bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tools for editing the mammalian mitochondrial genome
Authors: Moraes Carlos T 
Published: May 2024

Abstract
The manipulation of animal mitochondrial genomes has long been a challenge due to the lack of an effective transformation method. With the discovery of specific gene editing enzymes, designed to target pathogenic mitochondrial DNA mutations (often heteroplasmic), the selective removal or modification of mutant variants has become a reality. Because mitochondria cannot efficiently import RNAs, CRISPR has not been the first choice for editing mitochondrial genes. However, the last few years witnessed an explosion in novel and optimized non-CRISPR approaches to promote double-strand breaks or base-edit of mtDNA in vivo. Engineered forms of specific nucleases and cytidine/adenine deaminases form the basis for these techniques. I will review the newest developments that constitute the current toolbox for animal mtDNA gene editing in vivo, bringing these approaches not only to the exploration of mitochondrial function, but also closer to clinical use.
Challenges in IBD Research 2024: Novel Technologies
Authors: Prasad Shalini , Cross Raymond K , Monroe Mary Beth , Dolinger Michael T , Motte Rachel , Hong Sungmo , Stidham Ryan W , Kumar Narendra , Levine Deborah , Larijani Anthony , Simone Ashley , Chachu Karen A , Wyborski Russell , Heller Caren A , Moss Alan C , Schwerbrock Nicole M J , Selaru Florin M 
Published: May 2024

Abstract
Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization.
Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics.
Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment.
Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there’s a collective effort to enhance patient care and outcomes for individuals affected by IBD.
Challenges in IBD Research 2024: Precision Medicine
Authors: Syed Sana , Boland Brigid S , Bourke Lauren T , Chen Lea Ann , Churchill Laurie , Dobes Angela , Greene Adam , Heller Caren , Jayson Christina , Kostiuk Benjamin , Moss Alan , Najdawi Fedaa , Plung Lori , Rioux John D , Rosen Michael J , Torres Joana , Zulqarnain Fatima , Satsangi Jack 
Published: May 2024

Abstract
Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.
A payroll efficiency analysis of Europe’s top football leagues
Authors: Villa G , Lozano S 
Published: May 2024

Abstract
Accepted by: Ali Emrouznejad
Top European football teams have large budgets mainly due to the high wage bills they pay to the players. Therefore, it would be interesting to determine if these football teams are paying inflated salaries considering the sports results that they obtain each season in both national and international competitions. This study focuses on the top five European football leagues (Italian, Spanish, English, French and German). We propose a novel non-convex, non-parametric metafrontier analysis approach to determine whether the football clubs are overpaying their players considering their sporting performance. Goals against in both national and international competitions are modelled as undesirable outputs. Each football team is benchmarked first within its own league and then against all five leagues. From this, apart from estimating the payroll efficiency of each team, the average efficiency of each of these five leagues can also be computed. An exhaustive analysis and discussion of the results is presented using data from three seasons (2020–2023). Some ‘important’ football clubs pay salaries that are not justified by their performance when compared with other, more modest, clubs that pay salaries more in line with the sports results obtained. Ligue 1 is the league that, on average, makes the most efficient use of their payroll, followed by the Bundesliga and, somewhat behind, La Liga and Serie A. The Premier League occupies the last position in terms of average payroll efficiency.
Hepatitis B Virus DNA and RNA Persist in Liver After Serologic Recovery in Persons With Hepatitis C Virus
Authors: Grudda Tanner , Thomas David L , Kirk Gregory D , Mehta Shruti H , Astemborski Jacquie , Lauer Georg M , Balagopal Ashwin , Thio Chloe L 
Published: May 2024

Abstract
After recovery from a hepatitis B virus (HBV) infection, reactivation can occur with immunosuppression; thus, it is assumed that replication competent HBV persists in the liver. We sought to detect persistent HBV from 13 people with spontaneous recovery. We quantified HBV DNA and RNA in core liver biopsy specimens (median, 1.72 × 106 cells) from persons who inject drugs. Of 13 biopsy specimens, 8 (61%) had evidence of HBV DNA or RNA and 5 (38%) had both HBV DNA and RNA. Messenger RNAs were derived from covalently closed circular DNA and integrated HBV DNA. Here, we show prevalent HBV DNA and RNA despite clinical recovery in persons who inject drugs.
CoRTEx: contrastive learning for representing terms via explanations with applications on constructing biomedical knowledge graphs
Authors: Ying Huaiyuan , Zhao Zhengyun , Zhao Yang , Zeng Sihang , Yu Sheng 
Published: May 2024

Abstract

Objectives
Biomedical Knowledge Graphs play a pivotal role in various biomedical research domains. Concurrently, term clustering emerges as a crucial step in constructing these knowledge graphs, aiming to identify synonymous terms. Due to a lack of knowledge, previous contrastive learning models trained with Unified Medical Language System (UMLS) synonyms struggle at clustering difficult terms and do not generalize well beyond UMLS terms. In this work, we leverage the world knowledge from large language models (LLMs) and propose Contrastive Learning for Representing Terms via Explanations (CoRTEx) to enhance term representation and significantly improves term clustering.

Materials and Methods
The model training involves generating explanations for a cleaned subset of UMLS terms using ChatGPT. We employ contrastive learning, considering term and explanation embeddings simultaneously, and progressively introduce hard negative samples. Additionally, a ChatGPT-assisted BIRCH algorithm is designed for efficient clustering of a new ontology.

Results
We established a clustering test set and a hard negative test set, where our model consistently achieves the highest F1 score. With CoRTEx embeddings and the modified BIRCH algorithm, we grouped 35 580 932 terms from the Biomedical Informatics Ontology System (BIOS) into 22 104 559 clusters with O(N) queries to ChatGPT. Case studies highlight the model’s efficacy in handling challenging samples, aided by information from explanations.

Conclusion
By aligning terms to their explanations, CoRTEx demonstrates superior accuracy over benchmark models and robustness beyond its training set, and it is suitable for clustering terms for large-scale biomedical ontologies.
Impact of high-quality, mixed-domain data on the performance of medical language models
Authors: Griot Maxime , Hemptinne Coralie , Vanderdonckt Jean , Yuksel Demet 
Published: May 2024

Abstract

Objective
To optimize the training strategy of large language models for medical applications, focusing on creating clinically relevant systems that efficiently integrate into healthcare settings, while ensuring high standards of accuracy and reliability.

Materials and Methods
We curated a comprehensive collection of high-quality, domain-specific data and used it to train several models, each with different subsets of this data. These models were rigorously evaluated against standard medical benchmarks, such as the USMLE, to measure their performance. Furthermore, for a thorough effectiveness assessment, they were compared with other state-of-the-art medical models of comparable size.

Results
The models trained with a mix of high-quality, domain-specific, and general data showed superior performance over those trained on larger, less clinically relevant datasets (P &lt; .001). Our 7-billion-parameter model Med5 scores 60.5% on MedQA, outperforming the previous best of 49.3% from comparable models, and becomes the first of its size to achieve a passing score on the USMLE. Additionally, this model retained its proficiency in general domain tasks, comparable to state-of-the-art general domain models of similar size.

Discussion
Our findings underscore the importance of integrating high-quality, domain-specific data in training large language models for medical purposes. The balanced approach between specialized and general data significantly enhances the model’s clinical relevance and performance.

Conclusion
This study sets a new standard in medical language models, proving that a strategically trained, smaller model can outperform larger ones in clinical relevance and general proficiency, highlighting the importance of data quality and expert curation in generative artificial intelligence for healthcare applications.
Effectiveness of Postburn Pruritus Treatment and Improvement of Insomnia—A Randomized Trial
Authors: Arko-Boham Elliott , Paintsil Albert Bedford , Arko-Boham Benjamin , Adjei George Obeng 
Published: May 2024

Abstract
Postburn pruritus is difficult to assess and treat. Antihistamines used in its treatment provide little relief. Identification of the itch neuronal pathway has inspired new alternatives, including gabapentin, for its management. The study compared the effectiveness of cetirizine, gabapentin, and a combination of gabapentin and cetirizine in treating postburn pruritus. Burn patients were randomly assigned to treatment with Cetirizine (n = 23), Gabapentin (n = 23), or Cetirizine plus Gabapentin (n = 23). A baseline assessment of the intensity or the severity of pruritus was evaluated, after which treatment commenced with standard doses of the 3 study regimens. Quality of sleep was assessed at baseline (day 0) and repeated on day 3, day 7, and day 14. Approximately 97% of participants presented with moderate or severe itch; 69% with acute itch; and the majority (94.2%) experienced pruritus between the first and fourth weeks. Gabapentin reduced itch by 92.9% in 14 days compared to cetirizine’s 61.8%. The combined effect of cetirizine and gabapentin was comparable using gabapentin alone. When the itch became protracted over 6 weeks, the effectiveness of cetirizine in controlling itch worsened. It reduced itch intensity by only 37.7%, whilst gabapentin did so at 89.4%. Itch intensity correlated positively with insomnia, and controlling itch intensity improved sleep. Gabapentin was more effective for the treatment of postburn pruritus than cetirizine. Controlling itch intensity improved sleep. In acute and moderate itch, low-dose gabapentin could be added if cetirizine is the drug intended for its treatment.
Elevated Cardiac Troponin I Level Associated to Cardiac Dysfunction in Burned Patients
Authors: Segura Carolina , Golovko George , Obias Isabel , Shah Suhaib , El Ayadi Amina , Wolf Steven , Song Juquan 
Published: May 2024

Abstract
Severely burned patients often develop cardiac dysfunction and heart failure. The purpose of this retrospective study is to evaluate the role of cardiac troponin I (cTI) and its association to patients with burns. Patients deidentified data were collected from a national database in May 2023. Adult patients with burns who had cTnI lab counted were enrolled in this study. Patients were grouped by the cTnI mean level within 72 h including patients with elevated cTnI levels at &gt;0.3 ng/mL (n = 2188 patients) and patients with nonelevated cTnI level (&lt;0.04 ng/mL) (n = 3200). The cohorts were further stratified by less than 20% TBSA mild burn population and &gt;20% TBSA severe burn population to replicate the severity of burns. The 30-day incidences of acute myocardial infarction (MI), sepsis, and mortality were investigated after the cohorts were propensity-matching balanced. The odds ratios (ORs) with 95% CI for MI were (9.829/7.081-13.645), sepsis (1.527/1.269-1.959), and mortality (2.586/2.110-3.170), respectively (P &lt; .05). The groups that were further stratified into mild burn and severe burn had the following results: The mild burn ORs and 95% CI for MI was (6.237/3.986-9.785), sepsis (1.603/1.132-2.270), and mortality was (2.298/1.629-3.242). The severe burn cohort had ORs and 95% CI for MI (3.145/1.469-6.732), sepsis (0.993/0.555-1.777), and mortality (2.934/1.924-4.475). In conclusion, the patients with earlier elevated cTnI levels had worse outcomes of MI and mortality in both severe and mild burns.
Irisin prevents trabecular bone damage and tumor invasion in a mouse model of multiple myeloma
Authors: Zerlotin Roberta , Oranger Angela , Pignataro Patrizia , Dicarlo Manuela , Sanesi Lorenzo , Suriano Clelia , Storlino Giuseppina , Rizzi Rita , Mestice Anna , Di Gioia Sante , Mori Giorgio , Grano Maria , Colaianni Graziana , Colucci Silvia 
Published: May 2024

Abstract
Bone disease associated with multiple myeloma (MM) is characterized by osteolytic lesions and pathological fractures, which remain a therapeutic priority despite new drugs improving MM patient survival. Antiresorptive molecules represent the main option for the treatment of MM-associated bone disease (MMBD), whereas osteoanabolic molecules are under investigation. Among these latter, we here focused on the myokine irisin, which is able to enhance bone mass in healthy mice, prevent bone loss in osteoporotic mouse models, and accelerate fracture healing in mice. Therefore, we investigated irisin effect on MMBD in a mouse model of MM induced by intratibial injection of myeloma cells followed by weekly administration of 100 μg/kg of recombinant irisin for 5 wk. By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume/Total Volume (P = .0028), Trabecular Number (P = .0076), Trabecular Fractal Dimension (P = .0044), and increasing Trabecular Separation (P = .0003) in MM mice. In cortical bone, irisin downregulates the expression of Sclerostin, a bone formation inhibitor, and RankL, a pro-osteoclastogenic molecule, while in BM it upregulates Opg, an anti-osteoclastogenic cytokine. We found that in the BM tibia of irisin-treated MM mice, the percentage of MM cells displays a reduction trend, while in the femur it decreases significantly. This is in line with the in vitro reduction of myeloma cell viability after 48 h of irisin stimulation at both 200 and 500 ng/mL and, after 72 h already at 100 ng/mL rec-irisin. These results could be due to irisin ability to downregulate the expression of Notch 3, which is important for cell-to-cell communication in the tumor niche, and Cyclin D1, supporting an inhibitory effect of irisin on MM cell proliferation. Overall, our findings suggest that irisin could be a new promising strategy to counteract MMBD and tumor burden in one shot.
Hover fly (Diptera: Syrphidae) diversity and seasonality in North Georgia apple and peach orchards
Authors: McCravy Kenneth W , Clem C Scott , Bailey Jordan B , Elgar Sabrina A , Blaauw Brett R 
Published: May 2024

Abstract
Crop pollination and natural biological control provided by beneficial insects have an economic worth of hundreds of billions of dollars annually. Apple and peach production in North Georgia are economically important industries that benefit from these ecological services. Hover flies are dual ecosystem service providers that have been relatively understudied in orchard ecosystems. We investigated the diversity and seasonal activity of hover flies in apple and peach orchards at 2 sites in North Georgia from March to October 2020 and 2021. Bowl traps were used to sample hover flies in orchard edge and interior habitats. The aphidophagous species Toxomerus geminatus (Say) (Diptera: Syrphidae) and Toxomerus marginatus (Say) (Diptera: Syrphidae) comprised 86.6% of the total hover flies collected. Apple orchards yielded the greatest hover fly presence, species richness, and Toxomerus spp. abundance. Hover fly richness and diversity were greatest during postbloom, but Toxomerus spp. abundance was greatest during the bloom period. No differences in presence, richness, diversity, or Toxomerus spp. abundance were found between edge and interior habitats. Toxomerus geminatus and T. marginatus were dominant from March through August, with T. geminatus being more abundant than T. marginatus in March, early April, and August. October sampling produced the greatest hover fly richness. Our results suggest that hover flies are abundant in North Georgia orchards and exhibit substantial spatial and temporal variation in richness and diversity. Expanded studies incorporating additional sampling efforts and methods are needed to further characterize the hover fly fauna and their impact on North Georgia apple and peach orchards.
Photoperiod and temperature synergistically regulate heading date and regional adaptation in rice
Authors: Zong Wubei , Guo Xiaotong , Zhang Kai , Chen Letian , Liu Yao-Guang , Guo Jingxin 
Published: May 2024

Abstract
Plants must accurately integrate external environmental signals with their own development to initiate flowering at the appropriate time for reproductive success. Photoperiod and temperature are key external signals that determine flowering time; both are cyclical and periodic, and they are closely related. In this review, we describe photoperiod-sensitive genes that simultaneously respond to temperature signals in rice (Oryza sativa). We introduce the mechanisms by which photoperiod and temperature synergistically regulate heading date and regional adaptation in rice. We also discuss the prospects for designing different combinations of heading date genes and other cold tolerance or thermo-tolerance genes to help rice better adapt to changes in light and temperature via molecular breeding to enhance yield in the future.
Biolistics-mediated transformation of hornworts and its application to study pyrenoid protein localization
Authors: Lafferty Declan J , Robison Tanner A , Gunadi Andika , Schafran Peter W , Gunn Laura H , Van Eck Joyce , Li Fay-Wei 
Published: May 2024

Abstract
Hornworts are a deeply diverged lineage of bryophytes and a sister lineage to mosses and liverworts. Hornworts have an array of unique features that can be leveraged to illuminate not only the early evolution of land plants, but also alternative paths for nitrogen and carbon assimilation via cyanobacterial symbiosis and a pyrenoid-based CO2-concentrating mechanism (CCM), respectively. Despite this, hornworts are one of the few plant lineages with limited available genetic tools. Here we report an efficient biolistics method for generating transient expression and stable transgenic lines in the model hornwort, Anthoceros agrestis. An average of 569 (±268) cells showed transient expression per bombardment, with green fluorescent protein expression observed within 48–72 h. A total of 81 stably transformed lines were recovered across three separate experiments, averaging six lines per bombardment. We followed the same method to transiently transform nine additional hornwort species, and obtained stable transformants from one. This method was further used to verify the localization of Rubisco and Rubisco activase in pyrenoids, which are central proteins for CCM function. Together, our biolistics approach offers key advantages over existing methods as it enables rapid transient expression and can be applied to widely diverse hornwort species.
Diagnostic value of serum STIP1 in HCC and AFP-negative HCC
Authors: Sun Haiqing , Liu Ning , Lou Jinli 
Published: May 2024

Abstract

Objective
This study aimed to investigate the diagnostic value of stress-induced phosphoprotein 1 (STIP1) in serum for hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP)–negative HCC (ANHC).

Methods
In this study, serum samples were collected from 158 HCC patients and 63 non-HCC patients. Logistic regression analysis was performed to identify independent risk factors associated with HCC and ANHC. The diagnostic values of each index for HCC and ANHC were analyzed using receiver operating characteristic (ROC) curve analysis.

Results
The STIP1, des-γ-carboxy prothrombin (DCP), and AFP levels were higher in the HCC groups than in the non-HCC groups (P &lt; .05). Age, DCP, STIP1, and hepatitis B virus infection were independent predictors of HCC (P &lt; .05). The diagnostic value of STIP1 for HCC was higher than that of DCP. Additionally, age, STIP1, and hepatitis B virus infection were independent predictors for ANHC patients. The ROC curve exhibited an area under the curve value of 0.919 for STIP1, with a diagnostic cutoff value of 68.5 U/mL. Moreover, 36 ANHC patients and 19 AFP-negative non-HCC patients were included to validate the diagnostic model. A total of 20 patients had STIP1 levels greater than 68.5 U/mL, resulting in diagnostic accuracy of 67.3%, sensitivity of 55.6%, and specificity of 89.5%.

Conclusion
STIP1 demonstrates excellent diagnostic value for HCC and ANHC.