bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Happens to Youth Baseball Players Diagnosed With Little League Shoulder and Little League Elbow Syndrome?
Authors: Jensen Evan J. , Pennock Andrew T. , Hulbert Molly A. , Tadlock Joshua C. , Paranjape Chinmay S. , Bryan Tracey P. 
Published: May 2024

Background:
The long-term prognosis of baseball and softball players diagnosed with Little League elbow (LLE) and Little League shoulder (LLS) is unknown. Many of these athletes are potentially at risk of developing future shoulder and elbow injuries that may require surgical intervention. This study’s purpose is to retrospectively assess 5-year patient-reported outcomes and career progression of a series of youth baseball and softball players diagnosed with LLE and LLS.

Methods:
This institutional review board-approved, single-center, retrospective study evaluated 5-year outcomes of a cohort of youth baseball and softball players diagnosed with LLE and LLS between 2013 and 2017. Demographic and clinical data was recorded including age, gender, primary position, and months played per year. A standardized phone survey was obtained approximately 5 years post-treatment to assess upper extremity function, career progression, and pain recurrence.

Results:
Sixty-one patients (44 LLE, 17 LLS) met the inclusion criteria and participated in a standardized phone survey. The mean age at the time of diagnosis was 13.2 years and all but one of the athletes were male. On average, about 80% (34/44 LLE, 15/17 LLS) played baseball 9 months or more per year. After diagnosis and nonoperative management, more than 80% (37/44 LLE, 14/17 LLS) were able to return to competition, but up to 40% of players changed positions (9/44 LLE, 7/17 LLS). Five years later, less than half (21/44 LLE, 8/17 LLS) were playing baseball actively. The recurrence rate was >20% (9/42 LLE, 6/17 LLS) with a mean time of recurrence of 8.8 months. Patients who experienced symptom recurrence were less likely to play baseball 5 years later and had lower patient-reported outcomes.

Conclusions:
A diagnosis of LLE and LLS in early adolescence can be a setback for a young athlete. Fortunately, most athletes will be able to return to competition with ∼50% still competing at 5 years. Very few will progress to future arm surgery, but recurrence rates are relatively high, and these athletes are less likely to participate in their sport 5 years later.

Level of Evidence:
Level IV—Retrospective cohort study.
Non–chest pain symptoms and likelihood of coronary occlusion in emergency department patients with ST segment elevation undergoing emergent coronary angiography
Authors: Ma Zhiyuan , Antoine Marc Kervin , Vefali Huseng , Manda Yugandhar , Salen Philip , Shoemaker Melinda , Stoltzfus Jill , Puleo Peter 
Published: May 2024

Objectives
Patients presenting with suspected ST segment elevation myocardial infarction frequently have symptoms in addition to chest pain, including dyspnea, nausea or vomiting, diaphoresis, and lightheadedness or syncope. These symptoms are often regarded as supporting the diagnosis of infarction. We sought to determine the prevalence of the non–chest pain symptoms among patients who were confirmed as having a critically diseased coronary vessel as opposed to those with no angiographic culprit lesion.

Methods
Data from 1393 consecutive patients with ST segment elevation who underwent emergent coronary angiography were analyzed. Records were reviewed in detail for symptoms, ECG findings, prior history, angiographic findings, and in-hospital outcomes.

Results
Dyspnea was present in 50.8% of patients, nausea or vomiting in 36.5%, diaphoresis in 51.2%, and lightheadedness/syncope in 16.8%. On angiography, 1239 (88.9%) patients had a culprit lesion and 154 (11.1%) were found not to have a culprit. Only diaphoresis had a higher prevalence among the patients with, as compared with those without a culprit, with an odds ratio of 2.64 (P < 0.001). The highest occurrence of diaphoresis was among patients with a totally occluded artery, with an intermediate frequency among patients with a subtotal stenosis, and the lowest prevalence among those with no culprit. These findings were consistent regardless of ECG infarct location, affected vessel, patient age, or sex. Among the subset of patients who presented without chest discomfort, none of the symptoms were associated with the presence of a culprit.

Conclusion
The presence of diaphoresis, but not dyspnea, nausea, or lightheadedness is associated with an increased likelihood that patients presenting with ST elevation will prove to have a culprit lesion. In patients who present with ST elevation but without chest discomfort, these symptoms should not be regarded as ‘chest pain equivalents’. Further objective data among patients with angiographic confirmation of culprit lesion status is warranted.
Insight into the potential of bone turnover biomarkers: integration in the management of osteoporosis and chronic kidney disease-associated osteoporosis
Authors: Brouwers Pauline , Bouquegneau Antoine , Cavalier Etienne 
Published: May 2024

Purpose of review
Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders.

Recent findings
Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment.

Summary
BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).
High Reliability in a Safety Net Hospital Leading to Operational Excellence
Authors: Didion Lisa , Whitfield Candice , Bishop Phyllis , Jones Alan E. , Henderson J. Michael 
Published: May 2024

Objective
The objective of this work was to establish sustainable systems for quality improvement in an Academic Medical Center and Safety Net Hospital.

Method
High reliability principles of leadership engagement, a culture of safety, and sustainable performance improvement were used. Target areas for improvement were clinical outcomes for patients, public reputation scores, and lower cost of care. The system was based on annual focused goals with specific targets, improvement teams, transparent scorecards, and data driven work. Program visibility was championed by leaders. Consistent education on quality, safety, efficiency, and effectiveness for all employees created buy-in. Data review and accountability tracked progress, helped resource allocation, and defined next steps.

Results
In the first 5 years, all patient quality and safety metrics improved between 10% and 60%. This improvement resulted in higher CMS Star Ranking and Leapfrog patient safety grade. The next phase included maximizing value by expanding into hospital operations and finance with a focus on improved clinical documentation and reduced length of stay and cost of care. Clinical documentation improvement led to a 15% increase in comorbidity capture. This positively impacted reported outcomes and hospital payment by appropriate risk adjustment. Length of stay was addressed with a new care coordination program and physician-driven utilization review.

Conclusions
High reliability principles are applicable in a resource limited healthcare system. Improved clinical and operational results were achieved through goal setting, improvement teams, and data driven projects leading to creation of an office of operational excellence.
Multiple Synchronous Thoracoabdominal Duplication Cysts With Ectopic Gastric Mucosa Detected on 99mTc-Pertechnetate Scintigraphy and SPECT/CT
Authors: Wakankar Ritwik , Sagar Sambit , Khan Dikhra , Dhiman Ayan , Kumar Rakesh 
Published: May 2024

Abstract
Thoracoabdominal duplication cysts are a congenital malformation of the posterior primitive foregut with synchronous thoracic and abdominal duplication cysts being found in up to 15% of cases. The presentation of duplication cysts depends on their location, size, and other factors, like the presence of ectopic functioning gastric mucosa, which is reported in 20%–30% of duplication cysts. 99mTc-pertechnetate scintigraphy along with SPECT/CT helps in the preoperative localization of ectopic functioning gastric mucosa in these duplication cysts. We report the scintigraphic and SPECT/CT findings of one such case, which helped in the final diagnosis and management of the patient.
A safety and feasibility analysis on the use of cold-stored platelets in combat trauma
Authors: Fisher Andrew D. , Stallings Jonathan D. , Schauer Steven G. , Graham Brock A. , Stern Caryn A. , Cap Andrew P. , Gurney Jennifer M. , Shackelford Stacy A. 
Published: May 2024

BACKGROUND
Damage-control resuscitation has come full circle, with the use of whole blood and balanced components. Lack of platelet availability may limit effective damage-control resuscitation. Platelets are typically stored and transfused at room temperature and have a short shelf-life, while cold-stored platelets (CSPs) have the advantage of a longer shelf-life. The US military introduced CSPs into the battlefield surgical environment in 2016. This study is a safety analysis for the use of CSPs in battlefield trauma.

METHODS
The Department of Defense Trauma Registry and Armed Services Blood Program databases were queried to identify casualties who received room-temperature–stored platelets (RSPs) or both RSPs and CSPs between January 1, 2016, and February 29, 2020. Characteristics of recipients of RSPs and RSPs-CSPs were compared and analyzed.

RESULTS
A total of 274 patients were identified; 131 (47.8%) received RSPs and 143 (52.2%) received RSPs-CSPs. The casualties were mostly male (97.1%), similar in age (31.7 years), with a median Injury Severity Score of 22. There was no difference in survival for recipients of RSPs (88.5%) versus RSPs-CSPs (86.7%; p = 0.645). Adverse events were similar between the two cohorts. Blood products received were higher in the RSPs-CSPs cohort compared with the RSPs cohort. The RSPs-CSPs cohort had more massive transfusion (53.5% vs. 33.5%, p = 0.001). A logistic regression model demonstrated that use of RSPs-CSPs was not associated with mortality, with an adjusted odds ratio of 0.96 (p > 0.9; 95% confidence interval, 0.41–2.25).

CONCLUSION
In this safety analysis of RSPs-CSPs compared with RSPs in a combat setting, survival was similar between the two groups. Given the safety and logistical feasibility, the results support continued use of CSPs in military environments and further research into how to optimize resuscitation strategies.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Posteruptive Loss of Enamel Proteins Concurs with Gain in Enamel Hardness
Authors: Karaaslan Hakan , Walker Alejandro R. , Gil-Bona Ana , Depalle Baptiste , Bidlack Felicitas B. 
Published: May 2024

ABSTRACTTooth enamel maturation requires the removal of proteins from the mineralizing enamel matrix to allow for crystallite growth until full hardness is reached to meet the mechanical needs of mastication. While this process takes up to several years in humans before the tooth erupts, it is greatly accelerated in in the faster developing pig. As a result, pig teeth erupt with softer, protein-rich enamel that is similar to hypomineralized human enamel but continues to harden quickly after eruption.Proteins, such as albumin, that bind to enamel crystals and prevent crystal growth and enamel hardening have been suggested as cause for hypomineralized human enamel that does not naturally harden after eruption. However, albumin is abundant in pig enamel. It is unclear whether fast posteruptive enamel hardening in pigs occurs despite the high protein content or requires a facilitated protein loss to allow for crystal growth.This study asked how the protein content in porcine enamel changes after eruption in relation to saliva. Based on previous data demonstrating the high albumin content in erupted porcine enamel, we hypothesize that following pre-eruptive maturation, enamel and saliva derived enzymes facilitate protein removal from porcine enamel after eruption. We analyzed enamel and the saliva proteome at three critical timepoints: at the time of tooth eruption, 2 weeks after eruption, and enamel 6 weeks after eruption. We used only fourth deciduous premolars and saliva samples from animals sacrificed at the respective time points to determine the organic content in tooth enamel, saliva, and saliva proteins within enamel.We found a decrease in the number of proteins and their abundancy in enamel with posteruptive time, including a decrease in serum albumin within enamel. The rapid decrease in the first two weeks is in line with previously reported rapid increase in mineral density of porcine enamel after eruption. In addition to the enamel proteases KLK-4 and MMP-20, we identified serine-, cysteine-, aspartic-, and metalloproteases. Some of these were only identified in enamel, while almost half of the enzymes are in common with saliva at all timepoints. Our findings suggest that the fast posteruptive enamel maturation in the porcine model coincides with saliva exchange and influx of saliva enzymes into porous enamel.
Realigning representational drift in mouse visual cortex by flexible brain-machine interfaces
Authors: Zhao Siyuan , Shen Hao , Qin Shanshan , Jiang Shouhao , Tang Xin , Lee Madeleine , Zhang Xinhe , Lee Jaeyong , Chen Juntao , Liu Jia 
Published: May 2024

AbstractThe ability to stably decode brain activity is crucial for brain-machine interfaces (BMIs), which are often compromised by recording instability due to immune responses and probe drifting. In addition, many brain regions undergo intrinsic dynamics such as “representational drift”, in which neural activities associated with stable sensation and action continually change over time. In this study, we employed tissue-like flexible electrode arrays for recording visual stimulus-dependent single-unit action potentials in the mouse visual cortex. The flexible electrode array enabled us to record action potentials from the same neurons over extended periods under visual stimuli, allowing us to characterize the representational drift during these stimuli. With this approach, we tested hypotheses about the origins and mechanisms of representational drift, tracked latent dynamics transformation, and modeled these dynamics with affine transformation. Our findings enabled the construction of a single, long-term stable, high-performance visual information decoder that accounts for representational drift, potentiating chronically stable flexible BMIs in brain regions experiencing representational drifts.
Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets
Authors: Agoro Rafiou , Myslinski Jered , Marambio Yamil G. , Janosevic Danielle , Jennings Kayleigh N. , Liu Sheng , Hibbard Lainey M. , Fang Fang , Ni Pu , Noonan Megan L. , Solis Emmanuel , Chu Xiaona , Wang Yue , Dagher Pierre C. , Liu Yunlong , Wan Jun , Hato Takashi , White Kenneth E. 
Published: May 2024

AbstractFGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution. Computational analysis identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point. FGF23 actions were sex independent but critically relied upon constitutive KL expression mapped within proximal tubule (S1-S3) and distal tubule (DCT/CNT) cell sub-populations. Temporal KL-dependent FGF23 responses drove unique and transient cellular identities, including genes in key MAPK- and vitamin D-metabolic pathways via early- (AP-1-related) and late-phase (EIF2 signaling) transcriptional regulons. Combining ATACseq/RNAseq data from a cell line stably expressing KL with thein vivoscRNAseq pinpointed genomic accessibility changes in MAPK-dependent genes, including the identification of FGF23-dependent EGR1 distal enhancers. Finally, we isolated unexpected crosstalk between FGF23-mediated MAPK signaling and pro-inflammatory TNF receptor activation via NF-κB, which blocked FGF23 bioactivityin vitroandin vivo. Collectively, our findings have uncovered novel pathways at the single cell level that likely influence FGF23-dependent disease mechanisms.Translational statementInflammation and elevated FGF23 in chronic kidney disease (CKD) are both associated with poor patient outcomes and mortality. However, the links between these manifestations and the effects of inflammation on FGF23-mediated mineral metabolism within specific nephron segments remain unclear. Herein, we isolated an inflammatory pathway driven by TNF/NF-κB associated with regulating FGF23 bioactivity. The findings from this study could be important in designing future therapeutic approaches for chronic mineral diseases, including potential combination therapies or early intervention strategies. We also suggest that further studies could explore these pathways at the single cell level in CKD models, as well as test translation of our findings to interactions of chronic inflammation and elevated FGF23 in human CKD kidney datasets.
Proteogenomics analysis of human tissues using pangenomes
Authors: Wang Dong , Bouwmeester Robbin , Zheng Ping , Dai Chengxin , Sanchez Aniel , Shu Kunxian , Bai Mingze , Umer Husen M. , Perez-Riverol Yasset 
Published: May 2024

AbstractThe genomics landscape is evolving with the emergence of pangenomes, challenging the conventional single-reference genome model. The new human pangenome reference provides an extra dimension by incorporating variations observed in different human populations. However, the increasing use of pangenomes in human reference databases poses challenges for proteomics, which currently relies on UniProt canonical/isoform-based reference proteomics. Including more variant information in human proteomes, such as small and long open reading frames and pseudogenes, prompts the development of complex proteogenomics pipelines for analysis and validation. This study explores the advantages of pangenomes, particularly the human reference pangenome, on proteomics, and large-scale proteogenomics studies. We reanalyze two large human tissue datasets using the quantms workflow to identify novel peptides and variant proteins from the pangenome samples. Using three search engines SAGE, COMET, and MSGF+ followed by Percolator we analyzed 91,833,481 MS/MS spectra from more than 30 normal human tissues. We developed a robust deep-learning framework to validate the novel peptides based on DeepLC, MS2PIP and pyspectrumAI. The results yielded 170142 novel peptide spectrum matches, 4991 novel peptide sequences, and 3921 single amino acid variants, corresponding to 2367 genes across five population groups, demonstrating the effectiveness of our proteogenomics approach using the recent pangenome references.
SaprotHub: Making Protein Modeling Accessible to All Biologists
Authors: Su Jin , Li Zhikai , Han Chenchen , Zhou Yuyang , He Yan , Shan Junjie , Zhou Xibin , Chang Xing , Jiang Shiyu , Ma Dacheng ,   The OPMC, Steinegger Martin , Ovchinnikov Sergey , Yuan Fajie 
Published: May 2024

AbstractTraining and deploying deep learning models pose challenges for users without machine learning (ML) expertise. SaprotHub offers a user-friendly platform that democratizes the process of training, utilizing, storing, and sharing protein ML models, fostering collaboration within the biology community—all without requiring extensive machine learning expertise. At its core, Saprot is an advanced, foundational protein language model. Through its ColabSaprot framework, it supports potentially hundreds of protein training and prediction applications, enabling the co-construction and co-sharing of these trained models. This enhances user engagement and drives community-wide innovation.
Transportability of patient outcomes from a US clinical trial to real-world populations - a case study using Lung-MAP S1400I (NCT02785952)
Authors: Gupta Alind , Chan Kelvin , Gomes Manuel , Duffield Stephen , Ramagopalan Sreeram , Kent Seamus , Subbiah Vivek , Cheung Winson , Bendavid Eran , Arora Paul 
Published: May 2024

2.AbstractBackgroundThe external validity of results from clinical trials to routine clinical practice is often questioned. This is sometimes because certain real world patient groups are excluded or underrepresented in clinical trials, or because standards of care in trials are different from those in real-world populations globally. This lack of external validity of trial results manifests as an efficacy-effectiveness gap. In this study, we aim to address the question of whether it is possible to extend results from a clinical trial to real-world populations across different countries. To do this, we use the Lung-MAP nonmatch sub-study S1400I trial (NCT02785952) as a case study.SettingSquamous cell lung carcinoma is a subtype of non-small cell lung cancer (NSCLC) accounting for 25-30% of cases. Compared to other NSCLC subtypes such as adenocarcinoma, the presence of actionable genetic variants is less common and there are fewer targeted therapies available for advanced/metastatic NSCLC (aNSCLC) of squamous subtype. Patients with squamous aNSCLC who progress on front-line chemotherapy commonly receive immunotherapy using immune checkpoint inhibitors such as nivolumab. The Lung-MAP nonmatch sub-study S1400I (NCT02785952) compared overall survival (OS) in patients with recurrent/stage IV squamous NSCLC randomized to receive either nivolumab monotherapy or nivolumab + ipilimumab combination therapy and found no significant difference in mortality rates between these groups. The trial included patients from the United States only.ObjectivesThe goal of this study is to evaluate the transportability of results fromNCT02785952in United States patients to real-world populations in the United States, Germany, France, England and Japan. Using individual-level data for OS fromNCT02785952, we will adjust for baseline characteristics from published studies of real-world populations in these countries and benchmark the predicted OS against Kaplan-Meier estimates reported by these studies for patients with squamous cell aNSCLC treated with nivolumab. Sensitivity analyses for unmeasured prognostic variables will be performed.