bluuebunny/crossref_metadata_2025_split huggingface dataset:
SunRISe-1: Phase 2b study of TAR-200 plus cetrelimab, TAR-200 alone, or cetrelimab alone in participants with high-risk nonmuscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin who are ineligible for or decline radical cystectomy.
Authors: Van Der Heijden Michiel Simon , Cutie Christopher , Hampras Shalaka , Indoria Charu , Stewart Rachel , Acharya Milin , Stromberg Katherine , Li Xiang , Beeharry Neil , Maffeo John , Jacob Joseph M 
Published: February 2022

TPS593 Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) unresponsive to intravesical bacillus Calmette–Guérin (BCG). TAR-200 is an intravesical drug delivery system for local continuous release of gemcitabine within the bladder. The current study will assess the rate of complete response (CR) upon treatment with TAR-200 + systemic cetrelimab (CET [anti–PD-1 antibody]), TAR-200, and CET in BCG-unresponsive participants with HR-NMIBC who are ineligible for or decline radical cystectomy (RC). Methods: SunRISe-1 (NCT04640623) is an open-label, parallel-group, multicenter phase 2b study designed to assess the efficacy and safety of TAR-200 + CET, TAR-200 alone, and CET alone in participants with BCG-unresponsive HR-NMIBC. Eligible participants are aged ≥ 18 years with ECOG PS 0, 1, or 2 and recurrent or persistent histologically confirmed HR-NMIBC (carcinoma in situ) with or without papillary disease (T1, high-grade Ta), who have been diagnosed within 12 months of last BCG treatment and are ineligible for or declined RC. Participants (N≈200) are randomized 2:1:1 to receive TAR-200 + CET (Cohort 1, n≈100), TAR-200 (Cohort 2, n≈50), or CET (Cohort 3, n≈50). In Cohorts 1 and 2, participants receive intravesical TAR-200 every 3 weeks through Week 24, and every 12 weeks thereafter until Week 96. In Cohorts 1 and 3, participants receive CET until Week 78. Primary disease assessments (cystoscopy, urine cytology, transurethral resection of bladder tumor [TURBT], and magnetic resonance imaging/computed tomography) are made at baseline; subsequent cystoscopy and centrally read urine cytology are performed every 12 weeks through Year 2, every 24 weeks until end of Year 3, and in Year 4 and Year 5 in accordance with institutional standards of care. TURBT is conducted at 24 and 48 weeks. The primary end point for the 3 cohorts is overall CR rate at any time point. Secondary end points include duration of response (ie, from time of first CR achieved to first evidence of recurrence, progression, or death [whichever is earlier] for participants who achieve a CR), overall survival, PK immunogenicity of cetrelimab, safety and tolerability, and patient-reported outcomes. Exploratory end points include incidence and time to cystectomy (measured from randomization to date of cystectomy), biomarkers, and health care resource utilization. This study opened in January 2021 and is enrolling participants at ≈165 study sites worldwide. Currently, the study is active in 13 countries with 12 participants enrolled as of September 12, 2021. Clinical trial information: NCT04640623.
A prospective, single-center, phase II randomized controlled trial to evaluate the safety, feasibility, and preliminary efficacy of exercise during intravesical therapy for nonmuscle invasive bladder cancer.
Authors: Arthuso Fernanda Z. , Fairey Adrian S. , Boulé Normand G. , Courneya Kerry S. 
Published: February 2022

TPS600 Background: Non-muscle invasive bladder cancer (NMIBC) accounts for about 75% of newly diagnosed bladder cancers. The treatment for NMIBC initially involves transurethral resection of the bladder tumor followed by six weeks of induction intravesical therapy. NMIBC has a high rate of recurrence (31-78%) and progression (15%). Moreover, bladder cancer and its treatments may affect patient functioning, quality of life, and increase the risk of cardiovascular mortality. Exercise is a safe and effective intervention for many cancer patients groups, however, no studies have examined exercise during intravesical therapy for NMIBC. Bladder cancer and exeRcise trAining during intraVesical thErapy (BRAVE) is the first phase II randomized controlled trial designed to evaluate the safety, feasibility, and preliminary efficacy of exercise for NMIBC patients during intravesical therapy. An exploratory aim is to track the short-term bladder cancer recurrence and progression rates for each trial arm. Methods: BRAVE has a target sample size of 66 men or women diagnosed with NMIBC undergoing intravesical therapy with chemotherapy or immunotherapy agents. Participants are being randomly assigned to usual care or exercise intervention, which consists of three supervised, high-intensity interval training sessions/week for 12-weeks. Safety is being evaluated by any adverse events during the physical fitness assessments or exercise sessions. Feasibility will be evaluated by eligibility, recruitment, adherence, and attrition rates. Preliminary efficacy endpoints are cardiorespiratory fitness assessed by peak oxygen consumption (VO2peak) at 6-week (post-intravesical therapy) and 3-month surveillance cystoscopy; and complete response (CR), defined as negative cytology, imaging, and cystoscopy and, when indicated, a negative biopsy. CR will be assessed at 3-month and one-year surveillance cystoscopy follow-up. Statistical analyses will follow the intention-to-treat approach. Analysis of covariance will compare between-group VO2peak differences at post-intervention (pre-cystoscopy). Study enrolment started May 24, 2021 and is ongoing. As of October 4, 2021, we have screened 17 NMIBC patients scheduled for intravesical therapy for eligibility; 16 (94%) were ineligible for medical (n = 11), language (n = 3), or location (n = 2) reasons. All the medical reasons included severe cardiovascular diseases. One eligible patient declined due to travel distance to the facility. In the face of a slower-than-expected recruitment rate, eligibility was extended to patients in the maintenance phases of treatment for NMIBC, where patients receive three weekly instillations of intravesical therapy. Clinical trial information: NCT04593862.
A phase 2 study of the efficacy and safety of INCMGA00012 in advanced penile squamous cell carcinoma (PSqCC): ORPHEUS.
Authors: Garcia del Muro Xavier , Riva François , Cuellar M. Andres , Maroto-Rey Pablo , Castellano Daniel E. , Giannatempo Patrizia , Climent Duran Miguel Angel A. , Necchi Andrea , Pérez-Valderrama Begoña , Gomez De Liano Lista Alfonso , Garcias-Espana Carmen , Puente Javier , Ros Silverio , Santander Carmen , Masini Cristina , Martínez de Falcon Marta , Garcia Almudena , Sampayo-Cordero Miguel , Malfettone Andrea , Paez David 
Published: February 2022

TPS8 Background: PSqCC is a rare tumor with poor prognosis and limited therapeutic options. The current standard of care for advanced disease has been palliative platinum-based chemotherapy, with only marginal survival benefit. Recent data has shown that the majority of PSqCC patients present high levels of programmed death-ligand 1 (PD-L1). The ORPHEUS trial is evaluating the efficacy and safety of INCMGA00012 –a programmed cell death 1 (PD-1) antagonist– in patients with unresectable, locally advanced or metastatic PSqCC. Methods: ORPHEUS is an international, multicenter, open-label, single-arm, phase 2 clinical trial. Eligible patients are male aged ≥18 years with locally advanced or metastatic PSqCC, ECOG performance status of 0-1, adequate organ function, a life expectancy of ≥12 weeks, and with no prior treatment with PD-1 or PD-L1/2 agents. A total of 18 patients will be enrolled to receive INCMGA00012 500 mg administered intravenously on day 1 of each 28-day cycle. Treatment will continue until progressive disease or unacceptable toxicity. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune-related RECIST will be performed approximately every 8 weeks for the first 6 months and every 12 weeks thereafter until progressive disease. The primary endpoint is objective response rate. Secondary objectives include additional efficacy outcomes (clinical benefit rate, progression-free survival (PFS), 6-month PFS, duration of response, time to progression, overall survival, and maximum tumor shrinkage) and safety evaluated as per NCI-CTCAE 5.0. Exploratory objectives will evaluate efficacy based on immune-related RECIST; predictive and prognostic biomarkers; impact of INCMGA00012 on human immunodeficiency virus (HIV) control in patients known to be HIV-positive. The sample size calculation is based on an exact binomial test. At least 4 responders (22.2%) among 18 patients will be adequate to justify further investigation of this strategy. The analyses were designed to attain an 80% power, with a 10% dropout rate assumption, at a nominal one-sided α level of 5%. The response probabilities for null (H0) and alternative hypotheses (H1) were H0: ≤ 5% and H1: ≥ 25%, respectively. All 18 planned patients have been enrolled since the trial began in March 2020. Clinical trial information: NCT04231981.
Identification of Recurrent Insertions and Deletions in Exon 18 and 19 of Human Epidermal Growth Factor Receptor 2 as Potential Drivers in Non–Small-Cell Lung Cancer and Other Cancer Types
Authors: Yin Yan , Song Lijie , Shi Dongsheng , Liu Bin , Li Xiangke , Yang Minjie , Liu Bihao , Wang Dejuan , Qin Jianwen 
Published: February 2022

PURPOSE Human epidermal growth factor receptor 2 (HER2) belongs to the same family as epidermal growth factor receptor (EGFR) and is known as an important cancer driver gene. Insertions and deletions (indels) are frequent driver mutations in both EGFR and HER2. The most common HER2 indels are the exon 20 insertions within the kinase domain, while others are rarely reported. Our study aimed to investigate other indels of HER2 that may act as driver mutations in Chinese patients with different cancer types. METHODS In this retrospective study, patient samples were subjected to targeted sequencing covering HER2 and other cancer-related genes. Mutation profiles of patients harboring HER2 exon 18/19 indels were described. Identified HER2 exon 18/19 indels in our study were compared with external data from COSMIC. In silico and in vitro analyses were performed on selected indels of HER2 exon 18 and 19, respectively. RESULTS A total of 25 indels in HER2 exon 18/19, 17 of which being recurrent, were identified in 20 of 53,591 patients with lung cancer (0.037%), two of 5,888 patients with colorectal cancer (0.034%), two of 3,774 patients with breast cancer (0.053%), and one of 14 patients with urothelial carcinoma of the renal pelvis (7.1%). Most patients harboring HER2 exon 18/19 indels were absent of known driver mutations. In lung cancer, mutation profiles were comparable between patients carrying HER2 exon 18/19 indels and the two established HER2 drivers (exon 20 insertions and S310 mutations). The in silico and in vitro analyses suggested an activated state conferred by HER2 exon 18/19 indels, which could be targeted by different tyrosine kinase inhibitors. CONCLUSION Our study revealed a class of rare but unique indels in HER2 exon 18/19, which may act as driver mutations in several cancer types.
Quasinormal modes of novel 4D Einstein-Gauss-Bonnet Anti-de Sitter black holes
Authors: Ma Hong 
Published: February 2022

Abstract
We comprehensively analyze the Quasinormal Modes (QNMs) of the external matter field perturbation (including scalar, electromagnetic and Dirac field perturbation) and the gravitational perturbation (including odd and even parity perturbation) of novel 4D Einstein-Gauss-Bonnet (EGB) black holes (BHs) in Anti-de Sitter (AdS) spacetime. The corresponding master equation in the form of perturbations and their respective effective potential is derived. Here we focus on the influence of the cosmological constant Λ, coupling parameters α and angular quantum numbers l on the QNMs frequency of novel 4D EGB AdS BHs. The results show that with the increase of the absolute value of the coupling parameters α and angular quantum numbers l, the oscillation of the novel 4D EGB BHs is enhanced, but the decay decreases. However, as the absolute value of the cosmological constant Λ increases, the oscillation and decay of the novel 4D EGB BHs becomes faster and faster. Therefore, the analysis of QNMs by the dynamic evolution image provides direct evidence for the local stability of the novel 4D EGB AdS BHs.
Markov property of Lagrangian turbulence
Authors: Fuchs A. , Obligado M. , Bourgoin M. , Gibert M. , Mininni P. D. , Peinke J. 
Published: February 2022

Abstract
Based on direct numerical simulations with point-like inertial particles, with Stokes numbers St = 0, 0.5, 3, and 6, transported by homogeneous and isotropic turbulent flows, we present in this letter for the first time evidence for the existence of Markov property in Lagrangian turbulence. We show that the Markov property is valid for a finite step size larger than a Stokes-number-dependent Einstein-Markov coherence time scale. This enables the description of multi-scale statistics of Lagrangian particles by Fokker-Planck equations, which can be embedded in an interdisciplinary approach linking the statistical description of turbulence with fluctuation theorems of non-equilibrium stochastic thermodynamics and local flow structures. The formalism allows estimation of the stochastic thermodynamics entropy exchange associated with the particles Lagrangian trajectories. Entropy-consuming trajectories of the particles are related to specific evolution of velocity increments through scales and may be seen as intermittent structures. Statistical features of Lagrangian paths and entropy values are thus fixed by the fluctuation theorems.
Estimated number of deaths directly avoided because of COVID-19 vaccination among older adults in Colombia in 2021: an ecological, longitudinal observational study
Authors: Rojas-Botero Maylen Liseth , Fernández-Niño Julián Alfredo , Arregocés-Castillo Leonardo , Ruiz-Gómez Fernando 
Published: February 2022

Background: Colombia’s national COVID-19 vaccination plan began in February of 2021. It gave priority to older adults, who constituted 77.7% of deaths from this illness in the year 2020. The main goal of the plan is to decrease specific mortality and the number of serious COVID-19 cases, however, the number of deaths avoided by this strategy is unknown. The objective of this study was to estimate the number of avoided deaths in Colombia by fully vaccinating older adults against COVID-19, during the first year of the implementation of the national vaccination plan. Methods: This study took on the design of an ecological, longitudinal study. Full vaccination coverage for older adults was calculated for each epidemiological week and age group from March to December 2021, based on which the number of avoided COVID-19 deaths was estimated. A sensitivity analysis was performed taking into account variations in the vaccines’ effectiveness by age group. Results: In Colombia, over 5.3 million adults 60 years of age and older received full COVID-19 vaccinations between March and December 2021. During that same period, nearly 46,000 deaths of older adults from this cause were registered. We estimated that vaccination has avoided around 22,000 more older adults from dying from COVID-19 in Colombia, that is, 32.4% of expected deaths in 2021. According to the sensitivity analysis, the number of lives saved ranged from 19,597 to 36,507. Conclusions: Colombia’s strategy to vaccinate older adults against COVID-19 has avoided mortality for this age group from being 48.0% higher than what was observed during the study period. Even more lives have been saved when taking into account the parameters that were defined and the omission of the contribution from partial vaccinations.
Necrotizing sialometaplasia
Authors: Patel Monica , Cullotty K , Richards A 
Published: February 2022

In this case of a 45-year-old woman, who attended the primary care service at Birmingham Dental Hospital with widespread ulceration affecting the hard palate, histopathological, haematological and immunological testing confirmed a diagnosis of necrotizing sialometaplasia (NS), a rare benign minor salivary gland condition. The aetiology of NS is unknown; however, it is thought to represent necrosis of the mucoserous acini due to ischaemia. The clinical features of NS are similar to of squamous cell carcinoma and histopathological investigations may be required to exclude malignancy. CPD/Clinical Relevance: The article highlights the importance of recognizing necrotizing sialometaplasia to prevent misdiagnosis and ensure correct management is undertaken.
Inference is bliss: Simulation for power estimation for an observational study of a cholera outbreak intervention
Authors: Ratnayake Ruwan , Checchi Francesco , Jarvis Christopher I. , Edmunds W. John , Finger Flavio 
Published: February 2022

Background
The evaluation of ring vaccination and other outbreak-containment interventions during severe and rapidly-evolving epidemics presents a challenge for the choice of a feasible study design, and subsequently, for the estimation of statistical power. To support a future evaluation of a case-area targeted intervention against cholera, we have proposed a prospective observational study design to estimate the association between the strength of implementation of this intervention across several small outbreaks (occurring within geographically delineated clusters around primary and secondary cases named ‘rings’) and its effectiveness (defined as a reduction in cholera incidence). We describe here a strategy combining mathematical modelling and simulation to estimate power for a prospective observational study.

Methodology and principal findings
The strategy combines stochastic modelling of transmission and the direct and indirect effects of the intervention in a set of rings, with a simulation of the study analysis on the model results. We found that targeting 80 to 100 rings was required to achieve power ≥80%, using a basic reproduction number of 2.0 and a dispersion coefficient of 1.0–1.5.

Conclusions
This power estimation strategy is feasible to implement for observational study designs which aim to evaluate outbreak containment for other pathogens in geographically or socially defined rings.
Exploring the impact of COVID-19 on women’s alcohol use, mental health, and experiences of intimate partner violence in Wakiso, Uganda
Authors: Miller Amanda P. , Mugamba Stephen , Bulamba Robert M. , Kyasanku Emmanuel , Nkale James , Nalugoda Fred , Nakigozi Gertrude , Kigozi Godfrey , Nalwoga Grace K. , Kagaayi Joseph , Watya Stephen , Wagman Jennifer A. 
Published: February 2022

Introduction
Uganda confirmed its first COVID-19 case in March 2020, leading to country-wide closures and a stay-at-home order. Infectious disease pandemics can overwhelm adaptive coping capacity (e.g., general self-efficacy and resilience) and increase the risk for mental distress. For individuals experiencing intimate partner violence (IPV) and cohabitating with a perpetrator, stay-at-home orders can also increase risk of violence, which can further exacerbate mental distress. The present study explores women’s perceived self-efficacy and resilient coping, mental health outcomes (depression and COVID-19 related anxiety), hazardous alcohol use and IPV in the context of Uganda’s national 2020 lockdown.

Methods
A phone-based survey was undertaken from June-August of 2020 in Wakiso District, Uganda. The study sample consisted of Africa Medical and Behavioral Sciences Organization (AMBSO) Population Health Surveillance (APHS) study participants who agreed to be contacted for future research. The analytic sample was restricted to women aged 13–80 years. Bivariate analysis and multivariable models explored associations between experiences of IPV and measures of adaptive coping, mental health and alcohol use.

Results
A total of 556 women aged 13–79 years (mean age of 33.4 years) participated. Over half (55%) were currently married. The majority (60%) reported a decrease in alcohol use during the lockdown. Nearly half of the sample were experiencing physical or verbal IPV and reported an increase in violence during the lockdown. In adjusted analysis, alcohol use was associated with four times greater odds of recent physical IPV (aOR 4.06, 95% CI = 1.65–10.02, p = 0.0024), while participants had lower odds of experiencing any form of IPV as general self-efficacy increased (aOR 0.95, 95% CI = 0.91–0.99, p = 0.0308).

Conclusion
Lockdown measures in Uganda may have mitigated increased alcohol consumption. IPV was exacerbated during lockdown; more than 2 in 5 IPV victims experienced increased physical or verbal violence. Development of programming and policies aimed at mitigating women’s risk of IPV during future lockdowns are needed.
Urgency and Its Association With Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis
Authors: Sninsky Jared A. , Barnes Edward L. , Zhang Xian , Long Millie D. 
Published: February 2022

INTRODUCTION:
Urgency, the immediate need to defecate, is common in active ulcerative colitis (UC). We investigated the association of urgency in patients with UC with (i) quality of life (QoL) domains and (ii) future hospitalizations, corticosteroid use, and colectomy for UC.

METHODS:
We conducted a cross-sectional and subsequent longitudinal study within Inflammatory Bowel Disease Partners, a patient-powered research network. We described associations of levels of urgency in patients with UC with Patient-Reported Outcomes Measurement Information System QoL domains. We conducted a longitudinal cohort to determine associations between baseline urgency and subsequent hospitalization, corticosteroid use, or colectomy for UC within 12 months. We used bivariate statistics and logistic regression models to describe independent associations.

RESULTS:
A total of 632 patients with UC were included in the cross-sectional study. After adjusting for clinical variables, rectal bleeding, and stool frequency, urgency defined as “hurry,” “immediately,” and “incontinence” increased the odds of social impairment (odds ratio [OR] 2.05 95% confidence interval [CI] 1.24–3.4, OR 2.76 95% CI 1.1–6.74, and OR 7.7 95% CI 1.66–38.3, respectively) compared with “no hurry.” Urgency also significantly increased the odds of depression, anxiety, and fatigue. Urgency was associated with a significant increase in risk of hospitalizations and corticosteroids, whereas “hurry,” “immediately,” and “incontinence” increased the odds of colectomy within 12 months by 1.42 (1.15–1.75), 1.90 (1.45–2.50), and 3.69 (2.35–5.80).

DISCUSSION:
We demonstrated that urgency is a patient-reported outcome independently associated with compromised QoL and future risk of hospitalizations, corticosteroids, and colectomy. Our findings support the consideration of urgency as a UC-specific patient-reported outcome and its use as an outcome in clinical trials to capture QoL and risk of clinical decompensation.