bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective Correction of Columellar Base Deviation in Primary Unilateral Cleft Lip Repair: A Muscle-Driven Method
Authors: Saito Takafumi , Hattori Yoshitsugu , Tu Junior Chun-Yu , Lo Lun-Jou 
Published: June 2023

Summary:
Columellar base deviation is a common and challenging deformity in patients with unilateral cleft lip. Debate continues on its surgical correction without sufficient studies to establish effective management. This article presents the authors’ experience in correcting the columellar base deviation with the muscle-driven method in primary lip repair. The key is to perform extensive muscle dissection and reconstruction. In the medial lip segment, muscle dissection is performed subcutaneously up to the contralateral nostril floor for effective lengthening and rotation. In the lateral lip segment, muscle dissection is executed in both submucosal and subcutaneous planes, and muscle component is extensively separated from the lip skin and buccal mucosa. The lateral muscle flap is advanced and reattached to the contralateral nostril floor and columellar base using a subcutaneous sustaining suture. Cinching suture between columellar base and alar base is performed. These 2 sutures help centralize and overcorrect the columellar base. Bilateral muscle components are reoriented and approximated in a Z-plasty format for lengthening of the lip. The patients were followed up for at least 3 years. Quantitative measurements of deviation in columellar base angulation were taken and revealed 55.8 ± 2.6 degrees (before nasoalveolar molding), 29.6 ± 1.7 degrees (after nasoalveolar molding), and 2.8 ± 0.4 degrees (postoperative follow-up), respectively. The muscle-driven method represents a safe and effective technique to correct columellar base deviation in patients with unilateral cleft lip.
Masseteric Nerve Ultrasound Identification for Dynamic Facial Reanimation Purposes
Authors: Blasi Marc , Ribera Àngels , de la Fuente Javier , Ayté Tomás , Malagón Paloma , Carrasco Lopez Cristian , Higueras Carmen 
Published: June 2023

Background:
The masseteric nerve is one of the main options to neurotize free muscle flaps in irreversible long-term facial paralysis. Several preoperative skin-marking techniques for the masseteric nerve have been proposed to limit the surgical dissection area, shorten the surgical time, and enable a safer dissection. However, these have shown variability among them, and cannot visualize the nerve preoperatively. The authors designed an observational study to validate a high-frequency ultrasound (HFUS) nerve identification technique.

Methods:
A systematic HFUS examination was designed and performed to visualize the masseteric nerve in 64 hemifaces of healthy volunteers. One-third were randomly selected to undergo an additional HFUS-guided needle electrostimulation to validate the HFUS image.

Results:
The masseteric nerve was identified by HFUS in 96.9% of hemifaces (95% CI, 0.89 to >0.99) and showed almost perfect agreement with direct needle stimulation as calculated with Cohen kappa coefficient (0.95; 95% CI, 0.85 to 1.00). The masseteric nerve was found within the masseter muscle, in between the deeper muscle bellies, at 18.3 mm (SD ±2.2) from the skin. Only in 12.9% of cases (95% CI, 0.06 to 0.24) did its course become adjacent to the mandible periosteum. Other important features, such as disposition in relation to the parotid gland, or if the nerve was covered directly by a thick intramuscular aponeurosis, could be well observed by HFUS.

Conclusion:
HFUS enables masseteric nerve identification and can provide the surgeon with specific information on anatomical relations for each examined individual before surgery.
The Role of 68Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up
Authors: Eshet Yael , Tau Noam , Levanon Keren , Bernstein-Molho Rinat , Globus Ofer , Itay Amit , Shapira Tal , Oedegaard Cecilie , Eifer Michal , Davidson Tima , Nidam Meital , Gal-Yam Einav , Domachevsky Liran 
Published: June 2023

Purpose

68Ga–fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response assessment and follow-up.

Methods
We followed up patients with FAPI-avid invasive lobular breast cancer (ILC) before and after treatment changes and correlated qualitative maximal intensity projection images and quantitative tumor volume with CT results and blood tumor biomarkers.

Results
Six consenting ILC breast cancer patients (53 ± 8 years old) underwent a total of 24 scans (baseline for each patient and 2–4 follow-up scans). We found a strong correlation between 68Ga-FAPI tumor volume and blood biomarkers (r = 0.7, P < 0.01), but weak correlation between CT and 68Ga-FAPI maximal intensity projection–based qualitative response assessment.

Conclusions
We found a strong correlation between ILC progression and regression (as assessed by blood biomarkers) and 68Ga-FAPI tumor volume. 68Ga-FAPI PET/CT could possibly be used for disease response assessment and follow-up.
Giant Malignant Meningioma Penetrates the Skull
Authors: Zhang Zheng , Li Aijun , Liu Jingyi , Cheng Yingxin , Ma Jinyuan , Xing Hongshun 
Published: June 2023

Meningioma is a primary tumor of the central nervous system, most commonly found in the middle-aged and elderly. Most meningiomas are benign, whereas malignant meningiomas account for only 1% of all meningiomas. Meningiomas usually grow slowly, and patients often have headaches and epilepsy as the first symptoms. According to the location of the tumor, there can also be vision, visual field, olfactory, hearing impairment, and so on. Surgery is the main treatment. A case of giant malignant meningioma penetrating the skull is reported. The patient was a 67-year-old male with a left parietal scalp mass about 1 year ago, which gradually enlarged to the size of 6×6 cm and had no other symptoms. Imaging examination showed that the tumor eroded the skull, and the density was uneven. After surgical resection (Simpson grade I), poorly differentiated meningioma (World Health Organization Grade Ⅲ) was returned pathologically. After operation, the patient recovered well.
An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents
Authors: Gerard Justin , Mueck Krislynn , Lubkin David , Hatton Gabrielle , Brill Jason , Boukas Konstantinos , Cox Charles , Wade Charles , Cotton Bryan 
Published: June 2023

BACKGROUND
Low-titer group O whole blood (LTOWB) use has been associated with improved survival and less blood transfusions in adult trauma patients. Its use in pediatric trauma has been shown to be safe when using leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:50. We set out to evaluate the safety, hemostatic potential, and impact on pediatric outcomes at a center using non-leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:200.

METHODS
Patients younger than 18 years, who received emergency-release, uncrossed matched blood, and presented to our trauma center from November 2017 to April 2021 were included. Patients were divided into those receiving any LTOWB and those receiving only RBC and or plasma (COMP). Primary outcome was 30-day survival.

RESULTS
One hundred sixty-four patients received emergency release blood products. Of these, 73 received at least one unit of LTOWB. The LTOWB group were younger (14 years vs. 13 years), more likely to be male (87% vs. 49%), and to have sustained penetrating trauma (44% vs. 23%); all p < 0.05. Low-titer group O whole blood patients received more blood than their COMP counterparts prior to arrival. Serial hemolysis panels (K+, bilirubin, LDH, haptoglobin) obtained at 24 hours, 48 hours, and 72 hours were similar between groups; all p > 0.05. There was no difference in survival by univariate analysis but after adjusting for inverse probability of treatment weights there was an observed association between WB administration and improved survival, with an odds ratio of 2.48 (1.15–5.47).

CONCLUSION
Non-leukoreduced, LTOWB in anti-A/anti-B antibody titers of <1:200 appear safe in children and adolescents. While patients receiving LTOWB had more evidence of shock, higher torso injury severity, and received more prehospital blood products, there may be a mortality benefit with whole blood. Larger, multicenter studies are needed.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Susceptibility and disease modifier genes in amyotrophic lateral sclerosis: from genetic associations to therapeutic implications
Authors: Willemse Sean W. , van Es Michael A. 
Published: June 2023

Purpose of review
Amyotrophic lateral sclerosis (ALS) is a severe disease characterized by the degeneration of motor neurons. Large-scale genetic studies have now identified over 60 genes that are associated with ALS, which in large part have also been functionally characterized. The purpose of this review is to outline how these advances are being translated into novel therapeutic strategies.

Recent findings
The emergence of techniques that allow the specific therapeutic targeting of a (mutant) gene, in particular antisense oligonucleotide therapy (ASOs), have led to the first successful gene therapy for SOD1-ALS and multiple other gene-targeted trials are underway. This includes genetic variants that modify the disease phenotype as well as causal mutations.

Summary
Technological and methodological advances are enabling researchers to unravel the genetics of ALS. Both causal mutations and genetic modifiers are viable therapeutic targets. By performing natural history studies, the phenotype-genotype correlations can be characterized. In conjunction with biomarkers for target engagement and international collaboration, this makes performing gene-targeted trials ALS feasible. The first effective treatment has now been developed for SOD1-ALS and, with multiple studies underway, it seems realistic that more therapies will follow.
Polymorphisms in Intron 1 of HLA-DRA Differentially Associate with Type 1 Diabetes and Celiac Disease and Implicate Involvement of Complement System Genes C4A and C4B
Authors: Aydemir Özkan , Bailey Jeffrey A. , Agardh Daniel , Lernmark Åke , Noble Janelle A. , Svärd Agnes Andersson , Blankenhorn Elizabeth P. , Parikh Hemang , Ziegler Anette-G. , Toppari Jorma , Akolkar Beena , Hagopian William A. , Rewers Marian J. , Mordes John P. ,   TEDDY Study Group
Published: June 2023

ABSTRACTPolymorphisms in genes in the human leukocyte antigen (HLA) class II region comprise the most important inherited risk factors for many autoimmune diseases including type 1 diabetes (T1D) and celiac disease (CD): both diseases are positively associated with the HLA-DR3 haplotype (DRB1*03:01-DQA1*05:01-DQB1*02:01). Studies of two different populations have recently documented that T1D susceptibility in HLA-DR3 homozygous individuals is stratified by a haplotype consisting of three single nucleotide polymorphisms (“tri-SNP”) in intron 1 of theHLA-DRAgene. In this study, we use a large cohort from the longitudinal “The Environmental Determinants of Diabetes in the Young” (TEDDY) study to further refine the tri-SNP association with T1D and with autoantibody-defined T1D endotypes. We found that the tri-SNP association is primarily in subjects whose first-appearing T1D autoantibody is to insulin. In addition, we discovered that the tri-SNP is also associated with celiac disease (CD), and that the particular tri-SNP haplotype (“101”) that is negatively associated with T1D risk is positively associated with risk for CD. The opposite effect of the tri-SNP haplotype on two DR3-associated diseases can enhance and refine current models of disease prediction based on genetic risk. Finally, we investigated possible functional differences between the individuals carrying high and low-risk tri-SNP haplotypes, and found that differences in complement system genes C4A and C4B may underlie the observed divergence in disease risk.
EVALUATION OF THE SAFETY AND TOLERABILITY OF EXOGENOUS KETOSIS INDUCED BY ORALLY ADMINISTERED FREE BETA-HYDROXYBUTYRATE IN HEALTHY ADULT SUBJECTS
Authors: Pimentel-Suarez Lisa Isabel , Soto-Mota Luis Adrian 
Published: June 2023

ABSTRACTBeta-hydroxybutyrate (D-BHB) is a metabolite with intrinsic signalling activity that has gained attention as a potentially clinically useful supplement. There are available supplements for inducing ketosis: ketone salts, ketone esters, and medium-chain triglycerides. Even when all of them raise the beta-hydroxybutyrate in the blood and all are safe and well tolerated, they significantly differ in their safety profile, their palatability, and their price. A fourth and potentially interesting option is to use biologically identical beta-hydroxybutyrate, while it is already commercially available in the United States (American Ketone LLC) and Greater China (MedPHA Ltd). However, its safety and tolerability had not yet been documented in the scientific literature. We evaluated the safety and tolerability of orally administered Free D-BHB in a gender and age-balanced sample of 24 asymptomatic and overtly healthy adults. No participant showed acid-base abnormalities or electrolyte abnormalities. Secondary symptoms were reported after only 6.2% of all drink takes and none of the reports described the symptom as “severe”. The most frequently reported secondary effects (19/720 or 2.6%) were gastrointestinal discomfort, headache (7/720 or 1%), and loss of appetite (7/720 or 1%). No correlation between weight-adjusted dose and frequency of secondary symptoms was observed. Free D-BHB was a safe and well-tolerated intervention for inducing sustained exogenous ketosis. Being bio-identical, salt-free, and lacking intermediate metabolites, this form of supplementation could have a larger safety spectrum than salt or alcohol-based exogenous ketones. More research is warranted to assess its clinical efficacy in those clinical scenarios in which achieving ketosis rapidly could be beneficial.KEY MESSAGESWhat is already known on this topic-Ketogenic supplements could be useful therapeutic tools in certain time-sensitive circumstances. A previously unexplored but attractive option is using bio-identical D-BHB.What this study adds-Diluted Free D-BHB is a safe and well-tolerated intervention for inducing sustained exogenous ketosis.How this study might affect research, practice, or policy-Being bio-identical, salt-free, further research is warranted on the potential clinical uses of Free-BHB.
Visualising candidate behaviour in computer-based testing: UsingClickMapsfor exploringClickStreamsin undergraduate and postgraduate medical examinations
Authors: McManus I. C. , Chis Liliana , Ferro Albert , Oram S. Helen , Galloway James , O’Neill Vikki , Myers Gil , Sturrock Alison 
Published: June 2023

AbstractBackgroundThe rapid introduction of computer-based testing (CBT) in UK (United Kingdom) undergraduate and postgraduate medical education, mainly as a result of the COVID-19 pandemic, has generated large amounts of examination data, which we call theClickStream. As candidates navigate through exams, read questions, view images, choose answers and sometimes change answers and return, re-read, and make further changes, the multiple actions are recorded as a series of time-stamped clicks or keystrokes. Analysing that mass of data is far from simple, and here we describe the creation ofClickMaps, which allow examiners, educationalists and candidates to visualise behaviour in examinations.MethodsAs an example ofClickMaps, we describe data from a single examination lasting three hours, with 100 ‘best-of-five’ questions, which was one of two papers sat in 2021 by 508 candidates as a part of the MRCP(UK) Part 2 exam. TwoClickMapswere generated for each candidate. TheFull ClickMapallows the complete three-hours of the examination to be visualised, while theEarly ClickMap, shows in more detail how candidates responded during the first six minutes of presentation of each of the 100 questions in the exam.ResultsSince the primary purpose of this paper is expository, detailed descriptions and examples ofClickMapsfrom eleven candidates were chosen to illustrate different patterns of responding, both common and rare, and to show how straightforward areClickMapsto read and interpret.ConclusionsThe richness of the data inClickStreamsallows a wide range of practical and theoretical questions to be asked about how candidates behave in CBTs, which are considered in detail.ClickMapsmay also provide a useful method for providing detailed feedback to candidates who have taken CBTs, not only of their own behaviour but also for comparison with different strategies used by other candidates, and the possible benefits and problems of different approaches. In research terms, educationalists urgently need to understand how differences inClickMapsrelate to differences in student characteristics and overall educational performance.
Lower Dynamic Cerebral Autoregulation following Acute Bout of Low-Volume High-Intensity Interval Exercise in Chronic Stroke Compared to Healthy Adults
Authors: Whitaker Alicen A. , Aaron Stacey E. , Chertoff Mark , Brassard Patrice , Buchanan Jake , Nguyen Katherine , Vidoni Eric D. , Waghmare Saniya , Eickmeyer Sarah M. , Billinger Sandra A. 
Published: June 2023

AbstractFluctuating blood pressure during high-intensity interval exercise (HIIT) may challenge dynamic cerebral autoregulation (dCA), specifically post-stroke after an injury to the cerebrovasculature. We hypothesized dCA would be attenuated at rest and during a sit-to-stand, immediately following and 30 min after HIIT in individuals post-stroke compared to age- and sex-matched controls (CON). HIIT switched every minute between 70% and 10% estimated maximal watts for 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were recorded. Resting dCA measured spontaneous fluctuations in MAP and MCAv via transfer function analysis. For sit-to-stand, time delay before an increase in cerebrovascular conductance index (CVCi = MCAv/MAP), rate of regulation, and %change in MCAv and MAP were measured. Twenty-two individuals post-stroke (age 60±12 yrs, 31±16 months) and twenty-four CON (age 60±13 yrs) completed the study. VLF gain (p=0.02, η2=0.18) and normalized gain (p=0.01, η2=0.43) had a group-by-time interaction, with CON improving immediately and 30 min after HIIT. Individuals post-stroke had impaired VLF phase (p=0.03, η2=0.22) immediately following HIIT compared to CON. We found no differences in the sit-to-stand. Our study showed lower resting dCA up to 30 min after HIIT in individuals post-stroke compared to CON while the sit-to-stand response was maintained.
Apixaban drug level monitoring in hemodialysis
Authors: Schietzel Simeon , Limacher Andreas , Moor Matthias B. , Czerlau Cecilia , Vogt Bruno , Aregger Fabienne , Uehlinger Dominik E. 
Published: June 2023

AbstractBackgroundApixaban is increasingly being used in hemodialysis patients. However, uncertainty remains regarding appropriate dosing and risk of accumulation.MethodsWe analyzed apixaban drug levels from a tertiary care dialysis unit collected between August 2017 and January 2023. We compared 2.5 mg once versus twice daily dosing. We applied mixed-effects models analyses including dialysis modality, adjusted standard Kt/V, ultrafiltration and dialyzer characteristics.ResultsWe analyzed 143 apixaban drug levels from 24 patients. Mean (SD) age was 64.2 (15.3) years (45.2% female), median (IQR) follow up 12.5 (5.5 - 21) months. For the 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 - 72.1) and 71.3 (48.8 - 104.1) ng/mL (P < 0.001). Drug levels were below the detection limit in 30 % and 14 %. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. 95thpercentile did not exceed those of non-CKD populations taking 5 mg twice daily. Drug levels before a bleeding (8 episodes) were significantly higher than those without a subsequent bleeding: 115 (SD 51.6) versus 65.9 (SD 31.6) ng/mL (P < 0.001). Patients with versus without a bleeding took concomitant antiplatelet therapy in 86% versus 6% (P < 0.001). In 21% of patients, drug level monitoring resulted in change of dosing.ConclusionApixaban drug monitoring might be a contributory tool to increase safety in patients on hemodialysis. Further prospective outcome studies are warranted to investigate possible target levels.
Real-life course and effectiveness of melatonin treatment for sleep disturbances in children with autism spectrum disorder
Authors: Sadeh Hadar , Meiri Gal , Zigdon Dikla , Ilan Michal , Faroy Michal , Michaelovski Analya , Tsadaka Yair , Dinstein Ilan , Menashe Idan 
Published: June 2023

AbstractObjectiveMelatonin is considered the most effective pharmacological treatment for the sleep disturbances that are reported in >50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking.MethodsIn this retrospective cohort study, we assessed the adherence to melatonin treatment and its effect on sleep quality and daytime behavior in children with ASD via a parental phone questionnaire of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence.ResultsMelatonin was recommended for ∼8% of children in the ANCAN database. These children were characterized by more severe autistic symptomatology. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of >28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR=0.142, 95%CI=0.036-0.565; and aHR=0.195, 95%CI=0.047-0.806, respectively).ConclusionsOur findings highlight the real-life safety and effectiveness of melatonin treatment in children with ASD. Increasing the awareness of this treatment among families and health providers will help to reduce the burden associated with sleep disturbances in children with ASD and their families.
Pandemic Vaccination Strategies: Global Optimization
Authors: Thompson James , Benitez-Paez Fernando , Guerrero Omar 
Published: June 2023

AbstractIn the event of a global pandemic, caused by an infectious disease of humans, we consider the scenario in which a safe and effective vaccine is available, with limited supply. We then investigate the optimal distribution of doses across countries and age groups. We employ a system of SIR equations to model the pandemic dynamics and utilize genetic algorithms to identify optimal allocations that minimize either total infections or total deaths. Our findings reveal that strategies aimed at reducing infections differ from those aimed at reducing deaths, with neither strategy advocating proportional dose allocation between countries based on population size. Our findings moreover bring to light potential ethical challenges associated with the implementation of strategy optimization.