bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Accountable Care Teams to Improve Timely Discharge: A Pilot Study
Authors: Orewa Gregory N. , Feldman Sue S. , Hearld Kristine Ria , Kennedy Kierstin Cates , Hall Allyson G. 
Published: August 2021

Background and Objective:
Hospitals worldwide are faced with the problem of discharging patients on time. Delayed discharge creates domino effects with significant implications for hospitals. The accountable care team (ACT) is a multidisciplinary, unit-based approach to identifying opportunities to improve patient care and address inefficiencies in care delivery and throughput, including assuring timely discharges. In response to concerns about emergency department boarding times and delays in timely discharge, the ACT recommended a set of strategies to improve communication across team members and to reduce wait times for transportation within and outside the hospital. Collectively these strategies were thought to increase the proportion of patients discharged on time. In this article, we describe and assess changes in timely discharge resulting from the implementation of strategies recommended by the ACT.

Methods:
This study uses a retrospective, quasi-experimental design to compare the percentage of discharges by 1 pm of hospital units implementing the ACT intervention to those units not implementing the intervention. Median discharge time was compared pre- and post-implementation using the Wilcoxon rank sum test. Difference-in-differences modeling was employed to assess whether changes in the percentage of discharges by 1 pm differed between units implementing the intervention and units not implementing the intervention.

Results:
One month post-implementation, the percentage discharged by 1 pm was statistically significantly higher for units implementing the intervention (53.6%) compared with comparison units (22.5%, t = −4.48, P < .01). Statistically significant differences in the percentage discharged by 1 pm were also seen at 3 and 6 months post-implementation. The median discharge time showed a statistically significant decrease by 77 minutes from the baseline to intervention period (P < .01).

Conclusion:
The result from the study suggests that ACTs can be used to develop approaches aimed at improving patient care in general, and discharge efficiencies in particular. Health care organizations are encouraged to utilize and then evaluate the specific activities of multidisciplinary teams aimed at developing recommendations for practice improvement.
Presentation, Treatment, and Prognosis of Esophageal Carcinoma in a Nationwide Comparison of Sweden and the Netherlands
Authors: Kalff Marianne C. , Gottlieb-Vedi Eivind , Verhoeven Rob H. A. , van Laarhoven Hanneke W. M. , Lagergren Jesper , Gisbertz Suzanne S. , Markar Sheraz R. , van Berge Henegouwen Mark I. 
Published: August 2021

Objective:
This population-based study aimed to compare presentation, treatment allocation and survival of potentially curable esophageal cancer patients between Sweden and the Netherlands.

Summary of Background data:
Identification of inter-country differences in treatment allocation and survival may be used for targeted esophageal cancer care improvement.

Methods:
Nationwide datasets were acquired from a Swedish cohort study and the Netherlands Cancer Registry. Patients with potentially curable (cT1-T4a/Tx, cN0/+, cM0/x) esophageal adenocarcinoma or squamous cell carcinoma (SCC) diagnosed in 2011–2015 were included. Multivariable logistic regression provided odds ratios (OR) for treatment allocation, and multivariable Cox model provided hazard ratios (HR) for overall survival, all with 95% confidence intervals (CI), adjusted for age, sex, year, tumor sub-location and stage.

Results:
Among 1980 Swedish and 7829 Dutch esophageal cancer patients, Swedish patients were older (71 vs 69 years, P <0.001) and had higher cT-stage (cT3: 49% vs 46%, P <0.001). After adjustment for confounders, Swedish patients were less frequently allocated to curative treatment (adenocarcinoma: OR=0.31, 95%CI 0.26–0.36; SCC: OR=0.28, 95%CI 0.22–0.36). Overall survival was lower in Swedish patients (adenocarcinoma: HR=1.36, 95%CI 1.27–1.46; SCC: HR=1.38, 95%CI 1.24–1.53), also when allocated to curative treatment (adenocarcinoma: HR=1.12, 95%CI 1.01–1.24; SCC: HR=1.34, 95%CI 1.14–1.59).

Conclusion:
Swedish patients with potentially curable esophageal cancer were less frequently allocated to curative treatment, and showed lower survival compared to Dutch patients. The less pronounced inter-country survival difference after curative treatment suggests that the overall survival difference could at least partly be due to relative undertreatment of Swedish patients. Shared curative treatment thresholds across Europe may help improve survival of esophageal cancer patients.
Incisional Surgical Site Infections After Mass and Layered Closure of Upper Abdominal Transverse Incisions
Authors: Grąt Michał , Morawski Marcin , Krasnodębski Maciej , Borkowski Jan , Krawczyk Piotr , Grąt Karolina , Stypułkowski Jan , Maczkowski Bartosz , Figiel Wojciech , Lewandowski Zbigniew , Kobryń Konrad , Patkowski Waldemar , Krawczyk Marek , Wróblewski Tadeusz , Otto Włodzimierz , Paluszkiewicz Rafał , Zieniewicz Krzysztof 
Published: August 2021

Objective:
To compare the early results of mass and layered closure of upper abdominal transverse incisions.

Summary of Background Data:
Contrary to midline incisions, data on closure of transverse abdominal incisions are lacking.

Methods:
This is the first analysis of a randomized controlled trial primarily designed to compare mass with layered closure of transverse incisions with respect to incisional hernias. Patients undergoing laparotomy through upper abdominal transverse incisions were randomized to either mass or layered closure with continuous sutures. Incisional surgical site infection (incisional-SSI) was the primary end-point. Secondary end-points comprised suture-to-wound length ratio (SWLR), closure duration, and fascial dehiscence (clinicatrials.gov NCT03561727).

Results:
A total of 268 patients were randomized to either mass (n=134) or layered (n=134) closure. Incisional-SSIs occurred in 24 (17.9%) and 8 (6.0%) patients after mass and layered closure, respectively (P =0.004), with crude odds ratio (OR) of 0.29 [95% confidence interval (95% CI) 0.13–0.67; P =0.004]. Layered technique was independently associated with fewer incisional-SSIs (OR: 0.29; 95% CI 0.12–0.69; P =0.005). The number needed to treat, absolute, and relative risk reduction for layered technique in reducing incisional-SSIs were 8.4 patients, 11.9%, and 66.5%, respectively. Dehiscence occurred in one (0.8%) patient after layered closure and in two (1.5%) patients after mass closure (P >0.999). Median SWLR were 8.1 and 5.6 (P <0.001) with median closure times of 27.5 and 25.0 minutes (P =0.044) for layered and mass closures, respectively.

Conclusions:
Layered closure of upper abdominal transverse incisions should be preferred due to lower risk of incisional-SSIs and higher SWLR, despite clinically irrelevant longer duration.
CuNA: Cumulant-based Network Analysis of genotype-phenotype associations in Parkinson’s Disease
Authors: Bose Aritra , Platt Daniel E. , Haiminen Niina , Parida Laxmi 
Published: August 2021

AbstractParkinson’s Disease (PD) is a progressive neurodegenerative movement disorder characterized by loss of striatal dopaminergic neurons. Progression of PD is usually captured by a host of clinical features represented in different rating scales. PD diagnosis is associated with a broad spectrum of non-motor symptoms such as depression, sleep disorder as well as motor symptoms such as movement impairment, etc. The variability within the clinical phenotype of PD makes detection of the genes associated with early onset PD a difficult task. To address this issue, we developed CuNA, a cumulant-based network analysis algorithm that creates a network from higher-order relationships between eQTLs and phenotypes as captured by cumulants. We also designed a multi-omics simulator, CuNAsim to test CuNA’s qualitative accuracy. CuNA accurately detects communities of clinical phenotypes and finds genes associated with them. When applied on PD data, we find previously unreported genes INPP5J, SAMD1 and OR4K13 associated with symptoms of PD affecting the kidney, muscles and olfaction. CuNA provides a framework to integrate and analyze RNA-seq, genotype and clinical phenotype data from complex diseases for more targeted diagnostic and therapeutic solutions in personalized medicine. CuNA and CuNAsim binaries are available upon request.
Combining SNP-to-gene linking strategies to pinpoint disease genes and assess disease omnigenicity
Authors: Gazal Steven , Weissbrod Omer , Hormozdiari Farhad , Dey Kushal , Nasser Joseph , Jagadeesh Karthik , Weiner Daniel , Shi Huwenbo , Fulco Charles , O’Connor Luke , Pasaniuc Bogdan , Engreitz Jesse M. , Price Alkes L. 
Published: August 2021

AbstractAlthough genome-wide association studies (GWAS) have identified thousands of disease-associated common SNPs, these SNPs generally do not implicate the underlying target genes, as most disease SNPs are regulatory. Many SNP-to-gene (S2G) linking strategies have been developed to link regulatory SNPs to the genes that they regulate in cis, but it is unclear how these strategies should be applied in the context of interpreting common disease risk variants. We developed a framework for evaluating and combining different S2G strategies to optimize their informativeness for common disease risk, leveraging polygenic analyses of disease heritability to define and estimate their precision and recall. We applied our framework to GWAS summary statistics for 63 diseases and complex traits (average N=314K), evaluating 50 S2G strategies. Our optimal combined S2G strategy (cS2G) included 7 constituent S2G strategies (Exon, Promoter, 2 fine-mapped cis-eQTL strategies, EpiMap enhancer-gene linking, Activity-By-Contact (ABC), and Cicero), and achieved a precision of 0.75 and a recall of 0.33, more than doubling the precision and/or recall of any individual strategy; this implies that 33% of SNP-heritability can be linked to causal genes with 75% confidence. We applied cS2G to fine-mapping results for 49 UK Biobank diseases/traits to predict 7,111 causal SNP-gene-disease triplets (with S2G-derived functional interpretation) with high confidence. Finally, we applied cS2G to genome-wide fine-mapping results for these traits (not restricted to GWAS loci) to rank genes by the heritability linked to each gene, providing an empirical assessment of disease omnigenicity; averaging across traits, we determined that the top 200 (1%) of ranked genes explained roughly half of the heritability linked to all genes. Our results highlight the benefits of our cS2G strategy in providing functional interpretation of GWAS findings; we anticipate that precision and recall will increase further under our framework as improved functional assays lead to improved S2G strategies.
Pre-diagnostic plasma metabolomics and the risk of exfoliation glaucoma
Authors: Kang Jae H. , Zeleznik Oana , Frueh Lisa , Lasky-Su Jessica , Eliassen A. Heather , Clish Clary , Rosner Bernard A. , Pasquale Louis R. , Wiggs Janey L. 
Published: August 2021

ABSTRACTObjectiveTo identify pre-diagnostic plasma metabolomic biomarkers associated with risk of exfoliation glaucoma (XFG).MethodsWe conducted a metabolomic study using a 1:1 matched nested case-control study design within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Participants provided blood samples in 1989-’90 (NHS) and 1993-’95 (HPFS); we identified 205 participants who newly developed XFG during follow-up to 2018 (average time to diagnosis from blood draw =11.8 years); XFG was confirmed with medical record review. We profiled plasma metabolites using liquid chromatography- mass spectrometry and identified 379 known metabolites that passed quality control checks. Metabolites were transformed using probit scores for normality. We used multivariable-adjusted logistic regression adjusting for matching factors (such as age, residential latitude, season and time of blood draw), glaucoma family history and other covariates. Metabolite Set Enrichment Analysis was used to identify metabolite classes associated with risk of XFG. Number of effective tests (NEF) and False Discovery Rate (FDR) were used to adjust for multiple comparisons.ResultsMean age of cases (n=205) at diagnosis was 71 years; 84% were women and >99% were Caucasian; matched controls (n=205) all reported eye exams as of the matched cases’ index date. A total of 33 metabolites were nominally significantly associated with XFG risk (p<0.05) and 4 metabolite classes were significantly associated (FDR<0.05). Overall, adverse associations were observed for the classes of lysophosphatidylcholines (FDR=0.02) and phosphatidylethanolamine plasmalogens (FDR=0.004). Inverse associations were observed for triglycerides (FDR<0.001) and steroid and steroid derivatives (FDR=0.03); in particular, the multivariable-adjusted odds ratio for XFG risk associated with each 1 standard deviation increase in plasma cortisone levels was 0.49 (95% CI=0.32-0.74; NEF=0.05). Results did not differ materially by time between blood draw and diagnosis, latitude of residence (< or ≥41°N latitude), age (< or ≥60 years), sex or glaucoma family history.ConclusionsFour broad classes of metabolites (including steroids such as cortisone and 3 lipid classes) in pre-diagnostic plasma collected almost a decade before diagnosis were associated with XFG risk; these results should be confirmed in future studies.
Spatiotemporal changes in along-tract profilometry of cerebellar peduncles in cerebellar mutism syndrome
Authors: Toescu Sebastian M. , Bruckert Lisa , Jabarkheel Rashad , Yecies Derek , Zhang Michael , Clark Christopher A. , Mankad Kshitij , Aquilina Kristian , Grant Gerald A. , Feldman Heidi M. , Travis Katherine E. , Yeom Kristen W. 
Published: August 2021

AbstractCerebellar mutism syndrome, characterised by mutism, emotional lability and cerebellar motor signs, occurs in up to 39% of children following resection of medulloblastoma, the most common malignant posterior fossa tumour of childhood. Its pathophysiology remains unclear, but prior studies have implicated damage to the superior cerebellar peduncles. In this study, the objective was to conduct high-resolution spatial profilometry of the cerebellar peduncles and identify anatomic biomarkers of cerebellar mutism syndrome.In this retrospective case-control study, twenty-eight children with medulloblastoma (mean age 8.8 ± 3.8 years) underwent diffusion MRI at four timepoints over one year. Forty-nine healthy children (9.0 ± 4.2 years), scanned at a single timepoint, served as age- and sex-matched controls. Automated Fibre Quantification was used to segment cerebellar peduncles and compute fractional anisotropy at 30 nodes along each tract.Thirteen patients developed cerebellar mutism syndrome. Fractional anisotropy was significantly lower in the distal segments of the superior cerebellar peduncle pre-operatively in all patients (p=0.01). Pre-operative changes in fractional anisotropy did not predict cerebellar mutism syndrome. However, post-operative reductions in fractional anisotropy were highly specific to the distal left superior cerebellar peduncle, and were most pronounced at follow-up timepoints (p=0.042,0.038), in those that developed cerebellar mutism syndrome compared to patients that did not.High spatial resolution cerebellar profilometry identifies a site-specific alteration of the distal segment of the superior cerebellar peduncle unique to cerebellar mutism syndrome with important surgical implications in the treatment of these devastating tumours of childhood.
Development and performance evaluation of a low-cost in-house rRT-PCR assay in Ecuador for the detection of SARS-CoV-2
Authors: Salinas Marco A. , Aguirre Diana F. , De la Torre David I. , Pérez-Galarza Jorge , Pibaque Ronny J. , Beltran Paul A. , Veloz Tatiana J. , Baldeón Lucy Y. 
Published: August 2021

ABSTRACTAntecedentsEcuador has had the greatest fatality rate from Coronavirus (COVID-19) in South America during the SARS-CoV-2 pandemic. To control the pandemic, it is necessary to test as much population as possible to prevent the spread of the SARS-CoV-2 infection. For the Ecuadorian population, accessing a PCR test is challenging, since commercial screening kits tend to be expensive. Objective: the objective of this study was to develop an in-house duplex rRT-PCR protocol for the detection of SARS-CoV-2 that contributes to the screening while keeping quality and low testing costs. Results: An in-house duplex rRT-PCR protocol based on the viral envelope (E) gene target of SARS-CoV-2 and a human ribonuclease P gene (RP) as an internal control is reported. The protocol was optimized to obtain primers E with an efficiency of up to 94.45% and detection of 100% of SARS-CoV-2 up to 15 copies per uL. The clinical performance was determined by a sensibility of 93.8% and specificity of 98.3%. Conclusion: we developed, standardized, and validated a low-cost, sensitive in-house duplex rRT-PCR assay that may be utilized in low-income countries.
Returning Actionable Genomic Results in a Research Biobank: Analytic Validity, Clinical Implementation and Resource Utilization
Authors: Blout Zawatsky Carrie L. , Shah Nidhi , Machini Kalotina , Perez Emma , Christensen Kurt D. , Zouk Hana , Steeves Marcie , Koch Christopher , Uveges Melissa , Shea Janelle , Gold Nina , Krier Joel , Boutin Natalie , Mahanta Lisa , Rehm Heidi L. , Weiss Scott T. , Karlson Elizabeth W. , Smoller Jordan W. , Lebo Matthew S. , Green Robert C. 
Published: August 2021

AbstractOver 100 million research participants around the world have had research array-based genotyping (GT) or sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to patient recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.
Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort
Authors: Israel Ariel , Merzon Eugene , Schäffer Alejandro A. , Shenhar Yotam , Green Ilan , Golan-Cohen Avivit , Ruppin Eytan , Magen Eli , Vinker Shlomo 
Published: August 2021

AbstractImportanceIsrael was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time.ObjectiveTo determine whether time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection.DesignThis is a retrospective cohort study performed in a large state-mandated health care organization in Israel.ParticipantsAll fully vaccinated adults who have received a RT-PCR test between May 15, 2021 and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded.Main Outcome and MeasurePositive result for the RT-PCR test.ResultsThe cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group.Conclusions and RelevanceIn this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, we observe a significant increase of the risk of infection in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.
Cytogenetic & Molecular analysis in Premature Ovarian Failure
Authors: sahni Chetan , dada Rima 
Published: August 2021

ABSTRACTIntroductionPremature Ovarian Failure (POF) being a heterogeneous genetic disease involves the interaction of multiple genetic defects and environmental factors and has been associated with several chromosomal abnormalities, single gene mutations, and genetic polymorphisms. BMP15 is a member of the transforming growth factor β (TGF-β) family. BMP15 gene product (protein) have 3 domians, mature domain (c-terminal region) of BMP15 binds to receptors located on granulosa cell surface to participate in key steps regarding ovarian function, such as granulosa cell proliferation and follicle maturation, ovulation rate modulation, oocyte competence determination and regulating granulosa cell sensitivity to FSH. Single nucleotide polymorphisms (SNPs) of the BMP-15 gene are associated with POF.Materials & Methods30 POF patients and 30 healthy age matched controls were recruited for cytogenetic and molecular analysis. 10 ml whole blood was collected for karyotyping and PCR and PCR was performed for known SNPs of BMP-15 gene (−9C>G, 538G>A, 788insTCT and 852C>T) respectively. Amplified PCR products were sequenced commercially.Observation/ResultThirty cases (mean age 30 years) and thirty healthy controls (mean age 23 years) were recruited for the study. On cytogenetic analysis 2 cases had a 45, XO chromosomal complement. One case was heterozygous for the SNP (−9C>G) and one control was homozygous for the same SNP.DiscussionThe prevalence of this SNP was about 10.7% in cases & 3.3% in healthy controls. This polymorphism in promoter region may cause altered expression of the gene and results in POF.