bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroblastic Tumor Recurrence Associated With Opsoclonus Myoclonus Ataxia Syndrome Relapse a Decade After Initial Resection and Treatments
Authors: Bacchus Micky K. , Anderson David S. , Berko Esther R. , States Lisa J. , Bagatell Rochelle , Hopkins Sarah E. , Batra Vandana
Published: March 2023

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors.
Significance of CEBPE Gene Promoter Polymorphism (Rs2239630 G > A) Assessment in Childhood B-cell Acute Lymphoblastic Leukemia
Authors: Aref Salah , El-Ghonemy Mohamed , Shimaa Hendawy , Darwish Ahmad , Abdelmabood Suzy , Khaled Nada
Published: March 2023

Background:

A significant association has been reported between CEBPE gene promoter polymorphisms (rs2239630 G > A) and the incidence of B-cell acute lymphoblastic leukemia (B-ALL). However, no previous study on this issue has been included among the Egyptian cohort of pediatric patients with B-ALL. Therefore, this study was designed to address the associations between CEBPE polymorphisms and susceptibility to B-ALL, as well as its impact on the outcome of B-ALL Egyptian patients with B-ALL.

Patients and Methods:

In the current study, we evaluated the rs2239630 polymorphism in 225 pediatric patients and 228 controls to assess the association of different rs2239630 genotypes with childhood susceptibility to B-ALL and the impact on the outcome of the patients.

Results:

The frequency of the A allele was significantly higher in the cases of B-ALL compared with the control group (P = 0.004). By analyzing different genotypes for the predictive value of disease development, the GA and AA genotypes have been identified to be the highest among multivariate factors with an odds ratio of 3.330 (95% CI: 1.105-10.035). Likewise, the A allele was significantly associated with the shortest overall survival.

Conclusions:

CEBPE gene promoter polymorphism (rs2239630 G > A) AA is frequently associated with B-ALL; and has the worst overall survival among the 3 genotypes, followed by the GA and GG genotypes (P < 0.001)
Do We Need a Strictly Lateral Radiograph for Fracture Management of Forearm Buckle Fractures in Children?
Authors: Harbrecht Andreas , Hackl Michael , Leschinger Tim , Krane Felix , Müller Lars P. , Wegmann Kilian
Published: March 2023

Objectives

Buckle fractures of the distal forearm are a common fracture entity in children treated conservatively. Diagnostics primarily include radiographs in 2 planes. Inadequate images may occur in the mostly very young patients. Therefore, additional lateral radiographs are often obtained to assess a possible angular tilt. The aim of this study is to investigate whether a strictly lateral x-ray image has an influence on fracture management.

Methods

Seventy-three children with buckle fractures of the distal forearm were included in this retrospective analysis. All cases were analyzed by quality of radiographs, necessity to obtain an additional lateral radiograph, and what influence on fracture management resulted. Follow-up was performed 2 to 4 weeks after immobilization.

Results

Thirty-five girls and 38 boys with a mean age of 7.16 years were included; 40 had fractured right and 33 had fractured left arms, respectively. Isolated distal radius fractures occurred in 48 cases, isolated distal ulna fractures in 6 cases, and both bones in 19 cases. Initial radiographic images were evaluated as inadequate in 25 cases. In each of those cases, an additional lateral image was obtained by fluoroscopy without resulting in an alternated fracture management protocol, which was chosen conservatively in each case and resulted in excellent clinical outcome at follow-up examination.

Conclusions

Based on our results, the acquisition of additional lateral radiographs seems to be unnecessary in the diagnostic procedure of buckle fractures of the distal forearm, in case a possible palmar or dorsal angulation cannot be entirely assessed on the initial set of radiographs. An additional lateral image had no influence on fracture management, which was chosen conservatively in every case and led to excellent clinical results.

Level of evidence: level III.
Methodological Issues Relevant to Blinding in Physical Medicine and Rehabilitation Research
Authors: Annaswamy Thiru , Cunniff Kegan , Rizzo JR , Naeimi Tahereh , Kumbhare Dinesh , Batavia Mitchell
Published: March 2023

Blinding in research is important and the field of PM&R poses special consideration due to the patient populations and treatment methodologies used. Historically, blinding has been increasingly relevant to conducting good quality research. The main reason to blind is to reduce bias. There are several strategies to blinding. At times, when blinding is not possible, alternatives to blinding include sham control and description of study and control groups. Illustrative examples of blinding used in PM&R research are described in this article along with how to assess success and fidelity of blinding.
Comparison Clinical Effects of Hypertonic Dextrose and Steroid Injections on Chronic Subacromial Bursitis: A Double-Blind Randomized Controlled Trial
Authors: Lin Lien-Chieh , Lee Yu-Hao , Chen Yi-Wen , Hsu Tzu-Herng , Vitoonpong Timporn , Liou Tsan-Hon , Huang Shih-Wei
Published: March 2023

Objective

To determine and compare the treatment efficacy of subacromial steroid injections and dextrose prolotherapy (DPT) for chronic subacromial bursitis patients.

Design

54 patients with chronic subacromial bursitis were enrolled in this double-blind randomized controlled trial. Shoulder pain and disability index (SPADI) and visual analog scale (VAS) were the primary outcomes.

Results

The steroid group (n = 26) exhibited significant VAS score improvements comparing to baseline at weeks 2, 6, and 12; the DPT group (n = 28) exhibited VAS score improvements at weeks 6, and 12. The steroid group displayed significant SPADI score improvements compared to baseline at weeks 2, 6, and 12, the DPT group exhibited significant score decreases at weeks 2, and 6. Compared with the DPT group, the steroid group demonstrated significantly greater decreases in VAS scores at weeks 2, and 6; the steroid group showed significantly greater decreases in SPADI scores at weeks 2, 6, and 12.

Conclusion

Both hypertonic DPT and steroid injections can provide short-term improvements of pain and disability among chronic subacromial bursitis patients. Moreover, steroid injections showed better effectiveness than hypertonic DPT in ameliorating pain and improving function.
Artifact Reduction From Dental Material in Photon-Counting Detector Computed Tomography Data Sets Based on High-keV Monoenergetic Imaging and Iterative Metal Artifact Reduction Reconstructions—Can We Combine the Best of Two Worlds?
Authors: Risch Franka , Decker Josua A. , Popp Daniel , Sinzinger Andrea , Braun Franziska , Bette Stefanie , Jehs Bertram , Haerting Mark , Wollny Claudia , Scheurig-Muenkler Christian , Kroencke Thomas J. , Schwarz Florian
Published: March 2023

Objective

The aim of this study was to compare the effectiveness of common strategies for artifact reduction of dental material in photon-counting detector computed tomography data sets.

Materials and Methods

Patients with dental material who underwent clinically indicated CT of the neck were enrolled. Image series were reconstructed using a standard and sharp kernel, with and without iterative metal artifact reduction (IMAR) (Qr40, Qr40IMAR, Qr60, Qr60IMAR) at different virtual monoenergetic imaging (VMI) levels (40–190 keV). On representative slice positions with and without dental artifacts, mean and standard deviation of CT values were measured in all series at identical locations. The mean absolute error of CT values (

) and the artifact index (AIX) were calculated and analyzed focusing on 3 main comparisons: (a) different VMI levels versus 70 keV, (b) standard versus sharp kernel, and (c) nonuse or use of IMAR reconstruction. The Wilcoxon test was used to assess differences for nonparametric data.

Results

The final cohort comprised 50 patients. Artifact measures decreased for VMI levels >70 keV, yet only significantly so for reconstructions using IMAR (maximum reduction, 25%). The higher image noise of the sharp versus standard kernel is reflected in higher AIX values and is more pronounced in IMAR series (maximum increase, 38%). The most profound artifact reduction was observed for IMAR reconstructions (maximum reduction

: 84%; AIX: 90%).

Conclusions

Metal artifacts caused by large amounts of dental material can be substantially reduced by IMAR, regardless of kernel choice or VMI settings. Increasing the keV level of VMI series, on the other hand, only slightly reduces dental artifacts; this effect, however, is additive to the benefit conferred by IMAR reconstructions.
The Downside of Botulinum Injections for Anterocollis: A Case Series and a Review of the Literature
Authors: Yahalom Gilad , Atlan Eden , Janah Amir , Dominko Melania , Israel Ilana , Rajz Gustavo , Mausbach Stefan , Eichel Roni
Published: March 2023

Objectives

This is a case series and a review of the literature of therapeutic outcomes of botulinum toxin (BT) injections for anterocollis.

Methods

Data collected included gender, age, age at onset, muscles targeted, and doses injected. Routine forms were filled out during each visit: Patient Global Impression of Change, Clinician Global Impression of Severity, Tsui scale. The effect duration and side effects (SEs) of the previous treatment were noted.

Results

We described 4 patients (3 men, 13 visits) with anterocollis, as primary postural abnormality of the neck, emphasizing the therapeutic response to BT injection. Mean age at onset was 75.3 ± 7.0 years, age at first injection was 80.7 ± 3.5 years. The mean total dose per treatment was 290.0 ± 95.6 units. Patient Global Impression of Change with any grade of favorable effect was reported in 27.3% of the treatments. In objective assessment, Global Impression of Severity and Tsui scores did not show a consistent tendency of improvement. Neck weakness was prevalent in 18.2% of the visits of the anterocollis group while no other SEs were noted. We found 15 articles describing experience with BT for anterocollis in 67 patients (19 in deep and 48 in superficial neck muscles).

Conclusions

This case series describes the poor outcome of BT treatment for anterocollis, with low efficacy and bothersome SE. Levator scapulae injection for anterocollis is not effective and is highly associated with head drop and should perhaps be abandoned. Injection to the longus colli might give some benefit in non-responders.
Influences on policy-formulation, decision-making, organisation and management for maternal, newborn and child health in Bangladesh, Ethiopia, Malawi and Uganda: the roles and legitimacy of a multi-country network
Authors: Akter Kohenour , Shawar Yusra Ribhi , Tesfa Anene , Daniels-Howell Callie , Seruwagi Gloria , Kyamulabi Agnes , Dube Albert , Gonfa Geremew , Mwaba Kasonde ,   QCN Evaluation Group, Kinney Mary , English Mike , Shiffman Jeremy , Djellouli Nehla , Colbourn Tim
Published: March 2023

The Network for Improving Quality of Care for Maternal, Newborn and Child Health (QCN) is intended to facilitate learning, action, leadership and accountability for improving quality of care in member countries. This requires legitimacy—a network’s right to exert power within national contexts. This is reflected, for example, in a government’s buy-in and perceived ownership of the work of the network.

During 2019– 2022 we conducted iterative rounds of stakeholder interviews, observations of meetings, document review, and hospital observations in Bangladesh, Ethiopia, Malawi, Uganda and at the global level. We developed a framework drawing on three frameworks: Tallberg and Zurn which conceptualizes legitimacy of international organisations dependent on their features, the legitimation process and beliefs of audiences; Nasiritousi and Faber, which looks at legitimacy in terms of problem, purpose, procedure, and performance of institutions; Sanderink and Nasiritousi, to characterize networks in terms of political, normative and cognitive interactions. We used thematic analysis to characterize, compare and contrast institutional interactions in a cross-case synthesis to determine salient features.

Political and normative interactions were favourable within and between countries and at global level since collective decisions, collaborative efforts, and commitment to QCN goals were observed at all levels. Sharing resources and common principles were not common between network countries, indicating limits of the network. Cognitive interactions—those related to information sharing and transfer of ideas— were more challenging, with the bi-directional transfer, synthesis and harmonization of concepts and methods, being largely absent among and within countries. These may be required for increasing government ownership of QCN work, the embeddedness of the network, and its legitimacy.

While we find evidence supporting the legitimacy of QCN from the perspective of country governments, further work and time are required for governments to own and embed the work of QCN in routine care.
Mendelian randomization study of diabetes and dementia in the Million Veteran Program
Authors: Litkowski Elizabeth M , Logue Mark W , Zhang Rui , Charest Brian R , Lange Ethan M , Hokanson John E , Lynch Julie A , Vujkovic Marijana , Phillips Lawrence S , Hauger Richard L , Lange Leslie A , Raghavan Sridharan
Published: March 2023

Structured Abstract

INTRODUCTION

Diabetes and dementia are diseases of high healthcare burden worldwide. Individuals with diabetes have 1.4 to 2.2 times higher risk of dementia. Our objective was to evaluate evidence of causality between these two common diseases.

METHODS

We conducted a one-sample Mendelian randomization (MR) analysis in the U.S. Department of Veterans Affairs Million Veteran program. The study included 334,672 participants ≥65 years of age with type 2 diabetes and dementia case-control status and genotype data.

RESULTS

For each standard deviation increase in genetically-predicted diabetes, we found increased odds of three dementia diagnoses in non-Hispanic White participants (all-cause: OR=1.07[1.05-1.08],P=3.40E-18; vascular: OR=1.11[1.07-1.15],P=3.63E-09, Alzheimer’s: OR=1.06[1.02-1.09],P=6.84E-04) and non-Hispanic Black participants (all-cause: OR=1.06[1.02-1.10],P=3.66E-03, vascular: OR=1.11[1.04-1.19],P=2.20E-03, Alzheimer’s: OR=1.12 [1.02-1.23],P=1.60E-02) but not in Hispanic participants (allP>.05).

DISCUSSION

We found evidence of causality between diabetes and dementia using a one-sample MR study, with access to individual level data, overcoming limitations of prior studies utilizing two-sample MR techniques.
Mpox vaccine and infection-driven human immune signatures
Authors: Cohn Hallie , Bloom Nathaniel , Cai Gianna , Clark Jordan , Tarke Alison , Bermúdez-González Maria C , Altman Deena , Lugo Luz Amarilis , Lobo Francisco Pereira , Marquez Susanna ,   PVI study group, Chen Jin-Qiu , Ren Wenlin , Qin Lili , Crotty Shane , Krammer Florian , Grifoni Alba , Sette Alessandro , Simon Viviana , Coelho Camila H.
Published: March 2023

Background

Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS’ immunogenicity and inform vaccine administration and design.

Methods

We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection.

Findings

Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection.

Interpretation

JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells.

Funding

Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.
Deep learning based phenotyping of medical images improves power for gene discovery of complex disease
Authors: Flynn Brianna I. , Javan Emily M. , Lin Eugenia , Trutner Zoe , Koenig Karl , Anighoro Kenoma O. , Kun Eucharist , Gupta Alaukik , Singh Tarjinder , Jayakumar Prakash , Narasimhan Vagheesh M.
Published: March 2023

Electronic health records (EHRs) are often incomplete and inaccurate, reducing the power of genome-wide association studies (GWAS). Moreover, the variables within these records are often represented in binary codes, masking variation in disease severity among individuals. For some diseases, such as knee osteoarthritis (OA), radiographic assessment is the primary means of diagnosis and can be performed directly from medical images. In this work, we trained a deep learning model (DL-binary) to ascertain knee OA cases from anteroposterior (AP) dual-energy absorptiometry (DXA) scans and achieved clinician level performance. Applying this model across 29,257 individuals from the UK Biobank (UKB), we identified 2,603 (240%) more cases than currently diagnosed in the ICD-10 record. Individuals diagnosed as cases by DL-binary had higher rates of self-reported knee pain, knee pain for longer durations and with increased severity compared to control individuals. We trained another deep learning model to measure the minimum knee joint space width (mJSW), a quantitative phenotype linked to knee OA severity. Despite the DL-binary phenotype and mJSW being highly genetically correlated (92%), the heritability of mJSW was an order of magnitude greater than the ICD-10 code M17 or DL-binary phenotypes. In a GWAS run on mJSW, we identified 18 genome-wide significant loci, as opposed to 1 and 6 at the same sample size using either case-control (DL-binary and ICD-10 code M17) phenotype. This improved power also translated to better polygenic risk score (PRS) prediction for knee OA diagnosis in a holdout dataset of 371,686 individuals. We also show that reduced mJSW, but neither case-control phenotype is associated with increased risk of adult fractures, a leading cause of injury-related death in older individuals. For diseases with radiographic diagnosis, our results demonstrate the enormous potential for using deep learning to phenotype at biobank scale, both for improving power for gene discovery and for epidemiological analysis.
Cross-sectional analysis of Open payments for physicians at designated hemophilia centers in the US (2018-2020)
Authors: Haslam Alyson , Prasad Vinay
Published: March 2023

Introduction

Physicians who treat hemophilia, and especially directors at hemophilia centers, are in a position to be unduly influenced by payments from pharmaceutical companies who make costly hemophilia drugs. It is from this perspective that we analyzed payments made to physicians at hemophilia centers in the US, focusing on center directors.

Materials and methods

In a cross-sectional analysis we searched the CDC’s Hemophilia Treatment Center Directory for physicians (2022) and then abstracted general payments for physicians on Open Payments (2018-2020) and calculated one-year average payments. We searched academic websites to determine physician role (hemophilia center director, non-director, or non-center director).

Results

There were 420 physicians in the hemophilia physician directory – 270 physicians/professors, 103 directors of hemophilia centers, and 47 other directors. Directors of hemophilia centers had higher median one-year general payments, compared to other directors and physician/professors ($4910 vs $79 vs $87, respectively; p<0.0001). Takeda Pharmaceutical Company Limited, F-Hoffmann La Roche Ltd/Genentech, and Novo Nordisk have the largest hemophilia drug market share and were the three companies with the most payments to physicians.

Conclusions

High payments, especially among individuals who have responsibility over the success of hemophilia centers and clinics, may result in competition with the interest of the patients at these centers and clinics.
Rapid whole-brain high-resolution myelin water fraction mapping from extremely under-sampled magnetic resonance imaging data using deep neural network
Authors: Gong Zhaoyuan , Khattar Nikkita , Kiely Matthew , Triebswetter Curtis , Bouhrara Mustapha
Published: March 2023

Changes in myelination are a cardinal feature of brain development and the pathophysiology of several cerebral diseases, including multiple sclerosis and dementias. Advanced magnetic resonance imaging (MRI) methods have been developed to probe myelin content through the measurement of myelin water fraction (MWF). However, the prolonged data acquisition and post-processing times of current MWF mapping methods pose substantial hurdles to their clinical implementation. Recently, fast steady-state MRI sequences have been implemented to produce high spatial resolution whole-brain MWF mapping within ∼ 20 min. Despite the subsequent significant advances in the inversion algorithm to derive MWF maps from steady-state MRI, the high-dimensional nature of such inversion does not permit further reduction of the acquisition time by data under-sampling. In this work, we present an unprecedented reduction in the computation (∼ 30 s) and the acquisition time (∼ 7 min) required for whole-brain high-resolution MWF mapping through a new Neural Network (NN)-based approach, named: Relaxometry of Extremely Under-SamplEd Data (NN-REUSED). Our analyses demonstrate virtually similar accuracy and precision in derived MWF values using the NN-REUSED approach as compared to results derived from the fully-sampled reference method. The reduction in the acquisition and computation times represents a breakthrough toward clinically practical MWF mapping.
Efficacy and Safety of Cannabis Transdermal Patch for Alleviating Psoriasis Symptoms: Protocol for a Randomized Controlled Trial (CanPatch)
Authors: Sermsaksasithorn Pim , Asawanonda Pravit , Phutrakool Phanupong , Ondee Thunnicha , Chariyavilaskul Pajaree , Payungporn Sunchai , Pongpirul Krit , Hirankarn Nattiya
Published: March 2023

Background

Existing topical psoriasis treatments are partially effective or have long-term side effects for a proportion of people with psoriasis; therefore, effective and safe treatment options are required. Cannabidiol, a cannabinoid inCannabis sativa, reverses the etiology of psoriasis through skin receptors according to in vitro research. Cannabidiol transdermal patches may be an effective treatment for psoriasis, although the efficacy and safety data are limited.

Methods and analysis

This is a randomized double-blind controlled trial comparing cannabidiol (CBD) with minimal tetrahydrocannabinol (THC) patches with placebo patches (1:1 ratio) daily applied to comparable lesions of each patient with mild to moderate plaque-type psoriasis performed in a university hospital in Thailand (n=60). The primary outcome is the local psoriasis severity index (LPSI). The local severity index of psoriasis, the itch score using the visual analog scale, and adverse events will be evaluated on day 0, 30, 60, and 90 of the study. Furthermore, on days 0 and 90 of this study, biological samples will be taken for the evaluation of the skin, gut, and mouth microbial profile of 50% of randomly selected individuals.

Conclusions

This study aims to investigate the efficacy and safety of cannabidiol transdermal patches in alleviating the symptoms of psoriasis. We will also examine personal impacts on the efficacy and safety of patches, such as the microbial profile. The results of this study may highlight a novel topical treatment option that reduces suffering in patients with psoriasis.

Ethics and dissemination

This study was registered with the. The protocol is being considered by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University. The results of this study will be faithfully presented through conferences or published articles.
Application of deep learning to classify skeletal growth phase on 3D radiographs
Authors: Ameli Nazila , Lagravere Manuel , Lai Hollis
Published: March 2023

Cervical 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 Summary

The 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

BACKGROUND

Biallelic 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 OBJECTIVES

We 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.

PARTICIPANTS

Severely 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 MEASURES

Weight, 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.

RESULTS

We 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.

CONCLUSIONS

Children 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

Background

Distinguishing 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.

Methods

We 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.

Results

Our 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.

Conclusion

We 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 messages

Latent 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

The 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

Evolutionary 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

N-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

Argonaute 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

Background

Difficulties 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.

Methods

We 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.

Results

The 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).

Conclusion

Our 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

Tuberculosis, 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.