bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of loss to follow-up in the Canadian Longitudinal Study on Aging: a retrospective cohort study
Authors: Farid Doaa , Li Patricia , Dasgupta Kaberi , Rahme Elham 
Published: September 2022

BackgroundSystematic loss to follow-up (LFU) creates selection bias and hinders generalisability in longitudinal cohort studies. Little is known about LFU risks in underserved populations including immigrants, those with depressive symptoms and language minorities. We used the Canadian Longitudinal Study on Aging (baseline 2012–2015 and 3-year follow-up 2015–2018) comprehensive and tracking cohorts to examine the association of language with LFU and its effect modification by immigrant status and depressive symptoms among participants from Quebec and those from outside Quebec.MethodsLanguage was English-speaking, French-speaking and Bilingual according to the language participants’ reported being able to converse in. Language minorities were French-speakers outside Quebec and English-speakers inside Quebec. LFU was withdrawal or not providing follow-up data. Logistic regression models assessed the associations of interest.ResultsOur cohort included 49 179 individuals (mean age 63.0, SD 10.4 years; 51.4% female). Overall, 7808 (15.9%) were immigrants and 7902 (16.1%) had depressive symptoms. Language was 4672 (9.5%) French-speaking, 33 532 (68.2%) English-speaking and 10 976 (22.3%) Bilingual. Immigration ≤20 years (OR 1.84, 95% CI 1.34 to 2.53) or arrival at age >22 years (1.32, 95% CI 1.10 to 1.58) and depressive symptoms (1.23, 95% CI 1.13 to 1.46) had higher LFU risks. Bilingual (vs French-speaking) had lower LFU risk outside (0.45, 95% CI 0.24 to 0.86) and inside Quebec (0.78, 95% CI 0.63 to 0.98). LFU risk was higher in French-speakers (vs English-speakers) outside (2.33, 95% CI 1.19 to 4.55), but not inside Quebec. Female, higher income, higher education and low nutritional risk had lower LFU risks.ConclusionSpeaking only French (vs Bilingual), having depressive symptoms and immigrant status increased LFU risks, with the latter not modifying the language effect.
Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases
Authors: Testard Quentin , Vanhoye Xavier , Yauy Kevin , Naud Marie-Emmanuelle , Vieville Gaelle , Rousseau Francis , Dauriat Benjamin , Marquet Valentine , Bourthoumieu Sylvie , Geneviève David , Gatinois Vincent , Wells Constance , Willems Marjolaine , Coubes Christine , Pinson Lucile , Dard Rodolphe , Tessier Aude , Hervé Bérénice , Vialard François , Harzallah Ines , Touraine Renaud , Cogné Benjamin , Deb Wallid , Besnard Thomas , Pichon Olivier , Laudier Béatrice , Mesnard Laurent , Doreille Alice , Busa Tiffany , Missirian Chantal , Satre Véronique , Coutton Charles , Celse Tristan , Harbuz Radu , Raymond Laure , Taly Jean-François , Thevenon Julien 
Published: September 2022

BackgroundDespite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%–20%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and/or WES.MethodsThis study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.ResultsOn the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704 bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.ConclusionCombining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.
Clinical applicability of the Polygenic Risk Score for breast cancer risk prediction in familial cases
Authors: Lakeman Inge M M , Rodríguez-Girondo Mar D M , Lee Andrew , Celosse Nandi , Braspenning Merel E , van Engelen Klaartje , van de Beek Irma , van der Hout Annemiek H , Gómez García Encarna B , Mensenkamp Arjen R , Ausems Margreet G E M , Hooning Maartje J , Adank Muriel A , Hollestelle Antoinette , Schmidt Marjanka K , van Asperen Christi J , Devilee Peter 
Published: September 2022

BackgroundCommon low-risk variants are presently not used to guide clinical management of familial breast cancer (BC). We explored the additive impact of a 313-variant-based Polygenic Risk Score (PRS313) relative to standard gene testing in non-BRCA1/2Dutch BC families.MethodsWe included 3918 BC cases from 3492 Dutch non-BRCA1/2BC families and 3474 Dutch population controls. The association of the standardised PRS313with BC was estimated using a logistic regression model, adjusted for pedigree-based family history. Family history of the controls was imputed for this analysis. SEs were corrected to account for relatedness of individuals. Using the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) V.5 model, lifetime risks were retrospectively calculated with and without individual PRS313. For 2586 cases and 2584 controls, the carrier status of pathogenic variants (PVs) inATM,CHEK2andPALB2was known.ResultsThe family history-adjusted PRS313was significantly associated with BC (per SD OR=1.97, 95% CI 1.84 to 2.11). Including the PRS313in BOADICEA family-based risk prediction would have changed screening recommendations in up to 27%, 36% and 34% of cases according to BC screening guidelines from the USA, UK and the Netherlands (National Comprehensive Cancer Network, National Institute for Health and Care Excellence, and Netherlands Comprehensive Cancer Organisation), respectively. For the population controls, without information on family history, this was up to 39%, 44% and 58%, respectively. Among carriers of PVs in known moderate BC susceptibility genes, the PRS313had the largest impact forCHEK2andATM.ConclusionsOur results support the application of the PRS313in risk prediction for genetically uninformative BC families and families with a PV in moderate BC risk genes.
Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme
Authors: Yang Chia-Feng , Liao Ting-Wei Ernie , Chu Yen-Ling , Chen Li-Zhen , Huang Ling-Yi , Yang Tsui-Feng , Ho Hui-Chen , Kao Shu-Min , Niu Dau-Ming 
Published: September 2022

BackgroundStarting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres.MethodsIn this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups.ResultsThe average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects.ConclusionVery early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.
Brain neuronal and glial damage during acute COVID-19 infection in absence of clinical neurological manifestations
Authors: Plantone Domenico , Locci Sara , Bergantini Laura , Manco Carlo , Cortese Rosa , Meocci Martina , Cavallaro Dalila , d'Alessandro Miriana , Bargagli Elena , De Stefano Nicola 
Published: September 2022

BackgroundTo assess whether SARS-CoV-2 infection may affect the central nervous system, specifically neurons and glia cells, even without clinical neurological involvement.MethodsIn this single centre prospective study, serum levels of neurofilament light chain (sNfL) and glial fibrillar acidic protein (sGFAp) were assessed using SimoaTM assay Neurology 2-Plex B Assay Kit, in 148 hospitalised patients with COVID-19 without clinical neurological manifestations and compared them to 53 patients with interstitial pulmonary fibrosis (IPF) and 108 healthy controls (HCs).ResultsAge and sex-corrected sNfL levels were higher in patients with COVID-19 (median log10-sNfL 1.41; IQR 1.04–1.83) than patients with IPF (median log10-sNfL 1.18; IQR 0.98–1.38; p<0.001) and HCs (median log10-sNfL 0.89; IQR 0.72–1.14; p<0.001). Likewise, age and sex-corrected sGFAP levels were higher in patients with COVID-19 (median log10-sGFAP 2.26; IQR 2.02–2.53) in comparison with patients with IPF (median log10-sGFAP 2.15; IQR 1.94–2.30; p<0.001) and HCs (median log10-sGFAP 1.87; IQR 0.64–2.09; p<0.001). No significant difference was found between patients with HCs and IPF (p=0.388 for sNfL and p=0.251 for sGFAp). In patients with COVID-19, a prognostic model with mortality as dependent variable (26/148 patients died during hospitalisation) and sNfl, sGFAp and age as independent variables, showed an area under curve of 0.72 (95% CI 0.59 to 0.84; negative predictive value (NPV) (%):80,positive predictive value (PPV)(%): 84; p=0.0008).ConclusionThe results of our study suggest that neuronal and glial degeneration can occur in patients with COVID-19 regardless of overt clinical neurological manifestations. With age, levels of sNfl and GFAp can predict in-hospital COVID-19-associated mortality and might be useful to assess COVID-19 patient prognostic profile.
Elevated CEA and CA 19-9 Levels within the Normal Ranges Increase the Likelihood of CRC Recurrence in the Chinese Han Population
Authors: Wang Lujia , Zhang Guangkai , Shen Jiafeng , Shen Yujiang , Cai Guojun 
Published: September 2022

Objective. This study aimed to determine if variations in the expression profiles of CA 19-9 and carcinoembryonic antigen (CEA) within the reference range could serve as possible biomarkers for postoperative CRC recurrence. Method. This retrospective cohort investigation enrolled 2,596 cases of CRC that received curative surgery. Serum CEA/CA 19-9 were measured through chemiluminescence immunoassay (CLIA). Results. During follow-up (median follow-up = 5.2 years), in total, 837 patients experienced recurrence. The fully adjusted hazard ratios (HRs) were significantly higher, ≥1 standard deviation (±SD), in patients with upregulated CEA/CA 19-9 levels (

HRCEA
=
7.06

;

HRCA

19
−
9
=
3.98

) than in those with downregulated CEA/CA 19-9 levels. The likelihood of recurrence remained consistently greater in cases of elevated CEA/CA 19-9 levels during sensitivity analyses. Conclusions. The findings of this analysis showed that variations in CEA/CA 19-9 expression profiles within the reference range impact CRC recurrence.
Preclinical and Clinical Trial Results Using Talazoparib and Low-Dose Chemotherapy
Authors: Wainberg Zev A. , Singh Arun S. , Konecny Gottfried E. , McCann Kelly E. , Hecht J. Randolph , Goldman Jonathan , Chmielowski Bartosz , Finn Richard S. , O'Brien Neil , Von Euw Erika , Price Megan M. , Martinez Diego , Yonemoto Lisa , Brennan Meghan , Glaspy John A. , Slamon Dennis J. 
Published: September 2022

Abstract

Purpose:
On the basis of preclinical data, we hypothesized that low doses of chemotherapy (10% of therapeutic doses) with full dose of a PARP inhibitor could have improved efficacy and tolerability.

Patients and Methods:
In this phase I dose-escalation study, patients with BRCA-normal advanced malignancies were assigned to either talazoparib/temozolomide or talazoparib/irinotecan. Talazoparib was dose-escalated from 500 mcg to 1 mg daily before dose escalation of temozolomide/irinotecan. The starting dose of temozolomide was 25 mg/m2/day orally on days 1 to 5 and irinotecan was 25 mg/m2/day intravenously on days 1 and 15. The primary objectives of this trial were safety and tolerability, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD).

Results:
Of 40 patients enrolled, 18 (mean: 7 prior therapies) were enrolled in talazoparib + temozolomide and 22 in talazoparib + irinotecan. DLTs were hematologic in both arms, but all hematologic adverse events resolved with either treatment interruption and/or dose reductions of talazoparib. The MTDs were talazoparib 1 mg + temozolomide 37.5 mg/m2 and talazoparib 1 mg + irinotecan 37.5 mg/m2. There were four partial responses in the talazoparib + temozolomide arm and five in the talazoparib + irinotecan arm for a response rate of 23% (9/40). The pharmacokinetic profiles of talazoparib + temozolomide/irinotecan were similar to that of talazoparib monotherapy. Responses were seen independent of homologous recombination (HR) status and HR deficiency score.

Conclusions:
These results show that talazoparib with low-dose temozolomide or irinotecan is reasonably well tolerated and demonstrates clinical activity in a wide range of cancers. Randomized trials of talazoparib with or without low-dose chemotherapy are ongoing in small cell lung cancer and ovarian cancer.
Molecular Profile Changes in Patients with Castrate-Resistant Prostate Cancer Pre- and Post-Abiraterone/Prednisone Treatment
Authors: Sicotte Hugues , Kalari Krishna R. , Qin Sisi , Dehm Scott M. , Bhargava Vipul , Gormley Michael , Tan Winston , Sinnwell Jason P. , Hillman David W. , Li Ying , Vedell Peter T. , Carlson Rachel E. , Bryce Alan H. , Jimenez Raphael E. , Weinshilboum Richard M. , Kohli Manish , Wang Liewei 
Published: September 2022

Abstract

We identified resistance mechanisms to abiraterone acetate/prednisone (AA/P) in patients with metastatic castration-resistant prostate cancer (mCRPC) in the Prostate Cancer Medically Optimized Genome-Enhanced Therapy (PROMOTE) study.

We analyzed whole-exome sequencing (WES) and RNA-sequencing data from 83 patients with metastatic biopsies before (V1) and after 12 weeks of AA/P treatment (V2). Resistance was determined by time to treatment change (TTTC).

At V2, 18 and 11 of 58 patients had either short-term (median 3.6 months; range 1.4–4.5) or long-term (median 29 months; range 23.5–41.7) responses, respectively. Nonresponders had low expression of TGFBR3 and increased activation of the Wnt pathway, cell cycle, upregulation of AR variants, both pre- and posttreatment, with further deletion of AR inhibitor CDK11B posttreatment. Deletion of androgen processing genes, HSD17B11, CYP19A1 were observed in nonresponders posttreatment. Genes involved in cell cycle, DNA repair, Wnt-signaling, and Aurora kinase pathways were differentially expressed between the responder and non-responder at V2. Activation of Wnt signaling in nonresponder and deactivation of MYC or its target genes in responders was detected via SCN loss, somatic mutations, and transcriptomics. Upregulation of genes in the AURKA pathway are consistent with the activation of MYC regulated genes in nonresponders. Several genes in the AKT1 axis had increased mutation rate in nonresponders. We also found evidence of resistance via PDCD1 overexpression in responders.

Implications:
Finally, we identified candidates drugs to reverse AA/P resistance: topoisomerase inhibitors and drugs targeting the cell cycle via the MYC/AURKA/AURKB/TOP2A and/or PI3K_AKT_MTOR pathways.
The Tricky Concept of ‘Educational Equity’ – In Search of Conceptual Clarity
Authors: Edgar Stephen 
Published: September 2022

Abstract
Within the social sciences, the term equity has a helpful and precise meaning – referring to a differentiated response to an individual’s distinct needs or circumstances. However, since the 2000s ‘equity’ has been recontextualised within national and international education policymaking as a generic term. This recontextualisation has led to ‘equity’ being used uncritically to refer to a range of related, and sometimes contradictory, concepts. This article draws on the literature to identify five framings of ‘educational equity’ within recent policy. It suggests that only one of these – which emphasises responsiveness to individual needs or characteristics – has clear conceptual alignment with the core principle of equity. The others either relate more strongly to the principle of equality or emphasise the tracking and measurement of outcomes. This article highlights the need for conceptual clarity to ensure the principle of equity is a helpful one in informing research, policy, and practice.
Projecting Future Precipitation in the Yellow River Basin Based on CMIP6 Models
Authors: Sun Zhouliang , Liu Yanli , Zhang Jianyun , Chen Hua , Shu Zhangkang , Chen Xin , Jin Junliang , Guan Tiesheng , Liu Cuishan , He Ruimin , Wang Guoqing 
Published: September 2022

Abstract
Water resources severely constrain high-quality development in the Yellow River basin (YRB). Predicting the trend of precipitation on the basis of satisfying precision has important guiding significance for future regional development. Using the projected precipitation in 12 CMIP6 models, this study applied the most appropriate correction method for each model from four quantile-mapping methods and projected future changes of annual precipitation in the YRB and three key regions. The projection uncertainty was quantitatively assessed by addressing model spread (MS) and range. The precipitation anomaly under all four scenarios would increase for the YRB and key regions. The increasing rates (the linear coefficient) from Shared Socioeconomic Pathway 126 (SSP126) to SSP585 were 30–62, 60–103, 84–122, and 134–204 mm (100 yr)−1, respectively. The largest increase was the sediment-yielding region, which reached about 40–60 mm in 2031–60 and 70–125 mm in 2061–90. The 400-mm isohyet was projected to move continuously to the northwest in the future. The uncertainty quantified by MS was reduced by 85.9%–94.6%, and projection ranges were less than 50 mm (about 10% of climatology) in most parts of YRB. From the increasing trend of future precipitation in the YRB, it can be inferred that the arid region will shrink. It may be a good opportunity to implement ecological conservation and high-quality development of the YRB successfully.

Significance Statement
We want to understand the spatial–temporal evolution pattern of future precipitation in the Yellow River basin (YRB) under climate change scenarios. In the future, the precipitation in the YRB and the three key regions will increase, with the sediment-yielding region increasing the most, and the arid region will shrink. Our findings confirm that the spatial–temporal patterns of precipitation in the YRB will change significantly under climate change scenarios. These findings will guide ecological protection and regional social and economic development in the YRB. Future research should focus on adaptation strategies of agricultural production patterns to climate change.
Do Hoosiers Forget How to Drive in the Snow Each Year?
Authors: Hitchens Nathan M. 
Published: September 2022

Abstract
The winter season in many U.S. states includes snowfall, and with it comes comments about how drivers always seem to “forget” how to drive in snow when the first snowfall of the season occurs. This study assesses the accuracy of this popular sentiment during Indiana winters from 2007 to 2020. The number of motor vehicle crashes, injuries, and fatalities during the first snowfall of the season was compared with those during subsequent snow events. A grid of 46 cells was constructed to subdivide the state, and instances of snowfall and crashes were aggregated within each cell each day during the study period. Daily crash, injury, and fatality totals in each cell were normalized by their respective means and standard deviations, allowing for data from all cells to be combined into a single dataset. Four snow accumulation thresholds were examined: 1, 13, 25, and 51 mm. Distributions at each threshold show that more crashes occur on average on days with the first snowfall of the winter season than on other days with snowfall, regardless of the accumulation threshold used. Statistical tests support this result, showing significant differences between the mean numbers of crashes at each of the four snowfall thresholds. There were also significantly more injuries on the first snowfall day and more fatalities, although fatalities were only significant for the 13-mm snowfall threshold.

Significance Statement
The purpose of my research is to answer the question: are there more motor vehicle crashes on the first day with snow each winter when compared with the number of crashes on other days with snowfall in the state of Indiana? Using four snowfall thresholds of increasing amounts, statistical tests comparing daily crashes on first snowfall and other snowfall days showed that there were significantly more crashes on average on the first day with snowfall each winter, regardless of the amount of snow accumulation. This supports the popular notion that crashes occur more frequently the first time it snows each year, although it is more likely attributed to drivers reacclimating to snowy road conditions than to forgetfulness.
Clinical Phenotypic Variability and Significance of Pneumolabyrinth After Tympanum-Penetrating Injury
Authors: Yu Huiqian , Cai Guoyu , Wu Jingfang , Li Qingzhong 
Published: September 2022

Objectives This study aimed to investigate the clinical manifestations, treatment, and prognosis of traumatic pneumolabyrinth caused by tympanic membrane (TM) perforation. Methods Clinical data were collected from 3 cases of traumatic pneumolabyrinth occurring between 2015 and 2021 and 22 cases were identified from 20 articles in PubMed database that reported pneumolabyrinth due to tympanum-penetrating injury. Intervention Nonoperative treatment was performed in Cases 1 and 3. Middle ear inspection was performed 1 year after the injury due to worsening vertigo upon head movement in Case 2. Main outcome measures Hearing outcomes and vestibular evaluations were presented for the 3 cases, and all comparable cases in the literature were reviewed. Results All 25 patients had a history of traumatic TM perforation, with perforations mostly located in the posterior or posterior superior quadrant (16 cases). Air signs were observed in the vestibule in all 25 patients, 15 of whom revealed stapes luxation into the vestibule. Conservative treatments were performed in 8 cases, and exploratory surgery in 17 cases. Most patients were free of vertigo (23/25). There were no significant hearing improvements in 15 cases, while hearing recovery or improvement was observed in 9 cases. Conclusions The clinical manifestations of pneumolabyrinth due to tympanum-penetrating injuries vary widely. Importantly, the degree of hearing loss is not directly related to the subjectively perceived vertigo but to the location and extent of pneumolabyrinth.