bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial results of a phase II study of nivolumab(N) and ipilimumab(I) in genitourinary malignancies with neuroendocrine differentiation.
Authors: McGregor Bradley Alexander , Xie Wanling , Bilen Mehmet Asim , Campbell Matthew T , Mortazavi Amir , Huang Jiaming , Sunkara Rajitha , Ravi Praful , Shah Amishi Yogesh , Baca Sylvan , Sonpavde Guru P. , Bellmunt Joaquim , Siefker-Radtke Arlene O. , Signoretti Sabina , Van Allen Eliezer Mendel , Beltran Himisha , McKay Rana R. , Choueiri Toni K. 
Published: February 2022

569 Background: Patients with metastatic genitourinary malignancies with neuroendocrine have limited therapeutic options following platinum therapy. Given encouraging results in initial cohort analysis for small cell urinary tract carcinoma, a cohort of any genitourinary malignancy with neuroendocrine differentiation was added to a multicenter, single arm, multi-cohort phase II trial to evaluate the efficacy of N and I in this setting. (NCT 03333616) Methods: Eligible patients had metastatic or locally advanced genitourinary malignancy with neuroendocrine differentiation with an ECOG performance status of 0-2; they may have received any line of prior therapy excluding prior immunotherapy. Patients underwent baseline biopsy and received treatment with N 3 mg/kg and I 1 mg/kg intravenously every 3 weeks for 4 cycles with continued maintenance of N 480 mg IV every 4 weeks. Imaging was performed at 12 weeks and then every 8 weeks through month 6 and then every 12 weeks thereafter. The primary endpoint was investigator assessed objective response rate (ORR) by RECIST 1.1. Results: A total of 27 patients were enrolled between 06/27/2018 and 06/21/2021, 10 (37%) had urinary tract cancer and 17 (63%) had prostate cancer (19 in expansion cohort, 3 urinary tract and 5 prostate cancer from earlier cohorts). The majority (n=25, 93%) patients received prior systemic therapy. Nine (33%) patients received all 4 doses of N and I during the induction period. Nine (33%) patients (7 of whom received 4 cycles N+I) received N maintenance (median number of cycles 9 (range, 2-37)). Median follow-up was 6.8 (range, 0.9-37.3) months. Objective response was achieved in 8 (30%, 80% CI 18%-44%) patients (Table). Median duration of response was not reached with 4 patients maintaining response >9 months. Median progression-free survival time was 2.6 (95% CI 1.8-6.5) months At time of analysis, 13 (48%) death events were reported due to progressive disease, in which 3 were bladder and 10 were prostate cancer. 8 (30%) patients developed treatment-related grade 3 or higher toxicities; one grade 5 toxicity was deemed treatment-unrelated. Conclusions: In this study we demonstrate N+I resulted in objective responses in patients with genitourinary malignancy with neuroendocrine differentiation. ORR of 50% in small cell carcinoma is bladder cancer is noteworthy and will be evaluated further in ongoing expansion cohort of bladder or upper tract carcinoma with variant histology. Clinical trial information: NCT03333616. [Table: see text]
Study EV-103 cohort L: Evaluating perioperative enfortumab vedotin monotherapy in cis-ineligible muscle invasive bladder cancer (MIBC) (trial in progress).
Authors: Hoimes Christopher J. , Flaig Thomas W. , Srinivas Sandy , Mar Nataliya , Petrylak Daniel P. , O'Donnell Peter H. , Bilen Mehmet Asim , Sasse Carolyn , Yu Yao , Birrenkott Matthew , Rosenberg Jonathan E. 
Published: February 2022

TPS587 Background: The current standard of care for patients (pts) with newly diagnosed MIBC is neoadjuvant cisplatin (cis)-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND). For the 20-50% pts who are cis-ineligible, the current standard of care is RC+PLND alone (Galsky Future Oncol 2021). Adjuvant therapy is currently recommended for cis-ineligible patients with high-risk features at cystectomy. Due to the high rates of recurrence in cis-ineligible pts with RC+PLND alone, there is a need to develop new therapies in this setting. Enfortumab vedotin (EV), an antibody-drug conjugate, delivers the microtubule-disrupting agent monomethyl auristatin E to cells expressing Nectin-4, which is highly expressed in urothelial cancer. In EV-301, a phase 3 study, EV showed an overall survival (OS) benefit vs chemotherapy in pts with locally advanced (la) or metastatic urothelial carcinoma (mUC) who had previously received platinum-based therapy and a PD-1 or PD-L1 inhibitor (Powles NEJM 2021). EV has also demonstrated activity and a tolerable safety profile in cis-ineligible pts with la/mUC (Yu Lancet Oncol 2021). Given the efficacy of EV in la/mUC, it is being evaluated as perioperative therapy in cis-ineligible MIBC in EV-103 cohort L. Methods: Study EV-103 (NCT03288545) la/mUC and MIBC cohorts were described previously (Hoimes ASCO 2019; Hoimes ASCO-GU 2020). Cohort L was added to evaluate EV monotherapy (n = 50) as perioperative therapy in cis-ineligible pts with MIBC (cT2-T4aN0M0 or cT1-T4aN1M0). Eligible pts are previously untreated for MIBC, ECOG 0-2, have CrCl ≥30 mL/min, and are medically fit for and agree to undergo curative intent RC+PLND. Pts with pT1 disease are eligible only if they have N1 disease. Pts receive 3 cycles of neoadjuvant EV (1.25 mg/kg IV) on Days 1 and 8 of each 3-week cycle, followed by RC+PLND and then 6 cycles of adjuvant EV starting 8 weeks post-RC on the same schedule. Pathological complete response rate per central pathology review is the primary endpoint. Secondary endpoints include event-free survival and disease-free survival by blinded independent central review and investigator, pathological downstaging rate per central pathology review, OS, safety and tolerability. Cohort L is currently enrolling pts in the US and Canada. Clinical trial information: NCT03288545.
FLASH irradiation induces lower levels of DNA damage ex vivo, an effect modulated by oxygen tension, dose, and dose rate
Authors: Cooper Christian R , Jones Donald , Jones George DD , Petersson Kristoffer 
Published: February 2022

Objective: FLASH irradiation reportedly produces less normal tissue toxicity, while maintaining tumour response. To investigate oxygen’s role in the ‘FLASH effect’, we assessed DNA damage levels following irradiation at different oxygen tensions, doses and dose rates. Methods: Samples of whole blood were irradiated (20 Gy) at various oxygen tensions (0.25–21%) with 6 MeV electrons at dose rates of either 2 kGy/s (FLASH) or 0.1 Gy/s (CONV), and subsequently with various doses (0–40 Gy) and intermediate dose rates (0.3–1000 Gy/s). DNA damage of peripheral blood lymphocytes (PBL) were assessed by the alkaline comet assay. Results: Following 20 Gy irradiation, lower levels of DNA damage were induced for FLASH, the difference being significant at 0.25% (p < 0.05) and 0.5% O2 (p < 0.01). The differential in DNA damage at 0.5% O2 was found to increase with total dose and dose rate, becoming significant for doses ≥20 Gy and dose rates ≥30 Gy/s. Conclusion: This study shows, using the alkaline comet assay, that lower levels of DNA damage are induced following FLASH irradiation, an effect that is modulated by the oxygen tension, and increases with the total dose and dose rate of irradiation, indicating that an oxygen related mechanism, e.g. transient radiation-induced oxygen depletion, may contribute to the tissue sparing effect of FLASH irradiation. Advances in knowledge: This paper is first to directly show that FLASH-induced DNA damage is modulated by oxygen tension, total dose and dose rate, with FLASH inducing significantly lower levels of DNA damage for doses ≥20 Gy and dose rates ≥30 Gy/s, at 0.5% O2.
Case Report: Hydranencephaly in a female newborn with congenital cytomegalovirus infection
Authors: Dewiyanti Lilia , Diyo Andrew Robert , Afandy Jonathan Edbert , . Jennefer , Pramana Cipta 
Published: February 2022

Background: Hydranencephaly is a congenital abnormality of the central nervous system characterized by massive hemispheric necrosis and ventricular dilatation with most of the cerebral hemispheres being replaced by membranous sacs filled with cerebrospinal fluid (CSF). Cytomegalovirus (CMV) infection can be one of the causes of hydranencephaly. The choice of therapy for hydranencephaly is a challenge because of poor prognosis, but now neural stem cell (NSC) transplantation may give new hope. Case report: We report a case of a female newborn born at term by cesarean section from a gravida 5, para 3, abortus 1 (G5P3A1) mother with suspected hydrocephalus. Head circumference was 35 cm at birth. The baby was born crying immediately, looked active, and did not appear cyanotic, but on the second day, the baby looked less active, moaned, showed acral cyanosis, and had a large fontanelle that was dilated and soft. Signs of hydrocephalus such as Macewen’s sign, setting sun phenomenon, and transillumination were found to be positive. Echocardiographic examination showed floppy interatrial septum and mild mitral regurgitation. Non-contrast computerized tomography (CT) scan of the head showed hydranencephaly. The toxoplasmosis, rubella, CMV, and herpes simplex virus (TORCH) screening showed positive anti-CMV immunoglobulin G (IgG). The baby underwent a ventriculoperitoneal (VP) shunt procedure with a head circumference of 36 cm before surgery. VP shunt was performed with an opening pressure of 15 cmH2O. Conclusions: After the VP shunt procedure, the baby's general condition improved with the head circumference within normal limits. The baby was discharged from the hospital after 16 days of treatment.
Case Report: Late complications of radiotherapy for breast cancer
Authors: Haddad Anis , Zoukar Olfa , Jemaa Yosra , Zouari Ines , Issa Rahma , Bayar Amel , Khouildi Ghada , Sebri Amal , Naguez Dalel , Boukadida Asma , Ghannouchi Mossaab , Faleh Raja 
Published: February 2022

The long term functional and aesthetic impact of breast neoplasia treatment partly reflects the consequences of high dose irradiation of the skin and subcutaneous tissue. This work, based on a case observed in our department and a review of the literature, aims to discuss certain secondary manifestations following breast irradiation and their therapeutic options. Our work reports the case of a premenopausal 46-year-old patient, treated for a right breast neoplasia. In July 2019, the patient underwent a Patey with simple postoperative follow-up. Histology substantiated the presence of an infiltrating ductal carcinoma SBRI. Mastectomy was followed by locoregional irradiation and adjuvant chemotherapy. Thirteen months after the end of irradiation, the patient reconsulted for functional impotence and pain at the level of the right upper limb. The clinical examination showed cutaneous sclerosis and lymphedema. An X-ray showing the non-metastatic fracture of the clavicle. The patient underwent physiotherapy sessions with slight improvement on the functional level and clear improvement on the sensory level with progressive disappearance of pain. Therapeutic options for complications of breast irradiation include massage, bandages, and physical exercise, often used in combination. The precise localization of the tumor bed and the application of appropriate clinical target volumes and planning target volumes are essential, as these concepts are fundamental for partial breast irradiation and avoid the complications of radiotherapy.
Clinical outcomes of COVID-19 patients with solid and hematological cancer: a meta-analysis and systematic review
Authors: Wahyuhadi Joni , Rusdi Fadhillah Putri , Ranuh I G. M. Aswin R. , Meizikri Rizki , Haq Irwan Barlian Immadoel , Susilo Rahadian Indarto , Al Farabi Makhyan Jibril 
Published: February 2022

Background: Previous research has consistently shown the significant difference in outcome between cancerous and non-cancerous patients with coronavirus disease 2019 (COVID-19). However, no studies have compared the clinical manifestation of COVID-19 in hematologic cancers patients and solid cancers patients. Therefore, we analyzed the outcome of COVID-19 patients with hematological cancer and primary solid cancer worldwide through a meta-analysis and systematic review. Methods: This meta-analysis and systematic review included English language articles published between December 2019 – January 2021 from Pubmed and Google Scholar. The Newcastle Ottawa Score was used to assess the quality and bias of included studies. The outcome measures were case-fatality rate and critical care events for COVID-19 patients with cancer and comorbidities. Results: The initial search found 8910 articles, of 20 were included in the analysis. Critical care events and mortality were higher in the hematological than primary solid cancer group (relative risk (RR)=1.22 & 1.65; p <0.001). Conversely, mortality was lower in patients with two or fewer comorbidities (RR=0.57; p<0.001) and patients under the 75-year-old group (RR=0.53; p< 0.05). Conclusions: Hematologic malignancy, age, and the number of comorbidities are predictor factors for worse prognosis in COVID-19 infection.
A practice-based clinical evaluation of a novel two-bottle dentine adhesive system
Authors: Burke FJ Trevor , Sands Peter , Crisp Russell J 
Published: February 2022

This study evaluated the handling of a recently introduced two bottle dentine adhesive system by a group of practice-based researchers. Twelve evaluators from the practice-based research group, the PREP Panel, were sent explanatory letters, a pack of the material under investigation, G2-Bond Universal, with a request to use it, where indicated, for 10 weeks and then to complete a questionnaire designed to elicit the evaluators' views on the handling of the materials. In total, 568 restorations were placed. The results from the questionnaire indicated good acceptance of the material, despite the fact that it required more clinical steps than the material previously used by the evaluators. CPD/Clinical Relevance: Results from this evaluation indicate that there is a place in a majority of evaluators' practices for a two-bottle adhesive system.
Measuring emotional preoperative stress by an app approach and its applicability to predict postoperative pain
Authors: Schiavo Carolina L. , Borges Rogério B. , Castro Stela M. J. , Wolmeister Anelise S. , de Souza Andressa , Martins Otávio R. S. , Galvão Gabriela S. , Nazario Kahio C. K. , Nickel Fabian J. , Caumo Wolnei , Stefani Luciana C. 
Published: February 2022

Background
The Brief Measure of Emotional Preoperative Stress (B-MEPS) was developed to evaluate the preoperative individual vulnerability to emotional stress. To obtain a refined version of B-MEPS suitable for an app approach, this study aimed: (i) to identify items with more discriminant properties; (ii) to classify the level of preoperative emotional stress based on cut-off points; (iii) to assess concurrent validity through correlation with the Central Sensitization Inventory (CSI) score; (iv) to confirm whether the refined version of B-MEPS is an adequate predictive measure for identification of patients prone to intense postoperative pain.

Methods
We include 1016 patients who had undergone surgical procedures in a teaching hospital. The generalized partial credit model of item response theory and latent class model were employed, respectively, to reduce the number of items and to create cut-off points. We applied the CSI and assessed pain by Visual Analog Scale (0–10) and by the amount of postoperative morphine consumption.

Results
The refined B-MEPS shows satisfactory reliability (Cronbach’s alpha 0.79). Preoperative emotional stress, according to the cut-off points, is classified into categories: low, intermediate or high stress. The refined B-MEPS exhibited a linear association with the CSI scores (r2 = 0.53, p < 0.01). Patients with higher levels of emotional stress displayed a positive association with moderate to severe pain and greater morphine consumption.

Conclusion
The refined version of B-MEPS, along with an interface of easy applicability, assess emotional vulnerability at the bedside before surgery. This app may support studies focused on intervening with perioperative stress levels.
Epidemiology and disease burden of androgenetic alopecia in college freshmen in China: A population-based study
Authors: He Fanping , Shen Minxue , Zhao Zhixiang , Liu Yicong , Zhang Shuping , Tang Yan , Xie Hongfu , Chen Xiang , Li Ji 
Published: February 2022

Objective
To evaluate the epidemiology and disease burden of androgenetic alopecia (AGA) in college freshmen in China.

Methods
This population-based cross-sectional survey was carried out among 9227 freshmen of two comprehensive universities in two cities of China (Changsha and Xiamen) from September 2018 to October 2018. Questionnaires covering basic issues, surrounding demographic information, history of diseases, living habits, comorbidities, etc. were completed online in a self-reported manner Dermatological examination was performed by certified dermatologists. The disease burden of AGA, which includes health-related quality of life, symptoms of anxiety, symptoms of depression and quality of sleep, was measured by EQ-5D-3L, PHQ-2, GAD-2 and PSQI, respectively.

Results
The prevalence of AGA in college freshmen in China was 5.3/1000. Male was significantly associated with higher prevalence of AGA (7.9/1000, P<0.01) while female with lower risk of AGA (OR = 0.29, P = 0.002). There was no significant association between BMI and AGA, nor predilection of AGA in the Han nationality or the other ethnic minorities. Annual household income or parental highest educational level exerted no significant influence on the prevalence of AGA. Rosacea (OR = 3.22, P = 0.019) was significantly associated with higher prevalence of AGA while acne seemed not to be related to AGA. The scores of EQ-5D, GAD-2, PHQ-2 and PSQI were not significantly different between students with and without AGA.

Conclusion
The onset of AGA in Chinese college freshmen differ between genders and was significantly associated with rosacea.
COVID-19 and gender-based violence service provision in the United States
Authors: Sapire Rachel , Ostrowski Jennifer , Maier Malia , Samari Goleen , Bencomo Clarisa , McGovern Terry 
Published: February 2022

Introduction
Gender-based violence (GBV) policies and services in the United States (U.S.) have historically been underfunded and siloed from other health services. Soon after the onset of the COVID-19 pandemic, reports emerged noting increases in GBV and disruption of health services but few studies have empirically investigated these impacts. This study examines how the existing GBV funding and policy landscape, COVID-19, and resulting state policies in the first six months of the pandemic affect GBV health service provision in the U.S.

Methods
This is a mixed method study consisting of 1) an analysis of state-by-state emergency response policies review; 2) a quantitative analysis of a survey of U.S.-based GBV service providers (N = 77); and 3) a qualitative analysis of in-depth interviews with U.S.-based GBV service providers (N = 11). Respondents spanned a range of organization types, populations served, and states.

Results
Twenty-one states enacted protections for GBV survivors and five states included explicit exemptions from non-essential business closures for GBV service providers. Through the surveys and interviews, GBV service providers note three major themes on COVID-19’s impact on GBV services: reductions in GBV service provision and quality and increased workload, shifts in service utilization, and funding impacts. Findings also indicate GBV inequities were exacerbated for historically underserved groups.

Discussion
The noted disruptions on GBV services from the COVID-19 pandemic overlaid long-term policy and funding limitations that left service providers unprepared for the challenges posed by the pandemic. Future policies, in emergency and non-emergency contexts, should recognize GBV as essential care and ensure comprehensive services for clients, particularly members of historically underserved groups.
The Effect of Travel Personnel Knowledge on Compliance Levels With Covid -19 Health Protocols During the 14-Day Mandiri Isolation Period in Malaka District
Authors: Fahik Paskalia Frida , Roga Anderias Umbu , Ratu Jacob M. , Nalle Agus A. , Lada Christina Olly 
Published: February 2022

The traveler from outside Malacca Regency carried out independent isolation for 14 days by implementing the COVID-19 health protocol, namely washing hands with soap under running water, wearing masks, maintaining distance, not crowding.
This study aims to analyze the effect of the knowledge of travelers on the level of compliance with the COVID-19 health protocol, using a quantitative analytical research approach or method with a cross sectional study approach. The object of research is the knowledge of travelers in Wehali village, Central Malaka District, which was carried out in December 2020 by filling out a validated questionnaire. The population in the study was 58 respondents, the variables in this study were 2, namely the independent variable was the knowledge of the traveler and the dependent variable was adherence to the COVID-19 health protocol.
Report from the HarmoSter study: impact of calibration on comparability of LC-MS/MS measurement of circulating cortisol, 17OH-progesterone and aldosterone
Authors: Fanelli Flaminia , Cantù Marco , Temchenko Anastasia , Mezzullo Marco , Lindner Johanna M. , Peitzsch Mirko , Hawley James M. , Bruce Stephen , Binz Pierre-Alain , Ackermans Mariette T. , Heijboer Annemieke C. , Van den Ouweland Jody , Koeppl Daniel , Nardi Elena , MacKenzie Finlay , Rauh Manfred , Eisenhofer Graeme , Keevil Brian G. , Vogeser Michael , Pagotto Uberto 
Published: February 2022

Abstract

Objectives
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended for measuring circulating steroids. However, assays display technical heterogeneity. So far, reproducibility of corticosteroid LC-MS/MS measurements has received scant attention. The aim of the study was to compare LC-MS/MS measurements of cortisol, 17OH-progesterone and aldosterone from nine European centers and assess performance according to external quality assessment (EQA) materials and calibration.

Methods
Seventy-eight patient samples, EQA materials and two commercial calibration sets were measured twice by laboratory-specific procedures. Results were obtained by in-house (CAL1) and external calibrations (CAL2 and CAL3). We evaluated intra and inter-laboratory imprecision, correlation and agreement in patient samples, and trueness, bias and commutability in EQA materials.

Results
Using CAL1, intra-laboratory CVs ranged between 2.8–7.4%, 4.4–18.0% and 5.2–22.2%, for cortisol, 17OH-progesterone and aldosterone, respectively. Trueness and bias in EQA materials were mostly acceptable, however, inappropriate commutability and target value assignment were highlighted in some cases. CAL2 showed suboptimal accuracy. Median inter-laboratory CVs for cortisol, 17OH-progesterone and aldosterone were 4.9, 11.8 and 13.8% with CAL1 and 3.6, 10.3 and 8.6% with CAL3 (all p<0.001), respectively. Using CAL1, median bias vs. all laboratory-medians ranged from −6.6 to 6.9%, −17.2 to 7.8% and −12.0 to 16.8% for cortisol, 17OH-progesterone and aldosterone, respectively. Regression lines significantly deviated from the best fit for most laboratories. Using CAL3 improved cortisol and 17OH-progesterone between-method bias and correlation.

Conclusions
Intra-laboratory imprecision and performance with EQA materials were variable. Inter-laboratory performance was mostly within specifications. Although residual variability persists, adopting common traceable calibrators and RMP-determined EQA materials is beneficial for standardization of LC-MS/MS steroid measurements.