bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updating Pediatric Reference Ranges at Seattle Children’s Hospital Using an Indirect Approach
Authors: Pape Ari , Dickerson Jane 
Published: October 2024

Abstract

Background
The aim of this project was to evaluate the accuracy of historical reference ranges at our institution. Our population of interest is children (&lt;18 years old) within a large city. Ideally, reference intervals are determined using the direct method by performing studies on healthy volunteers. However, this approach has many challenges including being resource intensive, and, particularly in the pediatric population, difficulty in obtaining the required number of healthy volunteers for every age range. Given these challenges, a second approach, the indirect approach, has also been utilized to update reference ranges. This approach uses retrospective data analysis on data that was not specifically collected for evaluation of a reference range. Abnormal values are filtered out using a variety of methods.

Methods
For our project we pulled all outpatient data between 10/3/2020 and 06/30/2023 for the following analytes: albumin, ALP, AST, ALT, BUN, calcium, chloride, CO2, conjugated bilirubin, delta bilirubin, potassium, sodium, total bilirubin, total protein, and unconjugated bilirubin. We limited each patient to their first result for each analyte on the basis that analytes being measured more than once are more likely to be abnormal, and to limit bias. We also pulled the age (in days) and legal sex for each patient. The Tukey method was used to exclude outliers on the assumption that most data points would be normal, so any outliers would represent abnormal values from potentially not healthy patients. For each analyte and every age range the frequency of each value was plotted and the percentage of values within the current reference range, 2.5th percentile, and 97.5th percentile were calculated. A reference range was considered accurately representative of the normal population at our institution if the percentage of values within the reference range was greater than or equal to 80%.

Results
The “in range” percentage for albumin, ALT, BUN, calcium, chloride, conjugated bilirubin, delta bilirubin, creatinine, and total bilirubin was greater than 80% for all age ranges tested. Potassium, sodium, and unconjugated bilirubin each had one age range where the percent “in range” was less than 80% (2 days – 3 months, &lt; 1 week, and &lt; 1 month respectively), however the sample number for these age ranges was considered too low to make any significant conclusions (n=273, n=11, and n=21 respectively). ALP, AST, CO2, and total protein each had at least one age range where the percent “in range” was less than 80% and a substantial number of data points was available. In these cases, we proposed changing the reference interval to the calculated 2.5th and 97.5th percentiles based on our retrospective data analysis or verifying an externally validated pediatric reference interval from the CALIPER study.
Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function
Authors: Brown Hannah , Spies Nicholas , Farnsworth Christopher 
Published: October 2024

Abstract
Limited studies assess reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs). 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR} was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement (Kappa = 0.48, 95% confidence interval: 0.46-0.51) and positive correlation (r = 0.51; p&lt;0.0001) between ALP and GGT was observed. For ALP and GGT, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &gt;50 years, respectively. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Manufacturer RIs agreed well with the IRIs for most subsets, but differed for ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &gt;50 years. Further investigation of the impact of preselecting patient populations on IRIs and a direct RI study on select patient subsets is worth investigation.
Long-term Functional and Aesthetic Outcomes of Labiaplasty: A Review of the Literature
Authors: McGrattan Meghan , Majeed Amna , Hanna Steven A 
Published: October 2024

Abstract

The incidence of female genital cosmetic surgery (FGCS), and specifically labiaplasty, is on the rise. Common motivators for labiaplasty include hygiene concerns, functional impairment, difficulties with physical or sexual activity, and dissatisfaction with genital appearance, among others. However, there have been few reports on long-term functional and aesthetic outcomes and complications of labiaplasty. The aim of this literature review was to report on long-term outcomes of labiaplasty, defined as ≥1 year postoperatively, to inform safety and efficacy recommendations for the procedure. A comprehensive literature review was conducted on PubMed (National Institutes of Health, Bethesda, MD) and Embase (Elsevier, Amsterdam, the Netherlands) from inception to December 1, 2023, following PRISMA guidelines. Articles were selected according to predetermined eligibility criteria. A manual search was performed to identify additional relevant studies. Nine studies reported on the long-term postoperative complications associated with labiaplasty, with a cumulative total of 748 patients. The most commonly reported complications included postoperative asymmetry (n = 45, 6.02%), scarring (n = 14, 1.87%), and the need for revisional surgery (n = 42, 5.61%). Of note, the majority of patients (n = 621 of 748) were reported to not have any postoperative complications. In the 7 studies that reported on psychological outcomes associated with labiaplasty, all reported sustained improvement in genital appearance scores as well as aesthetic and sexual satisfaction over the long term.

Level of Evidence: 3 (Therapeutic)
Anti-symmetric framework for balanced learning of protein–protein interactions
Authors: Tang Tao , Li Tianyang , Li Weizhuo , Cao Xiaofeng , Liu Yuansheng , Zeng Xiangxiang 
Published: October 2024

Abstract

Motivation
Protein–protein interactions (PPIs) are essential for the regulation and facilitation of virtually all biological processes. Computational tools, particularly those based on deep learning, are preferred for the efficient prediction of PPIs. Despite recent progress, two challenges remain unresolved: (i) the imbalanced nature of PPI characteristics is often ignored and (ii) there exists a high computational cost associated with capturing long-range dependencies within protein data, typically exhibiting quadratic complexity relative to the length of the protein sequence.

Result
Here, we propose an anti-symmetric graph learning model, BaPPI, for the balanced prediction of PPIs and extrapolation of the involved patterns in PPI network. In BaPPI, the contextualized information of protein data is efficiently handled by an attention-free mechanism formed by recurrent convolution operator. The anti-symmetric graph convolutional network is employed to model the uneven distribution within PPI networks, aiming to learn a more robust and balanced representation of the relationships between proteins. Ultimately, the model is updated using asymmetric loss. The experimental results on classical baseline datasets demonstrate that BaPPI outperforms four state-of-the-art PPI prediction methods. In terms of Micro-F1, BaPPI exceeds the second-best method by 6.5% on SHS27K and 5.3% on SHS148K. Further analysis of the generalization ability and patterns of predicted PPIs also demonstrates our model’s generalizability and robustness to the imbalanced nature of PPI datasets.

Availability and implementation
The source code of this work is publicly available at https://github.com/ttan6729/BaPPI.
Optimizing Western blotting immunodetection: Streamlining antibody cocktails for reduced protocol time and enhanced multiplexing applications
Authors: Yamani L Z , Alsamman Khaldoon , El-Masry Omar S 
Published: October 2024

Abstract
Adaptive, rather than innate, immunity relies mainly on antigen–antibody recognition. This recognition is driven by the binding of specific antibody paratopes to distinct epitopes found on antigens. This interaction is pivotal for immune responses that have been re-purposed for diagnostic and therapeutic purposes. This article focuses on Western blotting, an in vitro technique performed for protein immunodetection. Traditionally, this technique requires separate incubations of both primary and secondary antibodies, for which these antibodies recognize different antigen epitopes (conventional method). We propose a modified protocol combining both antibodies, involving a single incubation step that reduces time and conserves reagents (non-conventional/improved method). This improved protocol will enhance efficiency without compromising detection accuracy. It will support multiplexing, enabling the simultaneous detection of multiple proteins. Despite the positive results found by applying available antibodies, further optimization is required for a more thorough evaluation, to ensure that all antibodies consistently yield successful results in every detection attempt for broader use. Our findings indicate that the tested antibody cocktails remained stable over time, which suggests potential for commercialization of this modified Western blot protocol with a wide scope towards multiplex diagnostic application.
Colorectal cancer prevalence in faecal immunochemical test non-returners: potential for health inequality in symptomatic referral pathways
Authors: Gerrard Adam D , Coxon Jonty , Maeda Yasuko , Theodoratou Evropi , Dunlop Malcolm G , Din Farhat V N 
Published: October 2024

Abstract

Background
This study aimed to describe the faecal immunochemical test non-return rate of those referred with high-risk symptoms of colorectal cancer from primary care, and the clinical outcomes of the ‘non-returners’.

Methods
From January 2019 to July 2021, patients referred to secondary care with symptoms suspicious of colorectal cancer and a referral priority of urgent or urgent suspicion of cancer were sent a faecal immunochemical test. All patients were investigated regardless of faecal immunochemical test return or result. Demographics and clinical outcomes such as colorectal cancer prevalence were compared between those who returned a faecal immunochemical test and non-returners.

Results
Of 7345 patients included in the study, 874 (11.9%) did not return a faecal immunochemical test. Non-returner characteristics included male sex (P = 0.040), younger age (median age 57 versus 65 years, P &lt; 0.001), per rectal bleeding (P &lt; 0.001) and lower socioeconomic status (median Scottish Index of Multiple Deprivation, 6 versus 7, P &lt; 0.001) compared with those who returned a faecal immunochemical test. Of 6294 patients undergoing colorectal investigation, there was a greater prevalence of colorectal cancer (5.4% versus 3.6% P = 0.032) and significant bowel pathology than in the non-returners (15.3% versus 9.8%, P &lt; 0.001). With a median follow-up of 25 months, the colorectal cancer prevalence for the entire 7345 cohort was equal between those who returned and did not return a faecal immunochemical test (3.2% versus 3.8%, P = 0.108). Of note, the non-returners diagnosed with colorectal cancer were younger (median age 64 versus 73 years, P &lt; 0.001) and from a lower socioeconomic area (median Scottish Index of Multiple Deprivation 4 versus 7, P = 0.015) than faecal immunochemical test returners.

Conclusion
Patients referred to secondary care, with symptoms suspicious of colorectal cancer, that did not return a faecal immunochemical test had a similar colorectal cancer prevalence to those that returned the test.
Artificial intelligence evaluation of electrocardiographic characteristics and interval changes in transgender patients on gender-affirming hormone therapy
Authors: Adel Fadi W , Sang Philip , Walsh Connor , Maheshwari Arvind , Cummings Paige , Attia Zachi , Mangold Kathryn , Davidge-Pitts Caroline , Lopez-Jimenez Francisco , Friedman Paul , Noseworthy Peter A , Mankad Rekha 
Published: October 2024

Abstract

Aims
Gender-affirming hormone therapy (GAHT) is used by some transgender individuals (TG), who comprise 1.4% of US population. However, the effects of GAHT on electrocardiogram (ECG) remain unknown. The objective is to assess the effects of GAHT on ECG changes in TG.

Methods and results
Twelve-lead ECGs of TG on GAHT at the Mayo Clinic were inspected using a validated artificial intelligence (AI) algorithm. The algorithm assigns a patient’s ECG male pattern probability on a scale of 0 (female) to 1 (male). In the primary analysis, done separately for transgender women (TGW) and transgender men (TGM), 12-lead ECGs were used to estimate the male pattern probability before and after GAHT. In a subanalysis, only patients with both pre- and post-GAHT EGCs were included. Further, the autopopulated PR, QRS, and QTc intervals were compared before and after GAHT. Among TGW (n = 86), the probability (mean ± SD) of an ECG male pattern was 0.84 ± 0.25 in the pre-GAHT group, and it was lowered to 0.59 ± 0.36 in the post-GAHT group (n = 173, P &lt; 7.8 × 10−10). Conversely, among TGM, male pattern probability was 0.16 ± 0.28 (n = 47) in the pre-GAHT group, and it was higher at 0.41 ± 0.38 in the post-GAHT group (n = 53, P &lt; 2.4×10−4). The trend persisted in the subanalysis. Furthermore, both the PR (P = 5.68 × 10−4) and QTc intervals (P = 6.65×10−6) prolonged among TGW. Among TGM, the QTc interval shortened (P = 4.8 × 10−2).

Conclusion
Among TG, GAHT is associated with ECG changes trending towards gender congruence, as determined by the AI algorithm and ECG intervals. Prospective studies are warranted to understand GAHT effects on cardiac structure and function.
The win ratio in cardiology trials: lessons learnt, new developments, and wise future use
Authors: Pocock Stuart J , Gregson John , Collier Timothy J , Ferreira Joao Pedro , Stone Gregg W 
Published: October 2024

Abstract
The win ratio method for analysing a composite clinical hierarchy of outcomes is growing in popularity especially in cardiovascular trials. This article gives a perspective on its use so far and the issues derived from that experience. Specifically, it focuses on the limitations of a conventional composite outcome; how does the win ratio work, what does it mean, and how to display its findings; guidance on choosing an appropriate clinical hierarchy of outcomes including clinical events, quantitative outcomes, and other options; the additional value of the win difference as a measure of absolute benefit: extension to stratified win ratio, subgroup analysis, matched win ratio, and covariate adjustment; determining trial size for a win ratio outcome; specific insights such as adaptive designs, use of repeat events, and use of margins and time averages for quantitative outcomes; a critique of potential misuses; availability of statistical software; and a statistical appendix on the methodological details. Throughout, each principle is illustrated by examples from specific cardiology trials. The article concludes with a set of recommendations for future use of the win ratio.
Contact with young children is a major risk factor for pneumococcal colonization in older adults
Authors: Wyllie Anne L , Yolda-Carr Devyn , Hislop Maikel S , Mbodj Sidiya , Wurst Loren , Waghela Pari , Alexander-Parrish Ronika , Grant Lindsay R , Arguedas Adriano , Gessner Bradford D , Weinberger Daniel M 
Published: October 2024

AbstractImportant questions remain about the sources of transmission of pneumococcus to older adults in the community. This is critical for understanding the potential effects of using pneumococcal conjugate vaccines (PCVs) in children and older adults. For non-institutionalized individuals, we hypothesized that the most likely source of adult-to-adult transmission is within the household. We designed a longitudinal study to sample adults ≥60 years of age living in the same household (New Haven, CT, USA), without younger residents in the household. Saliva samples and social and health questionnaires were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB, lytA, and serotype. Across two study seasons (November 2020–August 2021, November 2021–September 2022), 121 individuals from 61 households completed all six visits; 62 individuals were enrolled in both seasons. Overall, 52/1088 (4.8%) samples tested positive for pneumococcus, with 27/121 (22.3%) individuals colonized at least once. Several individuals were colonized at multiple time points; two individuals were colonized at 5/6 time points and two at all six. In 5 instances, both household members were carriers in the same season, though not necessarily at the same time. Pneumococcal carriage was substantially higher among individuals who had contact with children (10.0% vs. 1.6%). Contact with young children was the most important factor that influenced pneumococcal acquisition rates. While there were several instances where both adult household members were colonized at the same time or at sequential visits, these individuals typically had contact with children. As such, PCV immunization can directly protect older adults who have contact with children.
Quest for Orthologs in the Era of Biodiversity Genomics
Authors: Langschied Felix , Bordin Nicola , Cosentino Salvatore , Fuentes-Palacios Diego , Glover Natasha , Hiller Michael , Hu Yanhui , Huerta-Cepas Jaime , Coelho Luis Pedro , Iwasaki Wataru , Majidian Sina , Manzano-Morales Saioa , Persson Emma , Richards Thomas A , Gabaldón Toni , Sonnhammer Erik , Thomas Paul D , Dessimoz Christophe , Ebersberger Ingo 
Published: October 2024

Abstract
The era of biodiversity genomics is characterized by large-scale genome sequencing efforts that aim to represent each living taxon with an assembled genome. Generating knowledge from this wealth of data has not kept up with this pace. We here discuss major challenges to integrating these novel genomes into a comprehensive functional and evolutionary network spanning the tree of life. In summary, the expanding datasets create a need for scalable gene annotation methods. To trace gene function across species, new methods must seek to increase the resolution of ortholog analyses, e.g. by extending analyses to the protein domain level and by accounting for alternative splicing. Additionally, the scope of orthology prediction should be pushed beyond well-investigated proteomes. This demands the development of specialized methods for the identification of orthologs to short proteins and noncoding RNAs and for the functional characterization of novel gene families. Furthermore, protein structures predicted by machine learning are now readily available, but this new information is yet to be integrated with orthology-based analyses. Finally, an increasing focus should be placed on making orthology assignments adhere to the findable, accessible, interoperable, and reusable (FAIR) principles. This fosters green bioinformatics by avoiding redundant computations and helps integrating diverse scientific communities sharing the need for comparative genetics and genomics information. It should also help with communicating orthology-related concepts in a format that is accessible to the public, to counteract existing misinformation about evolution.
How to (or how not to) implement crowdsourcing for the development of health interventions: lessons learned from four African countries
Authors: Kpokiri Eneyi E , Phiri Mwelwa M , Martinez-Alvarez Melisa , Tembo Mandikudza , Chikwari Chido Dziva , Nzvere Farirai , Doyle Aoife M , Tucker Joseph D , Hensen Bernadette 
Published: October 2024

Abstract
Crowdsourcing strategies are useful in the development of public health interventions. Crowdsourcing engages end users in a co-creation process through challenge contests, designathons or online collaborations. Drawing on our experience of crowdsourcing in four African countries, we provide guidance on designing crowdsourcing strategies across seven steps: deciding on the type of crowdsourcing strategy, convening a steering committee, developing the content of the call for ideas, promotion, evaluation, recognizing finalists and sharing back ideas or implementing the solutions.