bluuebunny/crossref_metadata_2025_split 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.

Summary
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.

Summary
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.
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

SummaryThe 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 SummaryMolecular 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

AbstractDialysis 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

1AbstractForecasts 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

AbstractThe 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

AbstractBackgroundPharmacologic 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.ObjectivesWe pursued genetic association analyses to compare the genetic architecture of HFpEF with that of HFrEF.MethodsWe 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.ResultsWe 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.ConclusionsThe 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 AbstractWe 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

AbstractPurpose/ObjectiveWhereas 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/MethodsWe 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.ResultsThe 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.ConclusionsDetailed 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

AbstractWastewater 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 AbstractSynopsisRespiratory 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

AbstractThe 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

AbstractObjectiveTo 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.ResultsCFA 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.ConclusionsThe 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.