bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Mutational Landscape in Chinese Patients With Advanced Breast Cancer
Authors: Zhang Jiayang , Wang Nan , Zheng Tiantian , Lu Tan , Zhang Ruyan , Ran Ran , Li Kun , Huang Yong , Xie Feng , Zhang Yue , Jia Shidong , Yu Jianjun , Li Huiping 
Published: April 2022

BackgroundGenetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes.MethodsWe collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations.ResultsThe median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02).ConclusionsThe most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.
Racial/Ethnic Differences in Health-Related Quality of Life Among Gay and Bisexual Prostate Cancer Survivors
Authors: Bates Alex J. , Rosser B. R. Simon , Polter Elizabeth J. , Wheldon Christopher W. , Talley Kristine M. C. , Haggart Ryan , Wright Morgan , Mitteldorf Darryl , West William , Ross Michael W. , Konety Badrinath R. , Kohli Nidhi 
Published: April 2022

IntroductionProstate cancer treatment has established effects on the health-related quality of life (HRQOL) of patients. While racial/ethnic differences in HRQOL have been explored in heterosexual patients, this is the first study to examine racial/ethnic differences in a cohort of sexual minority prostate cancer survivors.MethodsWe used data from the Restore-1 study, an online cross-sectional survey of sexual and gender minority (SGM) prostate cancer survivors in North America, to explore the association between race/ethnicity and HRQOL. General mental and physical HRQOL was assessed using the Short-Form Health Survey version 2 (SF-12). The frequency and distress of prostate cancer specific symptoms was assessed using the Expanded Prostate Cancer Composite (EPIC) scale. Multivariable linear regression was used to estimate mean differences in HRQOL between sexual minority men of color and their white, non-Hispanic counterparts after adjustment for pertinent demographic and medical characteristics.ResultsAmong 190 participants, 23 (12%) self-identified as non-white and/or Hispanic. In unadjusted analysis, sexual minority men of color compared to their white counterparts reported worse HRQOL scores in the EPIC hormonal summary (73.8 vs. 81.8) and hormonal function (70.9 vs 80.5) domains. Clinically important differences between men of color and their white counterparts were seen in the EPIC bowel function (mean difference (MD): -4.5, 95% CI: -9.9, 0.8), hormonal summary (MD: -8.0, 95% CI: -15.6, -0.4), hormonal function (MD: -9.6, 95% CI: -17.6, -1.6), and hormonal bother (MD: -6.7, 95% CI: -14.4, 1.1) domains. After adjustment for covariates, clinically important differences persisted between men of color and white, non-Hispanic men on the hormonal summary (74.4 vs. 81.7), hormonal function (71.3 vs. 80.3), and hormonal bother (77.0 vs. 82.7) domains.ConclusionsThis exploratory study provides the first evidence that sexual minority men of color may have worse HRQOL outcomes compared to white, non-Hispanic sexual minority men following prostate cancer treatment.
Risk Factors for Unfavorable Pathological Types of Intravesical Recurrence in Patients With Upper Urinary Tract Urothelial Carcinoma Following Radical Nephroureterectomy
Authors: Zhu Jun , Zhang Xiaoqing , Yu Wei , Li Xuesong , He Zhisong , Zhou Liqun , Zhang Zhongyuan , Xiong Gengyan 
Published: April 2022

BackgroundNumerous studies have investigated the risk factors of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC). However, few studies explore the predictors for unfavorable pathological types of IVR following RNU.MethodsWe retrospectively reviewed 155 patients diagnosed with bladder cancer (BC) following RNU. Binary logistic regression was used for the univariable and multivariable analyses. Nomograms were developed based on the multivariable analysis. The concordance index (C-index) was used to assess the performance of the nomograms. We performed internal validation by generating calibration plots.ResultsMuscle-invasive BC (MIBC) was significantly correlated with operation interval (p = 0.004) and UTUC T-stage (p = 0.016). Operation interval (p = 0.002) and UTUC T-stage (p = 0.028) were also risk factors for BC &gt; 3 cm. UTUC grade (p = 0.015), operation interval (p = 0.003), and hydronephrosis (p = 0.049) were independent predictors for high-grade BC (HGBC). MIBC (p = 0.018) and surgical approach (p = 0.003) were associated with multifocal IVR. Besides, MIBC and HGBC were associated with UTUC grade (p = 0.009), operation interval (p = 0.001), and hydronephrosis (p = 0.023). Moreover, only operation interval (p = 0.036) was a predictor for BC with at least one unfavorable pathological type. We developed nomograms for MIBC, HGBC, BC &gt; 3 cm, and MIBC and/or HGBC. The calibration curves of the nomograms showed good agreement between the observation and prediction cases. The C-indexes of the nomograms were 0.820 (95% CI, 0.747–0.894), 0.728 (95% CI, 0.649–0.809), 0.770 (95% CI, 0.679–0.861), and 0.749 (95% CI, 0.671–0.827), respectively.ConclusionsThe current study found that operation interval, UTUC T-stage, UTUC grade, surgical approach, and hydronephrosis are independent predictors for unfavorable pathological types of IVR following RNU. Nomograms based on these predictors were developed and internally validated to assess the risk of developing unfavorable pathological types of IVR. Furthermore, patients at high risk of developing unfavorable pathological types BC may benefit from more active follow-up 1 year after RNU by early detection of IVR.
Outcomes and Risk Factors of Patients With COVID-19 and Cancer (ONCORONA): Findings from The Philippine CORONA Study
Authors: Espiritu Adrian I. , Larrazabal Ramon B. , Sy Marie Charmaine C. , Villanueva Emilio Q. , Anlacan Veeda Michelle M. , Jamora Roland Dominic G. 
Published: April 2022

BackgroundA study conducted in China on patients with coronavirus disease 2019 (COVID-19) showed that cancer conferred a five times increased risk for needing intensive care admission and mortality; No data has yet been collected and published from the Philippines. Thus, the investigators conducted this substudy to determine the association of having a history of cancer with clinical outcomes among patients included in the Philippine CORONA Study.MethodologyMulti-center, retrospective cohort designResultsA total of 244 patients had a history of cancer, out of 10,881 COVID-19 hospital admissions. After adjusting for different confounding variables of interest, having cancer was significantly associated with a 75% increased odds of having severe/critical COVID-19 at nadir (CI 95% 1.32, 2.33; p &lt; 0.001). After adjusting for different confounding variables of interest, having cancer was significantly associated with the following time-to-event outcomes: 72% increase in hazard of in-hospital mortality (CI 95% 1.37, 2.16; p &lt; 0.001), 65% increase in hazard of respiratory failure (CI 95% 1.31, 2.08; p &lt; 0.001), and 57% increase in hazard of being admitted to ICU (CI 95% 1.24, 1.97; p &lt; 0.001).ConclusionA history of cancer conferred poorer clinical outcomes on adult, hospitalized COVID-19 patients.
Silencing circOMA1 Inhibits Osteosarcoma Progression by Sponging miR-1294 to Regulate c-Myc Expression
Authors: Shi Yubo , Tian Yunyun , Sun Xiangran , Qiu Yonglong , Zhao Yingchun 
Published: April 2022

BackgroundSeveral studies have reported that circRNAs have a crucial function in the tumorigenesis of various cancers. However, the expression and function of circOMA1 in osteosarcoma is unknown.MethodscircOMA1 was identified through bioinformatics analysis. qRT-PCR was used to assess the expressions of circOMA1, miR-1294, and c-Myc in osteosarcoma tissues. Further, we performed functional experiments to explore the biological function of circOMA1 in osteosarcoma. Moreover, a luciferase reporter assay, RNA immunoprecipitation (RIP), and fluorescence in situ hybridisation (FISH) assay were performed to demonstrate the association between circOMA1 and miR-1294.ResultscircOMA1 exhibited considerable upregulation in osteosarcoma tissues compared with adjacent normal tissues. Silencing circOMA1 suppressed osteosarcoma progression in vitro and in vivo. Mechanically, circOMA1 functioned as a sponge of miR-1294 to upregulate c-Myc expression.ConclusioncircOMA1 played the role of an oncogene in osteosarcoma and promoted osteosarcoma progression by mediating the miR-1294/c-Myc pathway, which might be a new target for treating osteosarcoma.
Pediatric Intestinal Pseudo-Obstruction: Progress and Challenges
Authors: Turcotte Marie-Catherine , Faure Christophe 
Published: April 2022

BackgroundChronic intestinal pseudo-obstruction is a rare disorder and represents the most severe form of gastrointestinal dysmotility with significant morbidity and mortality. Emerging research shows considerable differences between the adult and pediatric population with intestinal pseudo-obstruction and the term Pediatric Intestinal Pseudo-Obstruction (PIPO) was recently proposed.PurposeThe aim of this article is to provide pediatric gastroenterologists and pediatricians with an up to date review of the etiology and underlining pathophysiology, clinical features, diagnostic and management approaches currently available for PIPO and to discuss future perspectives for the diagnosis and management of this rare disease.
Thioredoxin-1 Activation by Pterostilbene Protects Against Doxorubicin-Induced Hepatotoxicity via Inhibiting the NLRP3 Inflammasome
Authors: Tan Shiqing , Bai Jie , Xu Mingxi , Zhang Longying , Wang Ying 
Published: April 2022

Background: Doxorubicin (DOX) has been widely used in cancer treatment. However, DOX can cause a range of significant side effects, of which hepatotoxicity is a common one, and therefore limits its clinical use. Pterostilbene (PTS) has been shown to exhibit anti-oxidant and anti-inflammatory effects in the treatment of liver diseases but whether PTS could protect against hepatotoxicity in DOX-treated mice is unknown.Methods: In our study, we use C57/BL6J mice and the HepG2 cell line. We divided the mice in 4 groups: the control, the PTS treatment, the DOX treatment, and the DOX + PTS treatment group. Liver histopathology was judged by performing hematoxylin–eosin and Masson staining. Immunohistochemistry was used to perform the expression of NLRP3. The levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) were evaluated. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and DCFH-DA staining were used to evaluate the oxidative injury. Western blot and real-time PCR were applied to evaluate the expressions of proteins and mRNA. MTT was used to evaluate DOX-induced cell injury and the protective effects of PTS. Recombinant Trx-1 was used to analyze the mechanism of PTS. A TUNEL assay was used to detect apoptosis in DOX-induced HepG2 cells and the protective effects of PTS.Results: PTS ameliorated DOX-induced liver pathological changes and the levels of AST and ALT. PTS also decreased the level of MDA, increased the level of SOD, GSH, and the expression of Trx-1 in DOX-treated mice. PTS decreased the levels of NLRP3 and IL-1β mRNA and the expressions of their proteins in DOX-treated mice. In addition, PTS also decreased the expression of Cleaved Caspase-3 and BAX and increased the expression of BCL-2. In vitro, after treatment with recombinant Trx-1, ROS and NLRP3 inflammasome were both decreased. Treatment with PTS could rescue the downregulation of Trx-1, decreased the ROS level and the NLRP3 inflammasome, and protected HepG2 cells against DOX-induced apoptosis.Conclusion: The results show that PTS exhibits protective effects against DOX-induced liver injuries via suppression of oxidative stress, fibrosis, NLRP3 inflammasome stimulation, and cell apoptosis which might lead to a new approach of preventing DOX-induced hepatotoxicity.
Methods for the Cost-Effective Production of Bacteria-Derived Double-Stranded RNA for in vitro Knockdown Studies
Authors: Verdonckt Thomas-Wolf , Vanden Broeck Jozef 
Published: April 2022

RNA interference (RNAi) is a highly conserved pathway for the post-transcriptional regulation of gene expression. It has become a crucial tool in life science research, with promising potential for pest-management applications. To induce an RNAi response, long double-stranded RNA (dsRNA) sequences specific to the target gene must be delivered to the cells. This dsRNA substrate is then processed to small RNA (sRNA) fragments that direct the silencing response. A major obstacle to applying this technique is the need to produce sufficiently large amounts of dsRNA in a very cost-effective manner. To overcome this issue, much attention has been given to the development and optimization of biological production systems. One such system is the E. coli HT115 strain transformed with the L4440 vector. While its effectiveness at inducing knockdowns in animals through feeding of the bacteria has been demonstrated, there is only limited knowledge on the applicability of bacteria-derived dsRNA for in vitro experiments. In this paper, we describe and compare methods for the economical (43.2 €/mg) and large-scale (mg range) production of high-quality dsRNA from the HT115 bacterial system. We transformed the bacteria with constructs targeting the Helicoverpa-specific gene Dicer2 and, as a non-endogenous control, the Green Fluorescent Protein gene (GFP). First, we compared the total RNA extraction yields of four cell-lysis treatments: heating, lysozyme digestion, sonication, and a control protocol. Second, we assessed the quality and purity of these extracted dsRNAs. Third, we compared methods for the further purification of dsRNAs from crude RNA extracts. Finally, we demonstrated the efficiency of the produced dsRNAs at inducing knockdowns in a lepidopteran cell line. The insights and results from this paper will empower researchers to conduct otherwise prohibitively expensive knockdown studies, and greatly reduce the production times of routinely or large-scale utilized dsRNA substrates.
Cardiac Autonomic Modulation and Response to Sub-Maximal Exercise in Chilean Hypertensive Miners
Authors: Lang Morin , Mendt Stefan , Paéz Valeria , Gunga Hanns-Christian, , Bilo Grzegorz , Merati Giampiero , Parati Gianfranco , Maggioni Martina Anna 
Published: April 2022

Cardiac autonomic modulation in workers exposed to chronic intermittent hypoxia (CIH) has been poorly studied, especially considering hypertensive ones. Heart rate variability (HRV) has been proven as valuable tool to assess cardiac autonomic modulation under different conditions. The aim of this study is to investigate the cardiac autonomic response related to submaximal exercise (i.e., six-minute walk test, 6MWT) in hypertensive (HT, n = 9) and non-hypertensive (NT, n = 10) workers exposed for &gt; 2 years to CIH. Participants worked on 7-on 7-off days shift between high altitude (HA: &gt; 4.200 m asl) and sea level (SL: &lt; 500 m asl). Data were recorded with electrocardiography (ECG) at morning upon awakening (10 min supine, baseline), then at rest before and after (5 min sitting, pre and post) the 6MWT, performed respectively on the first day of their work shift at HA, and after the second day of SL sojourn. Heart rate was higher at HA in both groups for each measurement (p &lt; 0.01). Parasympathetic indices of HRV were lower in both groups at HA, either in time domain (RMSSD, p &lt; 0.01) and in frequency domain (log HF, p &lt; 0.01), independently from measurement’s time. HRV indices in non-linear domain supported the decrease of vagal tone at HA and showed a reduced signal’s complexity. ECG derived respiration frequency (EDR) was higher at HA in both groups (p &lt; 0.01) with interaction group x altitude (p = 0.012), i.e., higher EDR in HT with respect to NT. No significant difference was found in 6MWT distance regarding altitude for both groups, whereas HT covered a shorter 6MWT distance compared to NT (p &lt; 0.05), both at HA and SL. Besides, conventional arm-cuff blood pressure and oxygen blood saturation values (recorded before, at the end and after 5-min recovery from 6MWT), reported differences related to HA only. HA is the main factor affecting cardiac autonomic modulation, independently from hypertension. However, presence of hypertension was associated with a reduced physical performance independently from altitude, and with higher respiratory frequency at HA.
Changes in Prevalence and Severity of Domestic Violence During the COVID-19 Pandemic: A Systematic Review
Authors: Thiel Freya , Büechl Verena C. S. , Rehberg Franciska , Mojahed Amera , Daniels Judith K. , Schellong Julia , Garthus-Niegel Susan 
Published: April 2022

BackgroundTo contain the spread of COVID-19, governmental measures were implemented in many countries. Initial evidence suggests that women and men experience increased anger and aggression during COVID-19 lockdowns. Not surprisingly, media reports and initial empirical evidence highlight an increased risk for domestic violence (DV) during the pandemic. Nonetheless, a systematic review of studies utilizing participants' reports of potential changes in DV prevalence and severity during the pandemic as compared to pre-pandemic times is needed.ObjectiveTo examine empirical, peer-reviewed studies, pertaining to the potential change in prevalence and severity of different types of DV during the COVID-19 pandemic, as reported by study participants.Data SourcesElectronic EMBASE, MEDLINE, PsycINFO, and CINAHL searches were conducted for the period between 2020 and January 5, 2022. References of eligible studies were integrated by using a snowballing technique.Study SelectionA total of 22 primary, empirical, peer-reviewed studies published in English or German were included.ResultsOf the 22 studies, 19 were cross-sectional whereas 3 included both pre-pandemic and during pandemic assessments. Data synthesis indicates that severity of all types of DV as well as the prevalence of psychological/emotional and sexual DV increased for a significant number of victims in the general population during the pandemic. Evidence for changes in prevalence regarding economic/financial, physical, and overall DV remains inconclusive. There was considerable between-study variation in reported prevalence depending on region, sample size, assessment time, and measure.ConclusionsData synthesis partly supports the previously documented increase in DV. Governmental measures should consider the availability of easily accessible, anonymous resources. Awareness and knowledge regarding DV need to be distributed to improve resources and clinical interventions.
Causes of Missed Nursing Care During COVID-19 Pandemic: A Qualitative Study in Iran
Authors: Safdari Ali , Rassouli Maryam , Jafarizadeh Raana , Khademi Fatemeh , Barasteh Salman 
Published: April 2022

BackgroundThe unpredictable and variable nature of COVID-19 and the lack of healthcare resources has led to inadequate care for patients. This study aimed to explain the causes of missed nursing care during the COVID-19 pandemic from the perspective of Iranian nurses.MethodThis qualitative study was conducted using semi-structured interviews with 14 nurses caring for patients with COVID-19 in three hospitals in Iran. Sampling was performed by the purposive method. Data were analyzed using the conventional content analysis method. The interviews were first recorded and transcribed, and then the data were analyzed using the Elo and Kyngas method. Data management was done with MAXQDA software version 10. To achieve trustworthiness, the criteria presented by Lincoln and Guba were used.FindingsA total of 14 nurses participated in the study. The mean age of participants was 31.85 ± 4.95 years, and the mean number of years of work experience was 7.71 ± 4.44. Eleven participants were women. Among all participants, nine had a bachelor's degree and five had a master's degree. Four nurses had fixed shifts, while ten nurses had rotating shifts. The causes of missed nursing care were categorized into 4 groups. The category “unfulfilled care” comprised the reasons for forgetting care, neglecting care, arbitrary elimination of care, and compulsory elimination of care. The category of “care at improper time” consisted of interference of the care in patients' daily activities and interference with other healthcare providers' activities. The “incomplete cares” category comprised failure to complete the care period in hospital, interruption in care, and discontinuance of care after patient discharge. The last category, “incorrect care,” consisted of providing care regardless of the nursing process, providing care by unqualified professionals, and providing trial-and-error care.ConclusionThis study illustrates an understanding of the causes of missed nursing care during the COVID-19 pandemic from the perspective of nurses. The increasing demand for care caused by the pandemic and problems in the work environment has led to the failure of nurses to provide complete, correct care and sometimes miss parts of care to patients. Therefore, nursing policymakers and managers should develop and implement appropriate care protocols and instructions to minimize missed nursing care.