bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer
Authors: Dreyer Stephan B. , Rae Sarah , Bisset Kirsty , Upstill-Goddard Rosie , Gemenetzis Georgios , Johns Amber L. ,   Australian Pancreatic Cancer Genome Initiative,   Glasgow Precision Oncology Laboratory, Dickson Euan J. , Mittal Anubhav , Gill Anthony J. , Duthie Fraser , Pea Antonio , Lawlor Rita T. , Scarpa Aldo , Salvia Roberto , Pulvirenti Alessandra , Zerbi Alessandro , Marchesi Federica , McKay Colin J. , Biankin Andrew V. , Samra Jaswinder S. , Chang David K. , Jamieson Nigel B. 
Published: July 2021

Background:
The long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains suboptimal largely due to the absence of consideration of aggressive tumor biology.

Objective:
The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes.

Methods:
Clinicopathological data were obtained for 5 independent cohorts of consecutive unselected patients, totaling n = 1298, including n = 442 that underwent molecular subtyping. The main outcome measure was disease-specific survival following surgical resection for PDAC stratified according to the American Joint Commission for Cancer (TNM) staging criteria, margin status, and molecular subtype.

Results:
TNM staging criteria and margin status confers prognostic value only in tumors with classical pancreatic subtype. Patients with tumors that are of squamous subtype, have a poor outcome irrespective of favorable traditional pathological staging [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04–2.28, P = 0.032]. Margin status has no impact on survival in the squamous subtype (16.0 vs 12.1 months, P = 0.374). There were no differences in molecular subtype or gene expression of tumors with positive resection margin status.

Conclusions:
Aggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery.
Racial and Ethnic Bias Impact Perceptions of Surgeon Communication
Authors: Tran Thuy B. , Raoof Mustafa , Melstrom Laleh , Kyulo Namgyal , Shaikh Zameer , Jones Veronica C. , Erhunmwunsee Loretta , Fong Yuman , Warner Susanne G. 
Published: July 2021

Objective:
To evaluate patient satisfaction scores as a function of physician and patient race and sex.

Background:
Patient satisfaction is increasingly used as a surrogate for physician performance. How patient and surgeon race and ethnicity affect perceptions of surgeon communication and care is not widely explored.

Methods:
Press Ganey patient satisfaction surveys collected from January 2019 to September 2020 were studied. Multivariate logistic regressions were used to identify factors associated with favorable surgeon performance as a function of patient and surgeon demographics.

Results:
A total of 4732 unique outpatient satisfaction survey responses were analyzed. The majority of patients were White (60.5%), followed by Asian (8.6%), Black (4.2%), and Hispanic (4.3%). URM accounted for 8.9% of the 79 surgeons evaluated, and 34% were female. Black, Hispanic, and Asian patients were more likely to report unfavorable experiences than their White counterparts (P < 0.01). Spanish-speaking patients were most likely to perceive that surgeon show less respect for patient concerns (13.9% vs 9.3%, P = 0.004) and inadequate time spent explaining health concerns (12.6% vs 9.2%, P < 0.001). Female surgeons were more likely to achieve the highest overall ratings for effective communication, whereas Asian surgeons received lower scores. Asian surgeons were more likely than non-Asian surgeons to receive lower scores in explanation (37.3% vs 44.1%, P = 0.003). After adjusting for confounding factors, Asian surgeons had 26% lower odds of receiving favorable scores for overall communication (odds ratio: 0.736, 95% confidence interval: 0.619–0.877, P = 0.001).

Conclusions:
Both patient and surgeon race and sex drive negative perceptions of patient-physician communication. As URM report more negative experiences, further studies should focus on effects of surgeon cultural awareness on underrepresented patient satisfaction.
Age-related Opioid Exposure in Trauma: A Secondary Analysis of the Multimodal Analgesia Strategies for Trauma (MAST) Randomized Trial
Authors: Hatton Gabrielle E. , Kregel Heather R. , Pedroza Claudia , Puzio Thaddeus J. , Adams Sasha D. , Wade Charles E. , Kao Lillian S. , Harvin John A. 
Published: July 2021

Objective:
Evaluate the effect of age on opioid consumption after traumatic injury.

Summary Background Data:
Older trauma patients receive fewer opioids due to decreased metabolism and increased complications, but adequacy of pain control is unknown. We hypothesized that older trauma patients require fewer opioids to achieve adequate pain control.

Methods:
A secondary analysis of the multimodal analgesia strategies for trauma Trial evaluating the effectiveness of 2 multimodal pain regimens in 1561 trauma patients aged 16 to 96 was performed. Older patients (≥55 years) were compared to younger patients. Median daily oral morphine milligram equivalents (MME) consumption, average numeric rating scale pain scores, complications, and death were assessed. Multivariable analyses were performed.

Results:
Older patients (n = 562) had a median age of 68 years (interquartile range 61–78) compared to 33 (24–43) in younger patients. Older patients had lower injury severity scores (13 [9–20] vs 14 [9–22], P = 0.004), lower average pain scores (numeric rating scale 3 [1–4] vs 4 [2–5], P < 0.001), and consumed fewer MME/day (22 [10–45] vs 52 [28–78], P < 0.001). The multimodal analgesia strategies for trauma multi-modal pain regimen was effective at reducing opioid consumption at all ages. Additionally, on multivariable analysis including pain score adjustment, each decade age increase after 55 years was associated with a 23% reduction in MME/day consumed.

Conclusions:
Older trauma patients required fewer opioids than younger patients with similar characteristics and pain scores. Opioid dosing for post-traumatic pain should consider age. A 20 to 25% dose reduction per decade after age 55 may reduce opioid exposure without altering pain control.
Successful Implementation of Enhanced Recovery in Elective Colorectal Surgery is Variable and Dependent on the Local Environment
Authors: Cardell Chelsea F. , Knapp Leandra , Cohen Mark E. , Ko Clifford Y. , Wick Elizabeth C. 
Published: July 2021

Objective:
To evaluate local hospital success with enhanced recovery implementation as measured by colorectal surgery process measure (PM) compliance and characterize local environment factors associated with success within a contemporary quality improvement collaborative.

Summary Background Data:
Enhanced recovery programs (ERP) have proven an effective perioperative quality improvement strategy, but local variation in implementation can hinder patient outcome improvement.

Methods:
Individual hospitals participating in a national colorectal ERP quality improvement program were evaluated with quantitative (patient-level process and outcome) and qualitative (survey and structured interviews with hospital teams) data between 2017 and 2020. Hospitals with implementation success were identified: high performers (80% of elective colorectal surgery patients compliant with >6/9 PMs) and high improvers (top quartile of PM adherence improvement over time). Hospital and implementation characteristics were compared with chi-square tests. Trends in average annual outcome change were estimated with logistic and linear regression.

Results:
Of 207 total hospitals, 62 were characterized as High Performance and 52 as High Improvement. High Performance hospitals were larger, with more annual colorectal surgeries (128 vs 101, P = 0.039). Qualitative assessment revealed fewer barriers of staff buy-in and competing priorities, and more experience with standardized perioperative care in High Performance hospitals. High Improvement hospitals had lower baseline PM adherence (54.1% vs 69.6%, P < 0.001) and less experience with standardized perioperative care (30.8% vs 58.1%, P < 0.001) but were noted to have a positive trend in annual patient outcomes: annual morbidity (Δ-1.14% vs -0.20%, P = 0.035), readmission (Δ-1.85% vs 0.002%, P = 0.037), and prolonged length of stay (Δ-3.94 vs -1.19, P = 0.037) compared to Low Improvement hospitals.

Conclusions:
When evaluating a collection of hospitals implementing ERP, only half of hospitals reached consistent High Performance or high improvement. Characteristics of the local environment need further study to understand the barriers to effective implementation in a pragmatic setting.
Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation
Authors: Turgeon Michael K. , Shah Shimul A. , Delman Aaron M. , Tran Benjamin V. , Agopian Vatche G. , Wedd Joel P. , Magliocca Joseph F. , Kim Ahyoung , Cameron Andrew , Olyaei Ali , Orloff Susan L. , Anderson Matthew P. , Kubal Chandrashekhar A. , Cannon Robert M. , Locke Jayme E. , Simpson Mary A. , Akoad Mohamed E. , Wongjirad Chelsey P. , Emamaullee Juliet , Moro Amika , Aucejo Federico , Feizpour Cyrus A. , Vagefi Parsia A. , Nguyen Mindie H. , Esquivel Carlos O. , Dhanireddy Kiran , Subramanian Vijay , Chavarriaga Alejandro , Kazimi Marwan M. , Anderson Maia S. , Sonnenday Christopher J. , Kim Steven C. , Foley David P. , Abdouljoud Marwan , Salgia Reena J. , Moris Dimitrios , Sudan Debra L. , Ganesh Swaytha R. , Humar Abhinav , Doyle Majella , Chapman William C. , Maithel Shishir K. 
Published: July 2021

Objective:To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT).Summary of Background Data:In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimaltimingof direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate.Methods:The United States HCC LT Consortium (2015–2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS).Results:Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%,P< 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%,P< 0.01). Patients who received DAAs pre-LT, 0–3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P< 0.01) and 5-year RFS of 93%, 100%, and 83% (P= 0.01).Conclusions:The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.
The Incidence and Cumulative Risk of Major Surgery in Older Persons in the United States
Authors: Becher Robert D. , Vander Wyk Brent , Leo-Summers Linda , Desai Mayur M. , Gill Thomas M. 
Published: July 2021

Objective:
The objective of this study was to estimate the incidence and cumulative risk of major surgery in older persons over a 5-year period and evaluate how these estimates differ according to key demographic and geriatric characteristics.

Background:
As the population of the United States ages, there is considerable interest in ensuring safe, high-quality surgical care for older persons. Yet, valid, generalizable data on the occurrence of major surgery in the geriatric population are sparse.

Methods:
We evaluated data from a prospective longitudinal study of 5571 community-living fee-for-service Medicare beneficiaries, aged 65 or older, from the National Health and Aging Trends Study from 2011 to 2016. Major surgeries were identified through linkages with Centers for Medicare and Medicaid Services data. Population-based incidence and cumulative risk estimates incorporated National Health and Aging Trends Study analytic sampling weights and cluster and strata variables.

Results:
The nationally representative incidence of major surgery per 100 person-years was 8.8, with estimates of 5.2 and 3.7 for elective and nonelec-tive surgeries. The adjusted incidence of major surgery peaked at 10.8 in persons 75 to 79 years, increased from 6.6 in the non-frail group to 10.3 in the frail group, and was similar by sex and dementia. The 5-year cumulative risk of major surgery was 13.8%, representing nearly 5 million unique older persons, including 12.1% in persons 85 to 89 years, 9.1% in those ≥90 years, 12.1% in those with frailty, and 12.4% in those with probable dementia.

Conclusions:
Major surgery is a common event in the lives of community-living older persons, including high-risk vulnerable subgroups.
Misophonia Successfully Treated of With Fluoxetine: A Case Report
Authors: Sarigedik Enes , Yurteri Nihal 
Published: July 2021

Objective
A large number of people experience misophonia. In 2013, the Amsterdam Study Group recommended diagnostic criteria for misophonia. However, misophonia is not yet included in the Diagnostic and Statistical Manual of Mental Disorders. This report is the first report on drug use that directly affects misophonia and demonstrates a 14-year-old adolescent girl with misophonia successfully treated with fluoxetine.

Methods
The patient's misophonia symptoms had been continuing for approximately 2 years, and her quality of life was significantly reduced. Psychotherapy conditions could not be applied, and fluoxetine 10 mg/d was started and increased to 20 mg/d after a week. At the second-month follow-up, because of partial improvement, fluoxetine dose was increased to 30 mg/d.

Results
At the fourth-month follow-up, there was a 40% decrease in Amsterdam Misophonia Scale score with a 70% decrease in the children’s global assessment scale scores. By the 16th week, the overall functionality level was good at the end.

Conclusions
Fluoxetine may be used as an effective drug in the treatment of misophonia.
Continental-scale genomic analysis suggests shared post-admixture adaptation in Americas
Authors: Ongaro Linda , Mondal Mayukh , Flores Rodrigo , Marnetto Davide , Molinaro Ludovica , Alarcón-Riquelme Marta E. , Moreno-Estrada Andrés , Mabunda Nedio , Ventura Mario , Tambets Kristiina , Hellenthal Garrett , Capelli Cristian , Kivisild Toomas , Metspalu Mait , Pagani Luca , Montinaro Francesco 
Published: July 2021

AbstractAmerican populations are one of the most interesting examples of recently admixed groups, where ancestral components from three major continental human groups (Africans, Eurasians and Native Americans) have admixed within the last 15 generations. Recently, several genetic surveys focusing on thousands of individuals shed light on the geography, chronology and relevance of these events. However, despite the fact that gene-flow could drive adaptive evolution, it is not clear whether and how natural selection acted on the resulting genetic variation in the Americas.In this study, we analysed the patterns of local ancestry of genomic fragments in genome-wide data for ∼6,000 admixed individuals from ten American countries. In doing so, we identified regions characterized by a Divergent Ancestry Profile (DAP), in which a significant over or under ancestral representation is evident.Our results highlighted a series of genomic regions with Divergent Ancestry Profiles (DAP) associated with immune system response and relevant medical traits, with the longest DAP region encompassing the Human Leukocyte Antigen locus. Furthermore, we found that DAP regions are enriched in genes linked to cancer-related traits and autoimmune diseases. Then, analyzing the biological impact of these regions, we showed that natural selection could have acted preferentially towards variants located in coding and non-coding transcripts, and characterized by a high deleteriousness score.Taken together, our analyses suggest that shared patterns of post admixture adaptation occurred at continental scale in the Americas, affecting more often functional and impactful genomic variants.
The collective behavior of ant groups depends on group genotypic composition
Authors: Walsh Justin T. , Garonski Anna , Jackan Claire , Linksvayer Timothy A. 
Published: July 2021

AbstractIncreasingly, researchers document variation between groups in collective behavior, but the genetic architecture of collective behavior and how the genotypic composition of groups affects collective behavior remains unclear. Social insects are ideal for studying the effects of genetic variation on collective behavior because their societies are defined by social interactions. To explore how the genetic composition of groups affects collective behavior, we constructed groups of pharaoh ants (Monomorium pharaonis) from 33 genetically distinct colonies of known pedigree. The groups consisted of either all workers from the same single colony or workers from two genetically different colonies, and we assayed the exploration and aggression of the groups. We found that collective behavior depended on the specific genotypic combination of group members, i.e. we found evidence for genotype-by-genotype epistasis for both collective behaviors. Furthermore, the observed collective behavior of groups differed from the additive genetic expectations of groups, further demonstrating the importance of genotype-by-genotype effects. Finally, the collective aggression of the groups was negatively correlated with the pairwise relatedness estimates between workers within the group. Overall, this study highlights that specific combinations of genotypes influence group-level phenotypes and the difficulty of predicting group-level phenotypes using only additive models.
Over-Representation of Potential SP4 Target Genes within Schizophrenia-Risk Genes
Authors: Zhou Xianjin 
Published: July 2021

AbstractReduction of Sp4 expression causes age-dependent hippocampal vacuolization and many other intermediate phenotypes of schizophrenia in Sp4 hypomorphic mice. Recent human genetic studies from both the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) and the Genome-Wide Association Study (GWAS) validated SP4 as a schizophrenia-risk gene over the exome-wide or the genome-wide significance. Truncation of human SP4 gene has an odds ratio of 9.37 (3.38-29.7) for schizophrenia. Despite successful identification of many schizophrenia-risk genes, it is unknown whether and how these risk genes may interact with each other in the development of schizophrenia. By taking advantage of the specific localization of the GC-boxes bound by SP4 transcription factors, I analyzed the relative abundance of these GC-boxes in the proximal promoter regions of schizophrenia-risk genes. I found that the GC-box containing genes are significantly over-represented within schizophrenia-risk genes, suggesting that SP4 is not only a high-risk gene for schizophrenia, but may also act as a hub of network in regulation of many other schizophrenia-risk genes via these GC-boxes in the pathogenesis of schizophrenia.
Challenges and costs of asexuality: Variation in premeiotic genome duplication in gynogenetic hybrids from Cobitis taenia complex
Authors: Dedukh D. , Marta A. , Janko K. 
Published: July 2021

AbstractThe transition from sexual reproduction to asexuality is often triggered by hybridization. The gametogenesis of many hybrid asexuals involves a stage of premeiotic genomic endoreduplication leading to the production of clonal gametes and bypassing genomic incompatibilities that would normally cause hybrid sterility. However, it is still not clear at what gametogenic stage the endoreplication occurs, how many gonial cells it affects and whether its rate differs among clonal lineages. Here, we investigated meiotic and premeiotic cells of diploid and triploid hybrids of spined loaches (Cypriniformes: Cobitis) that reproduce by gynogenesis. We found that naturally as well as experimentally produced F1 hybrid strains undergo an obligatory genome duplication event to achieve asexuality, occurring in the gonocytes just before entering meiosis or, rarely, one or few divisions before meiosis. Surprisingly however, the genome endoreplication was observed only in a minor fraction of the hybrid’s gonocytes, while the vast majority were unable to duplicate their genomes and consequently could not proceed beyond pachytene due to defects in pairing and bivalent formation. We also noted that the rate of endoreplication was significantly higher among gonocytes of hybrids from successful natural clones than of experimentally produced F1 hybrids, indicating that interclonal selection may favour lineages which maximize the rate of premeiotic endoreduplication. We conclude that asexuality and hybrid sterility are intimately related phenomena and the transition from sexual reproduction to asexuality must overcome significant problems with genome incompatibilities with possible impact on reproductive potential.