bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Doctor of Nursing Practice help desk: An innovative approach to developing evidence‐based practice competency and providing DNP project support
Authors: Zellefrow Cindy , Casler Kelly , Masciola Randee , Tucker Sharon 
Published: November 2022

AbstractBackgroundThe 2021 American Association for Colleges of Nursing (AACN) Essentials for Professional Nursing Education identifies evidence‐based practice (EBP) as a core concept meant to be integrated across curricula. Integrating EBP in Doctor of Nursing Practice (DNP) programs is challenging because of barriers including persistent confusion between research, EBP, and quality improvement; low faculty confidence and competence in their EBP skills and mentoring; increased faculty workload with growing program enrollments; and limited opportunities for students and faculty to practice EBP skills.AimsThe aim of this initiative was to implement and evaluate an innovative education strategy to build DNP students' and faculty's EBP competency and confidence while mitigating barriers faced by DNP programs.MethodsA DNP Help Desk was created and implemented at a large, Midwestern college of nursing with participation and support from EBP experts. Student and faculty participation were tracked, and perceptions of the help desk were evaluated. Opportunities to evolve the help desk were identified and implemented.ResultsOutcomes included a self‐reported increase in student and faculty confidence and EBP competency, increased integration, and utilization of EBP in project work, elevated DNP project quality, and decreased demands on DNP project advisors.Linking Evidence to ActionEngaging in innovative strategies aimed at increasing EBP competency and confidence may lead to increased EBP engagement and positive outcomes for students, faculty, and DNP programs.
Investigation of Cool Roof Based on Reflective Paints, Evaporative Cooling, and Shading
Authors: Arghode Vaibhav Kumar 
Published: November 2022

Abstract
In this study, three different approaches are investigated for keeping the roof cool and reducing the heat flow inside a building located in Kanpur, India. In the first approach, various reflective paints are investigated and their performance degradation over a year is examined along with the cost-benefit analysis. In the second approach, the roof surface is kept wet, and due to water evaporation, the roof was kept cool. In the third approach, the effect of shading on the rooftop surface temperature is studied. It is observed that without any cooling, the rooftop temperature can rise about 20 °C above the ambient air temperature. The application of white acrylic paints can reduce this temperature rise to about 5–7 °C. However, after a year due to degradation, this temperature rise is about 10–12 °C. Using evaporative cooling the rooftop temperature can be lowered even below the ambient air temperature by about 3 °C. However, this approach will require active management of the system and consumption of water. The cost for the first two approaches is estimated to be about 5–6 Rs./sq.ft with a payback time of 2 years. Shading can reduce the temperature rise to about 5 °C. Structures meant for other purposes such as photovoltaic panels can serve the additional benefit of cooling the roof. Shading seems to be a robust and low-maintenance option, and cost analysis of structures meant primarily for shading the roof needs to be explored.
Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU)
Authors: Heltveit-Olsen Silje Rebekka , Sundvall Pär-Daniel , Gunnarsson Ronny , Snaebjörnsson Arnljots Egill , Kowalczyk Anna , Godycki-Cwirko Maciek , Platteel Tamara N , Koning Hilde A M , Groen Wim G , Åhrén Christina , Grude Nils , Verheij Theo J M , Hertogh Cees M P M , Lindbaek Morten , Hoye Sigurd 
Published: November 2022

IntroductionMethenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. However, the scientific evidence for the preventive effect and safety for longer-term use is limited. The aim of this study is to assess whether methenamine hippurate can reduce the incidence of UTIs in older women with recurrent UTIs.Methods and analysisThe ImpresU consortium is a collaboration between Norway, Sweden, Poland and the Netherlands. The study is a randomised, controlled, triple-blind phase IV clinical trial. Women ≥70 years with recurrent UTIs are screened for eligibility in a general practice setting. We aim to include 400 women in total, with 100 recruited from each collaborating country. The participants are randomised to treatment with methenamine hippurate 1 g or placebo tablets two times per day for a treatment period of 6 months, followed by a drug-free follow-up period of 6 months. The primary outcome is number of antibiotic treatments for UTIs during the treatment period. The secondary outcomes include number of antibiotic treatments for UTIs during the follow-up period and self-reported symptom of severity and duration of UTI episodes. Differences in complications between the treatment groups are measured as safety outcomes. We also aim to investigate whether strain characteristics or phylogenetic subgroups ofEscherichia colipresent in the urine culture at inclusion have a modifying effect on the outcomes.Ethics and disseminationEthical approvals are obtained in all participating countries. The results will be communicated in peer-reviewed journals and at scientific conferences.Trial registration numberClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235-15.
Correlation between PD-L1 expression of the tumour cells and lymphocytes infiltration in the invasive front of urothelial carcinoma
Authors: Chen Xiaohu , Chen Hanbin , Lin Rixu , Li Yulian , Guo Ying , Chen Qi , Zhang Yanyan , Cai Guoping , Hu Mengjun , Chen Guorong 
Published: November 2022

PurposeProgrammed cell death-ligand 1 (PD-L1) as a cell surface glycoprotein can inhibit T cell function when binding to its receptor, PD-1. The newly developed therapy of targeting PD-1/PD-L1 signal pathway has shown great promise for the treatment of non-small cell lung cancer as well as melanoma. Approved by Food and Drug Administration, atezolizumab has become the first new drug to treat advanced bladder cancer. The aim of this study is to evaluate whether PD-L1 is associated with the lymphocytes infiltration in the tumour microenvironment and to assess the prognostic value of PD-L1 expression.Materials and methodsAmong 96 invasive bladder urothelial carcinomas, some were used to construct tissue-microarrays, and some cases with shallow infiltration or large heterogeneity were performed, respectively, for the following work. By means of immunohistochemistry and HE, PD-L1 expression and immune cell infiltration in the invasive front of urothelial carcinoma were analysed.ResultsWe find that PD-L1 expression in tumour cells and lymphocytes are significantly associated with more tumour infiltrating lymphocytes (TILs) and more T cells. The integrated TILs, T-PD-L1 and I-PD-L1 are not significantly correlated with the overall survival (OS) of patients. However, the combination of T-PD-L1 and TILs, T-PD-L1 and I-PD-L1 is significantly correlated with the OS of patients. The T-PD-L1 (−)/TIL (−) group show the best prognosis and the T-PD-L1 (+)/I-PD-L1 (−) group show the worst prognosis. Furthermore, a multivariate analysis reveal that PD-L1 expression of lymphocytes is an independent prognostic factor for OS of patients.ConclusionsOur study reveal that PD-L1 of tumour cells are associated with the corresponding T cells infiltration and that the combination of T-PD-L1 and I-PD-L1, T-PD-L1 and TILs could be a relevant marker for the determination of the prognostic role of patients with the urothelial carcinoma.
MiR-125b-5p modulates the function of regulatory T cells in tumor microenvironment by targeting TNFR2
Authors: Jiang Mengmeng , Yang Yang , Niu Liling , Li Ping , Chen Yibo , Liao Ping , Wang Yifei , Zheng Jingbin , Chen Fengyang , He Huanhuan , Li Hui , Chen Xin 
Published: November 2022

BackgroundTumor necrosis factor receptor type 2 (TNFR2) is primarily expressed by CD4+FoxP3+regulatory T cells (Tregs), especially those present in tumor microenvironment. There is compelling evidence that TNFR2 plays a crucial role in the activation, expansion, and phenotypic stability of Tregs and promotes tumor immune evasion. Understanding of epigenetic regulation of TNFR2 expression in Tregs may help device a novel strategy in cancer immunotherapy.MethodsMiR-125b-5p-overexpressing or knockdown murine CD4 T cells and Tregs were constructed, and the effect of miR-125b-5p on Tregs proliferation, suppressive function and TNFR2 expression were examined. In vivo antitumor efficacy of Ago-125b-5p (miR-125b-5p agomir) was evaluated in MC38 tumor bearing mice, and tumor-infiltrating Tregs and CD8+cytotoxic T lymphocytes (CTLs) were analyzed. RNA-seq analysis was applied to reveal the genes and signaling pathways regulated by miR-125b-5p in Tregs.ResultsIn this study, we found that TNFR2 was a direct target of miR-125b-5p. Overexpression of miR-125b-5p decreased the proportion of Tregs and their expression of TNFR2 and consequently inhibited its proliferation and suppressive function by regulating the metabolism-related signaling pathways. Moreover, in colon cancer bearing mice, the administration of Ago-125b-5p markedly inhibited the tumor growth, which was associated with reduction of Tregs and increase of IFNγ+CD8+T cells in tumor environment. Furthermore, in human colon adenocarcinoma patients, we verified that miR-125b-5p expression was downregulated, and low levels of miR-125b-5p were associated with poor prognosis. Interestingly, the expression of miR-125b-5p and TNFR2 were negatively correlated.ConclusionsOur study for the first time found that the expression of TNFR2 by Tregs was regulated by miR-125b-5p. Our results showed that miR-125b-5p had the capacity to inhibit the expression of TNFR2 and immunosuppressive activity of Tregs and consequently enhanced the antitumor efficacy. This property of miR-125b-5p may be therapeutically harnessed in the treatment of human cancers.
Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases)
Authors: Gottenberg Jacques-Eric , Chaudier Aurore , Allenbach Yves , Mekinian Arsène , Amoura Zahir , Cacoub Patrice , Cornec Divi , Hachulla Eric , Quartier Pierre , Melki Isabelle , Richez Christophe , Seror Raphaele , Terrier Benjamin , Devauchelle-Pensec Valérie , Henry Julien , Gatfosse Marc , Bouillet Laurence , Gaigneux Emeline , Andre Vincent , Baulier Gildas , Saunier Aurélie , Desmurs Marie , Poulet Antoine , Ete Mathieu , Bienvenu Boris , Truchetet Marie-Elise , Michaud Martin , Larroche Claire , Dellal Azeddine , Leurs Amélie , Ottaviani Sebastien , Nielly Hubert , Vial Guillaume , Jaussaud Roland , Rouvière Bénedicte , Jeandel Pierre-Yves , Guffroy Aurelien , Korganow Anne-Sophie , Jouvray Mathieu , Meyer Alain , Chatelus Emmanuel , Sordet Christelle , Felten Renaud , Sibilia Jean , Litim-Ahmed-Yahia Samira , Kleinmann Jean-Francois , Mariette Xavier 
Published: November 2022

ObjectivesTo assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases.MethodsThe TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019.ResultsHundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety:11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy:the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued.ConclusionThese initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.
Experimental study on swelling pressure of low dry density compacted bentonites during saturation combining X-ray diffraction
Authors: Ruan Kunlin , Komine Hideo , Wang Hailong , Ito Dachi , Gotoh Takahiro 
Published: November 2022

A multi-ring and a newly developed swelling pressure apparatus were adopted for measuring swelling pressure of three low dry density bentonites (sodium type: MX-80 and Kunigel-V1; calcium type: Kunibond). Subsequently, slices from the multi-ring were observed using X-ray diffraction to obtain basal spacings. Distance between particles was calculated from a basal spacing database. Relations between microstructural changes, including basal spacing and distance between particles, and swelling pressure are discussed. Results show that calcium-type bentonites have greater swelling pressure than sodium-type bentonites during saturation. When bentonites have the same cation type, lower montmorillonite content bentonite obtains smaller swelling pressures than the high montmorillonite content ones. Basal spacing increases drastically first and then maintains a stable value during saturation. All three bentonites gradually reach the 3 w state along with wetting (MX-80 and Kunigel-V1: 1–3 w; Kunibond: 2–3 w). The distance between particles increases with the saturation time. During saturation, swelling pressure generally rises with increasing basal spacing and increasing distance between particles. The mechanism for swelling pressure development is discussed.
Gene Fusion Detection and Characterization in Long-Read Cancer Transcriptome Sequencing Data with FusionSeeker
Authors: Chen Yu , Wang Yiqing , Chen Weisheng , Tan Zhengzhi , Song Yuwei ,   Human Genome Structural Variation Consortium, Chen Herbert , Chong Zechen 
Published: November 2022

Abstract

Gene fusions are prevalent in a wide array of cancer types with different frequencies. Long-read transcriptome sequencing technologies, such as PacBio, Iso-Seq, and Nanopore direct RNA sequencing, provide full-length transcript sequencing reads, which could facilitate detection of gene fusions. In this work, we developed a method, FusionSeeker, to comprehensively characterize gene fusions in long-read cancer transcriptome data and reconstruct accurate fused transcripts from raw reads. FusionSeeker identified gene fusions in both exonic and intronic regions, allowing comprehensive characterization of gene fusions in cancer transcriptomes. Fused transcript sequences were reconstructed with FusionSeeker by correcting sequencing errors in the raw reads through partial order alignment algorithm. Using these accurate transcript sequences, FusionSeeker refined gene fusion breakpoint positions and predicted breakpoints at single bp resolution. Overall, FusionSeeker will enable users to discover gene fusions accurately using long-read data, which can facilitate downstream functional analysis as well as improved cancer diagnosis and treatment.

Significance:
FusionSeeker is a new method to discover gene fusions and reconstruct fused transcript sequences in long-read cancer transcriptome sequencing data to help identify novel gene fusions important for tumorigenesis and progression.
Lifetime Exposure to Cigarette Smoke and Risk of Ovarian Cancer by T-cell Tumor Immune Infiltration
Authors: Hathaway Cassandra A. , Wang Tianyi , Townsend Mary K. , Vinci Christine , Jake-Schoffman Danielle E. , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Conejo-Garcia Jose R. , Fridley Brooke L. , Tworoger Shelley S. 
Published: November 2022

Abstract

Background:
Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts the ovarian tumor immune microenvironment.

Methods:
Participants in the Nurses’ Health Study (NHS) and NHSII reported on early life exposure to cigarette smoke and personal smoking history on questionnaires (n = 165,760). Multiplex immunofluorescence assays were used to measure markers of T cells and immune checkpoints in tumor tissue from 385 incident ovarian cancer cases. We used Cox proportional hazards models to evaluate HRs and 95% confidence intervals (CI) for developing ovarian tumors with a low (&lt;median) or high (≥median) immune cell percentage by cigarette exposure categories.

Results:
Women exposed versus not to cigarette smoke early in life had a higher risk of developing ovarian cancer with low levels of T cells overall (CD3+: HR: 1.54, 95% CI: 1.08–2.20) and recently activated cytotoxic T cells (CD3+CD8+CD69+: HR: 1.45, 95% CI: 1.05–2.00). These findings were not statistically significant at the Bonferroni-corrected P value of 0.0083. Adult smoking was not significantly associated with tumor immune markers after Bonferroni correction.

Conclusions:
These results suggest early life cigarette smoke exposure may modestly increase risk of developing ovarian tumors with low abundance of total T cells and recently activated cytotoxic T cells.

Impact:
Future research should focus on understanding the impact of exposures throughout the life course on the ovarian tumor immune microenvironment.
Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA
Authors: Matsubara Nobuaki , de Bono Johann , Olmos David , Procopio Giuseppe , Kawakami Satoru , Ürün Yüksel , van Alphen Robbert , Flechon Aude , Carducci Michael A. , Choi Young Deuk , Hotte Sebastien J. , Korbenfeld Ernesto , Kramer Gero , Agarwal Neeraj , Chi Kim N. , Dearden Simon , Gresty Christopher , Kang Jinyu , Poehlein Christian , Harrington Elizabeth A. , Hussain Maha 
Published: November 2022

Abstract

Purpose:
The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment.

Patients and Methods:
Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATM alterations in ctDNA. Only patients from Cohort A (BRCA/ATM alteration positive by tissue testing) were evaluated. We compared clinical outcomes, including radiographic progression-free survival (rPFS) between the ctDNA subgroup and Cohort A.

Results:
Of the 181 (73.9%) Cohort A patients who gave consent for plasma sample ctDNA testing, 139 (76.8%) yielded a result and BRCA/ATM alterations were identified in 111 (79.9%). Of these, 73 patients received olaparib and 38 received control. Patients’ baseline demographics and characteristics, and the prevalence of HRR alterations were comparable with the Cohort A intention-to-treat (ITT) population. rPFS was longer in the olaparib group versus control [median 7.4 vs. 3.5 months; hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.21–0.53; nominal P &lt; 0.0001], which is consistent with Cohort A ITT population (HR, 0.34; 95% CI, 0.25–0.47).

Conclusions:
When tumor tissue testing is not feasible or has failed, ctDNA testing may be a suitable alternative to identify patients with mCRPC carrying BRCA/ATM alterations who may benefit from olaparib treatment.
Combination of Ribociclib with BET-Bromodomain and PI3K/mTOR Inhibitors for Medulloblastoma Treatment In Vitro and In Vivo
Authors: Jonchere Barbara , Williams Justin , Zindy Frederique , Liu Jingjing , Robinson Sarah , Farmer Dana M. , Min Jaeki , Yang Lei , Stripay Jennifer L. , Wang Yingzhe , Freeman Burgess B. , Yu Jiyang , Shelat Anang A. , Rankovic Zoran , Roussel Martine F. 
Published: November 2022

Abstract
Despite improvement in the treatment of medulloblastoma over the last years, numerous patients with MYC- and MYCN-driven tumors still fail current therapies. Medulloblastomas have an intact retinoblastoma protein RB, suggesting that CDK4/6 inhibition might represent a therapeutic strategy for which drug combination remains understudied. We conducted high-throughput drug combination screens in a Group3 (G3) medulloblastoma line using the CDK4/6 inhibitor (CDK4/6i) ribociclib at IC20, referred to as an anchor, and 87 oncology drugs approved by FDA or in clinical trials. Bromodomain and extra terminal (BET) and PI3K/mTOR inhibitors potentiated ribociclib inhibition of proliferation in an established cell line and freshly dissociated tumor cells from intracranial xenografts of G3 and Sonic hedgehog (SHH) medulloblastomas in vitro. A reverse combination screen using the BET inhibitor JQ1 as anchor, revealed CDK4/6i as the most potentiating drugs. In vivo, ribociclib showed single-agent activity in medulloblastoma models whereas JQ1 failed to show efficacy due to high clearance and insufficient free brain concentration. Despite in vitro synergy, combination of ribociclib with the PI3K/mTOR inhibitor paxalisib did not significantly improve the survival of G3 and SHH medulloblastoma-bearing mice compared with ribociclib alone. Molecular analysis of ribociclib and paxalisib-treated tumors revealed that E2F targets and PI3K/AKT/MTORC1 signaling genes were depleted, as expected. Importantly, in one untreated G3MB model HD-MB03, the PI3K/AKT/MTORC1 gene set was enriched in vitro compared with in vivo suggesting that the pathway displayed increased activity in vitro. Our data illustrate the difficulty in translating in vitro findings in vivo.
See related article in Mol Cancer Ther (2022) 21(8):1306–1317.