bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members
Authors: Delahunty Rachel , Nguyen Linh , Craig Stuart , Creighton Belinda , Ariyaratne Dinuka , Garsed Dale W. , Christie Elizabeth , Fereday Sian , Andrews Lesley , Lewis Alexandra , Limb Sharne , Pandey Ahwan , Hendley Joy , Traficante Nadia , Carvajal Natalia , Spurdle Amanda B. , Thompson Bryony , Parsons Michael T. , Beshay Victoria , Volcheck Mila , Semple Timothy , Lupat Richard , Doig Kenneth , Yu Jiaan , Chen Xiao Qing , Marsh Anna , Love Christopher , Bilic Sanela , Beilin Maria , Nichols Cassandra B. , Greer Christina , Lee Yeh Chen , Gerty Susan , Gill Lynette , Newton Emma , Howard Julie , Williams Rachel , Norris Christie , Stephens Andrew N. , Tutty Erin , Smyth Courtney , O'Connell Shona , Jobling Thomas , Stewart Colin J.R. , Tan Adeline , Fox Stephen B. , Pachter Nicholas , Li Jason , Ellul Jason , Mir Arnau Gisela , Young Mary-Anne , Gordon Louisa , Forrest Laura , Harris Marion , Livingstone Karen , Hill Jane , Chenevix-Trench Georgia , Cohen Paul A. , Webb Penelope M. , Friedlander Michael , James Paul , Bowtell David , Alsop Kathryn ,   on behalf of The Australian Ovarian Cancer Study, Ovarian Cancer Prognosis and Lifestyle Study and the TRACEBACK Study
Published: March 2022

PURPOSE Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.
Trends in Grade 5 Toxicity and Response in Phase I Trials in Hematologic Malignancy: 20-Year Experience From the Cancer Therapy Evaluation Program at the National Cancer Institute
Authors: Chihara Dai , Huang Erich P. , Finnigan Shanda R. , Cordes Lisa M. , Skorupan Nebojsa , Fukuda Yoko , Rubinstein Larry V. , Ivy S. Percy , Doroshow James H. , Nastoupil Loretta J. , Flowers Christopher R. , Takebe Naoko 
Published: March 2022

PURPOSECancer drug development has largely shifted from cytotoxic chemotherapy to targeted treatment in the past two decades. Although previous studies have highlighted improvement in response rates in recent phase I trials, disease-focused reporting is limited.METHODSWe integrated patient-level data for patients with hematologic malignancies who participated in phase I trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program between January 2000 and May 2019 and estimated the trend of grade 5 toxicity and response by disease subtype over time.RESULTSWe analyzed 161 trials involving 3,308 patients, all of whom were assessed for toxicity and 2,404 of whom were evaluable for response to therapy. The overall rate of grade 5 toxicities was 1.81% (95% CI, 1.36 to 2.27), with no significant change in the rate over time. Baseline characteristics associated with higher risk of grade 5 toxicity were age and performance status ≥ 2 at enrollment. Overall response rate (ORR) and complete response (CR) rate for all trials during the study period were 25.1% and 14.7%, respectively. A significant increase in both ORR and CR rate was observed over time (ORR, 18.5% in 2000-2005, 25.9% in 2006-2012, and 50.6% in 2013-2019, P < .001). ORR in phase I trials varied across disease subtypes: 20.2% in acute myeloid leukemia, 9.1% in myelodysplastic syndrome, 43.2% in lymphoma, 42.9% in chronic lymphocytic leukemia, 15.1% in acute lymphoblastic leukemia, and 16.5% in myeloma.CONCLUSIONOver time, the ORR and CR rates in phase I trials for hematologic malignancy have improved meaningfully, whereas the rate of toxicity-related death remains stable. This study provides broad experience that physicians can use when discussing the potential outcomes for patients with hematologic malignancy considering participation in phase I trials.
Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
Authors: Kasi Pashtoon M. , Fehringer Gordon , Taniguchi Hiroya , Starling Naureen , Nakamura Yoshiaki , Kotani Daisuke , Powles Thomas , Li Bob T. , Pusztai Lajos , Aushev Vasily N. , Kalashnikova Ekaterina , Sharma Shruti , Malhotra Meenakshi , Demko Zachary P. , Aleshin Alexey , Rodriguez Angel , Billings Paul R. , Grothey Axel , Taieb Julien , Cunningham David , Yoshino Takayuki , Kopetz Scott 
Published: March 2022

PURPOSE Earlier detection of cancer recurrence using circulating tumor DNA (ctDNA) to detect molecular residual disease (MRD) has the potential to dramatically affect cancer management. We review evidence supporting the use of ctDNA as a biomarker for detection of MRD and highlight the potential impact that ctDNA testing could have on the conduct of clinical trials. METHODS We searched the literature using MEDLINE (via PubMed) for articles from January 1, 2000, focusing on studies that assessed ctDNA as a predictor of cancer recurrence. Broadly focused searches on ctDNA and cancer were also performed to provide additional background information. www.clinialtrials.gov was searched to identify trials that incorporate ctDNA testing. RESULTS Numerous studies across different cancer types indicate that ctDNA-based MRD detection predicts recurrence with high sensitivity and specificity, and with lead times that precede standard imaging by up to 12 months. Recently, ctDNA testing has started being used to enroll MRD-positive patients at high risk of recurrence into trials, promising gains in statistical power that allow clinical utility to be demonstrated with smaller cohorts. Trials where ctDNA testing based-MRD detection is used to stratify patients into low or high-risk categories for treatment assignment are also ongoing. In addition, there is increasing evidence supporting the use of ctDNA dynamics or clearance as a surrogate end point, which could significantly reduce trial duration. CONCLUSION ctDNA-based trial enrichment across many cancers seems likely to become increasingly common for cost- and time-reduction benefits. Trial efficiency could also benefit from using ctDNA as a surrogate end point, leading to accelerated approval of new therapeutics. A clear demonstration of efficacy from trials that use ctDNA-based MRD detection to assign treatment could transform clinical practice.
Anti-angiogenic effect of the combination low-dose sorafenib and EGCG in HCC-induced Wistar rats
Authors: Irawan Andry , Prabowo Erik , Riwanto Ignatius , Atmodjo Wahyuni Lukita 
Published: March 2022

Background: Sorafenib is an expensive standard drug used for advanced hepatocellular carcinoma. Its combination with epigallo-3-catechin gallate leads to a reduced cost but equally effective anti-angiogenic effect. Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods: A total of 25 male Wistar rats (7-weeks-old) were randomly divided into 4 groups, namely Sham (K), Control (O), combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg bodyweight (BW) intraperitoneally for 10 weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for 2 weeks. Subsequently, the level of vascular endothelial growth factor (VEGF) and expression of microvascular density was examined using liver tissues. Results: There was a significant difference (p=0.007) in the level of VEGF between the group X1 (106,682 ± 41,024) and X2 (214,5162 ± 67,71652). However, the differences in VEGF level of group X1 and X2 compared to group O (318,101 ± 55,078) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 (36 ± 4,416) and X2 (26,2 ± 4,55) was not significantly different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with group O (176 ± 19). Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib as well as the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity to reduce the expression of microvascular density.
Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota
Authors: Petrillo Mauro , Querci Maddalena , Brogna Carlo , Ponti Jessica , Cristoni Simone , Markov Peter V , Valsesia Andrea , Leoni Gabriele , Benedetti Alessandro , Wiss Thierry , Van den Eede Guy 
Published: March 2022

Background: In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a ‘bacteriophage-like’ behaviour of SARS-CoV-2. Methods: We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Results: Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures. Conclusions: Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.
Detection of internal humidity in a transformer via optical interferometry
Authors: Jiang Chenlai , Peng Yue , Xue Liang , Jiang Chao , Yang Chuankai , Jiang Youhua , Chu Fenghong 
Published: March 2022

To detect the internal humidity of the transformer accurately and sensitively and eliminate the interference caused by electromagnetic fields, an interferometric measurement is proposed in this paper for the first time, to the best of our knowledge. The phase value distribution of the interferogram affected by humidity can be extracted quantitatively. The peak-to-peak value (P-P) of the phase image can reflect the humidity, according to theoretical analysis, and the main factors affecting the P-P are current and humidity. It has been tested by currents of 800 A, 1000 A, and 1200 A and different humidities. The paper reveals the relationship between humidity and P-P, proving that it is a reasonable application of real-time measurement of internal humidity in the transformer.
Nonfatal opioid overdoses before and after Covid-19: Regional variation in rates of change
Authors: Burgess-Hull Albert J. , Smith Kirsten E. , Panlilio Leigh V. , Schriefer Destiny , Preston Kenzie L. , Alter Aliese , Yeager Christopher , Chizmar Timothy , Delbridge Ted , Zamore Kenan , Beeson Jeff , Epstein David H. 
Published: March 2022

Background
The Covid-19 pandemic and its accompanying public-health orders (PHOs) have led to (potentially countervailing) changes in various risk factors for overdose. To assess whether the net effects of these factors varied geographically, we examined regional variation in the impact of the PHOs on counts of nonfatal overdoses, which have received less attention than fatal overdoses, despite their public health significance.

Methods
Data were collected from the Overdose Detection Mapping Application Program (ODMAP), which recorded suspected overdoses between July 1, 2018 and October 25, 2020. We used segmented regression models to assess the impact of PHOs on nonfatal-overdose trends in Washington DC and the five geographical regions of Maryland, using a historical control time series to adjust for normative changes in overdoses that occurred around mid-March (when the PHOs were issued).

Results
The mean level change in nonfatal opioid overdoses immediately after mid-March was not reliably different in the Covid-19 year versus the preceding control time series for any region. However, the rate of increase in nonfatal overdose was steeper after mid-March in the Covid-19 year versus the preceding year for Maryland as a whole (B = 2.36; 95% CI, 0.65 to 4.06; p = .007) and for certain subregions. No differences were observed for Washington DC.

Conclusions
The pandemic and its accompanying PHOs were associated with steeper increases in nonfatal opioid overdoses in most but not all of the regions we assessed, with a net effect that was deleterious for the Maryland region as a whole.
Compliance with the smoke-free public places legislation in Nepal: A cross-sectional study from Biratnagar Metropolitan City
Authors: Basnet Lila Bahadur , Budhathoki Shyam Sundar , Adhikari Biplov , Thapa Jeevan , Neupane Bandana , Moses Talibita , Dhimal Meghnath , Pokharel Paras K. , Ghimire Anup , Belbase Deepak , Khatri Sudip , Yadav Narendra Kumar , Pinder Richard J. 
Published: March 2022

Background
Smoke-free legislation banning tobacco smoking in public places was implemented across Nepal in 2014 with the ambition to reduce the impact of second-hand smoking. As part of a comprehensive policy package on tobacco control, the implementation of the legislation has seen a marked reduction in tobacco consumption. Yet there remains uncertainty about the level of compliance with smoke-free public places.

Objectives
This study assesses the compliance with smoke-free laws in public places and the factors associated with active smoking in public places in Biratnagar Metropolitan City, Nepal.

Methods
A cross-sectional study was conducted in the Biratnagar metropolitan city in Province 1 of Nepal from July to December 2019. A total of 725 public places within the metropolitan city were surveyed using a structured survey tool. Active smoking was the primary outcome of the study which was defined as smoking by any person during the data collection time at the designated public place.

Results
The overall compliance with smoke-free legislation was 56.4%. The highest compliance (75.0%) was observed in Government office buildings. The lowest compliance was observed in eateries, entertainment, and shopping venues (26.3%). There was a statistically significant association between active smoking and the presence of ‘no smoking’ notices appended at the entrance and the odds of active smoking in eateries, entertainment, hospitality, shopping venues, transportations and transits was higher compared to education and health care institutions. None of the ‘no smoking’ notices displayed fully adhered to the contents as prescribed by the law.

Conclusion
As more than half of the public places complied with the requirements of the legislation, there was satisfactory overall compliance with the smoke-free public places law in this study. The public venues (eateries, shopping venues and transportations) that are more frequently visited and have a high turnover of the public have lower compliance with the legislation. The content of the message in the ‘no smoking’ notices needs close attention to adhere to the legal requirements.
Prediction of prognosis in immunoglobulin a nephropathy patients with focal crescent by machine learning
Authors: Lin Xuefei , Liu Yongfang , Chen Yizhen , Huang Xiaodan , Li Jundu , Hou Yuansheng , Shen Miaoying , Lin Zaoqiang , Zhang Ronglin , Yang Haifeng , Hong Songlin , Liu Xusheng , Zou Chuan 
Published: March 2022

Background and objectives
Immunoglobulin a nephropathy (IgAN) is the most common primary glomerular disease in the world, with different clinical manifestations, varying severity of pathological changes, common complications of crescent formation in different proportions, and great individual heterogeneous in clinical outcomes. Therefore, we aim to develop a machine learning (ML) based predictive model for predicting the prognosis of IgAN with focal crescent formation and without obvious chronic renal lesions (glomerulosclerosis <25%).

Materials
We retrospectively reviewed biopsy-proven IgAN patients in our hospital and cooperative hospital from 2005 to 2017. The method of feature importance of random forest (RF) was applied to conduct feature exploration of feature variables to establish the characteristic variables that are closely related to the prognosis of focal crescent IgAN. Multiple ML algorithms were attempted to establish the prediction models. The area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) were applied to evaluate the predictive performance via three-fold cross validation (namely 2 training sets and 1 validation set).

Results
RF was used to screen the important features, the top three of which were baseline estimated glomerular filtration rate (eGFR), serum creatine and triglyceride. Ten important features were selected as important predictors for modeling on the basis of data-driven and medical selection, predictors include: age, baseline eGFR, serum creatine, serum triglycerides, complement 3(C3), proteinuria, mean arterial pressure (MAP) and Hematuria, crescents proportion of glomeruli, Global crescent proportion of glomeruli. In a variety of ML algorithms, the support vector machine (SVM) algorithm displayed better predictive performance, with Precision of 0.77, Recall of 0.77, F1-score of 0.73, accuracy of 0.77, AUROC of 79.57%, and AUPRC of 76.5%.

Conclusions
The SVM model is potentially useful for predicting the prognosis of IgAN patients with focal crescent shape and without obvious chronic renal lesions.
Relationship between no-visitation policy and the development of delirium in patients admitted to the intensive care unit
Authors: Shinohara Fumihide , Unoki Takeshi , Horikawa Megumi 
Published: March 2022

Background
Due to the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) pandemic, many hospitals imposed a no-visitation policy for visiting patients in hospitals to prevent the transmission of SARS-CoV-2 among visitors and patients. The objective of this study was to investigate the association between the no-visitation policy and delirium in intensive care unit (ICU) patients.

Methods
This was a single-center, before-after comparative study. Patients were admitted to a mixed medical-surgical ICU from September 6, 2019 to October 18, 2020. Because no-visitation policy was implemented on February 26, 2020, we compared patients admitted after this date (after phase) with the patients admitted before the no-visitation policy (before phase) was implemented. The primary outcome was the incidence of delirium during the ICU stay. Cox regression was used for the primary analysis and was calculated using hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates were age, sex, APACHE II, dementia, emergency surgery, benzodiazepine, and mechanical ventilation use.

Results
Of the total 200 patients consecutively recruited, 100 were exposed to a no-visitation policy. The number of patients who developed delirium during ICU stay during the before phase and the after phase were 59 (59%) and 64 (64%), respectively (P = 0.127). The adjusted HR of no-visitation policy for the number of days until the first development of delirium during the ICU stay was 0.895 (0.613–1.306).

Conclusion
The no-visitation policy was not associated with the development of delirium in ICU patients.
tratamento das figuras de linguagem em gramáticas setecentista e oitocentista de língua portuguesa
Authors: Nunes Darcijane dos Santos 
Published: March 2022

Esta pesquisa busca analisar qual o tratamento dado às figuras de linguagem (doravante F.L), na gramaticografia de língua portuguesa produzida nos séculos XVIII e XIX, mais especificamente em três fontes canônicas, a saber: A arte da grammatica de língua Portuguesa, de Antonio Reis Lobato, datada de 1770, a Grammatica Philosofica de Língua Portugueza, de Jerônimo Soares Barbosa, publicada em 1822 e a Grammatica Portugueza elementar fundada sob o methodo histórico-comparativo, de Teófilo Braga, publicada em 1876. Para tanto utilizamos como referencial teórico a noção de rede conceitual em Polachini (2018), relações lógicas entre termos, em Swiggers (2004; 2010); Paradigma Tradicional de Gramatização, em Vieira (2018). A presente pesquisa revelou as inconsistências e convergências dos autores das gramáticas analisadas no tocante ao tratamento dado às figuras de linguagem. A categoria rede conceitual possibilitou a percepção de continuidades e descontinuidades a partir das relações de equivalência, intersecção e contrariedade entre os metatermos analisados.