bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort
Authors: Arora Kanika , Tran Thinh N. , Kemel Yelena , Mehine Miika , Liu Ying L. , Nandakumar Subhiksha , Smith Shaleigh A. , Brannon A. Rose , Ostrovnaya Irina , Stopsack Konrad H. , Razavi Pedram , Safonov Anton , Rizvi Hira A. , Hellmann Matthew D. , Vijai Joseph , Reynolds Thomas C. , Fagin James A. , Carrot-Zhang Jian , Offit Kenneth , Solit David B. , Ladanyi Marc , Schultz Nikolaus , Zehir Ahmet , Brown Carol L. , Stadler Zsofia K. , Chakravarty Debyani , Bandlamudi Chaitanya , Berger Michael F. 
Published: September 2022

Abstract

Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions.

Significance:
We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including &gt;5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations.
This article is highlighted in the In This Issue feature, p. 2483
Drug–gene Interaction Screens Coupled to Tumor Data Analyses Identify the Most Clinically Relevant Cancer Vulnerabilities Driving Sensitivity to PARP Inhibition
Authors: Jamal Kunzah , Galbiati Alessandro , Armenia Joshua , Illuzzi Giuditta , Hall James , Bentouati Sabrina , Barrell Daniel , Ahdesmäki Miika ,   for the Functional Genomics Centre Group, O'Connor Mark J. , Leo Elisabetta , Forment Josep V. 
Published: September 2022

PARP inhibitors (PARPi) are currently indicated for the treatment of ovarian, breast, pancreatic, and prostate cancers harboring mutations in the tumor suppressor genes BRCA1 or BRCA2. In the case of ovarian and prostate cancers, their classification as homologous recombination repair (HRR) deficient (HRD) or mutated also makes PARPi an available treatment option beyond BRCA1 or BRCA2 mutational status. However, identification of the most relevant genetic alterations driving the HRD phenotype has proven difficult and recent data have shown that other genetic alterations not affecting HRR are also capable of driving PARPi responses. To gain insight into the genetics driving PARPi sensitivity, we performed CRISPR-Cas9 loss-of-function screens in six PARPi-insensitive cell lines and combined the output with published PARPi datasets from eight additional cell lines. Ensuing exploration of the data identified 110 genes whose inactivation is strongly linked to sensitivity to PARPi. Parallel cell line generation of isogenic gene knockouts in ovarian and prostate cancer cell lines identified that inactivation of core HRR factors is required for driving in vitro PARPi responses comparable with the ones observed for BRCA1 or BRCA2 mutations. Moreover, pan-cancer genetic, transcriptomic, and epigenetic data analyses of these 110 genes highlight the ones most frequently inactivated in tumors, making this study a valuable resource for prospective identification of potential PARPi-responsive patient populations. Importantly, our investigations uncover XRCC3 gene silencing as a potential new prognostic biomarker of PARPi sensitivity in prostate cancer.Significance:This study identifies tumor genetic backgrounds where to expand the use of PARPis beyond mutations in BRCA1 or BRCA2. This is achieved by combining the output of unbiased genome-wide loss-of-function CRISPR-Cas9 genetic screens with bioinformatics analysis of biallelic losses of the identified genes in public tumor datasets, unveiling loss of the DNA repair gene XRCC3 as a potential biomarker of PARPi sensitivity in prostate cancer.
Variants in the
GPR146
Gene Are Associated With a Favorable Cardiometabolic Risk Profile
Authors: Rimbert Antoine , Yeung Ming W. , Dalila Nawar , Thio Chris H.L. , Yu Haojie , Loaiza Natalia , Oldoni Federico , van der Graaf Adriaan , Wang Siqi , Said M. Abdullah , Blauw Lisanne L. , Girardeau Aurore , Bray Lise , Caillaud Amandine , Bloks Vincent W. , Marrec Marie , Moulin Philippe , Rensen Patrick C.N. , van de Sluis Bart , Snieder Harold , Di Filippo Mathilde , van der Harst Pim , Tybjaerg-Hansen Anne , Zimmerman Philip , Cariou Bertrand , Kuivenhoven Jan Albert 
Published: September 2022

Background:
In mice, GPR146 (G-protein–coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown.

Methods:

Common and rare genetic variants in the
GPR146
gene locus were used as research instruments in the UK Biobank. The Lifelines, The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare
GPR146
variants.

Results:

In the UK Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (
P
=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between
GPR146
gene expression and plasma lipid and liver enzyme levels.

Conclusions:

This study shows that carriers of new genetic
GPR146
variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans.
Alert‐Triggered Patient Education Versus Nurse Feedback for Nonadministered Venous Thromboembolism Prophylaxis Doses: A Cluster‐Randomized Controlled Trial
Authors: Haut Elliott R. , Owodunni Oluwafemi P. , Wang Jiangxia , Shaffer Dauryne L. , Hobson Deborah B. , Yenokyan Gayane , Kraus Peggy S. , Farrow Norma E. , Canner Joseph K. , Florecki Katherine L. , Webster Kristen L.W. , Holzmueller Christine G. , Aboagye Jonathan K. , Popoola Victor O. , Kia Mujan Varasteh , Pronovost Peter J. , Streiff Michael B. , Lau Brandyn D. 
Published: September 2022

Background
Many hospitalized patients are not administered prescribed doses of pharmacologic venous thromboembolism prophylaxis.

Methods and Results

In this cluster‐randomized controlled trial, all adult non–intensive care units (10 medical, 6 surgical) in 1 academic hospital were randomized to either a real‐time, electronic alert–triggered, patient‐centered education bundle intervention or nurse feedback intervention to evaluate their effectiveness for reducing nonadministration of venous thromboembolism prophylaxis. Primary outcome was the proportion of nonadministered doses of prescribed pharmacologic prophylaxis. Secondary outcomes were proportions of nonadministered doses stratified by nonadministration reasons (patient refusal, other). To test our primary hypothesis that both interventions would reduce nonadministration, we compared outcomes pre‐ versus postintervention within each cohort. Secondary hypotheses were tested comparing the effectiveness between cohorts. Of 11 098 patient visits, overall dose nonadministration declined significantly after the interventions (13.4% versus 9.2%; odds ratio [OR], 0.64 [95% CI, 0.57–0.71]). Nonadministration decreased significantly (
P
<0.001) in both arms: patient‐centered education bundle, 12.2% versus 7.4% (OR, 0.56 [95% CI, 0.48–0.66]), and nurse feedback, 14.7% versus 11.2% (OR, 0.72 [95% CI, 0.62–0.84]). Patient refusal decreased significantly in both arms: patient‐centered education bundle, 7.3% versus 3.7% (OR, 0.46 [95% CI, 0.37–0.58]), and nurse feedback, 9.5% versus 7.1% (OR, 0.71 [95% CI, 0.59–0.86]). No differential effect occurred on medical versus surgical units. The patient‐centered education bundle was significantly more effective in reducing all nonadministered (
P
=0.03) and refused doses (
P
=0.003) compared with nurse feedback (OR, 1.28 [95% CI, 1.0–1.61];
P
=0.03 for interaction).

Conclusions
Information technology strategies like the alert‐triggered, targeted patient‐centered education bundle, and nurse‐focused audit and feedback can improve venous thromboembolism prophylaxis administration.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03367364.
The Impact of Antithrombotic Medications on Postoperative Bleeding Events Following Hemorrhoidectomy
Authors: Dean Katherine R. , Pavuluri Haritha , Fox Sarah , Tan Xiyan , Watson Benjamin , Wallenborn Jacqueline Grace , Blestel George A. 
Published: September 2022

Background Bleeding complications are a risk associated with hemorrhoid procedures. Despite the prevalence of anticoagulant and antiplatelet therapies, including newer direct oral anticoagulants (DOACs) in the aging patient population there is a paucity of data regarding the impact of the use of antithrombotic therapy (AT) especially DOACs, on bleeding complications of hemorrhoid procedures. Methods We retrospectively reviewed charts of patients who had undergone a total of 1152 procedures, including hemorrhoid excision and ligation, at a single institution in the years 2016-2018. We noted whether they were prescribed AT, the indication for therapy, perioperative medication management, whether a PBE occurred, and how the PBE was managed. Results PBE’s were noted in 5.92% of patients on ATs, as opposed to 2.66% of patients not on ATs ( P = .014.) The odds ratio of having a PBE when on ATs vs not on ATs is 2.3 (95% CI 1.21 to 4.38, P = .011). Seven out of 40 (17.5%) total PBE’s required hospital admission or repeat procedure, and this was not associated with AT use. Surprisingly, although males represented most of the patients on ATs, females were statistically more likely to have a PBE following a hemorrhoidectomy if on ATs. Discussion Patients on AT have an elevated risk of PBE compared to patients not on AT. No significant difference was found between the two groups when considering only those PBE’s severe enough to require hospital admission or repeat procedure. Further research is required to establish clear guidelines regarding the perioperative management of AT for hemorrhoid procedures.
Determining the Attributes of Short-Term Migration to Kashmir, India
Authors: Shah Farah Farooq , Joshi D P Priyadarshi 
Published: September 2022

The research uses data from a multi-stage survey performed in 2019 to evaluate short-term migrants’ characteristics and sectoral transitions in Kashmir. After locating in-migrants in the selected clusters, we randomly selected 253 samples in a 70:30 urban–rural ratio. The IV-Probit is used to identify the features of short-term migration to the valley. Results reveal that short-term migrants are primarily absorbed in construction. In addition, most in-migrants are unskilled and come from marginalised communities. This study contributes to the knowledge on migration in a developing nation like India, particularly in Kashmir. In addition to temporarily increasing the urban inflow, short-term labour migration may assist the family left behind by remitting revenue. Hence, these results are critical for policymaking regarding mobility, urban development and the expanding construction sector. JEL Codes: J6; C2
Social causes and outcomes of acute transient psychotic disorder: A review of recent evidence
Authors: Carden John , Huxley Peter John , Poole Robert , Robinson Catherine , Salmoiraghi Alberto , Foulkes Joanne , Davies Sioned , Williams Seimon , Morris Nia , Meudell Alan 
Published: September 2022

Background: Reports of increasing presentations of new cases of acute psychosis both locally, nationally and internationally during the COVID-19 pandemic, warranted further investigation. International case reports almost exclusively reported only clinical outcome (e.g. remission of psychotic symptoms), and fail to report on social precipitants or social outcomes. This is a common omission when investigating new psychosis cases such as acute and transient psychotic disorder (ATPD). In order to assess social impacts and outcomes, we conducted a rapid review of recent evidence. Aims: To conduct a rapid review of the recent evidence of social outcomes on new cases of psychosis emerging during the COVID-19 pandemic. Method: Four databases (Medline, Embase, Psychinfo and Cochrane COVID-19) were searched for ATPD, psychosis and social outcomes in adults aged 18+. Duplicates were removed. There were no language limitations. Results: There were 24 papers consisting of 18 original data research papers and 6 reviews. Additionally, 33 papers/letters, reporting on 60 individual cases of psychosis emerging during the COVID-19 pandemic. These two sets of papers were reviewed separately. Many original data research papers and reviews were sub optimal in their quality, with 44% online surveys, with the remainder being routinely collected data. Conclusion: There is a consensus that clinical outcomes of ATPD and other brief psychotic disorders (BPD) are good in the short term. The focus only on symptomatic clinical presentation and outcomes, leaves a gap in our understanding regarding social stressors and longer term social outcomes. ATPD and BPD often may not come to the attention of Early Intervention in Psychosis services, and if they do, are discharged following symptomatic remission. Without an understanding of the social stress factors and social outcomes, opportunities may be missed to prevent increased social disability and future relapse with these presentations.
Thyroid Gland Flap for Prevention of Pharyngocutaneous Fistula After Total Laryngectomy
Authors: Song Bokhyun , Suh Ye-Jin , Kim Tae Hwan , Son Young-Ik , Choi Nayeon 
Published: September 2022

Objectives Pharyngocutaneous fistula (PCF) is the one of the major complications after total laryngectomy (TL), which can result in saliva leakage, rupture of major vessels, and increased hospitalization. Several flaps have been tried to prevent PCF during TL, and they are usually associated with donor site morbidity and uncertain viability in case of previously irradiated patients. This study aimed to report a novel bilateral pedicled thyroid gland flap (TGF) technique for delicate and effective reinforcement of neopharynx suture line after TL. Methods Bilateral pedicled TGF was performed for the reinforcement of neopharynx T-shape suture sites after TL in this case series. Results A total of five cases of the TGF were performed during TL, with four of them being salvage setting following previous chemoradiation therapy (CRT). The well-adapted and viable TGF status was confirmed by post-operative computed tomography scan and normally preserved thyroid hormone levels in all patients. No post-operative infections, hemorrhage, hypothyroidism, hypoparathyroidism, or PCF were reported. Conclusion The TGF is an effective and reliable flap in TL patents and should be considered as a method in neopharynx reconstruction, even in salvage TL following prior CRT.
Linking Student Achievement Growth to Professional Development Participation and Changes in Instruction: A Longitudinal Study of Elementary Students and Teachers in Title I Schools
Authors: Desimone Laura M. , Smith Thomas M. , Phillips Kristie J. R. 
Published: September 2022

Background/Context Most reforms in elementary education rely on teacher learning and improved instruction to increase student learning. This study increases our understanding of which types of professional development effectively change teaching practice in ways that boost student achievement. Purpose/Objective/Research Question/Focus of Study Our three-year longitudinal analysis answers two main research questions: (1) To what extent do teachers’ topic coverage, emphasis on memorization and solving novel problems, and time spent on mathematics instruction, predict student mathematics achievement growth? (2) To what extent does teacher participation in content-focused professional development predict the aspects of instruction found in our first analysis to be related to increases in student mathematics achievement growth? Population/Participants/Subjects This study uses data collected by the U.S. Department of Education for the Longitudinal Evaluation of School Change and Performance (LESCP) in 1997, 1998, and 1999. The LESCP drew its sample from 71 high-poverty schools in 18 school districts in 7 states. Our student-level analyses include 7,588 observations over three years of 4,803 students assigned to 457 teachers. Teacher-level analyses include the same 457 teachers in 71 schools over three years. Research Design This is a quasi-experimental longitudinal study. To answer our first research question, we employ a 4-level cross-classified growth model using MLwiN software, with time points nested within students, students cross-classified by teachers over the three years of the study, and teachers and students nested within schools. To answer our second question, we employ a series of hierarchical linear models (HLM) to test the relationship between instruction and professional development. Conclusions/Recommendations We found that (1) when teachers in third, fourth, and fifth grade focused more on advanced mathematics topics (defined as operations with fractions, distance problems, solving equations with one unknown, solving two equations with two unknowns, and statistics) and emphasized solving novel problems, student achievement grew more quickly; (2) when teachers focused more on basic topics (defined as measurement, rounding, multi-digit multiplication, and problem solving) and emphasized memorizing facts, student achievement grew more slowly; and (3) when teachers participated in professional development that focused on math content or instructional strategies in mathematics (in Year 1), they were more likely to teach in ways associated with student achievement growth. Specifically, they were more likely to teach advanced topics and emphasize solving novel problems. Effect sizes ranged from 1% to 15% of a standard deviation.
Coping Strategies Used by Older Cancer Survivors During the COVID-19 Pandemic: A Longitudinal Qualitative Study
Authors: Galica Jacqueline , Kilgour Heather M. , Oliffe John L. , Haase Kristen R. 
Published: September 2022

Objectives: The objective of this study is to longitudinally examine the coping strategies used by older cancer survivors (≥60 years of age) during COVID-19. Methods: An interpretive descriptive approach was used to collect and analyse qualitative data collected via 1:1 telephone interviews at three timepoints: June/July 2020, January 2021, and March 2021. Main Findings: Coping strategies used by older adults reflected the resources available to them, and their agency in self-triaging and deciding on resources to support their coping. These decisions were impacted by pandemic-imposed restrictions and necessitated readjustment over time. Three themes were developed to describe coping strategies (including any changes): adapting means and methods to connect with others; being intentional about outlook; and taking actions toward a brighter future. Conclusion: Older adults used a variety of coping strategies, though their reliance on resources beyond themselves (e.g., family/friends) indicates a need to add tailored resources to existing professional services.
Responsiveness and minimal clinically important difference of the five times sit-to-stand test in ambulatory individuals with spinal cord injury: A six-month prospective cohort study
Authors: Amatachaya Sugalya , Khuna Lalita , Thaweewannakij Thiwabhorn 
Published: September 2022

Objectives To explore the responsiveness and minimal clinically important differences of the five times sit-to-stand test in ambulatory individuals with spinal cord injury. Methods This six-month prospective cohort study was conducted in 109 individuals with spinal cord injury who could walk with or without a walking device for at least 10 meters. Participants were assessed for the five times sit-to-stand test in the four arm-placement conditions and standard measures to determine responsiveness of the test, at baseline, and one, three, and six months. At six months, participants were also interviewed for the global rating of change to estimate the minimal clinically important differences of the five times sit-to-stand test. Results The five times sit-to-stand test showed large internal responsiveness (standardized response means>0.83), with moderate external responsiveness as compared to the 10-meter walk test ( ρ = −0.28 to −0.48, p < 0.005). The changes in the outcomes >2.27 and >2 s could be used to indicate a level of minimal clinically important change for participants who executed the test with and without hands, respectively. Conclusion The five times sit-to-stand test is a responsiveness measure for ambulatory individuals with spinal cord injury. The levels of minimal clinically important differences found in this study (>2.27 and >2 s) can be applied as a useful benchmark for the decision of clinically relevant changes over time for these individuals.
Stochastic modelling of the home equity access scheme
Authors: Lamarra Tyson , Bruhn Aaron , Miller Michael 
Published: September 2022

The housing wealth of elderly homeowners is emerging as a key asset to support Australians in retirement. The Australian government's Home Equity Access Scheme allows elderly Australians to access the equity in their home and utilise this illiquid wealth. Through stochastic modelling of the scheme, this paper compares two strategies of drawing down housing wealth and provides a framework for comparing strategies that balances income, flexibility and longevity protection. The first strategy supplements other sources of retirement income, whereas the second strategy is similar to a contingent deferred annuity, with non-housing assets drawn down first. Although results vary by cohort and objective, the role of the scheme as a vehicle to protect against poverty in old age is emphasised. This reinforces the potential of home ownership as a financial asset in retirement, in addition to benefits conferred through housing ownership over the entire life cycle. JEL Classification: G22,G51