bluuebunny/crossref_metadata_2025_split huggingface dataset:
FANCA c.3624C&gt;T (p.Ser1208=) is a hypomorphic splice variant associated with delayed onset of Fanconi anemia
Authors: Ramanagoudr-Bhojappa Ramanagouda , Tryon Rebecca , Lach Francis P. , Donovan Frank X. , Maxwell Rochelle , Rosenberg Allana , MacMillan Margaret L. , Wagner John E. , Auerbach Arleen D. , Smogorzewska Agata , Chandrasekharappa Settara C. 
Published: January 2024

Abstract
Fanconi anemia (FA) is a hereditary, DNA repair deficiency disorder caused by pathogenic variants in any 1 of 22 known genes (FANCA-FANCW). Variants in FANCA account for nearly two-thirds of all patients with FA. Clinical presentation of FA can be heterogeneous and include congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. Here, we describe a relatively mild disease manifestation among 6 individuals diagnosed with FA, each compound heterozygous for 1 established pathogenic FANCA variant and 1 FANCA exon 36 variant, c.3624C&gt;T. These individuals had delayed onset of hematological abnormalities, increased survival, reduced incidence of cancer, and improved fertility. Although predicted to encode a synonymous change (p.Ser1208=), the c.3624C&gt;T variant causes a splicing error resulting in a FANCA transcript missing the last 4 base pairs of exon 36. Deep sequencing and quantitative reverse transcription polymerase chain reaction analysis revealed that 6% to 10% of the FANCA transcripts included the canonical splice product, which generated wild-type FANCA protein. Consistently, functional analysis of cell lines from the studied individuals revealed presence of residual FANCD2 ubiquitination and FANCD2 foci formation, better cell survival, and decreased late S/G2 accumulation in response to DNA interstrand cross-linking agent, indicating presence of residual activity of the FA repair pathway. Thus, the c.3624C&gt;T variant is a hypomorphic allele, which contributes to delayed manifestation of FA disease phenotypes in individuals with at least 1 c.3624C&gt;T allele.
Double-blind, randomized, placebo-controlled study to evaluate erenumab-specific central effects: an fMRI study
Authors: Basedau Hauke , Peng Kuan-Po , Schellong Marlene , May Arne 
Published: January 2024

Abstract
Objective
Given the findings of central effects of erenumab in the literature, we aimed to conduct a rigorous placebo-controlled, double-blind, randomized study to elucidate whether the observed changes are directly attributable to the drug.

Methods
We recruited 44 patients with migraine, randomly assigning them to either the erenumab 70 mg or the placebo group. 40 patients underwent fMRI scanning using a trigeminal nociceptive paradigm both, pre- and four weeks post-treatment. Participants kept a headache diary throughout the whole study period of two months in total. A clinical response was defined as a ≥30% reduction in headache frequency at follow-up. Details of this study have been preregistered in the open science framework: https://osf.io/ygf3t.

Results
Seven participants of the verum group (n=33.33%) and 4 of the placebo group (21.05%) experienced improvements in migraine activity, characterized by a minimum of 30% reduction in monthly headache frequency compared to baseline. The imaging data show an interaction between the verum medication and the response. Whilst numbers were too small for individual analyses (Verum vs. Placebo and Responder vs. Non-Responder), the variance-weighted analysis (Verum vs Placebo, scan before vs after weighted for response) revealed specific decrease in thalamic, opercular and putamen activity.

Interpretation
The central effects of erenumab could be reproduced in a placebo randomized design, further confirming its central role in migraine modulation. The mechanism, whether direct or secondary to peripheral mode of action, needs further exploration. It is important to note that the response rate to erenumab 70mg in this study was not as substantial as anticipated in 2019, when this study was planned. This resulted in a too small sample size for a subgroup analysis based on the responder status was associated with both the verum drug and the relative reduction in headache days.
Learning Urogenital Diseases in Oddity (LUDO)—a gamification-based innovation for learning urogenital diseases in emergency medicine
Authors: Mallick Asjad , Waheed Shahan 
Published: January 2024

AbstractUrogenital emergencies demand immediate attention within the field of emergency medicine, encompassing a range of critical conditions from ectopic pregnancies to kidney stones. Timely diagnosis and treatment are vital to prevent potential mortality and morbidity. However, due to the sensitive nature of these disorders and the cultural taboos surrounding them, accessing prompt medical care can be challenging. To bridge this gap, innovative gamification-based learning techniques, such as the Learning Urogenital Diseases in Oddity (LUDO), have been introduced for emergency medicine residents (Chou, What is gamification? Yukai Chou: Gamification and behavioral design, n.d.; Gamification '13: Proceedings of the first international conference on gameful design, research, and applications, 2013).LUDO is a timed, gamified exercise that offers residents an interactive and engaging platform to enhance their clinical knowledge related to urogenital disorders. Adapted from the well-known board game, LUDO fosters learning, collaboration, and cooperation among residents. This format is highly customizable and can be utilized by various learning groups.Participants, emergency medicine residents from different academic years, formed four teams, each distinguished by a unique color. The exercise utilized simple and accessible materials, including a LUDO board, LED stopwatch, laptop, colored hats, and a desk bell. Teams advanced their tokens through the board by correctly answering urogenital disorder-related questions within a specified time frame.LUDO’s objectives extended beyond token movement, assessing essential skills such as teamwork, time management, resource utilization, and strategic decision-making. The option to seek external resources, limited to five times per team, added an element of strategy. Facilitators evaluated participants’ performance through questionnaires and Likert scales.The results revealed that LUDO effectively promoted teamwork, communication, leadership, and problem-solving among emergency medicine residents. Resident feedback was overwhelmingly positive, with interest in adopting this format for other educational modules. The gamified approach encouraged engagement and motivation, with immediate feedback ensuring continuous learning.In conclusion, the incorporation of the LUDO gamified format provides an enjoyable and interactive learning experience for emergency medicine residents. It enhances engagement, fosters teamwork, and facilitates the rapid assimilation of crucial knowledge related to urogenital diseases. This adaptable approach holds promise for improving resident training in various clinical scenarios.
Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome
Authors: Kuo Tzu-chia , Lu Yang-bor , Yang Chieh-lun , Wang Bin , Chen Lin-xin , Su Ching-ping 
Published: January 2024

Abstract
Background
To investigate the association of four insulin resistance (IR) indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome (MetS), as well as to compare the diagnostic value of these indicators in identifying hepatic steatosis and fibrosis in individuals with MetS.

Methods
This cross-sectional study used the data from the National Health and Nutrition Examination Survey 2017–2018. IR indicators included homeostasis model assessment of IR (HOMA-IR), triglyceride/glucose (TyG) index, triglyceride glucose-waist-to-height ratio (TyG-WHtR), and metabolic score for IR (METS-IR). The main endpoints of this study were hepatic steatosis and hepatic fibrosis. Weighted univariate and multivariate logistic regression models were employed to evaluate the association between four IR indicators and both hepatic steatosis, hepatic fibrosis. The efficacy of various IR indicators in the detection of hepatic steatosis and hepatic fibrosis were assessed using receiver operating characteristics curve (ROC).

Results
A total of 876 participants with MetS were enrolled. Among the participants, hepatic steatosis was observed in 587 MetS individuals, while hepatic fibrosis was identified in 151 MetS individuals. In multivariate logistic regression model, HOMA-IR, TyG, TyG-WHtR, and METS-IR were related to the increased odd of hepatic steatosis. Additionally, HOMA-IR, TyG-WHtR, and METS-IR were associated with increased odd of hepatic fibrosis. According to the ROC analysis, the area under the curve (AUC) of the TyG-WHtR (AUC = 0.705, 95%CI: 0.668–0.743) was higher than HOMA-IR (AUC = 0.693, 95%CI: 0.656–0.730), TyG (AUC = 0.627, 95%CI: 0.587–0.666), and METS-IR (AUC = 0.685, 95%CI: 0.648–0.722) for identifying hepatic steatosis of MetS patients. Likewise, TyG-WHtR was also higher than HOMA-IR, TyG, and METS-IR for identifying hepatic fibrosis of MetS patients.

Conclusion
HOMA-IR, TyG-WHtR, and METS-IR may be associated with the risk of hepatic steatosis and fibrosis among the U.S. adult population with MetS. In addition, TyG-WHtR may have a good predictive value for hepatic steatosis and hepatic fibrosis.
Utilizing visual symptoms to distinguish dry eye from glaucoma, cataract, and suspect glaucoma patients: a cross-sectional study
Authors: Zhao David X. , Quintero Michael , Mihailovic Aleksandra , Akpek Esen , Karakus Sezen , Guo Lee , Ramulu Pradeep Y. 
Published: January 2024

Abstract
Background
The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects.

Methods
Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p < 0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions.

Results
Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD = 14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR = 15.0, 95% CI = 6.3–35.7) and spots in vision (OR = 2.8, 95% CI = 1.2–6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR = 9.2, 95% CI = 2.0–41.7), but less frequent poor peripheral vision (OR = 0.2, 95% CI = 0.06–0.7), difference in vision between eyes (OR = 0.09, 95% CI = 0.01–0.7), and missing patches of vision (OR = 0.06, 95% CI = 0.009–0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR = 4.5, 95% CI = 1.5–13.4) and vision variability across the week (OR = 4.7, 95% CI = 1.2–17.7) and were less likely to report worsening vision (OR = 0.1, 95% CI = 0.03–0.4) and blindness (OR = 0.1, 95% CI = 0.02–0.8).

Conclusion
Visual symptoms may serve as a complementary tool to distinguish dry eye from various ocular conditions, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions.
Recurrence of post-traumatic stress disorder: systematic review of definitions, prevalence and predictors
Authors: Brooks Samantha K , Greenberg Neil 
Published: January 2024

Abstract
Background
Many people will experience a potentially traumatic event in their lifetime and a minority will go on to develop post-traumatic stress disorder (PTSD). A wealth of literature explores different trajectories of PTSD, focusing mostly on resilient, chronic, recovered and delayed-onset trajectories. Less is known about other potential trajectories such as recurring episodes of PTSD after initial recovery, and to date there has been no estimate of what percentage of those who initially recover from PTSD later go on to experience a recurrence. This systematic review aimed to synthesise existing literature to identify (i) how ‘recurrence’ of PTSD is defined in the literature; (ii) the prevalence of recurrent episodes of PTSD; and (iii) factors associated with recurrence.

Methods
A literature search of five electronic databases identified primary, quantitative studies relevant to the research aims. Reference lists of studies meeting pre-defined inclusion criteria were also hand-searched. Relevant data were extracted systematically from the included studies and results are reported narratively.

Results
Searches identified 5,398 studies, and 35 were deemed relevant to the aims of the review. Results showed there is little consensus in the terminology or definitions used to refer to recurrence of PTSD. Because recurrence was defined and measured in different ways across the literature, and prevalence rates were reported in numerous different ways, it was not possible to perform meta-analysis to estimate the prevalence of recurrence. We also found no consistent evidence regarding predictors of PTSD recurrence.

Conclusion
A clear and consistent evidence-based definition of recurrence is urgently needed before the prevalence and predictors of recurrence can be truly understood.
Micro-computed tomography analysis of calcium hydroxide delivery efficacy in C-shaped canal system of mandibular second molars
Authors: Chen Min , Pradhan Babita , Meng Yajun , Tsauo Chialing , Zhou Xuedong , Huang Dingming , Ma Jingzhi , Gao Yuan 
Published: January 2024

Abstract
Background
Calcium hydroxide [Ca(OH)2] is widely accepted as a biocompatible interappointment intracanal medicament. This study aimed to analyze the efficacy of Ca(OH)2 placement into the C-shaped canal system of mandibular second molars using the syringe method with and without lentulo spiral utilizing micro-computed tomography (micro-CT).

Methods
Twenty-four extracted mandibular second molars were instrumented and classified into C-shaped floors (n = 12) and non-C-shaped floors (n = 12). Both groups were placed with Ca(OH)2 using the syringe system, then all teeth were scanned and cleaned, and placed with Ca(OH)2 again but with the syringe system followed by lentulo spiral and rescanned. The specimens were scanned using micro-CT to analyze the volume, volume percentage, uncontacted surface area, and uncontacted surface area percentage of Ca(OH)2 with the two delivery methods in the entire canal and at the apical 4 mm of the canal. Mann-Whitney test and Wilcoxon signed-rank test were used to determine the statistical differences among the groups.

Results
Syringe administration used in conjunction with lentulo spiral presented lower uncontacted surface area, a lower percentage of uncontacted surface area, larger volume, and a higher percentage of volume than syringe without lentulo spiral (P < 0.05). There was no significant difference between the C-shaped floor group and the non-C-shaped floor group (P > 0.05) in the Ca(OH)2 uncontacted surface area, volume, and percentages at different regions of canals and among different delivery techniques groups.

Conclusions
The lentulo spiral and syringe technique combination can increase the volume and contacted surface area of Ca(OH)2 in the C-shaped canal system of mandibular second molars.
White spot lesions: diagnosis and treatment – a systematic review
Authors: Lopes Pedro C. , Carvalho Teresa , Gomes Ana T. P. C. , Veiga Nelio , Blanco Letícia , Correia Maria José , Mello-Moura Anna Carolina Volpi 
Published: January 2024

Abstract
Background
White spot lesions represent the first stage of caries and their prevalence has been increasing in recent years, particularly in patients undergoing orthodontic treatment. DIferential diagnosis and lesion activity are essential to decide on the clinical approaches to treatment. The aim of this study is to understand if the new diagnostic tools such as fluorescence, microradiography and computed microtomography have the potential to change the conventional treatment of white spots”.

Methods
A systematic search of available studies in the literature was carried out, using PRISMA guidelines, in Pubmed and Scopus electronic databases and manually to identify relevant articles to answer the PICO question: “Do the new diagnostic tools have the potential to change the conventional treatment of white spots?”. This systematic review included randomized controlled trials (RCT), cross-sectional and longitudinal studies complying with the following inclusion criteria: (i) studies in humans, (ii) studies about white spot lesions, (iii) studies published between 2012 and 2023, (iv) studies having both diagnosis and treatment and (v) studies with full text available. In this review we excluded other systematic reviews of clinical trials and in vitro studies. The RoB tool was used to assess the risk of bias.

Results
The systematic literature search identified 143 potentially relevant references, which after applying the exclusion criteria, resulted in 20 articles. Regarding diagnostic methods, most articles found were based on conventional methods of visual examination (n:10) or fluorescence (n:7). The least referenced diagnostic techniques were based on the use of clinical photographs (n:2), cross-sectional microradiography (n:1) and computed microtomography (n:1). The use of DIAGNOdent was reported by 3 in vitro studies. With regard to therapies, most studies reported the use of infiltrating resin (n:7) and fluoride-based products (n:5). Other studies have reported the use of self-assembling peptide P11-4 (n:1), home care (n:1), casein phosphopeptide-amorphous calcium phosphate (n:2) and hydrochloric acid (n:1). Combination therapies were also considered.

Conclusion
Diagnostic tool does not have the potential to change the form of treatment, whether it is a conventional method or a more differentiated one.
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7
Authors: Chen Wujun , Wu Xiaolin , Hu Jianxia , Liu Xiaolei , Guo Zhu , Wu Jianfeng , Shao Yingchun , Hao Minglu , Zhang Shuangshuang , Hu Weichao , Wang Yanhong , Zhang Miao , Zhu Meng , Wang Chao , Wu Yudong , Wang Jie , Xing Dongming 
Published: January 2024

AbstractAtherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.
A comparative study of cardiovascular risk stratification methods in type 1 diabetes mellitus patients
Authors: de Araujo Fabiano Malard , Comim Fábio Vasconcellos , Lamounier Rodrigo N. , Pena Natália F. , Fajardo Virgínia C. , de Faria Regina Bicalho G. , Silva Yuri M. , Lauria Márcio Weissheimer 
Published: January 2024

AbstractThe Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease, ischemic stroke, heart failure, and peripheral arterial disease in type 1 diabetes mellitus(T1DM).The current study investigated the agreement between ST1RE and the Brazilian Society for Endocrinology and Metabology (SBEM) classification. Participants were included in the study if diagnosed with T1DM and had at least one outpatient visit in 2021. Patients with established cardiovascular disease and chronic kidney disease on dialysis were excluded. Clinical parameters were obtained from medical records, such as age, body mass index (BMI), blood pressure, physical activity, current smoking, microvascular target organ damage, levels of low-density lipoprotein cholesterol, creatinine, glycated hemoglobin (HbA1c), and albuminuria.Overall, 92 patients (38 males and 53 females) with an age median (P25; P75) of 33 years (25.5;42.5), BMI of 24.8 + 4.1 kg/m2, and duration of diabetes (mean ± SD) of 23.4 + 9.5 years were evaluated. There were no differences considering the gender for most analyzed variables, but a higher proportion of women exhibited microvascular complications such as microalbuminuria, macroalbuminuria, and retinopathy. Our results show a weak agreement in the 10-year cardiovascular risk estimation between SBEM and ST1RE classifications. According to SBEM criteria, 72.8% of patients were considered high-risk, while only 15.2% of patients received the same classification using ST1RE. The dissimilarities between these two classifications were also evident when age and gender factors were compared. While 60% of patients under 35 years were classified as high risk according to SBEM criteria, only 1.8% received this stratification risk in the ST1RE classification.The results indicate a low agreement between the 10-year cardiovascular event risk classification by SBEM and the classification by ST1RE for type 1 diabetes patients without established cardiovascular disease.