specifically, we searched electronic medical records for terms related to recommendation for SAR and discharge to SAR using text mining algorithms and a natural language processing (NLP) model to confirm these recommendations.

Results

We observed that the proportion of patients in the Hospital at Home program that were recommended for SAR (0.147) was significantly different from the proportion of patients who remained in the hospital (0.361). Further, of those patients who received a recommendation, only 1 patient in the Hospital at Home group was discharged to SAR, while nearly half of those in the control group (proportion = 0.499) were transferred to SAR.

Conclusion

The Hospital at Home program is a promising alternative to traditional inpatient care for patients with certain diagnoses and who meet certain clinical criteria.
CRISPR-based assays for point of need detection and subtyping of influenza
Authors: Zhang Yibin B. , Arizti-Sanz Jon , Bradley A’Doriann , Kosoko-Thoroddsen Tinna-Solveig F. , Sabeti Pardis C. , Myhrvold Cameron
Published: June 2023

The high disease burden of influenza virus poses a significant threat to human health and requires better methods to rapidly detect its many circulating species, subtypes, and variants. No current diagnostic technology meets the combined critical needs for a rapid, sensitive, specific, and cost-effective method for point-of-need (PON) influenza detection and discrimination with minimal equipment requirements. Here, we introduce such a method using SHINE (Streamlined Highlighting of Infections to Navigate Epidemics), a CRISPR-based RNA detection platform. We develop and validate four SHINE assays for the detection and differentiation of clinically relevant influenza species (A and B) and subtypes (H1N1 and H3N2). These optimized assays achieve 100% concordance with reverse-transcriptase real-time polymerase chain reaction (RT-qPCR) when tested on clinical samples. We also created duplex Cas12/Cas13 SHINE assays to simultaneously detect two targets and demonstrate its use in discriminating two alleles of an oseltamivir resistance (H275Y) mutation as well as to detect influenza A and human RNAse P, as a built-in internal control. Our assays have the potential to expand influenza detection outside of clinical laboratories in order to enhance influenza diagnosis and surveillance.
Newborn Care Practices in Health Facilities of Nepal: A Further Analysis from Nepal Health Facility Survey 2015 and 2021
Authors: Pandey Achyut Raj , Adhikari Bikram , Lamichhane Bipul , Dulal Bishnu , Saugat Pratap KC , Joshi Deepak , Baral Sushil Chandra
Published: June 2023

Introduction

Increased availability of Newborn care practices in health facilities (HFs) plays an important role in improving the survival and well-being of newborns. In this paper, we aimed to determine newborn care practices among HFs between 2015 and 2021, and associated factors among public and private HFs in Nepal.

Methods

We performed a secondary analysis of Nepal Health Facility Surveys 2015 and 2021. We summarized categorical variables with a weighted percent and 95% confidence interval (CI). We compared proportions using the z-test of proportion and reported differences in percentage points, 95% CI, and p-value. We applied univariate and multivariable logistic regression analysis to determine the association of the availability of seven newborn care practices.

Results

The percentage of facilities with all seven newborn care practices was 50.5% (95% CI: 44.6, 56.3) in 2015 and 83.7% (95%CI: 79.8, 87.0) in 2021 with an overall increase of 34.2 percent points (95% CI: 27.9, 38.7). The availability of all seven newborn care practices significantly increased from 2015 to 2021 in each subcategory of the ecological region, all provinces except Madhesh, and all types of HFs except federal/provincial hospitals. In 2021, private hospitals had lower odds of having all seven newborn care practices compared to federal/provincial hospitals (AOR= 0.17, 95% CI: 0.07, 0.04). Similarly, in 2021, Sudurpaschim province had 2.87 (95% CI: 1.06, 8.31) higher odds of having all seven newborn care practices compared to Koshi province. In 2021, newborn care practices did not differ significantly based on ecological belt, quality assurance activities, external supervision, delivery service-related training and frequency of HF meeting.

Conclusion

There was a significant increase in the availability of seven newborn care practices between 2015 and 2021 and in each category of ecological region, province, and type of facility. The type of facility and provinces were associated with the availability of newborn care practices among HFs in Nepal.
Personalized Tacrolimus Dosing After Liver Transplantation: A Randomized Clinical Trial
Authors: Khong Jeffrey , Lee Megan , Warren Curtis , Kim Un Bi , Duarte Sergio , Andreoni Kenneth A. , Shrestha Sunaina , Johnson Mark W. , Battula Narendra R. , McKimmy Danielle M. , Beduschi Thiago , Lee Ji-Hyun , Li Derek M. , Ho Chih-Ming , Zarrinpar Ali
Published: June 2023

Background

Inter- and intra-individual variability in tacrolimus dose requirements mandates empirical clinician-titrated dosing that frequently results in deviation from a narrow target range. Improved methods to individually dose tacrolimus are needed. Our objective was to determine whether a quantitative, dynamically-customized, phenotypic-outcome-guided dosing method termed Phenotypic Personalized Medicine (PPM) would improve target drug trough maintenance.

Methods

In a single-center, randomized, pragmatic clinical trial (NCT03527238), 62 adults were screened, enrolled, and randomized prior to liver transplantation 1:1 to standard-of-care (SOC) clinician-determined or PPM-guided dosing of tacrolimus. The primary outcome measure was percent days with large (>2 ng/mL) deviation from target range from transplant to discharge. Secondary outcomes included percent days outside-of-target-range and mean area-under-the-curve (AUC) outside-of-target-range per day. Safety measures included rejection, graft failure, death, infection, nephrotoxicity, or neurotoxicity.

Results

56 (29 SOC, 27 PPM) patients completed the study. The primary outcome measure was found to be significantly different between the two groups. Patients in the SOC group had a mean of 38.4% of post-transplant days with large deviations from target range; the PPM group had 24.3% of post-transplant days with large deviations; (difference -14.1%, 95% CI: -26.7 to -1.5 %, P=0.029). No significant differences were found in the secondary outcomes. In post-hoc analysis, the SOC group had a 50% longer median length-of-stay than the PPM group [15 days (Q1-Q3: 11-20) versus 10 days (Q1-Q3: 8.5-12); difference 5 days, 95% CI: 2-8 days, P=0.0026].

Conclusions

PPM guided tacrolimus dosing leads to better drug level maintenance than SOC. The PPM approach leads to actionable dosing recommendations on a day-to-day basis.

Lay Summary

In a study on 62 adults who underwent liver transplantation, researchers investigated whether a new dosing method called Phenotypic Personalized Medicine (PPM) would improve daily dosing of the immunosuppression drug tacrolimus. They found that PPM guided tacrolimus dosing leads to better drug level maintenance than the standard-of-care clinician-determined dosing. This means that the PPM approach leads to actionable dosing recommendations on a day-to-day basis and can help improve patient outcomes.
Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson’s disease: A follow-up study
Authors: Hong Chien-Tai , Chung Chen-Chih , Yu Ruan-Ching , Chan Lung
Published: June 2023

Synaptic dysfunction plays a key role in Parkinson’s disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. This study assessed the efficacy of plasma EV synaptic proteins as biomarkers in PD and their association with disease progression. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in unified PD rating scale (UPDRS) part II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS part II score and the postural instability and gait disturbance subscore in UPDRS part III than did the other PwP after adjustment for age, sex, and disease duration. These results indicate the promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers.
Burnout among labor and birth providers in northern Tanzania: A mixed-method study
Authors: Marchand Virginie , Watt Melissa H. , Minja Linda M. , Barabara Mariam L. , Mlay Janeth , Stephens Maya J. , Hanson Olivia , Mmbaga Blandina T. , Cohen Susanna R.
Published: June 2023

Burnout, characterized by emotional exhaustion, depersonalization, and a diminished sense of accomplishment, is a serious problem among healthcare workers. Burnout negatively impacts provider well-being, patient outcomes, and healthcare systems globally, and is especially worrisome in settings with a shortage of healthcare workers and resources. The goal of this study is to explore the experience of burnout in a population of labor and delivery (L&D) providers in Tanzania. We examined burnout using three data sources. A structured assessment of burnout was collected at four time points from a sample of 60 L&D providers in six clinics. The same providers participated in an interactive group activity from which we drew observational data on burnout prevalence. Finally, we conducted in-depth interviews (IDIs) with a subset of 15 providers to further explore their experience of burnout. At baseline, prior to any introduction to the concept, 18% of respondents met criteria for burnout. Immediately after a discussion and activity on burnout, 62% of providers met criteria. One- and three-months later, 29% and 33% of providers met criteria, respectively. In IDIs, participants saw the lack of understanding of burnout as the cause for low baseline rates and attributed the subsequent decrease in burnout to newly acquired coping strategies. The activity helped providers realize they were not alone in their experience of burnout. High patient load, low staffing, limited resources, and low pay emerged as contributing factors. Burnout was prevalent among a sample of L&D providers in northern Tanzania. However, a lack of exposure to the concept of burnout leads to providers being unaware of the issue as a collective burden. Therefore, burnout remains rarely discussed and not addressed, thus continuing to impact provider and patient health. Previously validated burnout measures cannot adequately assess burnout without a discussion of the context.
Pilot study of a ketogenic diet in bipolar disorder
Authors: Needham Nicole , Campbell Iain H , Grossi Helen , Kamenska Ivana , Rigby Benjamin P , Simpson Sharon A , McIntosh Emma , Bahuguna Pankaj , Meadowcroft Ben , Creasy Frances , Mitchell-Grigorjeva Maja , Norrie John , Gibbs Melissa C , McLellan Ailsa , Fisher Cheryl , Moses Tessa , Burgess Karl , Brown Rachel , Thrippleton Michael , Campbell Harry , Smith Daniel J
Published: June 2023

Background

Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. To date, no clinical trials have been conducted.

Aims

To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.

Methods

Euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet and a range of clinical, economic and functional outcome measures were assessed.

Results

Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet at 6-8 weeks. The completeness of the outcomes dataset was 95% for daily ketone measures, 95% for daily glucose measures and 95% for daily Ecological Momentary Assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (SD= 0.77, Median = 1.1), and 91% of all readings indicated ketosis indicating a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant takingSGLT2-inhibitor medication).

Conclusions

The recruitment and retention of euthymic individuals with bipolar disorder to a 6-8 week ketogenic diet intervention was feasible, with high outcome measure completion rates. The majority of participants reached and maintained ketosis and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Study Registration Number

ISRCTN61613198
Genetic inhibition of angiopoietin-like protein-3, lipoprotein-lipid levels and cardiometabolic diseases
Authors: Gobeil Émilie , Bourgault Jérôme , Mitchell Patricia L. , Houessou Ursula , Gagnon Eloi , Girard Arnaud , Paulin Audrey , Manikpurage Hasanga D. , Couture Christian , Marceau Simon , Bossé Yohan , Thériault Sébastien , Mathieu Patrick , Vohl Marie-Claude , Tchernof André , Arsenault Benoit J.
Published: June 2023

Background

RNA-based, antibody-based and gene editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular diseases (ASCVD) risk. We used Mendelian randomization (MR) to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischemic stroke (IS) and other cardiometabolic diseases.

Methods

We performed RNA-sequencing of 246 explanted liver samples to identify single-nucleotide polymorphisms (SNPs) associated with liver expression ofANGPTL3. We used genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n=35,359). We also identified 647 carriers ofANGPTL3protein-truncating variants (PTVs) associated with lower plasma triglyceride levels in the UK Biobank. We performed two-sample MR using SNPs that influenceANGPTPL3liver expression or ANGPTPL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank.

Results

In two-sample MR studies, common genetic variants influencingANGPTL3hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on LDL cholesterol, a weaker effect on apoB levels and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, carriers of rareANGPTL3PTVs providing lifelong reductions in median plasma triglyceride levels (-0.37 [interquartile range=0.41] mmol/L) had slightly lower apoB levels (-0.06±0.32] g/L) and similar CAD event rate compared to noncarriers (10.2% versus 10.9% in carriers versus noncarriers, p=0.60).

Conclusions

PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencingANGPTL3hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels will likely be required to reduce ASCVD risk.
Shifting patterns of dengue three years after Zika virus emergence in Brazil
Authors: Pinotti Francesco , Giovanetti Marta , de Lima Maricelia Maia , de Cerqueira Erenilde Marques , Alcantara Luiz CJ , Gupta Sunetra , Recker Mario , Lourenço José
Published: June 2023

The Zika virus (ZIKV) emerged in Brazil in 2015, causing large outbreaks across South America and the Caribbean. In the years that followed, many countries in these areas reported exceptionally low circulation of Dengue virus (DENV), which later resurged in 2018-2019. Several hypotheses have been proposed to explain low DENV transmission, yet no consensus has been reached so far. We show that while short-term cross-protection induced by ZIKV can explain the temporary disappearance of DENV, it also predicts, in contrast with observations, a rising mean age of DENV incidence in the post-ZIKV era. We further demonstrate that disease enhancement of DENV, especially in primary infections in ZIKV-positive hosts, is required to remedy these shortfalls. Our results suggest that both population-level immunity to DENV and ZIKV contributed positively to the reduction in mean age of DENV incidence.
Inequity in the face of success: Understanding geographic and wealth-based equity in success of facility-based delivery for under-5 mortality reduction in six countries
Authors: Ntawukuriryayo Jovial Thomas , VanderZanden Amelia , Amberbir Alemayehu , Teklu Alula , Huda Fauzia Akhter , Maskey Mahesh , Sall Mohamadou , Garcia Patricia J , Subedi Raj Kumar , Felix Sayinzoga , Hirschhorn Lisa R , Binagwaho Agnes
Published: June 2023

Background

Between 2000-2015, many low- and middle-income countries (LMICs) implemented evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M). Even among LMICs successful in reducing U5M, this drop was unequal subnationally, with varying success in EBI implementation. Building on mixed methods multi-case studies of six LMICs (Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal) leading in U5M reduction, we describe geographic and wealth-based equity in facility-based delivery (FBD), a critical EBI to reduce neonatal mortality which requires a trusted and functional health system, and comparethe implementation strategies and contextual factors which influenced success or challenges within and across the countries.

Methods

To obtain equity gaps in FBD coverage and changes in absolute geographic and wealth-based equity between 2000-2015, we calculated the difference between the highest and lowest FBD coverage across subnational regions and in the FBD coverage between the richest and poorest wealth quintiles. We extracted and compared contextual factors and implementation strategies associated with reduced or remaining inequities from the country case studies.

Results

The absolute geographic and wealth-based equity gaps decreased in three countries, with greatest drops in Rwanda – decreasing from 50% to 5% across subnational regions and from 43% to 13% across wealth quintiles. The largest increases were seen in Bangladesh – from 10% to 32% across geography – and in Ethiopia – from 22% to 58% across wealth quintiles. Facilitators to reducing equity gaps across the six countries included leadership commitment and culture of data use; in some countries, community or maternal and child health insurance was also an important factor (Rwanda and Peru). Barriers across all the countries included geography, while country-specific barriers included low female empowerment subnationally (Bangladesh) and cultural beliefs (Ethiopia). Successful strategies included building on community health worker (CHW) programs, with country-specific adaptation of pre-existing CHW programs (Rwanda, Ethiopia, and Senegal) and cultural adaptation of delivery protocols (Peru). Reducing delivery costs was successful in Senegal, and partially successful in Nepal and Ethiopia.

Conclusion

Variable success in reducing inequity in FBD coverage among countries successful in reducing U5M underscores the importance of measuring not just coverage but also equity. Learning from FBD interventions shows the need to prioritize equity in access and uptake of EBIs for the poor and in remote areas by adapting the strategies to local context.
Modifying gut integrity and microbiome in children with severe acute malnutrition using legume-based feeds (MIMBLE II): A Phase II trial
Authors: Walsh Kevin , Kiosia Agklinta , Olupot-Oupot Peter , Okiror William , Ssenyond Tonny , Okalebo Charles Bernard , Muhindo Rita , Mpoya Ayub , George Elizabeth C , Frost Gary , Maitland Kathryn
Published: June 2023

Background

Children hospitalised with severe malnutrition (SM) have high mortality and relapse/readmission rates. Current milk-based formulations targets restoring ponderal growth but not modification of gut barrier integrety or microbiome which increase risk of gram-negative sepsis and poor outcomes.

Objectives

We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes.

Methods

We conducted at Mbale Regional Referral Hospital, Uganda an open-label Phase II trial involving 160 Ugandan children with SM (mid-upper arm circumference (MUAC) <11.5cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n=80) versus WHO standard F75/F100 feeds (n=80). Co-primary outcomes were change in MUAC and mortality to Day 90. Secondary outcomes included weight gain (>5 g/kg/day),de novodevelopment of diarrhoea, time to diarrhoea and oedema resolution.

Findings

Increase in Day 90 MUAC was similar in LF and WHO arms (1.1 cm (interquatile range.IQR 1.1) vs 1.4cm (IQR 1.40) p=0.09. Day 90 mortality was similar 11/80 (13.8%) vs 12/80 (15%) respectively OR 0.91 (0.40 -2.07) p=0.83. There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the legume feed 10 children switched to WHO feeds. Per protocol analysis indicated a non-significant trend to lower Day 90 mortality and readmission rates in the legume feed (6/60: (10%) and (2/60: 3%) vs WHO feeds (12/71: 17.5%) and (4/71: 6%) respectively.

Conclusion

Further refinement of legume feeds and clinical trials are warrented given the poor outcomes in children with severe malnutrition.

Trial registration

ISRCTN 10309022.

Funding

Confidence in Concepts – Joint Translational Fund 2017(Imperial College, London)
Interpretable Speech Features vs. DNN Embeddings: What to Use in the Automatic Assessment of Parkinson’s Disease in Multi-lingual Scenarios
Authors: Favaro Anna , Tsai Yi-Ting , Butala Ankur , Thebaud Thomas , Villalba Jesús , Dehak Najim , Moro-Velázquez Laureano
Published: June 2023

Individuals with Parkinson’s disease (PD) develop speech impairments that deteriorate their communication capabilities. Speech-based approaches for PD assessment rely on feature extraction for automatic classification or detection. It is desirable for these features to be interpretable to facilitate their development as diagnostic tools in clinical environments. However, many studies propose detection techniques based on non-interpretable embeddings from Deep Neural Networks since these provide high detection accuracy, and do not compare them with the performance of interpretable features for the same task. The goal of this work was twofold: providing a systematic comparison between the predictive capabilities of models based on interpretable and non-interpretable features and exploring the language robustness of the features themselves. As interpretable features, prosodic, linguistic, and cognitive descriptors were employed. As non-interpretable features, x-vectors, Wav2Vec 2.0, HuBERT, and TRILLsson representations were used. To the best of our knowledge, this is the first study applying TRILLsson and HuBERT to PD detection. Mono-lingual, multi-lingual, and cross-lingual machine learning experiments were conducted on six data sets. These contain speech recordings from different languages: American English, Castilian Spanish, Colombian Spanish, Italian, German, and Czech. For interpretable feature-based models, the mean of the best F1-scores obtained from each language was 81% in mono-lingual, 81% in multi-lingual, and 71% in cross-lingual experiments. For non-interpretable feature-based models, instead, they were 85% in mono-lingual, 88% in multi-lingual, and 79% in cross-lingual experiments. On one hand, models based on non-interpretable features outperformed interpretable ones, especially in cross-lingual experiments. Among the non-interpretable features used, TRILLsson provided the most stable and accurate results across tasks and data sets. Conversely, the two types of features adopted showed some level of language robustness in multi-lingual and cross-lingual experiments. Overall, these results suggest that interpretable feature-based models can be used by clinicians to evaluate the evolution and the possible deterioration of the speech of patients with PD, while non-interpretable feature-based models can be leveraged to achieve higher detection accuracy.

Highlights

Both interpretable and non-interpretable features displayed robust behaviors.

Models based on non-interpretable features outperformed interpretable ones.

Interpretable feature-based models provide insights into speech and language deterioration.

Non-interpretable feature-based models can be used to achieve higher detection accuracy.
Unveiling Women’s Experiences Amidst the COVID-19 Pandemic in Nigeria: An Interpretive phenomenological analysis
Authors: Ndu M. , Teachman G. , Martin J. , Nouvet E.
Published: June 2023

Background

The past three years have seen an increasing gap in health inequalities in Nigeria’s health systems, with many women having trouble accessing health care due to persistent social determinants of health. Studies indicate that the amplified impact of the pandemic is due to the lack of contextual focus on response plans. This study used an interpretive phenomenological analysis to analyze women’s experiences with healthcare as the pandemic progressed in Nigeria.

Methods

Semi-structured interviews were conducted between August to November 2022. It was supplemented with three focus group discussions with mothers. The mothers were purposively recruited for their experiences with health care during the pandemic. The analysis of the interviews followed the interpretive phenomenological analysis approach.

Results

Twenty-four women aged 15 to 49 years with children between 0 and 5 years participated in this study. These women reported mixed experiences during the pandemic, with many attributing positive health behaviours to the pandemic. Following analysis, four themes emerged: i) Influence of diversity of Healthcare Practices and Beliefs on health-seeking behaviour; ii) Unpacking Systemic Barriers to Seeking Timely and Appropriate Health Care Services; iii) Women’s fear of contracting COVID-19; iv) Socioeconomic Burden for Holistic Health Care Delivery.

Conclusion

Health planners must examine contextual factors that drive health usage, especially potentially changing gender dynamics ahead of the next pandemic. This paper examined women’s decision to seek or not seek care, the type of care they received, and where they went for care. Women felt that the pandemic affected their decision to seek or not seek care. However, while they learned new behaviours that are now integrated into their daily lives, they also indicate that some behaviours are habitual and have persisted through the pandemic.
Seasonal purchase of antihistamines and ovarian cancer risk in the Cancer Loyalty Card Study (CLOCS): results from an observational case-control study
Authors: Brewer Hannah R. , Jiang Qianhui , Sundar Sudha , Hirst Yasemin , Flanagan James M.
Published: June 2023

Objective

Antihistamine use has previously been associated with a reduction in incidence of ovarian cancer, particularly in pre-menopausal women. Herein, we investigate antihistamine exposure in relation to ovarian cancer risk using a novel data resource by examining purchase histories from retailer loyalty card data.

Study Design

A subset of participants from the Cancer Loyalty Card Study (CLOCS) for which purchase histories were available were analysed in this study. Cases (n=153) were women in the UK with a first diagnosis of ovarian cancer between Jan 2018 – Jan 2022. Controls (n=120) were women in the UK without a diagnosis of ovarian cancer. Up to 6 years of purchase history was retrieved from two participating high street retailers from 2014-2022.

Main outcome measures

Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for ovarian cancer associated with antihistamine purchases, ever versus never, adjusting for age and oral contraceptive use. The association was stratified by season of purchase, age over and under 50 years, ovarian cancer histology, and family history.

Results

Ever purchasing antihistamines was not significantly associated with ovarian cancer overall in this small study (OR:0.68, 95% CI: 0.39,1.19). However, antihistamine purchases were significantly associated with reduced ovarian cancer risk when purchased only in spring and/or summer (OR: 0.37, 95% CI: 0.17,0.82) compared with purchasing all year (OR: 0.99, 95% CI: 0.51,1.92). In the stratified analysis, the association was strongest in non-serous ovarian cancer (OR: 0.41, 95% CI:0.18,0.93).

Conclusions

Antihistamine purchase is associated with reduced ovarian cancer risk when purchased seasonally in spring and summer. However, larger studies and more research is required to understand the mechanisms of reduced ovarian cancer risk related to seasonal purchases of antihistamines and allergies.
Multi-omic transcriptional, brain, and clinical variations in schizophrenia
Authors: Cui Long-Biao , Zhao Shu-Wan , Zhang Ya-Hong , Chen Kun , Fu Yu-Fei , Qi Ting , Wang Mengya , Fan Jing-Wen , Gu Yue-Wen , Liu Xiao-Fan , Li Xiao-Sa , Wu Wen-Jun , Wu Di , Wang Hua-Ning , Liu Yong , Yin Hong , van den Heuvel Martijn P. , Wei Yongbin
Published: June 2023

How genetic risk variants may relate to brain abnormalities is crucial for understanding cross-scale pathophysiological mechanisms underlying schizophrenia. The present study identifies brain structural correlates of variation in gene expression in schizophrenia and its clinical significance. Of 43 patients with schizophrenia, RNA-seq data from blood samples, MRI, and clinical assessments were collected, together with data from 60 healthy controls. Gene expression differentiation between schizophrenia and health controls was assessed and cross-referenced to schizophrenia-related genomic variations (GWAS on 76,755 patients and 243,649 controls and GWAS on 22,778 East Asian patients) and brain gene expressions (samples from 559 patients and 175 individuals). Multivariate correlation analysis was employed to examine associations across gene expression, brain volume, and clinical assessments. Differentially expressed genes in blood samples from patients with schizophrenia were significantly enriched for genes previously reported in genome-wide association studies on schizophrenia (P= 0.002, false discovery rate corrected) and were associated with gene expression differentiation in the brain (P= 0.016, 5,000 permutations). Transcriptional levels of differentially expressed genes were found to significantly correlate with gray matter volume in the frontal and temporal regions of cognitive brain networks in schizophrenia (q< 0.05, false discovery rate corrected). A significant correlation was further observed between gene expression, gray matter volume, and performance in the Wechsler Adult Intelligence Scale test (P= 0.031). Our findings suggest that genomic variations in schizophrenia are associated with differentiation in the blood transcriptome, which further plays a role in individual variations in macroscale brain structure and cognition.
Optimization of nutritional strategies using a mechanistic computational model in prediabetes: Application to the J-DOIT1 study data
Authors: Chen Julia H. , Fukasawa Momoko , Sakane Naoki , Suganuma Akiko , Kuzuya Hideshi , Pandey Shikhar , D’Alessandro Paul , Venkatapurapu Sai Phanindra , Dwivedi Gaurav
Published: June 2023

Lifestyle interventions have been shown to prevent or delay the onset of diabetes; however, inter-individual variability in responses to such interventions makes lifestyle recommendations challenging. We analyzed the Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) study data using a previously published mechanistic simulation model of type 2 diabetes onset and progression to understand the causes of inter-individual variability and to optimize dietary intervention strategies at an individual level. J-DOIT1, a large-scale lifestyle randomized intervention study, involved 2607 subjects with a 4.2-year median follow-up period. We selected 112 individuals from the J-DOIT1 study and calibrated the mechanistic model to each participant’s body weight and HbA1c time courses. We evaluated the relationship of physiological (e.g., insulin sensitivity) and lifestyle (e.g., dietary intake) parameters with variability in outcome. Finally, we used simulation analyses to predict individually optimized diets for weight reduction. The model predicted individual body weight and HbA1c time courses with a mean (±SD) prediction error of 1.0 kg (±1.2) and 0.14% (±0.18), respectively. Individuals with the most and least improved biomarkers showed no significant differences in model-estimated energy balance. A wide range of weight changes was observed for similar model-estimated caloric changes, indicating that caloric balance alone may not be a good predictor of body weight. The model suggests that a set of optimal diets exists to achieve a defined weight reduction, and this set of diets is unique to each individual. Our diabetes model can simulate changes in body weight and glycemic control as a result of lifestyle interventions. Moreover, this model could help dieticians and physicians to optimize personalized nutritional strategies according to their patients’ goals.
Mudan Granules for Diabetic Peripheral Neuropathy: A Systematic Review of Preclinical and Clinical Evidence
Authors: Zhou Jianlong , Zhu Lv , Li Yadi
Published: June 2023

Background

Mudan granules has been used in China to treat diabetic peripheral neuropathy (DPN), but there is a lack of systematic review of reports in this area. The aim of this systematic review was to evaluate the efficacy and safety of Mudan granules in the treatment of diabetic peripheral neuropathy.

Methods

Initial studies were searched from PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), VIP database, Wanfang electronic databases. The Cochrane Risk of Bias tool was used to evaluate the risk of bias. The meta-analysis was performed by Stata 16.0 software. For dichotomous and continuous outcomes, the relative risk (RR) and standardized mean difference (SMD) with 95% confidence interval (CI) were conducted, respectively.

Results

51 randomized controlled trials (RCTs) involving 5,416 patients were included. In the meta-analysis, compared with routine treatment (RT) alone, Mudan granules plus RT reduced Toronto clinical scoring system (TCSS) score (SMD, −0.52; 95% CI, −0.66 to −0.38;P< 0.01), total symptoms score (TSS) (SMD, −1.44; 95% CI, −2.88 to −0.00;P= 0.05), serum homocysteine (Hcy) levels (SMD, - 3.84; 95% CI, −5.99 to −1.70;P< 0.01), serum high sensitive C-reactive protein (hs-CRP) levels (SMD, −1.68; 95% CI, −3.29 to −0.08;P= 0.04), and improved total clinical efficacy (RR, 1.23; 95% CI, 1.19 to 1.27;P< 0.01) and serum superoxide dismutase (SOD) levels (SMD, 1.54; 95% CI, 1.13 to 1.95;P< 0.01). Besides, Mudan granules presented an adjuvant efficacy on median motor nerve conduction velocity (SMD, 1.61; 95% CI, 1.16 to 2.07), median sensory nerve conduction velocity (SMD, 1.73; 95% CI, 1.26 to 2.20), common peroneal motor nerve conduction velocity (SMD, 1.48; 95% CI, 1.10 to 1.86), common peroneal sensory nerve conduction velocity (SMD, 1.57; 95% CI, 1.23 to 1.92), tibial motor nerve conduction velocity (SMD, 1.34; 95% CI, 0.82 to 1.87), and tibial sensory nerve conduction velocity (SMD, 1.03; 95% CI, 0.86 to 1.20). In terms of adverse events, there was no statistically significant difference between the trial group and the control group (P=0.87). Five preclinical studies were also retrieved for the study. Animal studies have shown that Mudan granules have anti-oxidative stress effects and could reduce the inflammatory response. It may improve peripheral nerve injury in diabetic rats by modulating the TLR4/MyD88/NF-κB pathway, TLR4/p38 MAPK pathway and PI3K/AKT pathway.

Conclusions

Mudan granules presented an adjuvant efficacy on patients with DPN and could improve the oxidative stress and inflammatory levels in preclinical models. However, high-quality original studies are needed to further prove the evidence.
Hypothalamic subunit volumes in schizophrenia and bipolar spectrum disorders
Authors: Ruggeri Aurora , Nerland Stener , Mørch-Johnsen Lynn , Nordbø Jørgensen Kjetil , Barth Claudia , Wortinger Laura , Andreou Dimitrios , Andreassen Ole A. , Agartz Ingrid
Published: June 2023

Background

The hypothalamus is central to many hormonal and autonomous nervous system pathways. Emerging evidence indicates that these pathways may be disrupted in schizophrenia and bipolar disorder. Yet, few studies have examined the volumes of hypothalamic subunits in these patient groups. We compared hypothalamic subunit volumes in individuals with psychotic disorders to healthy controls.

Study Design

We included 344 patients with schizophrenia spectrum disorders (SCZ), 340 patients with bipolar disorders (BPD) and 684 age-and-sex-matched healthy controls (CTR). Total hypothalamus and five hypothalamic subunit volumes were extracted from T1-weighted MRI using an automated Bayesian segmentation method. Regression models, corrected for age, age2, sex, and segmentation-based intracranial volume (sbTIV), were used to examine diagnostic group differences, interactions with sex, and associations with clinical symptoms, antipsychotic medication, antidepressants and mood stabilizers.

Study Results

SCZ had larger volumes in the left inferior tubular subunit and smaller right anterior inferior, right anterior superior and right posterior hypothalamic subunits compared to CTR. BPD did not differ significantly from CTR for any hypothalamic subunit volume, however, there was a significant sex-by-diagnosis interaction. Analyses stratified by sex showed smaller right hypothalamus and right posterior subunit volumes in male patients, but not female patients, relative to same-sex controls. There was a significant association between BPD currently taking antipsychotic medication and the left inferior tubular subunits volumes.

Conclusions

Our results show regional-specific alterations in hypothalamus subunit volumes in individuals with SCZ, with relevance to HPA-axis dysregulation, circadian rhythm disruption and cognition impairment.

Highlights

Smaller right anterior-inferior, right anterior superior, right posterior and larger left inferior tubular subunit volumes were observed in individuals with schizophrenia spectrum disorders compared to healthy controls.

Smaller total right hypothalamus volume and smaller right posterior subunit volumes were found for males, but not females, with bipolar disorders.

There were no significant associations with clinical symptom dimensions.

Larger left inferior tubular subunits volumes were observed in individuals with bipolar disorders currently taking antipsychotic medication.
Molecular counting enables accurate and precise quantification of methylated ctDNA for tumor-naive cancer therapy response monitoring
Authors: Ye Patrick Peiyong , Viens Robb Andrew , Shelburne Katherine Elise , Langpap Sydne Scot , Bower Xavier Scott , Zhou Wen , Wignall Jan Christian , Zhu Joyce Jiawei , Woodward Brian D , Husain Hatim , Tsao David S , Atay Oguzhan
Published: June 2023

Personalized cancer treatment can significantly extend survival and improve quality of life for many patients, but accurate and real-time therapy response monitoring remains challenging. To overcome logistical and technical challenges associated with using imaging scans or assays that track the variant allele fraction (VAF) of somatic mutations in circulating tumor DNA (ctDNA) for response monitoring, we developed a tumor-naive liquid biopsy assay that leverages quantitative counting template (QCT) technology to accurately and precisely quantify methylated ctDNA (Northstar ResponseTM). Northstar ResponseTMachieves <10% coefficient of variation at 1% tumor fraction, which is 2x lower than VAF-based response monitoring approaches. The assay accurately distinguishes 0.25% absolute changes in contrived tumor fraction (AUC > 0.94) and performs well in 12 solid tumor types. Preliminary clinical results from patients with lung, colorectal, or pancreatic cancer demonstrate that Northstar ResponseTMdetects changes in ctDNA methylation that correlate with clinical outcomes. As a novel tool for therapy response monitoring, the assay’s serial measurements of ctDNA methylation can be precise, reflect clinical outcomes, and have potential to inform clinical decision making for cancer treatment.
Predicting Ventricular Tachycardia Circuits in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy using Genotype-specific Heart Digital Twins
Authors: Zhang Yingnan , Zhang Kelly , Prakosa Adityo , James Cynthia , Zimmerman Stefan L , Carrick Richard , Sung Eric , Gasperetti Alessio , Tichnell Crystal , Murray Brittney , Calkins Hugh , Trayanova Natalia
Published: June 2023

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophysiological (EP) remodeling. Here, we developed a novel genotype-specific heart digital twin (Geno-DT) approach to investigate the role of pathophysiological remodeling in sustaining VT reentrant circuits and to predict the VT circuits in ARVC patients of different genotypes. This approach integrates the patient’s disease-induced structural remodeling reconstructed from contrast-enhanced magnetic-resonance imaging and genotype-specific cellular EP properties. In our retrospective study of 16 ARVC patients with two genotypes: plakophilin-2 (PKP2,n= 8) and gene-elusive (GE,n= 8), we found that Geno-DT accurately and non-invasively predicted the VT circuit locations for both genotypes (with 100%, 94%, 96% sensitivity, specificity, and accuracy for GE patient group, and 86%, 90%, 89% sensitivity, specificity, and accuracy forPKP2patient group), when compared to VT circuit locations identified during clinical EP studies. Moreover, our results revealed that the underlying VT mechanisms differ among ARVC genotypes. We determined that in GE patients, fibrotic remodeling is the primary contributor to VT circuits, while inPKP2patients, slowed conduction velocity and altered restitution properties of cardiac tissue, in addition to the structural substrate, are directly responsible for the formation of VT circuits. Our novel Geno-DT approach has the potential to augment therapeutic precision in the clinical setting and lead to more personalized treatment strategies in ARVC.
Protein Vaccine Demonstrates Less Reactogenicity than mRNA – A Real World Study
Authors: Rousculp Matthew , Ziemiecki Ryan , Marchese Anthony M.
Published: June 2023

A prospective, observational study investigated the burden and impact of vaccine reactogenicity in adults from the United States and Canada who received an approved/authorized mRNA COVID-19 vaccine or the Novavax COVID vaccine as a booster dose. As part of the real-world study, reactogenic events captured via patient symptom diaries were compared. Results demonstrated that the overall percentage of Novavax COVID booster recipients experiencing any reactogenicity event (77.6%) was lower than that of mRNA doses (95.9%).