bluuebunny/crossref_metadata_2025_split huggingface dataset:
SpikeFlow: automated and flexible analysis of ChIP-Seq data with spike-in control
Authors: Bressan Davide , Fernández-Pérez Daniel , Romanel Alessandro , Chiacchiera Fulvio 
Published: August 2024

Abstract
ChIP with reference exogenous genome (ChIP-Rx) is widely used to study histone modification changes across different biological conditions. A key step in the bioinformatics analysis of this data is calculating the normalization factors, which vary from the standard ChIP-seq pipelines. Choosing and applying the appropriate normalization method is crucial for interpreting the biological results. However, a comprehensive pipeline for complete ChIP-Rx data analysis is lacking. To address these challenges, we introduce SpikeFlow, an integrated Snakemake workflow that combines features from various existing tools to streamline ChIP-Rx data processing and enhance usability. SpikeFlow automates spike-in data scaling and provides multiple normalization options. It also performs peak calling and differential analysis with distinct modalities, enabling the detection of enrichment regions for histone modifications and transcription factor binding. Our workflow runs in-depth quality control at all the processing steps and generates an analysis report with tables and graphs to facilitate results interpretation. We validated the pipeline by performing a comparative analysis with DiffBind and SpikChIP, demonstrating robust performances in various biological models. By combining diverse functionalities into a single platform, SpikeFlow aims to simplify ChIP-Rx data analysis for the research community.
RESPIRATORY BURST OXIDASE HOMOLOG 5.1 regulates H3K4me3 deposition and transcription after cold priming in cucumber
Authors: Di Qinghua , Zhou Mengdi , Li Yansu , Yan Yan , He Chaoxing , Wang Jun , Wang Xiaoqin , Yu Xianchang , Sun Mintao 
Published: August 2024

Abstract
Plants can maintain acquired cold tolerance for a long period after cold priming, even after the resumption of warmer temperatures. However, the transcriptional mechanisms active during the recovery period after cold priming remain unknown. Here, we found that in cucumber (Cucumis sativus), cold priming altered the Histone H3 lysine 4 trimethylation (H3K4me3) signal of sustainably-induced (memory) and non-sustainably-induced (NSI) genes during recovery. In addition, H3K4me3 marks on upregulated memory genes exhibited a specific epigenetic memory during recovery. However, the rank of the H3K4me3 signal on memory and NSI genes in the genome was independent of cold priming, which always contributed to and inhibited the formation of transcription patterns of memory and NSI genes, respectively. Furthermore, the short-lived increase of RESPIRATORY BURST OXIDASE HOMOLOG 5.1 (CsRBOH5.1) expression during recovery after cold priming was essential to maintain high levels of NADPH oxidase activity and apoplastic H2O2, causing cucumber to acquire cold priming and enhancing the maintenance of acquired cold tolerance (MACT). Interestingly, the expression of some key H3K4me3 methyltransferase genes and the accumulation of H3K4me3 on memory genes depended on CsRBOH5.1. Surprisingly, CsRBOH5.1 was essential for almost all genes to form the normal H3K4me3 signaling patterns during recovery, and the necessity was more obvious as recovery progressed. Moreover, transcriptional memory was completely lost in Csrboh5.1 mutants, and the transcriptional patterns of about 80% of NSI genes were disrupted. Overall, our results show that CsRBOH5.1 governs H3K4me3 deposition and cold-induced transcription during recovery after cold priming, affecting the acquisition of cold priming and the intensity of MACT.
Constructing vaccination slogans in the late stage of vaccine launch: an experimental study based on the framing effect theory
Authors: Gong Zepeng , Li Jie , Yu Chao , Feng Ke 
Published: August 2024

Abstract

Background
Vaccination is an important strategy for overcoming public health crises. Considerable studies have analyzed strategies to promote people’s willingness to vaccinate, but few have explored effective strategies based on the stage of vaccine launch. This study considered the framing effect theory to explore whether egoism, altruism and loss frames can boost vaccination willingness when people feel the vaccine is effective in the late stage of vaccine launch.

Methods
This study designed a scenario experiment consisting of three experimental groups (egoism, altruism and loss frames) and one control group (non-framed). Participants (N = 1085) from China were randomly assigned to any of the four groups. Vaccination willingness, perceived vaccine effectiveness and control variables included perceived susceptibility, perceived severity, worry about the side effects of vaccination and socio-demographics were collected.

Results
Perceived vaccine effectiveness and message frames can increase people’s willingness to be vaccinated. Message frames can amplify the positive impact of perceived effectiveness on vaccination willingness. Moreover, loss-framed messages had a stronger amplification effect than egoistic- and altruistic-framed messages.

Conclusions
Governments and other health authorities should prioritize the loss-framed approach when constructing vaccination slogans to maximize vaccination willingness when vaccines are considered effective at the late implementation stage of the vaccine strategy.
Dose estimation in patients from different protocols of 18F-FDG PET/CT studies and analysis of optimization strategies
Authors: Dwivedi Pooja , Kumar Jha Ashish , Mithun Sneha , Sawant Viraj , Vajarkar Vishal , Chauhan Manoj , Choudhury Sayak , Rangarajan Venkatesh 
Published: August 2024

Abstract
This study aimed to evaluate the dose in different protocols of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) procedure. The retrospective study involves 207 patients with confirmed malignancies who underwent PET/CT. Effective dose (E) from PET was estimated based on injected activity and dose coefficient as per International Commission on Radiation Protection (ICRP) 128. Estimation of E from CT was done utilizing the dose length product (DLP) method and conversion factors as per ICRP 102. There was a significant statistical difference observed in E between different PET/CT protocols (P &lt; .001). E of PET in the whole body (WB) was found to be 4.9 ± 0.9 mSv, whereas mean volume computed tomography dose indexvol, DLP, and E of CT in WB were 7.0 ± 0.2 mGy, 674.3 ± 80.7 mGy.cm, and 10.1 ± 1.2 mSv, respectively. No linear correlation was seen between the size-specific dose estimate and E of CT (r = −0.003; P = .978). The total mean E in WB PET/CT was 17.0 ± 1.7 mSv. CT dose was contributing more than PET dose in all protocols except brain PET/CT. Optimization strategies can be evaluated only if monitored periodically.
Endocrine, gender dysphoria, and sexual function benefits of gender-affirming bilateral orchiectomy: patient outcomes and surgical technique
Authors: Stelmar Jenna , Victor Robert , Yuan Nance , Smith Shannon M , Mallavarapu Samhita , Sandhu Sandeep , Garcia Maurice M 
Published: August 2024

Abstract

Background
Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature.

Aim
The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients’ preoperative decision-making priorities and postoperative satisfaction.

Methods
A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures.

Outcomes
Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients.

Results
The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone (P &lt; .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty.

Clinical Implications
For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief.

Strengths and Limitations
This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions.

Conclusion
Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty.
Two Uses of Purpose in Statutory Interpretation
Authors: Mancini Mark P 
Published: August 2024

Abstract
Despite apparent agreement on the approach to the interpretation of statutes in Canada, a system of limited parliamentary sovereignty, judges differ on a fundamental point: how purpose is used in interpretation. Some judges craft arguments that view the text as the medium through which the legislature expresses its intention, using purpose to shed light on the meaning of the text in defined ways (‘text-as-medium’ interpretation). Others see the background purposes or values of the statutory context as binding constraints in a coherent legal order, with text as merely a signal to meaning (‘purpose-as-medium’ interpretation). This paper argues that text-as-medium interpretation offers the most persuasive account of the use of purpose in interpretation, especially in a system of legislative sovereignty, which constrains interpretive choice. By bringing to light the commitments of these two interpretive arguments in the Canadian context for the first time, the paper also raises deeper normative questions about how to view legislation in a Westminster parliamentary democracy. These questions are fundamental to the relationship between sovereign legislatures and courts.
Our House Won’t Rebuild Itself: Peace, Love, and Hope as Tools to Transform Graduate Medical Education
Authors: Bullock Justin L. , McClintock Adelaide H. , Abe Ryan , Boos Markus D. , Best Jennifer A. 
Published: August 2024

Abstract
Graduate medical education (GME), the period of specialty and subspecialty training following attainment of a medical degree, is the final step in a continuum of medical education culminating in independent physician practice. This manuscript uses the metaphor “our house” to describe all aspects of the GME environment in which health care professionals and trainees learn and work. Our house’s inhabitants have unequivocally stated that our house is in a state of disrepair. While physicians-in-training inevitably face challenges on their journey to independent practice, those from historically marginalized backgrounds face these challenges compounded by the disproportionate impact of identity-based harms. The authors use critical and liberatory theories to explore dominant power dynamics in GME, classifying identity-based harms as silence, pain, and despair. To strive for true transformation, the authors advocate for a new set of house rules, a different way of coexisting based on the principles of liberatory design. The authors call on readers to rebuild the house of GME by drawing parallels between the foundational human values of peace, love, and hope and the educational principles of psychological safety, identity safety, and belonging. To transform GME, our community must make space in our house for all individuals to join and, indeed, to rebuild together.
Creating Optimal Clinical Learning Environments Through Interprofessional Bedside Rounding Models: Lessons From the iPACE Story
Authors: Hallen Sarah , Zelaya Melissa I. , White Patricia , Varaklis Kalli 
Published: August 2024

Abstract
The Interprofessional Partnership to Advance Care and Education (iPACE) model was developed and implemented at Maine Medical Center in 2017 as part of the Accreditation Council for Graduate Medical Education’s Pursuing Excellence in Clinical Learning Environments (CLE) demonstration project. The model is based on the belief that, in optimal CLEs, residents are trained in team-based, interprofessional collaborative care and use clinical care experiences to innovate in the areas of patient safety and quality of care. The model’s inclusion of systems engineering principles, such as design thinking, allows teams to design, customize, and iteratively improve their own iPACE model.
The iPACE model was further developed and disseminated with support from an American Medical Association Reimagining Residency grant and from the MaineHealth system’s medical education and clinical leadership. iPACE started as a small pilot project on a single inpatient unit and has evolved to become the standard for inpatient team rounds at the bedside. iPACE has received positive feedback from patients, demonstrated benefits to care team members and resident education, and proven its value to the health system through sustained reductions in length of stay and cost of care metrics. The iPACE project has fulfilled MMC’s original goal of intentionally redesigning its CLEs to expose residents to high-functioning interprofessional teams with the goal of improving patient care and safety. The model has shown direct learner benefits through increased faculty observation and improved quality of feedback. Interprofessional bedside rounding models like iPACE have the potential to imprint learners with the skills and behaviors essential to provide collaborative patient-centered care. Strategies exist that improve resident and faculty engagement in bedside rounding models like iPACE and should be employed to encourage teaching and learning at the bedside.
Shifting the Paradigm in Workforce Diversity: Prioritizing an Inclusive Environment in Graduate Medical Education
Authors: Anum-Addo Shaunte Y. , Hippolyte Jessica , Barber Aisha 
Published: August 2024

Abstract
A diverse physician workforce is important to achieving the goal of health equity. Recruitment efforts are often the focus of graduate medical education (GME) workforce diversity efforts. However, to achieve the goal of workforce diversity, a foundation of inclusivity is essential to address the experiences of trainees whose race and ethnicity are underrepresented in medicine (UIM).
Professional identity formation (PIF) describes the process through which trainees integrate their personal and professional identities as they learn to not only act but also feel like they belong in their professional role. The concept of PIF provides a framework to consider how GME leaders can intentionally address inclusivity in training programs. The process of PIF is influenced by many factors, including trainees’ clinical and nonclinical experiences, their treatment by others, as well as the training program’s structure, policy, and physical environment. The authors describe these factors influencing PIF and then, through the lens of PIF, describe approaches that programs and institutions have taken to address inclusivity by investing in the workforce, disrupting the hidden curriculum, revisiting policies and procedures, and examining the physical environment.
The authors encourage programs, institutions, and the greater GME community to leverage each learning environment’s unique strengths and root out challenges to enhance inclusivity for UIM trainees.
Toward a More Perfect Union
Authors: Sullivan Louis W. 
Published: August 2024

Abstract
In this essay, the author, Dr. Louis Sullivan, describes his life experiences, having been born in the American South during the period of legal racial segregation. Despite many obstacles, Dr. Sullivan became a physician who founded the predominantly Black Morehouse School of Medicine and served as Secretary of the United States Department of Health and Human Services.
In his efforts to improve the health of people from historically marginalized groups, including Black and Brown people as well as those experiencing poverty, Dr. Sullivan organized the Association of Minority Health Professions Schools. He chaired the Sullivan Commission to evaluate the strategies developed to increase the number of Black physicians in the nation. He supported development of the Office for Women’s Health and led efforts to create the National Institute for Minority Health and Health Disparities, both at the National Institutes of Health. When reflecting on his achievements, Dr. Sullivan cites his many mentors and allies who supported him in his career.
Despite significant, ongoing resistance to current efforts to advance diversity, equity, and inclusion in our society, Dr. Sullivan is optimistic that progress toward this goal will continue to be made. He imparts lessons about persistence and positivity and reflects on several initiatives to advance diversity, equity, and inclusion in the health professions and in our society more broadly.
Staged Management for Distal Femur Fractures: Impacts on Reoperation, Stiffness, and Overall Outcomes
Authors: Yeager Matthew T. , Rutz Robert W. , Roszman Alex , McGwin Gerald , Darnley James E. , Johnson Joseph P. , Spitler Clay A. 
Published: August 2024

OBJECTIVES:
To evaluate the outcomes of staged management with external fixation (ex-fix) before definitive fixation of distal femur fractures.

METHODS:

Design:
Retrospective cohort.

Setting:
Single Level I Trauma Center.

Patient Selection Criteria:
Adults treated operatively between 2004 and 2019 for distal femur fractures (OTA/AO 33A/33C) were identified using Current Procedural Terminology codes. Excluded cases were those with screw only fixation, acute distal femur replacement, 33B fracture pattern, no radiographs available, or did not have 6-months of follow-up.

Outcome Measures and Comparisons:
Postoperative complication rates including surgical site infection [SSI], reoperation to promote bone healing, final knee arc of motion <90 degrees, heterotopic ossification formation, and reoperation for stiffness were compared between patients treated with ex-fix before definitive fixation and those not requiring ex-fix.

RESULTS:
A total of 407 patients were included with a mean follow-up of 27 months [median (IQR) of 12 (7.33) months] (range 6–192 months). Most patients were male (52%) with an average age of 48 (range: 18–92) years. Ex-fix was utilized in 150 (37%) cases and 257 (63%) cases underwent primary definitive fixation. There was no difference in SSI rates (P = 0.12), final knee arc of motion <90 degrees (P = 0.51), and reoperation for stiffness (P = 0.41) between the ex-fix and no ex-fix groups. The 150 patients requiring ex-fix spent an average of 4.2 days (SD 3.3) in the ex-fix before definitive fixation. These patients were further analyzed by comparing the duration of time spent in ex-fix, <4 days (n = 82) and ≥4 days (n = 68). Despite longer time spent in ex-fix before definitive fixation, there was again no significant difference in any of the complication and reoperation rates when comparing the 2 groups, including final knee arc of motion <90 degrees (P = 0.63), reoperation for stiffness (P = 1.00), and SSI (P = 0.79).

CONCLUSION:
Ex-fix of distal femur fractures as a means of temporary stabilization before definitive open reduction internal fixation does not increase the risk of complications such as SSI, final knee arc of motion <90 degrees, or reoperations for bone healing or stiffness when compared with single-stage open reduction internal fixation of distal femur fractures.

LEVEL OF EVIDENCE:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Is the Orthopaedic Trauma Association-Open Fracture Classification Better Than the Gustilo-Anderson Classification at Predicting Fracture-Related Infections in the Tibia?
Authors: Khoury Philip , Hazra Nina , DeMartino Anthony , Birungi-Huff Kevina , Slobogean Gerard P. , O'Toole Robert V. , O'Hara Nathan N. 
Published: August 2024

OBJECTIVES:
To investigate and compare the predictive ability of the Orthopaedic Trauma Association-Open Fracture Classification (OTA-OFC) and the Gustilo-Anderson classification systems for fracture-related infections (FRI) in patients with open tibia fractures.

METHODS:

Design:
Retrospective cohort study.

Setting:
Academic trauma center.

Patient Selection Criteria:
Patients aged 16 years or older with an operatively treated open tibia fracture (OTA–AO 41, 42, and 43) between 2010 and 2021.

Outcome Measures and Comparisons:
The primary outcome was FRI. The OTA-OFC and the Gustilo-Anderson classifications were compared in their ability to predict FRI.

RESULTS:
Eight hundred ninety patients (mean age, 43 years [range, 17 to 96]; 75% men) with 912 open tibia fractures were included. In total, 142 (16%) had an infection. The OTA-OFC was not significantly better at predicting FRI than the Gustilo-Anderson classification (area under the curve, 0.66 vs. 0.66; P = 0.89). The Gustilo-Anderson classification was a stronger predictor of FRI than any single OTA-OFC domain, explaining 72% of FRI variance. Only the addition of the OTA-OFC wound contamination domain to Gustilo-Anderson significantly increased the variance explained (72% vs. 84%, P = 0.04). Embedded contamination increased the risk of FRI by approximately 10% as the risk of FRI with embedded contamination was 16% for type I or type IIs, 26% for type IIIAs, 45% for type IIIBs, and 46% for type IIICs.

CONCLUSIONS:
The more complex OTA-OFC system was not better than the Gustilo-Anderson classification system in predicting FRIs in patients with open tibia fractures. Adding embedded wound contamination to the Gustilo-Anderson classification system significantly improved its prognostic ability.

LEVEL OF EVIDENCE:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.