bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Diabetic and Non-Diabetic Individuals Outcomes Following Ankle ORIF Surgery Based on Physical Therapy Start Times
Authors: Jones Jared M. , Worts Phillip R. , Guyer Aaron J. 
Published: November 2022

Category: Ankle; Trauma Introduction/Purpose: The surgical correction of ankle fractures are one of the most common orthopedic procedures performed and about 13% of individuals undergoing these procedure are classified as diabetic. Diabetes, as a disease, impairs fracture healing due to decreased bone quality and cardiometabolic dysfunction. The use of early mobilization following ankle surSgery has improved post-operative outcomes in the 'healthy' populations; however, early mobilization or early physical therapy initiation in the diabetic populations has not been elucidated. Methods: Surgical correction CPT codes for ankle fracture were used to identify eligible patients followed by a retrospective chart review to confirm diagnosis and procedure(s) as well as collection of demographic information and pertinent medical history. Patient cases were examined over a two year period. Once the inclusion criteria was met, 209 unique patients were included in the analyses. Patients were grouped by diabetes status and early (i.e., <=8 weeks) or late mobilization (i.e., days post- op until physical therapy referral). Generalized linear models and a series Chi-squared tests, Fisher's Exact tests, one-way ANOVAs, and Mann Whitney U Tests were used to assess recovery duration, fracture healing, time to PT referral, medical history, and demographic information. Results: The diabetic group in our study was significantly older [60 (IQR:18) vs. 58 (26) years; p = 0.019] and had a higher BMI [34(8) vs. 29(10); p = 0.041] compared to our non-diabetic group but there were no differences in the proportions for sex or the fracture type by diabetic status. The non-diabetic group displayed a quicker fracture healing time [86(35) vs. 111(45) days; p = 0.04] but there were no differences in recovery duration or days until physical therapy was prescribed. The GLM analysis performed with recovery duration (i.e., time to medical clearance) found that late mobilization was a significant predictor (p < 0.001) of recovery duration but not diabetic diagnosis (p = 0.738). Conclusion: There appears to be a different demographic profile for diabetic patients experiencing an ankle fracture when compared to non-diabetic patients. The delay in physical therapy referral and presumably early mobilization appears to be the strongest predictor of recovery duration. Future research should utilize randomized controlled trials to determine if early mobilization is safe and effective at facilitating quicker fracture healing and recovery following the surgical correction of an ankle fracture in diabetic patients.
Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL
Authors: Torka Pallawi , Groman Adrienne , Wong Jerry , Nichols Jenna , Kader Angela , Mavis Cory , Anampa-Guzmán Andrea , Sait Sheila Jani , Block AnneMarie , Przespolewski Eugene , Mohr Alice , Lund Ian , McWhite Kenneth , Kostrewa Jessica , DeMarco Joseph , Johnson Michael , Darrall Andrea , Thomas Roshneke , Sundaram Suchitra , Ghione Paola , Hutson Alan , Hernandez-Ilizaliturri Francisco J. 
Published: November 2022

Abstract
The CORAL study highlighted the need to develop novel salvage regimens in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698). In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. CFZ 45 mg/m2 was selected as the recommended dose for expansion. Eleven additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent HDC-ASCT. An ORR of 85% was observed in patients with nongerminal center B-cell–like (non-GCB) DLBCL compared with only 13% in those with GCB DLBCL. Median progression-free survival (PFS) was 15.2 months (5.1 months, not reached [NR]), and median overall survival (OS) was 22.6 months (6.8 months, NR). Patients with non-GCB subtype had a significantly longer PFS (NR vs 6.6 months; P = .0001) and OS (NR vs 6.6 months; P = .001) than those with GCB subtype. C-R-ICE is well tolerated in patients with R/R DLBCL with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. Our data show that patients with non-GCB DLBCL benefit significantly from incorporating CFZ into second-line therapy and HDC-ASCT.
Failing the four-gamete test enables exact phasing: the Corners’ Algorithm
Authors: Gomez-Raya Luis , Rauw Wendy M. 
Published: November 2022

AbstractBackgroundFailing the four-gamete test for two polymorphic DNA markers is an indication that two or three rather than four haplotypes segregate in the population. The objective of this paper is to show that when just three haplotypes are segregating, all three haplotypes can be fully and unambiguously phase-resolved.Theory and methodsThe Corners’ Algorithm tests the four corners in a 3 × 3 table of two-locus genotypes. If one of the four corners is filled with zeroes, then the missing haplotype is identified and the phases of all three haplotypes can be unambiguously resolved for all individuals. Three applications of this method are proposed when the four-gamete test fails: (1) direct estimation of linkage disequilibrium (LD), (2) haplotype-based genome-wide association studies (GWAS) of three haplotypes (single-marker GWAS tests for two out of three haplotypes only), and (3) haplotyping of chromosomal regions that are comprised of pairs of single nucleotide polymorphisms (SNPs) that consist of just three haplotypes. An example based on 435 sows with performance records for total number of piglets born is used to illustrate the methods.ResultsOf 20,339 SNPs, approximately 50% of the pairs of flanking SNPs failed the four-gamete test. For those, the expectation maximization (EM) algorithm gave the same results. The average of the absolute value of the difference inr2between flanking SNPs across the genome between the two methods was 0.00082. Single-marker GWAS (using two of three haplotypes) detected significant associations for total number of piglets born on chromosomes 1, 2, 6, 9, 10, 12, 13, 14, 15, and 18. Haplotype-based GWAS using the third haplotype resolved with the Corners’ Algorithm detected additional significant associations for total number of piglets born on chromosomes 2, 5, 10, 13, 14, 15, and 18. Estimated substitution effects ranged from 0.40 to 1.35 piglets. Haplotyping of chromosomal regions that failed the four-gamete test for any pair of SNPs covered 961 Mb out of the 2249 Mb by the SNP array.ConclusionsThe Corner’s Algorithm allows to fully phase haplotypes when the four-gamete test fails. Longer haplotypes in chromosomal regions in which the four-gamete test fails for any pair of SNPs can be used as a multi-allelic marker with increased polymorphism information content.
Early changes in gene expression profiles in AML patients during induction chemotherapy
Authors: Jakobsen Ingrid , Sundkvist Max , Björn Niclas , Gréen Henrik , Lotfi Kourosh 
Published: November 2022

Abstract
Background
Elucidation of the genetic mechanisms underlying treatment response to standard induction chemotherapy in AML patients is warranted, in order to aid in risk-adapted treatment decisions as novel treatments are emerging. In this pilot study, we explored the treatment-induced expression patterns in a small cohort of AML patients by analyzing differential gene expression (DGE) over the first 2 days of induction chemotherapy.

Methods
Blood samples were collected from ten AML patients at baseline (before treatment initiation) and during the first 2 days of treatment (Day 1; approximately 24 h, and Day 2; approximately 48 h after treatment initiation, respectively) and RNA was extracted for subsequent RNA sequencing. DGE between time points were assessed by pairwise analysis using the R package edgeR version 3.18.1 in all patients as well as in relation to treatment response (complete remission, CR, vs non-complete remission, nCR). Ingenuity Pathway Analysis (Qiagen) software was used for pathway analysis and visualization.

Results
After initial data quality control, two patients were excluded from further analysis, resulting in a final cohort of eight patients with data from all three timepoints. DGE analysis demonstrated activation of pathways with genes directly or indirectly associated with NF-κB signaling. Significant activation of the NF-κB pathway was seen in 50% of the patients 2 days after treatment start, while iNOS pathway effects could be identified already after 1 day. nCR patients displayed activation of pathways associated with cell cycle progression, oncogenesis and anti-apoptotic behavior, including the STAT3 pathway and Salvage pathways of pyrimidine ribonucleotides. Notably, a significant induction of cytidine deaminase, an enzyme responsible for the deamination of Ara-C, could be observed between baseline and Day 2 in the nCR patients but not in patients achieving CR.

Conclusions
In conclusion, we show that time-course analysis of gene expression represents a feasible approach to identify relevant pathways affected by standard induction chemotherapy in AML patients. This poses as a potential method for elucidating new drug targets and biomarkers for categorizing disease aggressiveness and evaluating treatment response. However, more studies on larger cohorts are warranted to elucidate the transcriptional basis for drug response.
Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients
Authors: Wakai Haruki , Abe Natsumi , Tokuda Touno , Yamanaka Rika , Ebihara Satoshi , Izumaru Kensuke , Ishii Daisuke , Hyodo Toru , Yoshida Kazunari 
Published: November 2022

Abstract
Objectives
There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined.

Methods
Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients.

Results
The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL.

Conclusions
The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.
Why do men who have sex with men practice condomless sex? A systematic review and meta-synthesis
Authors: Shen Yan , Zhang Ci , Valimaki Maritta A. , Qian Hanzhu , Mohammadi Leila , Chi Yuanyuan , Li Xianhong 
Published: November 2022

Abstract
Background
Despite a large amount of behavioral interventions to reduce human immunodeficiency virus (HIV)-related high-risk sexual behaviors, consistent condom use remains suboptimal among men who have sex with men (MSM). However, current databases are lack of synthesized evidence to explain why MSM practiced condomless sex.

Objective
Our study aims to conduct a systematic review and meta-synthesis of 39 eligible qualitative studies to explore the barriers to condom use among MSM.

Methods
A systematic review and meta-synthesis of qualitative studies (1994–2021). On March 4, 2021, a comprehensive search was conducted in 14 electronic databases. The study was conducted based on the Joanna Briggs Institute’s recommendations.

Results
Thematic analysis produced six synthesized themes, which were classified into three levels according to the Social-ecology Model. Individual level barriers to condom use included physical discomfort, lack of HIV/STI-related knowledge and substance use; interpersonal-level barrier was mainly the condom stigma, namely regarding using condom as symbols of distrust or HIV/sexually transmitted infections (STIs) prevention, or as violating traditional cognition of sex, or as an embarrassing topic; environmental/structural-level barriers included situational unavailability, unaffordability of condoms and power imbalance in the sexual relationship.

Conclusion
This meta-synthesis offered in-depth understanding of condom use barriers for MSM and could guide the development of multifactorial interventions according to the identified barriers, especially targeting to reduce condom stigma, which has not been focused and intervened previously.
Comparing access to sexual and reproductive health services among sexual minority youths and their peers: findings from a national survey in China
Authors: Liang Yun , Hee Jiayi , Peng Chunxiao , Li Chunyan , Cao Wenzhen , Tang Kun 
Published: November 2022

Abstract
Background
Little is known about the access to measures of sexual and reproductive health (SRH) services among sexual minority communities in China, where sexuality-related stigma and discrimination remains high. The aim of this study is to investigate access to measures of SRH services among Chinese sexual minority youths (SMY) aged 17 to 24 years old.

Methods
This cross-sectional study utilizes data on 54,580 youths from the 2019–2020 National College Student Survey on Sexual and Reproductive Health, conducted across 31 provinces in mainland China. Multivariable logistic regression modelling was utilized to assess the access to SRH services among Chinese youth with different self-reported sexual orientation.

Results
The majority of respondents identified as heterosexual (77.6%). The remaining respondents identified as bisexual (9.0%), lesbian or gay (2.8%), others (3.02%), or unknown (7.51%). Gay men reported greater access to free contraceptives at health centers (OR 1.62, 95% CI: 1.32–1.99) and were more likely to have receive medical treatment for sexual and reproductive issues (OR 1.83, 95% CI: 1.26–2.63) compared to heterosexual men. Gay and bisexual men were also more likely to use condom at first sexual intercourse compared to heterosexual men (gay men: OR 1.38, 95% CI: 1.13–1.68; bisexual men: OR 1.33, 95% CI: 1.03–1.71). However, the associations were reversed among women (lesbians: OR 0.05, 95% CI: 0.03 to 0.08; bisexuals: 0.75, 95% CI: 0.65 to 0.86).

Conclusions
Although SMY reported higher utilization of SRH services compared to their heterosexual counterparts, access to SRH services remains low among Chinese youths. Greater focus should be placed on improving access to SMY-friendly SRH services among Chinese youths.
Adult essential extracorporeal membrane oxygenation (ECMO) skills for use in an e-learning program for ICU physicians, nurses and perfusionists: a consensus by a modified Delphi questionnaire
Authors: Peperstraete Harlinde , Steenhout Annelien , De Somer Filip , Depuydt Pieter , Hoste Eric , Van Herzeele Isabelle 
Published: November 2022

Abstract
Background
Education in ECMO starts with basic theory and physiology. For this type of training, self-assessment e-learning modules may be beneficial. The aim of this study was to generate consensus on essential ECMO skills involving various professional groups involved in caring for ECMO patients. These skills can be used for educational purposes: development of an e-learning program and fine-tuning of ECMO-simulation programs.

Methods
Experts worldwide received an e-mail inviting them to participate in the modified Delphi questionnaire. A mixture of ECMO experts was contacted. The expert list was formed based on their scientific track record mainly in adult ECMO (research, publications, and invited presentations). This survey consisted of carefully designed questionnaires, organized into three categories, namely knowledge skills, technical skills, and attitudes. Each statement considered a skill and was rated on a 5-point Likert-scale and qualitative comments were made if needed. Based on the summarized information and feedback, the next round Delphi questionnaire was developed. A statement was considered as a key competency when at least 80% of the experts agreed or strongly agreed (rating 4/5 and 5/5) with the statement. Cronbach’s Alpha score tested internal consistency. Intraclass correlation coefficient was used as reliability index for interrater consistency and agreement.

Results
Consensus was achieved in two rounds. Response rate in the first round was 45.3% (48/106) and 60.4% (29/48) completed the second round. Experts had respectively for the first and second round: a mean age of 43.7 years (8.2) and 43.4 (8.8), a median level of experience of 11.0 years [7.0-15.0] and 12.0 years [8.3-14.8]. Consensus was achieved with 29 experts from Australia (2), Belgium (16), France (1), Germany (1), Italy (1), Russia (2), Spain (1), Sweden, (1), The Netherlands (4). The consensus achieved in the first round was 90.9% for the statements about knowledge, 54.5% about technical skills and 75.0% about attitudes. Consensus increased in the second round: 94.6% about knowledge skills, 90.9% about technical skills and 75.0% about attitudes.

Conclusion
An expert consensus was accomplished about the content of “adult essential ECMO skills”. This consensus was mainly created with participation of physicians, as the response rate for nurses and perfusion decreased in the second round.
Outcomes of a US-Sino family medicine leadership program
Authors: Liu Jennifer , Koran- Scholl Jessica , Geske Jenenne , Harrison Jeff , Sitorius Mike , Jarzynka Kim 
Published: November 2022

Abstract
Background and objectives
The purpose of this study was to determine the outcomes of a two- week US-Sino Family Medicine Leadership Symposium for medical educators from China and how participants have integrated their learning into their teaching and practice of medicine.

Methods
Teaching topics emphasized principles of family medicine, teaching methods, assessment, and curriculum development. Each cohort received a wide range of practical, didactic and hands-on learning experiences. Online surveys were distributed anonymously to participants from the 2013–2019 cohorts to assess learner opinion and learner behavior change as a result of the leadership symposium. Quantitative measures assessed their level of integration of the topics into teaching and clinical practice and their satisfaction in the areas of teaching and leadership. They were also asked to provide qualitative feedback regarding incorporation of the content into their work.

Results
The survey response rate was 47.6% (39/82). Respondents stated that they incorporated topics such as basic interviewing skills and information on the patient-centered medical home into their teaching in China. The most applied clinical skills they were able to incorporate into their clinical environment in China included: Breaking Bad News, Simulations Sessions with practice, One-Minute Preceptor, and Interprofessional Education.

Conclusions
Results indicate that participants have demonstrated behavior changes that have led to the incorporation of the content into teaching and clinical practice. We demonstrated effectiveness of the curriculum in cultivating the teaching and practice of family medicine. The program appears to be a positive experience that has led to embracement of the roles as trainer and leader. 100% of the participants who completed the survey felt that the program improved patient confidence in their ability as a family doctor. Future assessment on barriers to their progress as teachers and leaders in family medicine would be helpful to explore.
Needs to address clinicians’ moral distress in treating unvaccinated COVID-19 patients
Authors: Klitzman Robert 
Published: November 2022

AbstractBackgroundMoral dilemmas have arisen concerning whether physicians and other providers should treat patients who have declined COVID vaccination and are now sick with this disease. Several ethicists have argued that clinicians have obligations to treat such patients, yet providing care to these patients has distressed clinicians, who have at times declined to do so. Critical questions thus emerge regarding how best to proceed.Main bodyProviders face moral tensions: whether to place the benefits to an unvaccinated patient over their duties to protect themselves and their families, staff and other patients, and goals of working collaboratively with patients. Clinicians’ duties to treat such patients arguably outweigh claims otherwise, but these obligations are creating moral conflict and distress for providers. Moral distress has been associated with burnout, post-traumatic stress disorder, and interpersonal and work difficulties. Given ongoing vaccine refusals, these problems are unlikely to disappear in the foreseeable future. Society has obligations to address this moral distress due to principles of reciprocity, and implicit social contracts, as part of which physicians risk their lives in caring for patients for the good of society as a whole. Responses are thus urgently needed at several levels: by hospitals, medical schools, professional societies, governments, media, providers and patients. Medical training on professionalism should address these stresses, probing why doctors have duties to treat these patients, but also how moral conflicts can ensue, and how best to address these tensions. Governments and institutions should thus alter relevant policies and devote more resources to addressing clinicians’ psychological strains. Institutions should also improve organizational culture. Public health organizations and the media described clinicians, earlier in the pandemic, as heroes, committed to treating COVID patients. This narrative should now be changed to highlight the strains that unvaccinated patients cause—endangering hospital staff and others.ConclusionsUnvaccinated COVID patients should receive care, but multi-level strategies, involving enhanced policies, education and practice are vital to alleviate ensuing moral distress, and thus aid these clinicians and their patients. Ethical arguments that providers must treat these patients have not considered these obligations’ effects on clinicians, but should do so.