bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructive Operation of Severe Orbital Hypertelorism With Computer-Assisted Precise Virtual Plan
Authors: Ouyang Long , Li Binghang , Xu Shixing , Jin Qi , Chen Ying , Gui Lai , Fu Jidi , Niu Feng 
Published: October 2022

Orbital hypertelorism correction is still a less precise procedure, with a simple preoperative design and surgical results often depending on the operator’s experience. In recent years, computer-assisted technology has been fully utilized in craniofacial surgery. This article aims to explore the clinical results of computer-assisted technology in orbital hypertelorism correction and discuss its advantages and effects on treatment. Four patients with orbital hypertelorism underwent intracranial and extracranial combined box osteotomy correction. Preoperative computed tomography scans were performed, and 3-dimensional 3D digital technology was used to measure the orbital spacing, virtually design the 3D cutting scheme, and guide the intraoperative 3D cutting to improve the accuracy of periorbital osteotomy and reduce the surgical risk. Four patients underwent successful surgery, and the average distance of the medial orbital wall was decreased from 43.6 to 23.4 mm. Computer-assisted box osteotomy shortens the operative time and provides better corrective results.
Limited Access to Alveolar Bone Graft Surgery Following Primary Cleft Lip and Palate Repair in Indonesia: A Questionnaire-Based Qualitative Study
Authors: Bangun Kristaninta , Halim Jessica , Tania Vika , Kreshanti Prasetyanugraheni , Pancawati Julieta , Atmodiwirjo Parintosa 
Published: October 2022

Introduction:
Cleft Lip and Palate is the most common craniofacial anomaly, and cleft lip and palate repair is widely performed. Alveolar cleft accompanies 75% of cleft lip cases and requires alveolar bone graft (ABG) surgery at mixed dentition age. However, studies on rates of ABG surgery are scarce.

Objective:
This study aims to investigate the low popularity of ABG and orthodontic care among patients with ABG history at Cleft and Craniofacial Centre, Cipto Mangunkusumo Hospital, Jakarta.

Method:
A total of 771 patients had orofacial cleft surgeries throughout 2015 to 2021. A descriptive analysis of labioplasty, palatoplasty, and ABG surgeries was presented. Questionnaire-based qualitative analysis of ABG was obtained from the patient’s guardians to evaluate the limitation and experience of conducting the surgery at our institution.

Results:
We distributed questionnaires to 13 patients with a history of ABG. ABG accounted for only 5% of total orofacial cleft surgeries. The average age of ABG surgery and orthodontic care initiation was 11 and 11.8 years old, respectively. About 82% had access to preoperative and postoperative orthodontic care; however, only 11% received PSO before 9 years old. The satisfaction rate was 100% and 75% in ABG patients with and without orthodontic care, respectively, reporting improved feeding, speech, teeth alignment, and esthetic result.

Conclusion:
Orofacial cleft management requires a multistage, comprehensive, and multidisciplinary approach. The number of ABG surgeries is low in developing countries, attributed to unequal access to ABG and orthodontic care, suggesting that limitations of knowledge, geography, and economy play a big role in Indonesian healthcare.
Psychophysiologic symptom relief therapy (PSRT) for post-acute sequelae of COVID-19: a non-randomized interventional study
Authors: Donnino Michael , Howard Patricia , Mehta Shivani , Silverman Jeremy , Cabrera Maria J , Yamin Jolin B , Balaji Lakshman , Tolin Rebecca , Berg Katherine M , Edwards Robert , Grossestreuer Anne V 
Published: October 2022

AbstractObjectiveTo determine if psychophysiologic symptom relief therapy (PSRT) will reduce symptom burden in patients suffering from post-acute sequelae of COVID-19 (PASC) who had mild/moderate acute COVID-19 disease without objective evidence of organ injury.Patients and MethodsTwenty-three adults under the age of 60 with PASC for at least 12 weeks following COVID-19 infection were enrolled in an interventional cohort study conducted via virtual platform between May 18, 2021 and August 7, 2022. Participants received PSRT during a 13 week (approximately 44 hour) course. Participants were administered validated questionnaires at baseline and at 4, 8, and 13 weeks. The primary outcome was change in somatic symptoms from baseline, measured using the Somatic Symptom Scale-8 (SSS-8).ResultsThe median duration of symptoms prior to joining the study was 267 days (IQR: 144, 460). The mean SSS-8 score of the cohort decreased from baseline by 8.5 (95% CI: 5.7-11.4), 9.4 (95% CI: 6.9-11.9), and 10.9 (95% CI: 8.3-13.5) at 4, 8, and 13 weeks respectively (all p<0.001). Participants also experienced statistically significant improvements across secondary outcomes including changes in dyspnea, fatigue, and pain (all p<0.001).ConclusionPSRT may effectively decrease symptom burden in patients suffering from PASC without evidence of organ injury. The study was registered onclinicaltrials.gov(NCT 04854772).
A method for estimating causal effects from heterogeneous clinical trials without a common control group using sequential regression and simulation: an individual participant data meta-analysis and validation study
Authors: Rudrapatna Vivek A. , Ravindranath Vignesh G. , Arneson Douglas V. , Mosenia Arman , Butte Atul J. , Wang Shan 
Published: October 2022

ABSTRACTBACKGROUNDThe advent of clinical trial data sharing platforms has created opportunities for making new discoveries and answering important questions using already collected data. However, existing methods for meta-analyzing these data require the presence of shared control groups across studies, significantly limiting the number of questions that can be confidently addressed. We sought to develop a method for meta-analyzing potentially heterogeneous clinical trials even in the absence of a common control group.METHODSThis work was conducted within the context of a broader effort to study comparative efficacy in Crohn’s disease. Following a search ofclnicaltrials.govwe obtained access to the individual participant data from nine trials of FDA-approved treatments in Crohn’s Disease (N=3392). We developed a method involving sequences of regression and simulation to separately model the placebo- and drug-attributable effects, and to simulate head-to-head trials against an appropriately normalized background. We validated this method by comparing the outcome of a simulated trial comparing the efficacies of adalimumab and ustekinumab against the recently published results of SEAVUE, an actual head-to-head trial of these drugs. This study was pre-registered on PROSPERO (#157827) prior to the completion of SEAVUE.FINDINGSUsing our method of sequential regression and simulation, we compared the week eight outcomes of two virtual cohorts subject to the same patient selection criteria as SEAVUE and treated with adalimumab or ustekinumab. Our primary analysis replicated the corresponding published results from SEAVUE (p=0·9). This finding proved stable under multiple sensitivity analyses.INTERPRETATIONThis new method may help reduce the bias of individual participant data meta-analyses, expand the scope of what can be learned from these already-collected data, and reduce the costs of obtaining high-quality evidence to guide patient care.FUNDINGNIH; UCSF Division of Gastroenterology and Bakar Computational Health Sciences Institute; University of San Francisco
GRAd-COV2 vaccine provides potent and durable immunity in randomised placebo-controlled phase 2 trial (COVITAR)
Authors: Capone Stefania , Fusco Francesco M. , Milleri Stefano , Borrè Silvio , Carbonara Sergio , Lo Caputo Sergio , Leone Sebastiano , Gori Giovanni , Maggi Paolo , Cascio Antonio , Lichtner Miriam , Cauda Roberto , Dal Zoppo Sarah , Cossu Maria V. , Gori Andrea , Roda Silvia , Confalonieri Paola , Bonora Stefano , Missale Gabriele , Codeluppi Mauro , Mezzaroma Ivano , Capici Serena , Pontali Emanuele , Libanore Marco , Diani Augusta , Lanini Simone , Battella Simone , Contino Alessandra M. , Piano Mortari Eva , Genova Francesco , Parente Gessica , Dragonetti Rosella , Colloca Stefano , Visani Luigi , Iannacone Claudio , Carsetti Rita , Folgori Antonella , Camerini Roberto ,   COVITAR study group
Published: October 2022

AbstractBackgroundSARS-CoV-2 ongoing pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccines portfolio. We report safety and immunogenicity of GRAd-COV2, a novel gorilla adenovirus-based COVID-19 vaccine, in a phase 2 trial aimed at identifying the appropriate dose and schedule.Method917 eligible adults aged 18 years or older, including participants with co-morbidities, were randomised to receive, 21 days apart, a single vaccine administration at 2×1011viral particles (vp) followed by placebo, or repeated vaccine administration at 1×1011vp, or two doses of placebo. Primary endpoints were the incidence of local and systemic solicited AEs for 7 days post each dose and the post-treatment (35 days after the first dose), geometric mean titers (GMTs) and geometric mean fold rise (GMFRs) of ELISA antibody responses to Spike protein. Additional humoral and cellular immune response parameters were monitored for up to six months.ResultsThe safety profile of GRAd-COV2 was characterized by short-term, mild-to-moderate pain and tenderness at injection site, fatigue, headache, malaise, and myalgia. Neither related SAEs nor deaths were reported. Humoral (binding and neutralizing) Ab responses peaked at day 35 after a single administration, were boosted by a second vaccination, were sustained until day 57 to then decline at day 180. Potent, VOC cross-reactive T cell responses peaked already after first dose with high frequencies of long-lived CD8 T cells.ConclusionGRAd-COV2 was safe, and induced robust immune responses after a single immunization; the second administration increased humoral but not cellular immune responses.Trial RegistrationClinicalTrials.govNCT04791423.FundingReiThera Srl
Meta-Analysis of Clinical Phenotype and Patient Survival in Neurodevelopmental Disorder with Microcephaly, Arthrogryposis, and Structural Brain Anomalies Due to Bi-allelic Loss of Function Variants in SMPD4
Authors: Marchiori Dean 
Published: October 2022

ABSTRACTA recently described, rare genetic condition known as Neurodevelopmental Disorder with Microcephaly, Arthrogryposis, and Structural Brain Anomalies (NEDMABA) has been identified in children with bi-allelic loss-of-function variants inSMPD4. The progression of this condition is not well understood with the limited case reports described so far exhibiting a severe and clinically diverse phenotype. A gap exists in the understanding of associations present in the heterogenous features of the clinical phenotype, and the expected survival probabilities of affected individuals. This is driven in part to the paucity of analysis-ready data on reported cases. This analysis aims to collate and standardise available case reports into a common dataset, to analyse and identify meaningful clusters in the clinical phenotype, and to quantify the survival probability for children with NEDMABA. To overcome the challenge of multidimensional data on very few subjects, we employ Multiple Correspondence Analysis (MCA) as a dimension reduction technique, which is then subject to cluster analysis and interpretation. To account for censoring in the data, Kaplan-Meier estimation is formulated to calculate patient survival time. The analysis correctly detected the classic phenotype for this condition, as well as a new distinct feature-cluster relating to findings of vocal cord paralysis, feeding dysfunction and respiratory failure. The survival probability for those affected was found to decline sharply in early infancy with median survival of 150 days, but with some surviving as long as 12.5 years. This wide range of outcomes is provisionally associated with different variant types however this conclusion could not be validated based on very low sample sizes. AnRpackage calledSMPD4was developed to publish standardised analysis-ready datasets used in this study. This analysis represents the first of its kind to help describe associations and trajectories of individuals with this newly reported condition, despite challenges with sparse and inconsistent data. This analysis can provide clinicians and genetic counsellors with better information to aide in decision making and support for families with this rare condition.
COVID19 Diagnosis Using Chest X-rays and Transfer Learning
Authors: Stubblefield Jonathan , Causey Jason , Dale Dakota , Qualls Jake , Bellis Emily , Fowler Jennifer , Walker Karl , Huang Xiuzhen 
Published: October 2022

ABSTRACTA pandemic of respiratory illnesses from a novel coronavirus known as Sars-CoV-2 has swept across the globe since December of 2019. This is calling upon the research community including medical imaging to provide effective tools for use in combating this virus. Research in biomedical imaging of viral patients is already very active with machine learning models being created for diagnosing Sars-CoV-2 infections in patients using CT scans and chest x-rays. We aim to build upon this research. Here we used a transfer-learning approach to develop models capable of diagnosing COVID19 from chest x-ray. For this work we compiled a dataset of 112120 negative images from the Chest X-Ray 14 and 2725 positive images from public repositories. We tested multiple models, including logistic regression and random forest and XGBoost with and without principal components analysis, using five-fold cross-validation to evaluate recall, precision, and f1-score. These models were compared to a pre-trained deep-learning model for evaluating chest x-rays called COVID-Net. Our best model was XGBoost with principal components with a recall, precision, and f1-score of 0.692, 0.960, 0.804 respectively. This model greatly outperformed COVID-Net which scored 0.987, 0.025, 0.048. This model, with its high precision and reasonable sensitivity, would be most useful as “rule-in” test for COVID19. Though it outperforms some chemical assays in sensitivity, this model should be studied in patients who would not ordinarily receive a chest x-ray before being used for screening.CCS CONCEPTSLife and Medical Sciences • Machine Learning • Artificial IntelligenceReference formatJonathan Stubblefield, Jason Causey, Dakota Dale, Jake Qualls, Emily Bellis, Jennifer Fowler, Karl Walker and Xiuzhen Huang. 2022. COVID19 Diagnosis Using Chest X-Rays and Transfer Learning.
Association Analysis ofLCORLGenetic Variant (rs657074013A>AT) with Body-Height and Skeletal Frame in Pakistani Goats
Authors: Khalid Areeb , Ashraf Hajra , Asim Hibba , Ayman Maleeka , Saif Rashid 
Published: October 2022

AbstractGoat is one of the most valued and cost-effective household animals serving humanity by providing its meat, milk, fiber, skin and manure. Particularly, meat and milk production depends on the physical traits of the animals e.g., large body-size/skeletal frame. Previous studies has shown that theLCORLgene is associated with the subject traits in humans and many other animal species. So, the current study is aimed to investigate the genetic variability/association of rs657074013A>AT variant within diverse goats from Pakistan. By using ARMS-PCR, a total of 51 samples were genotyped with allele-specific primer-set, results of the current study depicted that, 27% population is homozygous wild-type (A/A), 24% homozygous-mutant (AT/AT) and 49% is heterozygous (A/AT). Hardy Weinberg Equilibrium (HWE) analysis revealed that our overall sampled population obeys this principle withχ2(2,N= 51) = 0.046,p= 0.9730. Similarly, a significant genetic association was also envisioned by Chi-square statisticsp= 9.60 × 10−5using the PLINK data analysis toolset. Furthermore, alternative allele frequencies of 0.68 and 0.28 were also calculated within cases (n=25) and control (n=26) cohorts respectively along with an odds ratio of 5.242. As a nutshell, this pilot study improved our genomic insight by observing the variability and association of the subjectLCORLgenetic variant (c.828_829insA) in the Pakistani goat population, which may be used to improve this economically important trait by adopting marker-assisted breeding strategies and further investigated within other livestock species as well.
TsTX-κ beta (Ts8), a neurotoxin from the venom of the scorpionTityus serrulatus: antimicrobial and hemolytic activity
Authors: Oliveira Thiago de Jesus , Pereira Nayrob , Riciluca Katie Cristina Takeuti , do Nascimento Soraia Maria , Castro de Oliveira Ursula , da Silva Junior Pedro Ismael 
Published: October 2022

AbstractIncrease of infections caused by microorganisms resistant to conventional antibiotics is a health problem in Brazil and worldwide. The search for new molecules capable of inhibiting the growth of pathogens is a challenge for researchers, who find in venoms a rich source of biomolecules, including antimicrobial peptides (AMPs). The Brazilian scorpion,Tityus serrulatus, is one of the species that cause serious accidents, its venom is rich in neurotoxins that have been well characterized, highlighting their activities on channels (especially sodium and potassium). So, this work aimed to identify and characterize AMPs inT. serrulatusvenom. After milking and purification steps, the venom fractions were analyzed by liquid growth inhibition assay, the minimum inhibitory concentration (MIC) for different microorganisms was also tested. The fraction with antimicrobial activity was analyzed by electrophoresis and mass spectrometry, this AMP (molecular mass 6.881 kDa) has a similar amino acid sequences to TsTX-κ beta, a neurotoxin that acts on ion channels. The fragments from TsTX-κ beta were obtained, separated by high-performance liquid chromatography and subjected to biological tests. At high concentrations, these fragments showed hemolytic activity against human erythrocytes. Taken together, these data suggest that antimicrobial and hemolytic activities are associated by different sites from TsTX-κ beta, in addition to the identification of antimicrobial activity in a neurotoxin already known.Key ContributionMultifunction: antimicrobial and hemolytic activity associated to TsTX-κ beta, a neurotoxin that acts on potassium channels.
Structural Genomics of the Human Dopamine Receptor System
Authors: Xu Peiyu , Huang Sijie , Krumm Brian E. , Zhuang Youwen , Mao Chunyou , Zhang Yumu , Wang Yue , Huang Xi-Ping , Liu Yong-Feng , He Xinheng , Li Huadong , Yin Wanchao , Jiang Yi , Zhang Yan , Roth Bryan L. , Xu H. Eric 
Published: October 2022

AbstractThe dopamine system, including five dopamine receptors (D1R to D5R), plays essential roles in the central nervous system (CNS) and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders, including Parkinson’s Disease (PD) and schizophrenia. Here, we report five cryo-EM structures of all subtypes of human dopamine receptors in complex with G-protein and bound to the pan agonist, Rotigotine, which is used to treat PD and restless legs syndrome. The structures reveal the basis of Rotigotine binding modes to different dopamine receptors. Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity. The structures also uncover the mechanisms of the dopamine receptor activation, unique structural features among the five receptor subtypes, and the basis of G-protein coupling specificity. Our works provide a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system.
Energy extraction from air: structural basis of atmospheric hydrogen oxidation
Authors: Grinter Rhys , Kropp Ashleigh , Venugopal Hari , Senger Moritz , Badley Jack , Cabotaje Princess , Stripp Sven T. , Barlow Christopher K. , Belousoff Matthew , Cook Gregory M. , Vincent Kylie A. , Schittenhelm Ralf B. , Khalid Syma , Berggren Gustav , Greening Chris 
Published: October 2022

AbstractDiverse aerobic bacteria use atmospheric H2as an energy source for growth and survival. This recently discovered yet globally significant process regulates the composition of the atmosphere, enhances soil biodiversity, and drives primary production in certain extreme environments. Atmospheric H2oxidation has been attributed to still uncharacterised members of the [NiFe]-hydrogenase superfamily. However, it is unresolved how these enzymes overcome the extraordinary catalytic challenge of selectively oxidizing picomolar levels of H2amid ambient levels of the catalytic poison O2, and how the derived electrons are transferred to the respiratory chain. Here we determined the 1.52 Å resolution CryoEM structure of the mycobacterial hydrogenase Huc and investigated its mechanism by integrating kinetics, electrochemistry, spectroscopy, mass spectrometry, and molecular dynamics simulations. Purified Huc is an oxygen-insensitive enzyme that couples the oxidation of atmospheric H2at its large subunit to the hydrogenation of the respiratory electron carrier menaquinone at its small subunit. The enzyme uses a narrow hydrophobic gas channel to selectively bind atmospheric H2at the expense of O2, while three [3Fe-4S] clusters and their unusual ligation by a D-histidine modulate the electrochemical properties of the enzyme such that atmospheric H2oxidation is energetically feasible. Huc forms an 833 kDa complex composed of an octamer of catalytic subunits around a membrane-associated central stalk, which extracts and transports menaquinone a remarkable 94 Å from the membrane, enabling its reduction. These findings provide a mechanistic basis for the biogeochemically and ecologically critical process of atmospheric H2oxidation. Through the first characterisation of a group 2 [NiFe]-hydrogenase, we also uncover a novel mode of energy coupling dependent on long-range quinone transport and pave way for the development of biocatalysts that oxidize H2in ambient air.
The expected loss of feature diversity (versus phylogenetic diversity) following rapid extinction at the present
Authors: Overwater Marcus , Pelletier Daniel , Steel Mike 
Published: October 2022

AbstractThe current rapid extinction of species leads not only to their loss but also the disappearance of the unique features they harbour, which have evolved along the branches of the underlying evolutionary tree. One proxy for estimating the feature diversity (FD) of a setSof species at the tips of a tree is ‘phylogenetic diversity’ (PD): the sum of the branch lengths of the subtree connecting the species inS. For a phylogenetic tree that evolves under a standard birth–death process, and which is then subject to a sudden extinction event at the present (the simple ‘field of bullets’ model with a survival probability ofsper species) the proportion of the originalPDthat is retained after extinction at the present is known to converge quickly to a particular concave functionφPD(s) astgrows. To investigate how the loss ofFDmirrors the loss ofPDfor a birth–death tree, we modelFDby assuming that distinct discrete features arise randomly and independently along the branches of the tree at raterand are lost at a constant ratev. We derive an exact mathematical expression for the ratioφFD(s) of the two expected feature diversities (prior to and following an extinction event at the present) astbecomes large. We find that althoughφFDhas a similar behaviour toφPD(and coincides with it forv= 0), whenv >0,φFD(s) is described by a function that is different fromφPD(s). We also derive an exact expression for the expected number of features that are present in preciselyoneextant species. Our paper begins by establishing some generic properties of FD in a more general (non-phylogenetic) setting and applies this to fixed trees, before considering the setting of random (birth–death) trees.