bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of deep learning to classify skeletal growth phase on 3D radiographs
Authors: Ameli Nazila , Lagravere Manuel , Lai Hollis 
Published: March 2023

AbstractCervical vertebral maturation (CVM) is widely used to evaluate growth potential in the field of orthodontics. The aim of this study is to develop an artificial intelligence (AI) algorithm to automatically predict the CVM stages in terms of growth phases using the cone-beam computed tomographic (CBCT) images. A total of 30,016 slices obtained from 56 patients with the age range of 7-16 years were included in the dataset. After cropping the region of interest (ROI), a convolutional neural network (CNN) was built to classify the slices based on the presence of a good vision of vertebrae for classification of the growth stages. The output was used to train another model capable of categorizing the slices into phases of growth, which were defined as Phase I (prepubertal, CVM stages 1 and 2), phase II (circumpubertal, CVM stage 3), and phase III (postpubertal, CVM stages 4, 5, and 6). After training the model, 88 unused images belonging to 3 phases were used to evaluate the performance of the model using multi-class classification metrics. The average classification accuracy of the first and second CNN-based deep learning models were 96.06% and 95.79%, respectively on the validation dataset. The multi-class classification metrics applied to the new testing dataset also showed an overall accuracy of 84% for predicting the growth phase. Moreover, phase I ranked the highest accuracy in terms of F1 score (87%), followed by phase II (83%), and phase III (80%) on new images. Our proposed models could automatically detect the C2-C4 vertebrae required for CVM staging and accurately classify slices into 3 growth phases without the need for annotating the shape and configuration of vertebrae. This will result in developing a fully automatic and less complex system with reasonable performance, comparable to expert practitioners.Author SummaryThe skeletal age of orthodontic patients is a critical factor in planning the proper orthodontic treatment. Thus, an accurate assessment of the growth stage can result in better treatment outcomes and reduced treatment time. Traditionally, 2-D cephalometric radiographs obtained during the orthodontic examination were used for estimating the skeletal age using the three cervical vertebrae. However, this method was subjective and prone to errors as different orthodontists could interpret the features differently. Moreover, 2-D images provide only limited information as they only capture two dimensions and involve superimpositions of neighbour structures. In the present study, machine learning models are applied to 3-D cephalometric images to predict the growth stage of patients by analyzing the shape and pattern of cervical vertebrae. This method has the potential to improve treatment outcomes and reduce the treatment time for orthodontic patients. Additionally, it can contribute to the development of more personalized treatment plans and advance our understanding of the growth and development of the craniofacial complex.
High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor
Authors: Saeed Sadia , Khanam Roohia , Janjua Qasim M. , Manzoor Jaida , Ning Lijiao , Hanook Sharoon , Canouil Mickaël , Ali Muhammad , Ayesha Hina , Khan Waqas I. , Farooqi I. Sadaf , Yeo Giles S.H. , O’Rahilly Stephen , Bonnefond Amélie , Butt Taeed A. , Arslan Muhammad , Froguel Philippe 
Published: March 2023

ABSTRACTBACKGROUNDBiallelic pathogenic mutations inLEP, LEPRandMC4Rgenes controlling central leptin-melanocortin signalling cause early onset severe obesity. However, the long-term clinical outcomes of leptin signalling deficiency are unknown.DESIGN AND OBJECTIVESWe carried out a retrospective cross-sectional clinical investigation of a large cohort of children withLEP, LEPRorMC4Rdeficiency, to evaluate the progression of the disease and its impact on morbidity and mortality.PARTICIPANTSSeverely obese children from 454 consanguineous families of Pakistani origin were screened for mutations in the three genes using Sanger and exome sequencing. We identified 132 probands and 13 affected family members with homozygous pathogenic mutations inLEP, LEPRorMC4R.MAIN OUTCOME MEASURESWeight, height, and head circumference were measured by trained technicians using standardized protocols. WHO-anthro and anthroplus were used to assess BMI-standard deviation score. All affected individuals underwent detailed physical and clinical investigations by expert paediatric endocrinologist. Metabolic and oxidative stress biomarkers were measured in serum.RESULTSWe report a very high mortality in children withLEP(26%) andLEPR-deficiency (9%), mainly due to recurrent pulmonary and gastro-intestinal infections. In addition, 40% ofLEP- orLEPR-deficient surviving children experienced life-threatening episodes of pulmonary or gastro-intestinal infections. Oxidative stress as assessed by biomarkers, was significantly higher inLEPdeficiency compared to the other two mutant groups.CONCLUSIONSChildren with congenital deficiency of leptin or its receptor suffer a high mortality rate, and severe morbidity. Although effective therapies are available for both but as yet(orto-date) are not accessible in Pakistan. An appreciation of the severe impact of leptin or leptin receptor deficiency on educational attainment, morbidity and early mortality risks should spur efforts to deliver available life-saving drugs to these children as a matter of urgency.
Phenotypes of cough in children: a latent class analysis
Authors: Mallet Maria Christina , Pedersen Eva SL , Makhoul Ronny , Blanchon Sylvain , Hoyler Karin , Jochmann Anja , Latzin Philipp , Moeller Alexander , Regamey Nicolas ,   SPAC Study Team, Goutaki Myrofora , Spycher Ben D , Kuehni Claudia E 
Published: March 2023

ABSTRACTBackgroundDistinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we identified cough phenotypes and we aimed to validate them based on measurable traits, physician diagnoses, and prognosis.MethodsWe used data from 531 children aged 5–16 years from the Swiss Paediatric Airway Cohort—a multicentre clinical cohort of children seen in outpatient clinics since 2017. We included children with any parent-reported cough (i.e. cough without a cold, cough at night, cough more than others, or cough longer than 4 weeks) without current wheeze. We applied latent class analysis to identify phenotypes using 9 symptoms and characteristics and selected the best model using the Akaike Information Criterion. We assigned children to the most likely phenotype and compared the resulting groups with regards to parental history, comorbidities, measurable traits, physician diagnoses, and prognosis after 1 year.ResultsOur analysis distinguished 4 cough phenotypes: 1. unspecific dry cough (25%); 2. non-allergic infectious and night cough with snoring and otitis (4%); 3. allergic dry night cough with snoring (9%); and 4. allergic cough (61%). Children with the allergic phenotype often had family or personal history of atopy and were diagnosed with asthma. Fractional exhaled nitric oxide was highest for the allergic phenotype [median 17.9 parts per billion (ppb)] and lowest for the non-allergic infectious phenotype (median 7.0 ppb). Positive allergy test results differed across phenotypes (p<0.001) and were most common among the allergic (70%) and least common among the unspecific dry cough (31%) phenotypes. Subsequent wheeze was thrice as high among the allergic than the unspecific dry cough phenotype.ConclusionWe distinguished 4 clinically-relevant cough phenotypes; they differed by measurable traits, physician diagnoses, and prognosis. Although we excluded children with current wheeze, most children belonged to allergy-related phenotypes and possibly need allergy and asthma work-ups.Three key messagesLatent class analysis identified 4 cough phenotypes distinguished by measurable traits, diagnoses, and prognosis.Most children belonged to allergy-related phenotypes and possibly need allergy and asthma work-ups.Symptom-based cough phenotypes correlate with measurable traits and potentially apply to all healthcare settings.
Individual and organisational interactions, learning and information sharing in a multi-country implementation-focused quality of care network for maternal, newborn and child health: a social network analysis
Authors: Mukinda Fidele Kanyimbu , Djellouli Nehla , Akter Kohenour , Sarker Mithun , Tufa Asebe Amenu , Mwandira Kondwani , Seruwagi Gloria , Kyamulabi Agnes , Mwaba Kasonde , Marchant Tanya , Shawar Yusra R. , English Mike , Namakula Hilda , Gonfa Geremew ,   QCN Evaluation Group, Colbourn Tim , Kinney Mary V. 
Published: March 2023

AbstractThe Network for Improving Quality of Care for Maternal, Newborn and Child Health (QCN) was established to build a cross-country platform for joint-learning around quality improvement implementation approaches to reduce mortality. This paper describes and explores the structure of the QCN in four countries and at global level.Using Social Network Analysis (SNA), this cross-sectional study maps the QCN networks at global level and in four countries (Bangladesh, Ethiopia, Malawi and Uganda) and assesses the interactions among actors involved. A pre-tested closed-ended structured questionnaire was completed by 302 key actors in early 2022 following purposeful and snowballing sampling. Data were entered into an online survey tool, and exported into Microsoft Excel for data management and analysis. This study received ethical approval as part of a broader evaluation.The SNA identified 566 actors across the four countries and at global level. Bangladesh, Malawi and Uganda had multiple-hub networks signifying multiple clusters of actors reflecting facility or district networks, whereas the network in Ethiopia and at global level had more centralized networks. There were some common features across the country networks, such as low overall density of the network, engagement of actors at all levels of the system, membership of related committees identified as the primary role of actors, and interactions spanning all types (learning, action and information sharing). The most connected actors were facility level actors in all countries except Ethiopia, which had mostly national level actors.The results reveal the uniqueness and complexity of each network assessed in the evaluation. They also affirm the broader qualitative evaluation assessing the nature of these networks, including composition and leadership. Gaps in communication between members of the network and limited interactions of actors between countries and with global level actors signal opportunities to strengthen QCN.
Evolutionary constraint and innovation across hundreds of placental mammals
Authors: Christmas Matthew J. , Kaplow Irene M. , Genereux Diane P. , Dong Michael X. , Hughes Graham M. , Li Xue , Sullivan Patrick F. , Hindle Allyson G. , Andrews Gregory , Armstrong Joel C. , Bianchi Matteo , Breit Ana M. , Diekhans Mark , Fanter Cornelia , Foley Nicole M. , Goodman Daniel B. , Goodman Linda , Keough Kathleen C. , Kirilenko Bogdan , Kowalczyk Amanda , Lawless Colleen , Lind Abigail L. , Meadows Jennifer R. S. , Moreira Lucas R. , Redlich Ruby W. , Ryan Louise , Swofford Ross , Valenzuela Alejandro , Wagner Franziska , Wallerman Ola , Brown Ashley R. , Damas Joana , Fan Kaili , Gatesy John , Grimshaw Jenna , Johnson Jeremy , Kozyrev Sergey V. , Lawler Alyssa J. , Marinescu Voichita D. , Morrill Kathleen M. , Osmanski Austin , Paulat Nicole S. , Phan BaDoi N. , Reilly Steven K. , Schäffer Daniel E. , Steiner Cynthia , Supple Megan A. , Wilder Aryn P. , Wirthlin Morgan E. , Xue James R. ,   Zoonomia Consortium, Birren Bruce W. , Gazal Steven , Hubley Robert M. , Koepfli Klaus-Peter , Marques-Bonet Tomas , Meyer Wynn K. , Nweeia Martin , Sabeti Pardis C. , Shapiro Beth , Smit Arian F. A. , Springer Mark , Teeling Emma , Weng Zhiping , Hiller Michael , Levesque Danielle L. , Lewin Harris A. , Murphy William J. , Navarro Arcadi , Paten Benedict , Pollard Katherine S. , Ray David A. , Ruf Irina , Ryder Oliver A. , Pfenning Andreas R. , Lindblad-Toh Kerstin , Karlsson Elinor K. 
Published: March 2023

AbstractEvolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.
CYP4F2 is a human-specific determinant of circulating N-acyl amino acid levels
Authors: Tanzo Julia T. , Li Veronica L. , Wiggenhorn Amanda L. , Moya-Garzon Maria Dolores , Wei Wei , Lyu Xuchao , Dong Wentao , Tahir Usman A. , Chen Zsu-Zsu , Cruz Daniel E. , Deng Shuliang , Shi Xu , Zheng Shuning , Guo Yan , Sims Mario , Abu-Remaileh Monther , Wilson James G. , Gerszten Robert E. , Long Jonathan Z. , Benson Mark D. 
Published: March 2023

AbstractN-acyl amino acids are a large family of circulating lipid metabolites that modulate energy expenditure and fat mass in rodents. However, little is known about the regulation and potential cardiometabolic functions of N-acyl amino acids in humans. Here, we analyze the cardiometabolic phenotype associations and genetic regulation of four plasma N-fatty acyl amino acids (N-oleoyl-leucine, N-oleoyl-phenylalanine, N-oleoyl-serine, and N-oleoyl-glycine) in 2,351 individuals from the Jackson Heart Study. N-oleoyl-leucine and N-oleoyl-phenylalanine were positively associated with traits related to energy balance, including body mass index, waist circumference, and subcutaneous adipose tissue. In addition, we identify theCYP4F2locus as a human-specific genetic determinant of plasma N-oleoyl-leucine and N-oleoyl-phenylalanine levels. In vitro, CYP4F2-mediated hydroxylation of N-oleoyl-leucine and N-oleoyl-phenylalanine results in metabolic diversification and production of many previously unknown lipid metabolites with varying characteristics of the fatty acid tail group, including several that structurally resemble fatty acid hydroxy fatty acids (FAHFAs). By contrast, FAAH-regulated N-oleoyl-glycine and N-oleoyl-serine were inversely associated with traits related to glucose and lipid homeostasis. These data uncover a human-specific enzymatic node for the metabolism of a subset of N-fatty acyl amino acids and establish a framework for understanding the cardiometabolic roles of individual N-fatty acyl amino acids in humans.
Long-B prokaryotic Argonaute systems employ various effectors to confer immunity via abortive infection
Authors: Song Xinmi , Lei Sheng , Liu Shunhang , Liu Yanqiu , Fu Pan , Zeng Zhifeng , Yang Ke , Chen Yu , Li Ming , She Qunxin , Han Wenyuan 
Published: March 2023

SummaryArgonaute proteins (Agos) bind short nucleic acids as guides and are directed by them to recognize target complementary nucleic acids. Prokaryotic Agos (pAgos) are extremely diverse, with potential functions in microbial defense. The functions and mechanisms of a group of full-length yet inactive pAgos, long-B pAgos, remain enigmatic. Here, we show that most long-B pAgos constitute cell suicide systems together with their various associated proteins, including nucleases, Sir2-domain-containing proteins and trans-membrane proteins, respectively. Among them, the long-B pAgo-nuclease system utilizes an RNA-programmed and target-recognition-activated collateral DNA cleavage activity to sense invaders and kill the infected cells. This results in depletion of the invading plasmid from the cell population. Together, our data indicate that the long-B pAgo systems induce cell death with various effector proteins after recognition of invading nucleic acids, corresponding to an immune response via abortive infection.
Assessing the effectiveness of online emotion recognition training in healthy volunteers
Authors: Reed Zoe E , Suddell Steph , Eastwood Andy , Thomas Lilian , Dwyer Imogen , Penton-Voak Ian S , Jarrold Christopher , Munafò Marcus R , Attwood Angela S 
Published: March 2023

AbstractBackgroundDifficulties in facial emotion recognition are associated with a range of mental health and neurodevelopmental conditions and can negatively impact longer term social functioning. Interventions that target facial emotion recognition may therefore have important clinical potential, for example for autistic individuals. We investigated the effect of an emotion recognition training (ERT) task on emotion recognition ability and, importantly, whether training generalises to novel (non-trained) faces.MethodsWe conducted three online experimental studies with healthy volunteers completing a single ERT session to test: 1) the efficacy of our four-emotion ERT (training to improve recognition of angry, happy, sad and scared emotional expressions) (N=101), 2) the efficacy of our six-emotion ERT (adding disgusted and surprised) (N=109), and 3) the generalisability of ERT to novel (non-trained) facial stimuli (N=120). In all three studies, our primary outcome was total correct hits across all emotions. In Studies 1 and 2, this was compared across active training and control (sham) training groups (randomised). In Study 3, this was compared across groups who were trained on stimuli that were either the same identity (stimulus-congruent), or a different identity (stimulus-incongruent) to those they were tested on (randomised). Linear mixed effects models were used to test for effects of training.ResultsThe effect estimate from Study 1 was in the direction of improvement in the active training group, however, confidence intervals were wide (b=0.02, 95% CI=-0.02 to 0.07,p=0.27) and our effect may have been reduced due to ceiling effects. Study 2, with the additional emotions, indicated total hits were greater following active (vs. sham) training, which remained following inclusion of baseline covariates (b=0.07, 95% CI=0.03 to 0.12,p=0.002). Study 3 demonstrated that improvement post-training was similar across stimulus-congruent and incongruent groups (b=-0.01, 95% CI=-0.05 to 0.02,p= 0.52).ConclusionOur results indicate that ERT improves emotion recognition and that this improvement generalises to novel stimuli. Our data suggest six emotions should be used rather than four to avoid ceiling effects in training. Future studies should explore generalisability of facial stimuli of different ages and ethnicities as well as examining longer-term effects of ERT. The application of ERT as an intervention may be particularly beneficial to populations with known emotion recognition difficulties, such as autistic individuals.
An investigation of the impact of index case screening on commonly reported epidemiological estimates in tuberculosis (TB) household contact study
Authors: Dou Yangmingqiu , Li Tenglong 
Published: March 2023

AbstractTuberculosis, a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), remains as one of the biggest threats to public health worldwide. The purpose of this study is to investigate the impact of different screening criteria of the index cases on epidemiological estimates in the tuberculosis (TB) household contact study. Six different screening criteria were designed based on whether the index cases were adults and lived in the crowded environment, as well as their sputum smear and culture test results. Logistic regression was performed to determine the risk factors of TB. We found that gender, HIV-infection, smoking, malnutrition and diabetes were associated with Mtb infection. We also found significant differences of epidemiological estimates among observation groups screened by different criteria. The number of infections were relatively higher in the studies where index cases were screened as positive sputum smear and living in the crowded environment, indicating that index cases with positive sputum smear and live with more than two contacts in one room were likely to be more infectious in the household. Therefore, it is suggested that screening and treatment should be strengthened for those designs so that transmission of Mtb infection in the household can be reduced.
A Pilot Randomized Trial of Combined Cognitive-Behavioral Therapy and Exercise Training Versus Exercise Training Alone for the Management of Chronic Insomnia in Obstructive Sleep Apnea
Authors: Cammalleri Amanda , Perrault Aurore A. , Hillcoat Alexandra , Carrese-Chacra Emily , Tarelli Lukia , Patel Rahul , Baltzan Marc , Chouchou Florian , Dang-Vu Thien Thanh , Gouin Jean-Philippe , Pepin Veronique 
Published: March 2023

AbstractRationaleAmong individuals with obstructive sleep apnea, about 38% will present with comorbid chronic insomnia. Comorbid chronic insomnia and obstructive sleep apnea (COMISA) is associated with poorer daytime functioning and increased morbidity compared to either disorder alone. The treatment of insomnia among individuals with COMISA is suboptimal.ObjectivesTo assess the effects of an exercise-training intervention alone as well as a combined cognitive behavioral therapy and exercise training on insomnia symptoms in individuals with COMISA.MethodsIn a pilot randomized-controlled trial, 19 individuals with COMISA were allocated to one of two arms, each comprising of 2 phases of 8 weeks. The first phase examined the effects of exercise training versus relaxation training on insomnia severity and cardiorespiratory fitness. The second phase compared changes in Insomnia Severity Index (ISI) following exercise training alone (EX) or combined Cognitive Behavioural Therapy for Insomnia and exercise training (CBTi-EX). Self-reported insomnia severity, objective sleep parameters during overnight polysomnography, and cardiopulmonary fitness were collected at baseline, 8 and 16 weeks.ResultsExercise training increased VO2peakand reduced insomnia severity (Hedges’g= 0.82) when compared to relaxation training. Moreover, combined CBTi and exercise training yielded a larger improvement in insomnia severity (Hedges’g=1.48) than exercise training alone (EX). We observed no change in objective sleep measures in both groups.ConclusionsExercise training leads to moderate improvements in insomnia severity in individuals with COMISA. Combining exercise training with CBTi leads to larger reductions in insomnia symptoms, with effect sizes similar to the effects of CBTi alone in other populations with chronic insomnia.Clinical Trial information“Cognitive behavioural therapy combined with exercise training for adults with both insomnia and obstructive sleep apnea” - (https://doi.org/10.1186/ISRCTN63989489)