bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward interpretable and generalized mitosis detection in digital pathology using deep learning
Authors: Farooq Hasan , Saleem Saira , Aleem Iffat , Iftikhar Ayesha , Sheikh Umer Nisar , Naveed Hammad 
Published: May 2024

Objective The mitotic activity index is an important prognostic factor in the diagnosis of cancer. The task of mitosis detection is difficult as the nuclei are microscopic in size and partially labeled, and there are many more non-mitotic nuclei compared to mitotic ones. In this paper, we highlight the challenges of current mitosis detection pipelines and propose a method to tackle these challenges. Methods Our proposed methodology is inspired from recent research on deep learning and an extensive analysis on the dataset and training pipeline. We first used the MiDoG′22 dataset for training, validation, and testing. We then tested the methodology without fine-tuning on the TUPAC′16 dataset and on a real-time case from Shaukat Khanum Memorial Cancer Hospital and Research Centre. Results Our methodology has shown promising results both quantitatively and qualitatively. Quantitatively, our methodology achieved an F1-score of 0.87 on the MiDoG'22 dataset and an F1-score of 0.83 on the TUPAC dataset. Qualitatively, our methodology is generalizable and interpretable across various datasets and clinical settings. Conclusion In this paper, we highlight the challenges of current mitosis detection pipelines and propose a method that can accurately predict mitotic nuclei. We illustrate the accuracy, generalizability, and interpretability of our approach across various datasets and clinical settings. Our methodology can speed up the adoption of computer-aided digital pathology in clinical settings.
The Role of the Hip Capsule in Restoring Stability in the Initial Phase of Hip Distraction: An In Vivo Analysis
Authors: Mortensen Alexander J. , Featherall Joseph , Metz Allan K. , Rosenthal Reece M. , O’Neill Dillon C. , Froerer Devin L. , Khalil Ameen Z. , Tomasevich Kelly M. , Aoki Stephen K. 
Published: May 2024

Background: The labral suction seal has been shown to provide the majority of resistance in the initial phase of hip distraction. However, the effect of an unrepaired interportal capsulotomy and capsular repair on the initial phase of hip distractive stability in vivo is not well understood. Purpose: To investigate the effect of capsular repair on the initial phase of distractive stability of hip joints in patients with femoroacetabular impingement (FAI) syndrome. Study Design: Controlled laboratory study. Methods: Patients undergoing primary hip arthroscopy for FAI between March and August 2020 were prospectively enrolled. Total joint space was measured on fluoroscopic images at the medial and lateral edges of the sourcil at 12.5-lb (5.7-kg) axial traction intervals (up to 100 lb [45.4 kg]) in 3 capsular states: (1) native capsule, (2) interportal capsulotomy, and (3) capsular repair. Distraction on anteroposterior radiographs was calculated as the difference between total joint space at each traction interval and baseline joint space at 0 lb, normalized to millimeters. The native, capsulotomy, and capsular repair states were compared using Wilcoxon signed-rank and McNemar tests. Results: Included were 36 hips in 35 patients. The median force required to distract ≥3 mm was 75 lb (34.0 kg; 95% CI, 70-80 lb [31.8-36.3 kg]) in both the native and capsular repair states ( P = .629), which was significantly greater than the median force required to distract ≥3 mm in the capsulotomy state (50 lb [22.7 kg]; 95% CI, 45-55 lb [20.4-24.9 kg]) ( P < .001). The most rapid rates of change in joint space were observed at the traction interval at which hips first achieved ≥3 mm of distraction (n = 33 hips; 92%). Conclusion: The traction force at which hips distracted ≥3 mm was 75 lb (34.0 kg) in both the native capsular and capsular repair states. Significantly less traction force (50 lb [22.7 kg]) distracted hips ≥3 mm in the capsulotomy state. Complete capsular closure after interportal capsulotomy resulted in restoration of initial distractive stability relative to the unrepaired capsulotomy state at time zero after primary hip arthroscopy. Clinical Relevance: This study provides surgeons with an improved understanding of the additional stability to the hip joint from capsular repair after hip arthroscopy for FAI syndrome.
Barriers and Facilitators to Clinical Supervision in Ghana: A Scoping Review
Authors: Awiagah Sherrif Kwame , Dordunu Rebecca , Hukporti Nelson , Nukunu Promise Edem , Dzando Gideon 
Published: May 2024

Background Clinical supervision involves the professional relationship between an experienced and knowledgeable clinician and a less experienced clinician in which the experienced clinician provides support toward the skills development of the less experienced one. The concept, structure, and format of clinical supervision vary in various jurisdictions and is influenced by the availability of resources, the training needs of supervisees, and organizational structures. Aim The aim of this scoping review was to explore, map out and synthesize the available literature on the facilitators and barriers to clinical supervision in Ghana. Methods The methodological framework developed by Arksey and O’Malley and modified by Levac et al. for scoping reviews, and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews were used to ensure a coherent and transparent reporting of literature. A systematic search was conducted in PubMed, CINAHL, Scopus, Medline, and Google Scholar using key words and key terms. Articles published between January 1, 2000, and February 28, 2023, were included in the review. Results The initial search across all the databases yielded 208 results. Two independent reviewers completed both the title and abstract, and full text screenings. A third reviewer helped to resolve all discrepancies that arose during the screening process. The review included 20 articles and generated four themes: clinical supervision as a collaborative effort, feedback mechanism, training and adaptation, and challenges with implementation. Conclusion Findings from this review highlight that healthcare professionals in Ghana valued clinical supervision. However, the implementation of clinical supervision is faced with individual and systemic challenges. There is the need for on-going collaboration between educational and clinical institutions to develop modalities that promote clinical supervision in Ghana.
SR proteins in cancer: function, regulation, and small inhibitor
Authors: Bei Mingrong , Xu Jianzhen 
Published: May 2024

AbstractAlternative splicing of pre-mRNAs is a fundamental step in RNA processing required for gene expression in most metazoans. Serine and arginine-rich proteins (SR proteins) comprise a family of multifunctional proteins that contain an RNA recognition motif (RRM) and the ultra-conserved arginine/serine-rich (RS) domain, and play an important role in precise alternative splicing. Increasing research supports SR proteins as also functioning in other RNA-processing-related mechanisms, such as polyadenylation, degradation, and translation. In addition, SR proteins interact with N6-methyladenosine (m6A) regulators to modulate the methylation of ncRNA and mRNA. Dysregulation of SR proteins causes the disruption of cell differentiation and contributes to cancer progression. Here, we review the distinct biological characteristics of SR proteins and their known functional mechanisms during carcinogenesis. We also summarize the current inhibitors that directly target SR proteins and could ultimately turn SR proteins into actionable therapeutic targets in cancer therapy.
Social big data mining for the sustainable mobility and transport transition: findings from a large-scale cross-platform analysis
Authors: Stiebe Michael 
Published: May 2024

AbstractThe paper reports findings from a study that examining how cross-platform social media analysis can help to map the digital discourse on sustainable mobility and sustainable transport, and enhance the understanding of sociotechnical low-carbon transport transitions. Using the hashtag search queries #sustainabletransport and #sustainablemobility, 33,121 Tweets (2013–2021) and 8,089 Instagram images including captions (2017/2018–2021) were scraped using the Python modules Twint and Instaloader. Quantitative text and sentiment analyses were applied to the Tweets and image captions. Additionally, an automated machine learning-based image analysis of the Instagram images was conducted using object detection via OpenCV. Synthesized results formed the base for a cross-platform analysis inspired by Rogers’ method comprising hot topics/key themes, user mentions, sentiment polarity, and co-hashtags. Notably, electromobility emerged as a prominent theme, particularly on Instagram, while #sustainabletransport was closely associated with active travel, notably bicycling, and #sustainablemobility showcased a dominance of electromobility discourse. The study demonstrates the investigative potentials of cross-platform social media analysis studies to enhance the understanding of sociotechnical low-carbon transport transitions. Drawing on key results, the paper suggests an adapted version of the Geelsean Multi-Level Perspective on Sociotechnical Transitions.
Genome-wide association study identifies genomic regions associated with key reproductive traits in Korean Hanwoo cows
Authors: Haque Md Azizul , Lee Yun-Mi , Ha Jae-Jung , Jin Shil , Park Byoungho , Kim Nam-Young , Won Jeong-Il , Kim Jong-Joo 
Published: May 2024

Abstract
Background
Conducting genome-wide association studies (GWAS) for reproductive traits in Hanwoo cattle, including age at first calving (AFC), calving interval (CI), gestation length (GL), and number of artificial inseminations per conception (NAIPC), is of paramount significance. These analyses provided a thorough exploration of the genetic basis of these traits, facilitating the identification of key markers for targeted trait improvement. Breeders can optimize their selection strategies, leading to more efficient and sustainable breeding programs, by incorporating genetic insights. This impact extends beyond individual traits and contributes to the overall productivity and profitability of the Hanwoo beef cattle industry. Ultimately, GWAS is essential in ensuring the long-term genetic resilience and adaptability of Hanwoo cattle populations. The primary goal of this study was to identify significant single nucleotide polymorphisms (SNPs) or quantitative trait loci (QTLs) associated with the studied reproductive traits and subsequently map the underlying genes that hold promise for trait improvement.

Results
A genome-wide association study of reproductive traits identified 68 significant single nucleotide polymorphisms (SNPs) distributed across 29 Bos taurus autosomes (BTA). Among them, BTA14 exhibited the highest number of identified SNPs (25), whereas BTA6, BTA7, BTA8, BTA10, BTA13, BTA17, and BTA20 exhibited 8, 5, 5, 3, 8, 2, and 12 significant SNPs, respectively. Annotation of candidate genes within a 500 kb region surrounding the significant SNPs led to the identification of ten candidate genes relevant to age at first calving. These genes were: FANCG, UNC13B, TESK1, TLN1, and CREB3 on BTA8; FAM110B, UBXN2B, SDCBP, and TOX on BTA14; and MAP3K1 on BTA20. Additionally, APBA3, TCF12, and ZFR2, located on BTA7 and BTA10, were associated with the calving interval; PAX1, SGCD, and HAND1, located on BTA7 and BTA13, were linked to gestation length; and RBM47, UBE2K, and GPX8, located on BTA6 and BTA20, were linked to the number of artificial inseminations per conception in Hanwoo cows.

Conclusions
The findings of this study enhance our knowledge of the genetic factors that influence reproductive traits in Hanwoo cattle populations and provide a foundation for future breeding strategies focused on improving desirable traits in beef cattle. This research offers new evidence and insights into the genetic variants and genome regions associated with reproductive traits and contributes valuable information to guide future efforts in cattle breeding.
Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis
Authors: Cao Ziqin , Li Qiangxiang , Li Yajia , Wu Jianhuang 
Published: May 2024

Abstract
Background
While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework.

Methods
Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications.

Results
Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR.

Conclusion
Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.
Plastid DNA is a major source of nuclear genome complexity and of RNA genes in the orphan crop moringa
Authors: Marczuk-Rojas Juan Pablo , Salmerón Antonio , Alcayde Alfredo , Isanbaev Viktor , Carretero-Paulet Lorenzo 
Published: May 2024

Abstract
Background
Unlike Transposable Elements (TEs) and gene/genome duplication, the role of the so-called nuclear plastid DNA sequences (NUPTs) in shaping the evolution of genome architecture and function remains poorly studied. We investigate here the functional and evolutionary fate of NUPTs in the orphan crop Moringa oleifera (moringa), featured by the highest fraction of plastid DNA found so far in any plant genome, focusing on (i) any potential biases in their distribution in relation to specific nuclear genomic features, (ii) their contribution to the emergence of new genes and gene regions, and (iii) their impact on the expression of target nuclear genes.

Results
In agreement with their potential mutagenic effect, NUPTs are underrepresented among structural genes, although their overall transcription levels and broadness were only lower when involved exonic regions; the occurrence of plastid DNA generally did not result in a broader expression, except among those affected in introns by older NUPTs. In contrast, we found a strong enrichment of NUPTs among specific superfamilies of retrotransposons and several classes of RNA genes, including those participating in the protein biosynthetic machinery (i.e., rRNA and tRNA genes) and a specific class of regulatory RNAs. A significant fraction of NUPT RNA genes was found to be functionally expressed, thus potentially contributing to the nuclear pool.

Conclusions
Our results complete our view of the molecular factors driving the evolution of nuclear genome architecture and function, and support plastid DNA in moringa as a major source of (i) genome complexity and (ii) the nuclear pool of RNA genes.
Morning light treatment for inflammatory bowel disease: a clinical trial
Authors: Cohen-Mekelburg Shirley , Goldstein Cathy A. , Rizvydeen Muneer , Fayyaz Zainab , Patel Priya J. , Berinstein Jeffrey A. , Bishu Shrinivas , Cushing-Damm Kelly C. , Kim Hyungjin Myra , Burgess Helen J. 
Published: May 2024

Abstract
Background
Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD.

Methods
We will recruit sixty-eight individuals with biopsy-proven IBD and clinical symptoms and randomize them to 4-weeks of morning light treatment or 4-weeks of treatment as usual (TAU), with equivalent study contact. Patient-reported outcomes (IBD-related quality of life, mood, sleep), clinician-rated disease severity, and a biomarker of gastrointestinal inflammation (fecal calprotectin) will be assessed before and after treatment. Our primary objective will be to test the effect of morning light treatment versus TAU on IBD-related quality of life and our secondary objectives will be to test the effects on clinician-rated disease activity, depression, and sleep quality. We will also explore the effect of morning light treatment versus TAU on a biomarker of gastrointestinal inflammation (fecal calprotectin), and the potential moderating effects of steroid use, restless leg syndrome, and biological sex.

Discussion
Morning light treatment may be an acceptable, feasible, and effective adjunctive treatment for individuals with active IBD suffering from impaired health-related quality of life.

Trial registration
The study protocol was registered on ClinicalTrials.gov as NCT06094608 on October 23, 2023, before recruitment began on February 1, 2024.
Risk factors of adult isoniazid-resistant and rifampicin-susceptible tuberculosis in Nanjing, 2019–2021
Authors: Guo Jing , Han Yan , Zhang Xia , Lin Feishen , Chen Liangyu , Feng Xuebing 
Published: May 2024

Abstract
Introduction
This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults.

Method
The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB. Results: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037–2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971–4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123–2.461, p = 0.011) was identified as risk factors for Hr-TB. Conclusions: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.
Characteristics and outcome of pregnancy-related acute kidney injury in a teaching hospital in a low-resource setting: a five-year retrospective review
Authors: Berhe Ephrem , Teka Hale , Abraha Hiluf Ebuy , Abera Bisrat Tesfay , Gebru Marta Abrha , Gebremariam Tsega , Yahya Mohammedtahir , Amare Birhane , Tadesse Habtom , Gidey Hagos , Tesfay Fireweyni , Ebrahim Mohamedawel Mohamedniguss , Kidanemariam Rahel , Legesse Awol Yemane 
Published: May 2024

AbstractBackgroundPregnancy-related kidney injury contributes to a high burden of acute kidney injury in low-resource settings and causes maternal and perinatal morbidity and mortality. Few studies have examined the impact of acute kidney injury in resource-limited countries, with very limited research on pregnancy-specific disorders in Ethiopia. This study aimed to determine the characteristics of pregnancy-related acute kidney injury, outcomes and associated factors.MethodsA retrospective study was conducted to evaluate the clinical profile and maternal-fetal outcome of pregnancy-related acute kidney injury at Ayder Comprehensive Specialized Hospital in Tigray, Ethiopia, from January 1, 2017, to December 31, 2021. Maternal and fetal outcomes were analyzed using descriptive statistics. Multivariate logistic regression was used to determine the association between the dependent and independent variables.ResultsOf 27,350 mothers who delivered at Ayder Comprehensive Specialized Hospital between January 1, 2017, and December 31, 2021, a total of 187 women developed pregnancy-related acute kidney injury, a prevalence rate of 68 per 100,000 births. Preeclampsia, sepsis and pre-renal causes due to dehydration and hemorrhage were the most common causes of pregnancy-related acute kidney injury in this study. Hemodialysis was needed in 8.6% (n = 16) of patients. Of the 187 pregnancy-related acute kidney injuries, 143 (76.5%) recovered completely and 30 (16%) partially. The mortality rate was 7.5%. Preexisting chronic kidney disease (AOR = 30.13; 95% CI: 2.92, 310.84), use of vasoactive agents (AOR = 5.77; 95% CI: 1.47, 22.67), increase in creatinine per unit (AOR = 1.65; 95% CI: 1.11, 2.45) and complications related to acute kidney injury (AOR = 5.26; 95% CI: 1.73, 16.00) were determinants of the composite endpoints (partial renal recovery and death).ConclusionsThis study emphasizes acute kidney injury in resource-limited settings is a significant cause of maternal and fetal morbidity and mortality. The vast majority of patients with pregnancy-related acute kidney injury recovered completely from kidney injury. The main causes of pregnancy-related acute kidney injury were preeclampsia, sepsis and pre-renal associated with hemorrhage and dehydration. Preexisting renal disease, use of vasopressors, increase in creatinine per unit and complications associated with acute kidney injury were determining factors for concomitant fetomaternal mortality. Appropriate preventive strategies during prenatal care and prompt treatment are needed for pregnancy-related acute kidney injury.