bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does the Urethra Respond to Bladder Filling in Continent and Incontinent Women?
Authors: Geynisman-Tan Julia , Mou Tsung , Mueller Margaret G. , Kenton Kimberly
Published: December 2021

Objective

The objective of this study was to describe mean urethral pressure (MUP) during filling cystometry in continent and incontinent women.

Methods

Incontinent women were recruited from a urogynecology clinic if they answered “sometimes” or “always” to 1 of the items on the Medical, Epidemiologic, and Social Aspects of Aging questionnaire. Participants were categorized by Medical, Epidemiologic, and Social Aspects of Aging scores into stress urinary incontinence (SUI) or urgency urinary incontinence (UUI) groups. Continent women were recruited from the community. Multichannel urodynamics were performed using microtip catheters. Urethral pressure profiles were obtained with an empty bladder and at 100-mL increments during filling. Data were analyzed in SPSS. Continuous variables were compared with independent t test or analysis of variance, categorical variables with the χ2 test, and multivariable comparisons were made with linear regression.

Results

Eighty-six women (30 continent, 56 incontinent: 37 SUI, 19 UUI) with a mean ± SD age of 48 ± 15 years and a body mass index (BMI) of 31 ± 9 participated. Sixty-nine percent were White, 43% were postmenopausal, and 80% were parous. Continent women were younger (P < 0.001) and had a lower BMI (P = 0.004). Mean cystometric capacity was higher in women with SUI and continent women than in women with UUI (430 ± 142, 448 ± 101, and 332 ± 160, P = 0.04). Continent women had higher MUP at baseline when controlling for age, BMI, and parity (84 ± 35 cmH2O vs 62 ± 28 cmH2O; aR2 = 0.2, P = 0.02) compared with incontinent women. During filling, MUP in continent women was 20–30 cmH2O higher at all bladder volumes than incontinent women. Mean urethral pressure increased significantly between baseline and 300 mL in continent women (P < 0.005) and women with SUI (P = 0.04), but not in women with UUI (P = 0.48).

Conclusions

Continent women have greater baseline MUP and greater increases in MUP during bladder filling than incontinent women.
Influence of sex hormones on vestibular disorders
Authors: Mucci Viviana , Hamid Mohamed , Jacquemyn Yves , Browne Cherylea J.
Published: December 2021

Purpose of review

Vestibular disorders are gender distributed with a higher prevalence in women. Although research has increased in this field, the mechanisms underlying this unbalance is unclear. This review summarises recent advances in this research sphere, and briefly discusses sex hormone effects on various vestibular conditions and highlights some recent theories.

Recent findings

Recent work has identified a direct link between aberrant gonadal hormone levels and vestibular dysfunction. Benign paroxysmal positional vertigo research suggests that the disorder may be linked to the rapid decrease in oestrogen, observed in menopausal women, which disrupts otoconial metabolism within the inner ear. A successful hormonal therapeutic intervention study has advanced our knowledge of hormonal influences in the inner ear in Ménière's disease. Also, several studies have focused on potential mechanisms involved in the interaction between Vestibular Migraine, Mal de Debarquement Syndrome, and gonadal hormones.

In females, gonadal hormones and sex-specific synaptic plasticity may play a significant role in the underlying pathophysiology of peripheral and central vestibular disorders. Overall, this review concludes that clinical assessment of female vestibular patients requires a multifaceted approach which includes auditory and vestibular medicine physicians, gynaecologists and/or endocrinologists, in conjunction with hormonal profile evaluations.
Ménière's disease: new guidelines, subtypes, imaging, and more
Authors: Hoskin Justin L.
Published: December 2021

Purpose of review

This article reviews recent developments in Ménière's disease including etiologic, diagnostic, and therapeutic investigations that have changed the landscape for medical providers. These updates shed light onto the complex nature of Ménière's disease and generate additional means to provide optimal care to patients.

Recent findings

Given the multifactorial cause of Ménière's disease, five subtypes of Ménière's disease have recently been proposed. A knowledge of these subtypes will aid in the development of an appropriate treatment algorithm. Although newer treatments have not been developed, stepwise treatment algorithms have been proposed and can improve patient care. New MRI modalities and serum testing hold promise as clinical clues and biomarkers.

As these updated diagnostic criteria are used, Ménière's disease can be identified and treated more precisely. This will in turn allow for future randomized controlled studies to improve the quality of treatment options available. Future imaging, vestibular testing, and the potential for serum biomarkers may illuminate additional diagnostic criteria, only furthering the improvement in clinical care.
Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerability
Authors: Zarezadeh Faezeh , Arbabi Mohammad , Shamabadi Ahmad , Naderi Sina , Hasanzadeh Alireza , Ostadpour Mahsa , Samsami Faraneh – Sadat , Akhondzadeh Shahin
Published: December 2021

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam’s effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.
Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin
Authors: de Jong Florus C. , Laajala Teemu D. , Hoedemaeker Robert F. , Jordan Kimberley R. , van der Made Angelique C.J. , Boevé Egbert R. , van der Schoot Deric K.E. , Nieuwkamer Bart , Janssen Emiel A.M. , Mahmoudi Tokameh , Boormans Joost L. , Theodorescu Dan , Costello James C. , Zuiverloon Tahlita C.M.
Published: December 2021

The recommended treatment for patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvantBacillus Calmette-Guérin(BCG) bladder instillations. However, only 50% of patients benefit from this therapy. In case of progression to advanced disease, patients must undergo a radical cystectomy with significant morbidity and have a poor clinical outcome. Identifying tumors least likely to respond to BCG can translate into alternative treatments, such as early radical cystectomy or novel targeted or immunotherapies. Here we present molecular profiling of 132 BCG-naive, HR-NMIBC patients, and 44 post-BCG recurrences (34 matched), which uncovered three distinct BCG Response Subtypes (BRS1-3). Patients with BRS3 tumors have reduced recurrence and progression-free survival compared to BRS1-2. BRS3 tumors expressed high EMT-basal markers and had an immunosuppresive profile, which was confirmed with spatial proteomics. Tumors which recurred post-BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive HR-NMIBC patients and the molecular subtypes outperformed guideline recommended risk stratification based on clinicopathological variables. For clinical application, we validated that a commercially approved assay was able to accurately predict BRS3 tumors (AUROC 0.86). Our findings provide a potential clinical tool for improved identification of HR-NMIBC patients at the highest risk of progression, which can be used to select patients for early radical cystectomy or novel subtype-directed therapies.

One Sentence Summary

Molecular subtypes are predictive of response to intravesical Bacillus Calmette-Guérin immunotherapy in non-muscle invasive bladder cancer.
Long Term Humoral Immunity Decline in Hemodialysis Patients Following SARS-CoV-2 Vaccination
Authors: Goggins Eibhlin , Sharma Binu , Ma Jennie Z. , Gautam Jitendra , Bowman Brendan
Published: December 2021

Dialysis patients are extremely vulnerable to SARS-CoV-2 infection with high rates of hospitalization and mortality rates estimated at 20-30%. In January of 2021, the University of Virginia Dialysis Program initiated a program wide vaccination campaign administering Pfizer BioNTech mRNA SARS-CoV-2 (BNT162b2) vaccine. To characterize the time-dependent decline in humoral immunity, we performed a prospective cohort study measuring serial monthly semi quantitative IgG antibody levels to the SARS-CoV-2 spike protein receptor binding domain in fully vaccinated in-center hemodialysis patients. Measurements were taken beginning at 2 months post full vaccination through 6 months after full vaccination. Early results showed similar seroconversion rates as prior studies with 88% obtaining positive antibody levels. Those with prior infection obtained the highest antibody levels. Over the ensuing months, patient antibody levels declined at an adjusted average rate of 31% per month. At the conclusion of the study, 40% of patients remaining in the cohort possessed either negative or borderline IgG antibody levels. Projecting future antibody levels based on the slopes of antibody level decay suggests 65% of the cohort will progress to borderline or negative antibody levels at 10 months post full vaccination. In summary, we studied long term vaccine response following vaccination with the BNT162b2 mRNA vaccine in hemodialysis patients. Our data adds to the limited pool of data in this patient population and will help to inform the discussion about vaccine booster needs and frequency.
Comparing human and model-based forecasts of COVID-19 in Germany and Poland
Authors: Bosse Nikos I. , Abbott Sam , Bracher Johannes , Hain Habakuk , Quilty Billy J. , Jit Mark ,   Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, van Leeuwen Edwin , Cori Anne , Funk Sebastian
Published: December 2021

1

Forecasts based on epidemiological modelling have played an important role in shaping public policy throughout the COVID-19 pandemic. This modelling combines knowledge about infectious disease dynamics with the subjective opinion of the researcher who develops and refines the model and often also adjusts model outputs. Developing a forecast model is difficult, resource- and time-consuming. It is therefore worth asking what modelling is able to add beyond the subjective opinion of the researcher alone. To investigate this, we analysed different real-time forecasts of cases of and deaths from COVID-19 in Germany and Poland over a 1-4 week horizon submitted to the German and Polish Forecast Hub. We compared crowd forecasts elicited from researchers and volunteers, against a) forecasts from two semi-mechanistic models based on common epidemiological assumptions and b) the ensemble of all other models submitted to the Forecast Hub. We found crowd forecasts, despite being overconfident, to outperform all other methods across all forecast horizons when forecasting cases (weighted interval score relative to the Hub ensemble 2 weeks ahead: 0.89). Forecasts based on computational models performed comparably better when predicting deaths (rel. WIS 1.26), suggesting that epidemiological modelling and human judgement can complement each other in important ways.
Longitudinal study of DNA methylation and epigenetic clocks prior to and following test-confirmed COVID-19 and mRNA vaccination
Authors: Pang Alina PS , Higgins-Chen Albert T. , Comite Florence , Raica Ioana , Arboleda Christopher , Went Hannah , Mendez Tavis , Schotsaert Michael , Dwaraka Varun , Smith Ryan , Levine Morgan E. , Ndhlovu Lishomwa C. , Corley Michael J.
Published: December 2021

The host epigenetic landscape is rapidly changed during SARS-CoV-2 infection and evidence suggests that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation changes in immune cells and alterations to epigenetic clocks in blood relate to severe COVID-19. However, a longitudinal assessment of DNA methylation states and epigenetic clocks in blood from healthy individuals prior to and following test-confirmed non-hospitalized COVID-19 has not been performed. Moreover, the impact of mRNA COVID-19 vaccines upon the host epigenome remains understudied. Here, we first examined DNA methylation states in blood of 21 participants prior to and following test confirmed COVID-19 diagnosis at a median timeframe of 8.35 weeks. 261 CpGs were identified as differentially methylated following COVID-19 diagnosis in blood at an FDR adjusted P value <0.05. These CpGs were enriched in gene body and northern and southern shelf regions of genes involved in metabolic pathways. Integrative analysis revealed overlap among genes identified in transcriptional SARS-CoV-2 infection datasets. Principal component-based epigenetic clock estimates of PhenoAge and GrimAge significantly increased in people over 50 following infection by an average of 2.1 and 0.84 years. In contrast, PCPhenoAge significantly decreased in people under 50 following infection by an average of 2.06 years. This observed divergence in epigenetic clocks following COVID-19 was related to age and immune cell-type compositional changes in CD4+ T cells, B cells, granulocytes, plasmablasts, exhausted T cells, and naïve T cells. Complementary longitudinal epigenetic clock analyses of 36 participants prior to and following Pfizer and Moderna mRNA-based COVID-19 vaccination revealed vaccination significantly reduced principal component-based Horvath epigenetic clock estimates in people over 50 by an average of 3.91 years for those that received Moderna. This reduction in epigenetic clock estimates was significantly related to chronological age and immune cell-type compositional changes in B cells and plasmablasts pre- and post-vaccination. These findings suggest the potential utility of epigenetic clocks as a biomarker of COVID-19 vaccine responses. Future research will need to unravel the significance and durability of short-term changes in epigenetic age related to COVID-19 exposure and mRNA vaccination.
Genetic Architecture of Heart Failure with Preserved versus Reduced Ejection Fraction
Authors: Joseph Jacob , Hui Qin , Liu Chang , Aragam Krishna , Wang Zeyuan , Charest Brian , Huffman Jennifer E. , Demissie Serkalem , Djousse Luc , Casas Juan P. , Gaziano J. Michael , Cho Kelly , Wilson Peter W.F. , Phillips Lawrence S. ,   VA Million Veteran Program, O’Donnell Christopher J. , Sun Yan V.
Published: December 2021

Background

Pharmacologic clinical trials for heart failure (HF) with preserved ejection fraction (HFpEF) have been largely unsuccessful as compared to those for heart failure with reduced ejection fraction (HFrEF). Whether differences in the genetic underpinnings of these HF subtypes may provide insights into the disparate outcomes of these clinical trials remains unknown.

Objectives

We pursued genetic association analyses to compare the genetic architecture of HFpEF with that of HFrEF.

Methods

We created a non-Hispanic White cohort including 19,495 HFrEF and 19,589 HFpEF cases among 43,344 unclassified HF cases, and 258,943 controls without HF in the Veterans Health Administration Million Veteran Program. We then conducted genome-wide association studies of unclassified HF, HFrEF and HFpEF, followed by genetic correlation analyses and Mendelian randomization analyses of established HF risk factors with HFrEF and HFpEF.

Results

We found 13 loci associated with HFrEF at genome-wide significance, but only one associated with HFpEF. Among genome-wide significant loci for HFrEF, four loci were not associated with any HF risk factor. The single locus identified for HFpEF (FTO) is a known marker for obesity. Genetically determined associations were widely different between HFrEF and HFpEF for several risk factors including coronary artery disease, lipid levels, and pulse pressure.

Conclusions

The modest genetic discovery for HFpEF compared to HFrEF despite a robust sample size indicates that HFpEF, as currently defined, likely represents the amalgamation of several, distinct pathobiological entities. Development of consensus sub-phenotyping of HFpEF is paramount to better dissect the underlying genetic signals and contributors to HFpEF.

Condensed Abstract

We utilized a large, uniformly phenotyped, single cohort of heart failure sub-classified into heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) based on current clinical definitions, to conduct detailed genetic analyses of the two HF sub-types. We found different genetic architectures and distinct genetic association profiles of HFrEF and HFpEF suggesting differences in underlying pathobiology. Furthermore, the low yield of HFpEF genome-wide association study (GWAS) compared to similarly powered HFrEF GWAS underscores the heterogeneity of HFpEF and the urgent need for developing consensus sub-phenotyping of HFpEF to improve the discovery in genetic mechanisms and therapeutic interventions.
Detailed patient-individual reporting of lymph node involvement in oropharyngeal squamous cell carcinoma with an online interface
Authors: Ludwig Roman , Hoffmann Jean-Marc , Pouymayou Bertrand , Morand Grégoire , Däppen Martina Broglie , Guckenberger Matthias , Grégoire Vincent , Balermpas Panagiotis , Unkelbach Jan
Published: December 2021

Purpose/Objective

Whereas the prevalence of lymph node level (LNL) involvement in head & neck squamous cell carcinomas (HNSCC) has been reported, the details of lymphatic progression patterns are insufficiently quantified. In this study, we investigate how the risk of metastases in each LNL depends on the involvement of upstream LNLs, T-category, HPV status and other risk factors.

Materials/Methods

We retrospectively analyzed patients with newly diagnosed oropharyngeal HNSCC treated at a single institution, resulting in a dataset of 287 patients. For all patients, involvement of LNLs I-VII was recorded individually based on available diagnostic modalities (PET, MR, CT, FNA) together with clinicpathological factors. To analyze the dataset, a web-based graphical user interface (GUI) was developed, which allows querying the number of patients with a certain combination of co-involved LNLs and tumor characteristics.

Results

The full dataset and GUI is part of the publication. Selected findings are: Ipsilateral level IV was involved in 27% of patients with level II and III involvement, but only in 2% of patients with level II but not III involvement. Prevalence of involvement of ipsilateral levels II, III, IV, V was 79%, 34%, 7%, 3% for early T-category patients (T1/T2) and 85%, 50%, 17%, 9% for late T-category (T3/T4), quantifying increasing involvement with T-category. Contralateral levels II, III, IV were involved in 41%, 19%, 4% and 12%, 3%, 2% for tumors for tumors with and without midline extension, respectively. T-stage dependence of LNL involvement was more pronounced in HPV negative than positive tumors, but overall involvement was similar. Ipsilateral level VII was involved in 14% and 6% of patients with primary tumors in the tonsil and the base of tongue, respectively.

Conclusions

Detailed quantification of LNL involvement in HNSCC depending on involvement of upstream LNLs and clinicopathological factors may allow for further personalization of CTV-N definition in the future.
Respiratory Syncytial Virus (RSV) RNA in wastewater settled solids reflects RSV clinical positivity rates
Authors: Hughes Bridgette , Duong Dorothea , White Bradley J. , Wigginton Krista R. , Chan Elana M. G. , Wolfe Marlene K. , Boehm Alexandria B.
Published: December 2021

Wastewater based epidemiology (WBE) uses concentrations of infectious agent targets in wastewater to infer infection trends in the contributing community. To date, WBE has been used to gain insight into infection trends of gastrointestinal diseases, but its application to respiratory diseases has been limited to COVID-19. Here we report Respiratory Syncytial Virus (RSV) genomic RNA can be detected in wastewater settled solids at two publicly owned treatment works (POTWs). We further show that its concentration in settled solids is strongly associated with clinical positivity rates for RSV at sentinel laboratories across the state in 2021, a year with anomalous seasonal trends in RSV disease. Given that RSV infections have similar clinical presentations to COVID-19, can be life threatening for some, and immunoprophylaxis distribution for vulnerable people is based on outbreak identification, WBE represents an important tool to augment current RSV surveillance and public health response efforts.

Graphical Abstract

Synopsis

Respiratory Syncytial Virus RNA concentrations in settled solids from wastewater treatment plants are associated with state-wide RSV clinical positivity rates.
The reactogenicity and immunogenicity of a booster dose after the second dose of a protein subunit vaccine MVC-COV1901: An extension to an open-label, dose-escalation, and non-randomized phase 1 study
Authors: Hsieh Szu-Min , Chang Shan-chwen , Cheng Hao-Yuan , Shih Shin-Ru , Lien Chia En
Published: December 2021

The waning antibody levels after immunization and the emergence of SARS-CoV-2 variants of concern (VoC) negatively impact the vaccine-induced neutralization of SARS-CoV-2. In this extension to the phase 1 clinical study, we report the antibody durability until 180 days after the second dose of MVC-COV1901, and examined the reactogenicity and immunogenicity followed by a booster shot MVC-COV1901 administered to 45 healthy adults from 20 to 49 years of age on day 209. Adverse reactions after the booster dose were mostly mild and comparable to that of the first two doses. Neutralizing antibodies remained detectable on day 209 at 59.4, 79.4, and 113.2 (IU/mL) for low dose (LD), middle dose (MD), and high dose (HD) groups, respectively. At four weeks after the booster dose, neutralizing titers increased to 1719.6, 818.3, and 1345.6 for LD, MD, and HD groups, respectively. Our data also showed that three doses of MVC-COV1901-induced antibodies were still effective, albeit lowered neutralizing titers, against the Omicron variant.
Assessment of validity and reliability of the Tuberculosis Related Stigma Scale in Colombian patients
Authors: Castañeda-Daniels Neddy Pamela , Campo-Arias Adalberto , Pedrozo-Pupo John Carlos
Published: December 2021

Objective

To know the dimensionality and internal consistency of the Tuberculosis-Related Stigma Scale in patients living with tuberculosis in Santa Marta, Colombia. Method: One hundred and twenty-two patients between the ages of 18 and 75 participated (M=40.3, SD=14.9), 63.9% were men, 44.3% were single, 69.7% had low income, 80.3% had pulmonary tuberculosis, and 13.1% had co-infection with HIV. The Tuberculosis-Related Stigma Scale was applied; it is composed of two subscales: perceived and internalized stigma. The internal structure was explored by confirmatory factor analysis (EFA). Internal consistency was measured with Cronbach’s alpha and McDonald’s omega. Besides, the differential functioning of the scales according to gender was explored with Kendall’s tau-b coefficient.

Results

CFA did not show excellent goodness-of-fit indicators for the perceived stigma scale (Satorra-Bentler’s chi-square of 184.48, degree of freedom of 44, p=0.001, RMSEA of 0.16, 95%CI 0.14 - 0.19, CFI of 0.77, TLI of 0.72, and SRMR of 0.08) and internalized (Satorra-Bentler’s chi-square of 189.14, degree of freedom of 54, p=0.001; RMSEA of 0.14, 95%CI 0.12 - 0.17, CFI of 0.82, TLI of 0.78, and SRMR of 0.07). The alpha and omega coefficients were 0.89 and 0.91 for both scales, respectively. Non-gender differential functioning was observed; Kendall’s tau-b were between 0.00 and 0.15.

Conclusions

The Tuberculosis-Related Stigma Scale has an excellent internal consistency but poor goodness-of-fit indicators of unidimensionality. Evaluating the scale’s psychometric performance is recommenced in future research.
My family sold a cow to pay for my Traditional doctor and now there’s no money to travel to the HIV clinic: barriers to antiretroviral adherence among rural-Indigenous peoples living with HIV in the Comarca Ngäbe-Buglé, Panamá
Authors: Gabster Amanda , Socha Eliana , Pascale Juan Miguel , Talavero Gonzalo Cabezas , Castrellón Alezander , Quiel Yaremis , Gantes César , Mayaud Philippe
Published: December 2021

Introduction

The Comarca Ngäbe-Buglé (CNB) is an administratively autonomous Indigenous region in Western Panama that is home to over 200,000 individuals of Ngäbe and Buglé ethnicities. The CNB is the most impoverished region in Panama and is relatively isolated from outside influences, with limited roads, electricity, and internet connection. Around 1.5% of all rapid HIV tests are positive, compared to a national prevalence of 0.9%; in CNB, diagnosis tends to be late where 56.3% of individuals had an initial CD4 count of <350 cells/mm3. In this region, antiretroviral treatment (ART) dropout is five times higher than the national average; there is high early mortality due to opportunistic infections. This study aims to describe some of the barriers associated with ART adherence and retention in HIV care among PLHIV the CNB. A better understanding of factors that obstruct adherence could lead to more effective HIV care and prevention in CNB.

Methods

We conducted 21 semi-structured interviews with PLHIV who reside across all three regions of the CNB and who have attended an ART clinic at least once. The interviews took place between November 2018 and December 2019.

Discussion

Psychological health and social support and discrimination acted as both individual-level facilitators and barriers to adherence and retention. Notably, structural barriers included difficult access to ART care due to travel costs, ART shortages, and uncooperative Western/Traditional medical systems. Recommended interventions used in other Low- and Middle-Income settings include increasing peer and family-level support and community knowledge and understanding of HIV infection. Additionally, we suggest structural interventions, including decreasing cost and distance of travel to the ART clinic through decentralization of services and multi-month dispensing, decreasing food scarcity, and increasing collaboration between Western and Traditional providers.
Liver Volumetry from Magnetic Resonance Images with Convolutional Neural Networks
Authors: Saunders Sara L. , Clark Justin M. , Rudser Kyle , Chauhan Anil , Ryder Justin R. , Bolan Patrick J.
Published: December 2021

Measurements of liver volume from MR images can be valuable for both clinical and research applications. Automated methods using convolutional neural networks have been used successfully for this using a variety of different MR image types as input. In this work, we sought to determine which types of magnetic resonance images give the best performance when used to train convolutional neural networks for liver segmentation and volumetry.

Abdominal MRI scans were performed at 3 Tesla on 42 adolescents with obesity. Scans included Dixon imaging (giving water, fat, and T2* images) and low-resolution T2-weighted anatomical scans. Multiple convolutional neural network models using a 3D U-Net architecture were trained with different input images. Whole-liver manual segmentations were used for reference. Segmentation performance was measured using the Dice similarity coefficient (DSC) and 95% Hausdorff distance. Liver volume accuracy was evaluated using bias, precision, and normalized root mean square error (NRMSE).

The models trained using both water and fat images performed best, giving DSC = 0.94 and NRMSE = 4.2%. Models trained without the water image as input all performed worse, including in participants with elevated liver fat. Models using the T2-weighted anatomical images underperformed the Dixon-based models, but provided acceptable performance (DSC ≥ 0.92, NMRSE ≤ 6.6%) for use in longitudinal pediatric obesity interventions. The model using Dixon water and fat images as input gave the best performance, with results comparable to inter-reader variability and state-of-the-art methods.
Age-dependent normalisation functions for T-lymphocytes in healthy individuals
Authors: Schröter Juliane , Borghans José A. M. , Bitter W. Marieke , van Dongen Jacques J. M. , de Boer Rob J.
Published: December 2021

Lymphocyte numbers naturally change through age. Normalisation functions to account for this are sparse, and mostly disregard measurements from children in which these changes are most prominent. In this study, we analyse cross-sectional numbers of mainly T-lymphocytes (CD3+, CD3+CD4+ and CD3+CD8+) and their subpopulations (naive and memory) from 673 healthy Dutch individuals ranging from infancy to adulthood (0-62 years). We fitted the data by a delayed exponential function and received parameter estimates for each lymphocyte subset. Our modelling approach follows general laboratory measurement procedures in which absolute cell counts of T-lymphocyte subsets are calculated from observed percentages within a reference population that is truly counted (typically the total lymphocyte count). Consequently, we receive one set of parameter estimates per T-cell subset representing both the trajectories of their counts and percentages. We allow for an initial time delay of half a year before the total lymphocyte counts per µl of blood start to change exponentially, and we find that T-lymphocyte trajectories tend to increase during the first half a year of life. Thus, our study provides functions describing the general trajectories of T-lymphocyte counts and percentages of the Dutch population. These functions provide important references to study T-lymphocyte dynamics in disease, and allow one to quantify losses and gains in longitudinal data, such as the CD4+ T-cell decline in HIV-infected children, and/or the rate of T-cell recovery after the onset of treatment.
Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts
Authors: Betthauser Tobey J. , Bilgel Murat , Koscik Rebecca L. , Jedynak Bruno M. , An Yang , Kellett Kristina A. , Moghekar Abhay , Jonaitis Erin M. , Stone Charles K. , Engelman Corinne D. , Asthana Sanjay , Christian Bradley T. , Wong Dean F. , Albert Marilyn , Resnick Susan M. , Johnson Sterling C. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

Alzheimer’s disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modeling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer’s disease continuum.

Data were acquired from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of Aging (BLSA) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Amyloid PET was used to assess global amyloid burden. Three methods were evaluated for modeling amyloid accumulation using 10-fold cross-validation and hold-out validation where applicable. Estimated amyloid onset age was compared across all three modeling methods and cohorts. Cox regression and accelerated failure time models were used to investigate whether sex, apolipoprotein E genotype and e4 carriage were associated with amyloid onset age in all cohorts. Cox regression was used to investigate whether apolipoprotein E (e4 carriage and e3e3, e3e4, e4e4 genotypes), sex or age of amyloid onset were associated with the time from amyloid onset to impairment onset (global Clinical Dementia Rating ≥1) in a subset of 595 ADNI participants that were not impaired prior to amyloid onset.

Model prediction and estimated amyloid onset age were similar across all three amyloid modeling methods. Sex and apolipoprotein E-e4 carriage were not associated with PET-measured amyloid accumulation rates. Apolipoprotein E genotype and e4 carriage, but not sex, were associated with amyloid onset age such that e4 carriers became amyloid positive at an earlier age compared to non-carriers, and greater e4 dosage was associated with an earlier amyloid onset age. In the ADNI, e4 carriage, being female and a later amyloid onset age were all associated with a shorter time from amyloid onset to impairment onset. The risk of impairment onset due to age of amyloid onset was nonlinear and accelerated for amyloid onset age >65. These findings demonstrate the feasibility of modeling longitudinal amyloid accumulation to enable individualized estimates of amyloid onset age from amyloid PET imaging. These estimates provide a more direct way to investigate the role of amyloid and other factors that influence the timing of clinical impairment in Alzheimer’s disease.
Declines and pronounced state disparities in prescription opioid distribution in the United States
Authors: Madera Joshua D. , Ruffino Amanda E. , Feliz Adriana , McCall Kenneth L. , Davis Corey S. , Piper Brian J.
Published: December 2021

Background

The United States (US) opioid epidemic is a persistent and pervasive public health emergency that now claims the lives of over 100,000 Americans per year. There have been sustained efforts to reverse this crisis over the past decade, including a number of measures designed to decrease the use of prescription opioids for the treatment of pain. This study analyzed the changes in federal production quotas for prescription opioids and the distribution of prescription opioids for pain, and identified state-level differences between 2010 and 2019.

Methods and Findings

Data on opioid production quotas and distribution of ten prescription opioids (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol) for 2010 to 2019 were obtained from the Drug Enforcement Administration. Total opioid production quotas increased substantially from 2010 to 2013 before decreasing 41.5% from 2013 (87.6 morphine mg equivalent metric tons) to 2019 (51.3). The peak year for distribution of all ten prescription opioids was between 2010 and 2013, except for codeine (2015). The largest quantities of opioid distribution were observed in Tennessee (520.70 morphine mg equivalent or MME per person) and Delaware (251.45) in 2011 and 2019. There was a 52.0% overall decrease in opioid distribution per capita from 2010 to 2019, with the largest decrease in Florida (−61.6%) and smallest in Texas (−18.6%). The highest to lowest state ratio of total opioid distribution, corrected for population, decreased from 5.25 in 2011 to 2.78 in 2019. The mean 95th/5th ratio was relatively consistent in 2011 (4.78 +0.70) compared to 2019 (5.64+0.98). Southern states had the highest per capita distribution for eight of the ten opioids in 2019.

Conclusions

This study found a sustained decline in distribution of ten prescription opioids during the last half-decade. Distribution was non-homogeneous at the state level. Analysis of state-level differences revealed a three-fold difference in the 95th:5th percentile ratio between states which was unchanged over the past decade. Production quotas did not correspond with the distribution, particularly in the 2010-2016 period. Future research focused on identifying factors contributing to the observed regional variability in opioid distribution could prove valuable to understanding, and potentially remediating, the pronounced disparities in prescription opioid-related harm in the US.
Prevalence, Comorbidity, and Sociodemographic Correlates of Psychiatric Disorders in the All Of Us Biobank
Authors: Barr Peter B. , Bigdeli Tim B. , Meyers Jacquelyn M.
Published: December 2021

Importance

All of Us is a landmark initiative for population-scale research into the etiology of psychiatric disorders and disparities across various sociodemographic categories.

Objective

To estimate the prevalence, comorbidity, and demographic covariates of psychiatric and substance use disorders in the All of Us biobank.

Design, Setting, and Participants

We estimated prevalence, overlap, and demographic correlates for psychiatric disorders derived from electronic health records in the All of Us biobank (release 5; N = 331,380)

Exposures

Social and demographic covariates.

Main Outcome and Measures

Psychiatric disorders derived from ICD10CM codes and grouped into phecodes across six broad domains: mood disorders, anxiety disorders, substance use disorders, stress-related disorders, schizophrenia, and personality disorders.

Results

The prevalence of various disorders ranges from approximately 15% to less than 1%, with mood and anxiety disorders being the most common, followed by substance use disorders, stress-related disorders, schizophrenia, and personality disorders. There is substantial overlap among disorders, with a large portion of those with a disorder (~57%) having two or more registered diagnoses and tetrachoric correlations ranging from 0.43 – 0.74. The prevalence of disorders across demographic categories demonstrates that non-Hispanic whites, those of low socioeconomic status, women and those assigned female at birth, and sexual minorities are at greatest risk for most disorders.

Conclusions and Relevance

Although the rates of disorders in All of Us are lower than rates for disorders in the general population, there is considerable variation, comorbidity, and differences across social groups. Large-scale resources like All of Us will prove to be invaluable for understanding the causes and consequences of psychiatric conditions. As we move towards an era of precision medicine, we must work to ensure it is delivered in an equitable manner.
TIGIT as a therapeutic target of HPV-positive head and neck squamous cell carcinomas
Authors: Le Xiuning , Dang Minghao , Hegde Venkatesh L. , Jiang Bo , Slay Ravaen , Xiao Weihong , Akagi Keiko , Fresquez Joseph , Marcelo Kathrina L. , Luo Qianyun , Sinha Pragya , Yanamandra Ananta V. , Dunn Joe Dan , Bell Diana , Williams Michelle , Parra Edwin , Goepfert Ryan , Lai Stephen H. , Gross Neil , Agrawal Amit , Reuben Alexandre , Myers Jeffrey , Curran Michael A. , Sastry K. Jagannadha , Wang Linghua , Gillison Maura L.
Published: December 2021

The authors have withdrawn their manuscript because a major revision is in progress to incorporate additional data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Disruptions in Care: Consequences of the COVID-19 Pandemic in a Children’s Hospital
Authors: Diskin Catherine , Orkin Julia , Dharmaraj Blossom , Agarwal Tanvi , Parmar Arpita , Naughton Kelly Mc , Cohen Eyal , Sunderji Alia , Faraoni David , Fecteau Annie , Fischer Jason , Maynes Jason , Mahant Sanjay , Friedman Jeremy N
Published: December 2021

Background

Public health restrictions are an essential strategy to prevent the spread of COVID-19; however, unintended consequences of these interventions may have led to significant delays, deferrals and disruptions in medical care. This study explores clinical cases where the care of children was perceived to have been negatively impacted as a result of public health measures and changes in healthcare delivery and access due to the COVID-19 pandemic.

Methods

This study used a qualitative multiple case study design with descriptive thematic analysis of clinician-reported consequences of the COVID-19 pandemic on care provided at a children’s hospital. A quantitative analysis of overall hospital activity data during the study period was performed.

Results

The COVID-19 pandemic has resulted in significant change to hospital activity at our tertiary care hospital, including an initial reduction in Emergency Department attendance by 38% and an increase in ambulatory virtual care from 4% before COVID-19, to 67% in August, 2020. Two hundred and twelve clinicians reported a total of 116 unique cases. Themes including (1) timeliness of care, (2) disruption of patient-centered care, (3) new pressures in the provision of safe and efficient care and (4) inequity in the experience of the COVID-19 pandemic emerged, each impacting patients, their families and healthcare providers.

Conclusion

Being aware of the breadth of the impact of the COVID-19 pandemic across all of the identified themes is important to enable the delivery of timely, safe, high-quality, family-centred pediatric care moving forward.

What’s new

COVID-19 disrupted typical paediatric care delivery.

This study demonstrates the breadth of its’ impact on the delivery of timely, safe, equitable and patient and family centered care, highlighting considerations for paediatric providers as we move forward.
Health inequities in SARS-CoV-2 infection, seroprevalence, and COVID-19 vaccination: Results from the East Bay COVID-19 study
Authors: Adams Cameron , Horton Mary , Solomon Olivia , Wong Marcus , Wu Sean L. , Fuller Sophia , Shao Xiaorong , Fedrigo Indro , Quach Hong L. , Quach Diana L. , Meas Michelle , Lopez Luis , Broughton Abigail , Barcellos Anna L. , Shim Joan , Seymens Yusef , Hernandez Samantha , Montoya Magelda , Johnson Darrell M. , Beckman Kenneth B. , Busch Michael P. , Coloma Josefina , Lewnard Joseph A. , Harris Eva , Barcellos Lisa F.
Published: December 2021

Comprehensive data on transmission mitigation behaviors and both SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify COVID-19 risk factors and the impact of public health measures. From July 2020-March 2021, approximately 5,500 adults from the East Bay Area, California were followed over three data collection rounds to investigate the association between geographic and demographic characteristics and transmission mitigation behavior with SARS-CoV-2 prevalence. We estimated the populated-adjusted prevalence of antibodies from SARS-CoV-2 infection and COVID-19 vaccination, and self-reported COVID-19 test positivity. Population-adjusted SARS-CoV-2 seroprevalence was low, increasing from 1.03% (95% CI: 0.50-1.96) in Round 1 (July-September 2020), to 1.37% (95% CI: 0.75-2.39) in Round 2 (October-December 2020), to 2.18% (95% CI: 1.48-3.17) in Round 3 (February-March 2021). Population-adjusted seroprevalence of COVID-19 vaccination was 21.64% (95% CI: 19.20-24.34) in Round 3, with Whites having 4.35% (95% CI: 0.35-8.32) higher COVID-19 vaccine seroprevalence than non-Whites. No evidence for an association between transmission mitigation behavior and seroprevalence was observed. Despite >99% of participants reporting wearing masks, non-Whites, lower-income, and lower-educated individuals had the highest SARS-CoV-2 seroprevalence and lowest vaccination seroprevalence. Results demonstrate that more effective policies are needed to address these disparities and inequities.
Seroprevalence of SARS-CoV-2 antibodies prior to the widespread introduction of vaccine programmes in the WHO European Region, January - December 2020: a systematic review
Authors: Vaughan A , Duffell EF , Friedl GS , Lemos DS , Funk T , Nardone A , Valenciano M , Subissi L , Bergeri I , Broberg E , Penttinen P , Pebody R , Keramarou M
Published: December 2021

Background

Seroprevalence surveys are essential to assess the age-specific prevalence of pre-existing cross-reactive antibodies in the population with the emergence of a novel pathogen; to measure population cumulative seroincidence of infection, and to contribute to estimating infection severity. With the emergence of SARS-CoV-2, ECDC and WHO Regional Office for Europe have supported Member States in undertaking standardized population-based SARS-CoV-2 seroprevalence surveys across the WHO European Region.

Objectives

The objective of this study was to undertake a systematic literature review of SARS-CoV-2 population seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.

Methods

We systematically searched MEDLINE, ELSEVIER and the pre-print servers medRxiv and bioRxiv within the “COVID-19 Global literature on coronavirus disease” database using a predefined search strategy. We included seroepidemiology studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and ECDC.

Results

In total, 111 studies from 26 countries published or conducted between 01/01/2020 and 31/12/2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Eighty-one (73%) studies were assessed to be of low to medium risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7-5.2%); n=124), while sub-national estimates ranged from 0% to 52% (median 5.8% (IQR 2.3-12%); n=101), with the highest estimates in areas following widespread local transmission.

Conclusions

The review found evidence of low national SARS-CoV-2 seroprevalence (<10%) across the WHO European Region in 2020. The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes highlights the critical importance of vaccinating priority groups at risk of severe disease while maintaining reduced levels of transmission to minimize population morbidity and mortality.