bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning in Metopic Craniosynostosis: Does Phenotypic Severity Predict Long-Term Esthetic Outcome?
Authors: Blum Jessica D. , Beiriger Justin , Villavisanis Dillan F. , Morales Carrie , Cho Daniel Y. , Tao Wenzheng , Whitaker Ross , Bartlett Scott P. , Taylor Jesse A. , Goldstein Jesse A. , Swanson Jordan W. 
Published: August 2022

Background:
There have been few longitudinal studies assessing the effect of preoperative phenotypic severity on long-term esthetic outcomes in metopic craniosynostosis. This study evaluates the relationship between metopic severity and long-term esthetic outcomes using interfrontal angle (IFA) and CranioRate, a novel metopic synostosis severity measure.

Methods:
Patients with metopic craniosynostosis who underwent bifrontal orbital advancement and remodeling between 2012 and 2017 were reviewed. Preoperative computed tomography head scans were analyzed for IFA and CranioRate, a machine learning algorithm which generates quantitative severity ratings including metopic severity score (MSS) and cranial morphology deviation (CMD). Long-term esthetic outcomes were assessed by craniofacial surgeons using blinded 3-rater esthetic grading of clinical photos. Raters assessed Whitaker score and the presence of temporal hollowing, lateral orbital retrusion, frontal bone irregularities and/or “any visible irregularities.”

Results:
Preoperative scans were performed at a mean age of 7.7±3.4 months, with average MSS of 6/10, CMD of 200/300, and IFA of 116.8±13.8 degrees. Patients underwent bifrontal orbital advancement and remodeling at mean 9.9±3.1 months. The average time from operation to esthetic assessment was 5.4±1.0 years. Pearson correlation revealed a significant negative correlation between MSS and age at computed tomography (r=−0.451, P=0.004) and IFA (r=−0.371, P=0.034) and between IFA and age at surgery (r=−0.383, P=0.018). In multinomial logistic regression, preoperative MSS was the only independent predictor of visible irregularities (odds ratio=2.18, B=0.780, P=0.024) and preoperative IFA alone significantly predicted Whitaker score, with more acute IFA predicting worse Whitaker score (odds ratio=0.928, B=−0.074, P=0.928).

Conclusions:
More severe preoperative phenotypes of metopic craniosynostosis were associated with worse esthetic dysmorphology. Objective measures of preoperative metopic severity predicted long-term esthetic outcomes.
An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS)
Authors: Görgec Burak , Benedetti Cacciaguerra Andrea , Pawlik Timothy M. , Aldrighetti Luca A. , Alseidi Adnan A. , Cillo Umberto , Kokudo Norihiro , Geller David A. , Wakabayashi Go , Asbun Horacio J. , Besselink Marc G. , Cherqui Daniel , Cheung Tan To , Clavien Pierre-Alain , Conrad Claudius , D’Hondt Mathieu , Dagher Ibrahim , Dervenis Christos , Devar John , Dixon Elijah , Edwin Bjørn , Efanov Mikhail , Ettore Giuseppe M. , Ferrero Alessandro , Fondevilla Constantino , Fuks David , Giuliante Felice , Han Ho-Seong , Honda Goro , Imventarza Oscar , Kooby David A. , Lodge Peter , Lopez-Ben Santiago , Machado Marcel A. , Marques Hugo P. , O’Rourke Nick , Pekolj Juan , Pinna Antonio D. , Portolani Nazario , Primrose John , Rotellar Fernando , Ruzzenente Andrea , Schadde Erik , Siriwardena Ajith K. , Smadi Sameer , Soubrane Olivier , Tanabe Kenneth K. , Teh Catherine S.C. , Torzilli Guido , Van Gulik Thomas M. , Vivarelli Marco , Wigmore Stephen J. , Abu Hilal Mohammad 
Published: August 2022

Objective:
To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method.

Background:
Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking.

Methods:
This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS.

Results:
In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin.

Conclusions:
This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.
Impact of Axillary Lymph Node Dissection and Sentinel Lymph Node Biopsy on Upper Limb Morbidity in Breast Cancer Patients
Authors: Che Bakri Nur Amalina , Kwasnicki Richard M. , Khan Naairah , Ghandour Omar , Lee Alice , Grant Yasmin , Dawidziuk Aleksander , Darzi Ara , Ashrafian Hutan , Leff Daniel R. 
Published: August 2022

Objective:
To evaluate the impact of axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) on upper limb (UL) morbidity in breast cancer patients.

Background:
Axillary de-escalation is motivated by a desire to reduce harm of ALND. Understanding the impact of axillary surgery and disparities in operative procedures on postoperative arm morbidity would better direct resources to the point of need and cement the need for de-escalation strategies.

Methods:
Embase, MEDLINE, CINAHL, and PsychINFO were searched from 1990 until March 2020. Included studies were randomized-controlled and observational studies focusing on UL morbidities, in breast surgery patients. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of UL morbidity comparing SLNB and ALND at <12 months, 12 to 24 months, and beyond 24 months were analyzed.

Results:
Sixty-seven studies were included. All studies reported a higher rate of lymphedema and pain after ALND compared with SLNB. The difference in lymphedema and pain prevalence between SLNB and ALND was 13.7% (95% confidence interval: 10.5–16.8, P<0.005) and 24.2% (95% confidence interval: 12.1–36.3, P<0.005), respectively. Pooled estimates for prevalence of reduced strength and range of motion after SLNB and ALND were 15.2% versus 30.9% and 17.1% versus 29.8%, respectively. Type of axillary surgery, greater body mass index, and radiotherapy were some of the predictors for UL morbidities.

Conclusions:
Prevalence of lymphedema after ALND was higher than previously estimated. ALND patients experienced greater rates of lymphedema, pain, reduced strength, and range of motion compared with SLNB. The findings support the continued drive to de-escalate axillary surgery.
Persistent Hiccups Induced by Supratentorial Infarcts and Successful Treatments With Combination of Perampanel and Baclofen: A Case Report
Authors: Morita Kohei , Nuki Yoshitsugu , Hashizume Hiroya , Togo Masaya 
Published: August 2022

Case
A 52-year-old man developed a cerebral infarction from the right middle cerebral artery occlusion, and the infarction extensively damaged the right insula. Three months after the onset of the cerebral infarction, persistent hiccups appeared, occurring during sleep. The thoracic and abdominal cavities showed no lesions; hence, the hiccups were considered to be caused by central nervous system dysfunction. Administration of metoclopramide, chlorpromazine, and diazepam were ineffective, while levetiracetam had a partial effect. Combining perampanel with baclofen finally suppressed the symptoms.

Discussion
Lesions at the right insula impair respiratory reflex and may present with hiccups as a symptom of respiratory reflex disinhibition. Here, we review similar cases of treatment-resistant hiccups, as well as perampanel and baclofen efficacy in myoclonus cases.

Conclusions
Our patient's case suggested that perampanel with baclofen may be effective for myoclonus due to respiratory reflex disinhibition and can be used to treat hiccups derived from cerebral infarctions.
Lab practices that improve coronavirus disease 2019 detection accuracy using real-time PCR
Authors: Soufan Ghadir , Berro Nour , Nahle Sahar , Darwish Malak , Ghaddar Maysaa , Makki Mohamad , Younes Mahmoud , Sater Fadi Abdel 
Published: August 2022

ABSTRACT
The number of coronavirus disease 2019 (COVID-19) cases significantly increased with the emergence of multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has led to an ongoing effort focused on developing the diagnostic detection tests. Among the currently available tests, real-time reverse transcriptase PCR (RT-PCR) has been considered as the ‘golden method’ for the detection of SARS-COV-2. However, a significant number of inaccurate (false-negative/false-positive) results have been reported in spite of this method's reliability and effectiveness. These unreliable results may arise because of various issues encountered throughout the entire testing process starting with the sampling phase, going through the PCR process, and ending with the result analysis. This article aims to shed light on the errors that occur during the COVID-19 testing process and suggest ways to overcome them effectively. Accurate testing could be optimized by following the correct swabbing technique, using adequate RT-PCR kits and controls, setting clear lab guidelines, and properly interpreting the results.
Modular representation and control of floppy networks
Authors: Chen Siheng , Giardina Fabio , Choi Gary P. T. , Mahadevan L. 
Published: August 2022

Geometric graph models of systems as diverse as proteins, DNA assemblies, architected materials and robot swarms are useful abstract representations of these objects that also unify ways to study their properties and control them in space and time. While much work has been done in the context of characterizing the behaviour of these networks close to critical points associated with bond and rigidity percolation, isostaticity, etc., much less is known about floppy, underconstrained networks that are far more common in nature and technology. Here, we combine geometric rigidity and algebraic sparsity to provide a framework for identifying the zero energy floppy modes via a representation that illuminates the underlying hierarchy and modularity of the network and thence the control of its nestedness and locality. Our framework allows us to demonstrate a range of applications of this approach that include robotic reaching tasks with motion primitives, and predicting the linear and nonlinear response of elastic networks based solely on infinitesimal rigidity and sparsity, which we test using physical experiments. Our approach is thus likely to be of use broadly in dissecting the geometrical properties of floppy networks using algebraic sparsity to optimize their function and performance.
A KLHL40 3’ UTR splice-altering variant causes milder NEM8, an under-appreciated disease mechanism
Authors: Dofash Lein N.H. , Monahan Gavin , Servián-Morilla Emilia , Rivas Eloy , Faiz Fathimath , Sullivan Patricia , Oates Emily , Clayton Joshua , Taylor Rhonda L. , Davis Mark R. , Beilharz Traude , Laing Nigel G. , Cabrera-Serrano Macarena , Ravenscroft Gianina 
Published: August 2022

AbstractNemaline myopathy 8 (NEM8) is typically a severe autosomal recessive disorder associated with variants in the kelch-like family member 40 gene (KLHL40). Common features include fetal akinesia, fractures, contractures, dysphagia, respiratory failure, and neonatal death. Here, we describe a man in his 20s with relatively mild NEM8. He presented with hypotonia and bilateral femur fractures at birth, later developing bilateral Achilles’ contractures, scoliosis, and elbow and knee contractures. He had walking difficulties throughout childhood and became wheelchair bound during adolescence after prolonged immobilisation. Muscle MRI during adolescence indicated prominent fat replacement in his pelvic girdle, posterior compartments of thighs, and vastus intermedius. Muscle biopsy revealed nemaline bodies and intranuclear rods. RNA sequencing and western blotting of patient skeletal muscle indicated significant reduction in KLHL40 mRNA and protein respectively. Using gene panel screening, exome sequencing and RNA sequencing, we identified compound heterozygous variants in KLHL40; a truncating 10.9 kb deletion in trans with a likely pathogenic variant (c.*152G>T) in the 3’ untranslated region (UTR). Computational tools SpliceAI and Introme predicted the c.*152G>T variant created a cryptic donor splice site. RNA-seq and in vitro analyses indicated that the c.*152G>T variant induces multiple de novo splicing events that likely provoke nonsense mediated decay of KLHL40 mRNA explaining the loss of mRNA expression and protein abundance in the patient. Analysis of 3’ UTR variants in ClinVar suggests SNPs that introduce aberrant 3’ UTR splicing may be underrecognised in Mendelian disease. We encourage consideration of this mechanism during variant curation.
Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine
Authors: Mwimanzi Francis , Lapointe Hope R. , Cheung Peter K. , Sang Yurou , Yaseen Fatima , Kalikawe Rebecca , Datwani Sneha , Burns Laura , Young Landon , Leung Victor , Ennis Siobhan , Brumme Chanson J. , Montaner Julio S.G. , Dong Winnie , Prystajecky Natalie , Lowe Christopher F. , DeMarco Mari L. , Holmes Daniel T. , Simons Janet , Niikura Masahiro , Romney Marc G. , Brumme Zabrina L. , Brockman Mark A. 
Published: August 2022

ABSTRACTBackgroundLonger-term immune response data after three doses of COVID-19 mRNA vaccine remain limited, particularly among older adults and following Omicron breakthrough infection.MethodsWe quantified wild-type- and Omicron-specific serum IgG levels, ACE2 displacement activities and live virus neutralization up to six months post-third dose in 116 adults aged 24-98 years who remained COVID-19-naïve or experienced their first SARS-CoV-2 infection during this time.ResultsAmong 78 participants who remained COVID-19-naïve throughout follow-up, wild-type- and Omicron BA.1-specific IgG concentrations were comparable between younger and older adults, though BA.1-specific responses were consistently significantly lower than wild-type-specific responses in both groups. Wild-type- and BA.1-specific IgG concentrations declined at similar rates among COVID-19-naïve younger and older adults, with median half-lives ranging from 69-78 days. Antiviral antibody function declined substantially over time in COVID-19-naïve individuals, particularly older adults: by six months, BA.1-specific neutralization was undetectable in 96% of older adults, versus 56% of younger adults. SARS-CoV-2 infection, experienced by 38 participants, boosted IgG levels and neutralization above those induced by vaccination alone. Nevertheless, BA.1-specific neutralization remained significantly lower than wild-type, with BA.5-specific neutralization lower still.ConclusionsOur findings underscore the immune benefits of third COVID-19 mRNA vaccine doses in adults of all ages, but rapid decline of Omicron-specific neutralization activity in COVID-19-naïve individuals, particularly among older adults, demonstrates the need for fourth doses within 3-6 months to maintain systemic responses. Individuals who experienced SARS-CoV-2 breakthrough infection post-third vaccine dose however can likely delay a fourth dose beyond this timeframe.
Laboratory Validation and Clinical Implementation of Human Monkeypox Saliva-Based Tests
Authors: Allan-Blitz Lao-Tzu , Carragher Kevin , Sukhija-Cohen Adam , Li Hong , Klausner Jeffrey D. 
Published: August 2022

AbstractBackgroundImproved diagnostic capabilities and accessibility are essential for controlling the outbreak of Human Monkeypox.MethodsWe describe a saliva-based polymerase chain reaction (PCR) assay for Human Monkeypox, in vitro test performance, and clinical implementation of that assay at three testing sites in Los Angeles. Finally, using pre-specified search terms, we conducted a systematic rapid review of PubMed and Web of Science online databases of studies reporting the performance of oral pharyngeal or saliva-based tests for Human Monkeypox.ResultsLaboratory evaluation of the assay showed in silico inclusivity of 100% for 97 strains of Human Monkeypox, with an analytic sensitivity of 250 copies/mL, and 100% agreement compared to known positive and negative specimens. Clinical testing identified 22 cases of Human Monkeypox among 132 individuals (16.7%). Of those 22 cases, 16 (72.7%) reported symptoms, 4 (18.2%) without a rash at the time of testing. Our systematic rapid review identified 6 studies; 23 patients had tests performed on oropharyngeal specimens 100% agreed with the PCR test result of a lesion swab.ConclusionSaliva-based PCR tests are potential tools for outbreak control, and further evaluation of the performance of such tests is warranted.
Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection
Authors: Demko Zoe O , Yu Tong , Mullapudi Sarika K. , Varela Heslin M. Gabriela , Dorsey Chamia A. , Payton Christine B. , Tornheim Jeffrey A. , Blair Paul W. , Mehta Shruti H. , Thomas David L. , Manabe Yukari C. , Antar Annukka A.R. ,   the OutSMART Study Team
Published: August 2022

AbstractLittle data exist on long COVID outcomes beyond one year. In a cohort enrolled with mild-moderate acute COVID-19, a wide range of symptoms manifest at 6, 12, and 18 months. Endorsing over 3 symptoms associates with poorer quality of life in 5 domains: physical, social, fatigue, pain, and general health.
Adjusted booster schedules disperse age-dependent differences in antibody titers benefitting risk populations
Authors: Müller Lisa , Andrée Marcel , Moskorz Wiebke , Drexler Ingo , Hauka Sandra , Ptok Johannes , Walotka Lara , Grothmann Ramona , Hillebrandt Jonas , Ritchie Anastasia , Peter Laura , Walker Andreas , Timm Jörg , Adams Ortwin , Schaal Heiner 
Published: August 2022

AbstractWe provide follow-up data on the humoral immune response after COVID-19 vaccinations of a cohort aged below 60 and over 80 years. While anti-SARS-CoV-2 spike-specific IgG and neutralization capacity waned rapidly after initial vaccination, additional boosters highly benefitted humoral immune responses including neutralization of Omikron variants in the elderly cohort.
Developing a video expert panel as a reference standard to evaluate respiratory rate counting in paediatric pneumonia diagnosis: protocol for a cross-sectional study
Authors: Khan Ahad Mahmud , Ahmed Salahuddin , Chowdhury Nabidul Haque , Islam Md Shafiqul , McCollum Eric D , King Carina , Shi Ting , Nahar Kamrun , Simpson Robynne , Ahmed Ayaz , Rahman Md Mozibur , Baqui Abdullah H , Cunningham Steven , Campbell Harry ,   RESPIRE Collaboration
Published: August 2022

AbstractIntroductionManual counting of respiratory rate (RR) in children is challenging for health workers and can result in misdiagnosis of pneumonia. Some novel RR counting devices automate the counting of RR and classification of fast breathing. The absence of an appropriate reference standard to evaluate the performance of these devices is a challenge. If good quality videos could be captured, with RR interpretation from these videos systematically conducted by an expert panel, it could act as a reference standard. This study is designed to develop a video expert panel (VEP) as a reference standard to evaluate RR counting for identifying pneumonia in children.Methods and analysisUsing a cross-sectional design, we will enrol children aged 0-59 months presenting with suspected pneumonia at different levels of health facilities in Dhaka and Sylhet, Bangladesh. We will video record a physician/health worker counting RR manually and also using an automated RR counter (ChARM) from each child. We will establish a standard operating procedure for capturing quality videos, make a set of reference videos, and train and standardise the VEP members using the reference videos. After that, we will assess the performance of the VEP as a reference standard to evaluate RR counting. We will calculate the mean difference and proportions of agreement within ±2 breaths per minute and create Bland-Altman plots with limits of agreement between VEP members.Ethics and disseminationThe study protocol was approved by the National Research Ethics Committee of Bangladesh Medical Research Council (BMRC), Bangladesh (registration number: 39315022021) and Edinburgh Medical School Research Ethics Committee (EMREC), Edinburgh, UK (REC Reference: 21-EMREC-040). Dissemination of the study findings will be through conference presentations and publications in peer-reviewed scientific journals.Strengths and limitations of this studyExpert paediatricians will provide feedback to develop a standard operating procedure for videography of child chest movements.The video expert panel will be trained and standardized using the expert paediatrician-interpreted reference videos.Video expert panel members will be masked to respiratory rate counted by each other and to respiratory rate manual counts, and with the automated counter.Children with varying severity of illness will be enrolled from different levels of health facilities in Bangladesh.Despite the availability of multiple respiratory rate counters, only the ChARM device will be used in this study.
Distinctive features of lipoprotein profiles in stroke patients
Authors: Konishi Tomokazu , Hayashi Yurie , Fujiwara Risako , Kawata Shinpei , Ishikawa Tatsuya 
Published: August 2022

AbstractClasses of lipoproteins solubilize lipids in the blood, and their profiles are important for preventing atherosclerotic diseases. These can be identified by gel filtration HPLC, which has been analyzed in a manner that yields the same values as the de facto standard method, i.e., ultracentrifugation; however, previous studies have found that ultracentrifugation and its simplified alternatives, enzymatic methods, yield incorrect values. Here HPLC data of stroke patients and the controls were compared using data-driven analyses, without consideration for ultracentrifugation. The data well-separated patients from controls. In many patients, the level of HDL1 (a cholesterol scavenger) was low. The TG/cholesterol ratio of chylomicrons was found to be low in patients and high in the healthy elderly; the lower level may indicate a larger intake of animal fats. High levels of free glycerol in the elderly were hazardous, suggesting more dependence on lipids as an energy source. Statins had minimal effect on these factors. LDL cholesterol, the commonly-used risk indicator, was not a risk factor actually. Enzymatic methods failed to separate the patients from the control; hence, the existing guidelines for screening methods and medical treatment need to be revised. As an immediate step, glycerol would be an adaptable indicator.