bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Accuracy and Completeness of Artificial Intelligence Responses Against Established Otology Guidelines
Authors: Rossi Nicholas A. , Corona Kassandra K. , Yoshiyasu Yuki , Young Dayton L. , McKinnon Brian J.
Published: August 2024

Background:

The incorporation of artificial intelligence (AI), especially large language models like Generative Pretrained Transformer 4 (GPT-4), into medical practice is a burgeoning field of interest. This research evaluates the applicability of GPT-4 in otology by analyzing its responses to queries based on otologic clinical practice guidelines.

Methods:

Key guidelines from otology were selected, and corresponding questions were formulated to examine GPT-4’s interpretation and response accuracy. Two independent reviewers assessed the AI-generated answers for accuracy and completeness, using a structured Likert scale. A re-evaluation was conducted to evaluate the reproducibility of the results.

Results:

The analysis showed a high accuracy level (mean score: 4.75 of 5) and completeness (mean score: 2.88 of 3) in GPT-4’s responses. The interrater agreement, as indicated by Cohen κ, was substantial. GPT-4 consistently advised on individualized treatment plans and professional consultation, particularly for guidelines with weaker evidence, demonstrating its cautious approach to handling medical information.

Conclusion:

GPT-4 exhibits promising potential as an auxiliary tool in otology, providing accurate and comprehensive information. However, its role should be viewed as supplementary, with emphasis on continual updates and careful monitoring to align with evolving medical knowledge. Future studies are recommended to further explore the depth of AI application in diverse clinical scenarios and its real-time impact on clinical outcomes.
Sleep Duration, Insomnia, and Associated Factors Among Ukrainians 1 Year After Russia’s Full-Scale Invasion
Authors: Wang Shanshan , Hicks Madelyn Hsiao-Rei , Barrett Emily , Martsenkovskyi Dmytro , Holovanova Irina , Marchak Olga , Ishchenko Liudmyla , Fiedler Nancy , Haque Ubydul
Published: August 2024

Objective

We aimed to investigate the prevalence of sleep disturbances and associated factors among Ukrainians 1 year after Russia’s full-scale invasion.

Methods

Quota sampling was used to collect online survey data from 2364 adults living in Ukraine aged 18 to 79 years from April 5, 2023, to May 15, 2023. Short sleep duration was defined as sleep duration ≤6 hours and long sleep duration as ≥9 hours. Insomnia was assessed by the Insomnia Symptom Questionnaire.

Results

The prevalences of short sleep duration, long sleep duration, and insomnia were 39.4%, 6.9%, and 38.5%, respectively. Short sleep duration and insomnia were both more likely in females (short sleep duration: adjusted odds ratio [aOR] = 1.44; insomnia: aOR = 2.17), individuals with depression (short sleep duration: aOR = 1.61; insomnia: aOR = 7.76), affected by the 2014 Russian invasion (short sleep duration: aOR = 1.37; insomnia: aOR = 1.78), and with more trauma events (short sleep duration: quartile 3 [Q3] versus Q1: aOR = 1.88; Q4 versus Q1: aOR = 1.83; insomnia: Q3 versus Q1: aOR = 2.14; Q4 versus Q1: aOR = 2.32). Insomnia was more likely in Ukrainians with posttraumatic stress disorder (aOR = 2.95), anxiety (aOR = 4.57), and loneliness (aOR = 1.67). Essential public service was associated with short sleep duration (aOR = 1.64). Short sleep duration and insomnia were associated with lower quality of life in physical, psychological, and environmental domains. Insomnia was associated with the social relationships domain.

Conclusions

Sleep health among Ukrainian adults 1 year into the war is concerning, with more than one-third reporting inadequate sleep or insomnia. More studies are needed on impacts and interventions for sleep health during and after the war.
Neonatal Hair Cortisol and Birth Outcomes: An Empirical Study and Meta-Analysis
Authors: Deer LillyBelle K. , Demers Catherine H. , Hankin Benjamin L. , Doom Jenalee R. , Shields Grant S. , Hoffman M. Camille , Davis Elysia Poggi
Published: August 2024

Objective

Prenatal stress physiology is often posited as a predictor of birth outcomes, including gestational age at birth and birthweight. However, research has predominantly relied on indicators in the maternal system, with few studies examining hormones of the fetal system. The current study focuses on fetal cortisol in the third trimester, as measured in neonatal hair, as a biological factor that might be associated with birth outcomes (gestational age at birth and birthweight). We report findings from two studies: a longitudinal cohort (Study 1), and a meta-analysis of the existing literature (Study 2).

Methods—Study 1

Hair was collected for cortisol analysis from 168 neonates (55.95% female) shortly after birth. Gestational age at birth and birthweight were abstracted from medical records.

Methods—Study 2

An exhaustive search of four databases was conducted, yielding 155 total studies for screening. Papers reporting neonatal hair cortisol (collection <2 weeks postpartum) and birth outcomes among human neonates were retained for analysis, including Study 1 results (k = 9).

Results—Study 1

Higher neonatal hair cortisol was related to longer gestation (r = 0.28, p < .001) and higher birthweight, r = 0.16, p = .040. Sex did not moderate either association.

Results—Study 2

Across the nine studies, higher neonatal hair cortisol predicted both longer gestation (r = 0.35, p < .001, 95% confidence interval = 0.24–0.45) and higher birthweight (r = 0.18, p = .001, 95% confidence interval = 0.07–0.28). Neonatal sex did not moderate these associations.

Conclusions

Fetal cortisol exposure in the third trimester plays a role in normative maturation of the fetus, and findings reveal that higher cortisol is associated with positive birth outcomes.
Mediators of a Mindfulness-Based Intervention for Younger Breast Cancer Survivors: Effects on Depressive Symptoms
Authors: Korecki J Richard T. , Ganz Patricia A. , Partridge Ann H. , Wolff Antonio C. , Petersen Laura , Crespi Catherine M. , Bower Julienne E.
Published: August 2024

Objective

Depression is associated with poor outcomes in breast cancer patients, with higher prevalence among younger women. Although mindfulness-based interventions (MBIs) have demonstrated therapeutic effects, the mechanisms of intervention effects are poorly understood. We investigated whether rumination, self-kindness, intrusive thoughts about cancer, cancer-related worry, or a sense of meaning and peace mediated the intervention effects of an MBI, Mindful Awareness Practices (MAPs), on depressive symptoms. Additionally, we explored the same variables as mediators of a psychoeducation program, Survivorship Education (SE).

Methods

Women diagnosed with stage 0–III breast cancer at age <50 years were randomized to 6 weeks of MAPs (n = 85), SE (n = 81), or wait-list control (WLC; n = 81). During preintervention, postintervention, and 6-month follow-up (FU), we assessed depressive symptoms, rumination, self-kindness, intrusive thoughts, worry, and meaning and peace.

Results

MAPs and SE significantly reduced depressive symptoms at postintervention, and reductions remained through 6-month FU for MAPs. Models revealed that reductions in rumination (β = −0.68, 95% confidence interval [CI] = −1.64 to −0.07) and intrusive thoughts (β = 1.17, 95% CI = −2.17 to −0.37) and improvements in self-kindness (β = −1.09, 95% CI = −2.37 to −0.28) and meaning and peace (β = −1.09, 95% CI = −3.16 to −0.56) mediated MAPs’ effects at all time points. Reductions in worry (β = −1.34, 95% CI = −2.47 to −0.45]) mediated effects at postintervention only. Worry and intrusive thoughts mediated SE effects at postintervention and 6-month FU, respectively.

Conclusions

Findings identified depression-relevant mediators of MAPs’ effects, expanding the understanding of MBI mechanisms. Results highlight pathways that could be leveraged to optimize intervention outcomes.

Trial Registration

ClinicalTrials.gov identifier: NCT03025139.
Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia
Authors: Nie Dong-Lei , Shi Yan-Hong , Li Xin-Min , Wang Xiao-Jiang , Han Bao-Li , Zhang Guo-Fu
Published: August 2024

Purpose:

To investigate the clinical and radiographic features of PNLH and the relationship with pathologic features.

Materials and Methods:

A total of 11 patients in whom PNLH was confirmed in our department were retrospectively studied. The clinical and radiographic features were extracted and analyzed, and we also discussed the relationship between radiologic and pathologic features.

Results:

Of the 11 patients with PNLH, 5 were discovered incidentally, while 4 presented with chest symptoms. Laboratory tests showed no specificity and the lesions were located under the pleura with an adjacent pleural indentation. Most lesions were solid, with some showing signs of spiculation or spiculate protuberance. In some cases, hypodense areas and vocules were visible. The enhanced scan showed marked enhancement, but most had no lymph node enlargement, and there was no pleural effusion.

Conclusions:

The clinical manifestations of PNLH are nonspecific and the imaging features overlap with those of malignant lung tumors, and the diagnosis depends on pathologic examination.
Scalp Reconstruction With Free Tissue Transfer Using Descending Branch of Lateral Circumflex Femoral Vessels as Interposition Graft
Authors: Kim Rah Yoon , Lee Chang Jun , Baek Sang Oon
Published: August 2024

Despite the rich blood supply to the scalp, postoperative skin necrosis at the surgical site sometimes occurs, and unresolved defects often present a significant challenge for the surgeon. When planning a free flap for scalp reconstruction, distant anastomoses may be necessary if local recipient vessels are unavailable due to previous surgery. This study presents the authors' treatment strategy, which includes extending the pedicle length with arteriovenous bundle interposition grafts. Two patients who experienced surgical wound necrosis after bypass surgery for moyamoya disease underwent reconstruction for skin and soft tissue coverage. To evaluate the altered anatomical structures after the previous surgery, three-dimensional computed tomography angiography was performed, and preoperative photos were taken to accurately measure the expected defect. The surgical strategy was designed to accommodate their unique conditions, utilizing an arteriovenous interposition graft, which included 2 stages of microvascular anastomoses, for pedicle lengthening. The procedure successfully bridged the gap between distant recipient vessels and the extensive defect, and the wounds healed without major complications such as venous congestion or total flap loss. Both patients were satisfied with the surgical outcomes. Arteriovenous bundle interposition grafts can be a useful option for patients with complex scalp defects who lack local recipient vessels. The use of an anterolateral thigh flap with artery-to-artery anastomosis, utilizing the lateral circumflex femoral artery from the opposite side in this study, offers many advantages compared with traditional pedicle lengthening tools utilizing vein-to-artery anastomosis.
Revolutionizing Adult Micrognathia Treatment: Should Free Fibular Flap Become an Option?
Authors: Atmodiwirjo Parintosa , Bangun Kristaninta , Amanda Nadira F. , Djohan Michael
Published: August 2024

The management of micrognathia in adults necessitates intricate surgical procedures. A vascularized bone graft, notably the free fibular flap (FFF), offers a novel viable solution for repairing significant defects. However, the limited utilization of FFF in adult micrognathia contributes to gaps in understanding its outcomes. A retrospective case series of 2 patients aged 28 and 65, with severe micrognathia due to neglected trauma and osteoradionecrosis, underwent refracture and reconstruction with FFF. Intraoperatively, no significant complications occurred. The FFF were molded to fit the gaps of refractured mandible sites, with similar surgical approaches for both patients. Upon 3 months' follow up, their quality of life (QoL), structural changes, and sensation alterations were assessed and showed promising results. The sensory impairment caused did not hinder the quality of life. Thus, the free fibular flap demonstrates promising outcomes as the initial treatment for adult micrognathia, yielding minimal morbidities and significant functional and anatomic improvements.
Early Bone and Suture Reformations in Different Cranial Regions After Cranial Vault Remodeling for Sagittal Craniosynostosis
Authors: Chaisrisawadisuk Sarut , Phakdeewisetkul Kantapat , Sirichatchai Kanin , Hammam Elie , Prasad Vani , Moore Mark H.
Published: August 2024

Cranial vault remodeling (CVR) is a common procedure for correcting sagittal craniosynostosis. Some approaches leave significant craniectomy defects. The authors investigated the reosteogenesis in different cranial defect areas after CVR. A cross-sectional study was conducted in nonsyndromic sagittal craniosynostosis. Available early postoperative computed tomography (CT) scans were analyzed. The segmentation of three-dimensional reconstructed images was performed. Different cranial defect areas, including coronal, vertex, and occipital regions, were further investigated using an automated three-dimensional analysis software for reosteogenesis percentage. Forty-four CT scans were included. The average age at CVR was 8.8 months. The median time of postoperative CT scans was 6.1 weeks. The median bone reformation percentage of the entire cranial defect was 56.7%. Given the similar postoperative CT timing, the median bone reformation at the coronal, vertex, and occipital areas demonstrated 44.21%, 41.13%, and 77.75%, respectively (P < 0.001). In the simultaneously removed coronal and lambdoid sutures, there were 45% with coronal and lambdoid sutures reformation, followed by lambdoid suture reformation alone, no suture reformation and coronal reformation alone in 35%, 20%, and 0%, respectively (P = 0.013). There was no coronal reformation in the removed coronal suture group. However, 40% demonstrated lambdoid suture reformation after the isolated lambdoid suture removal. The occipital region has the highest reosteogenesis compared with the other cranial defects after CVR in nonsyndromic sagittal craniosynostosis. Within the removed previous patent sutures, the lambdoid suture reformation showed a higher rate than the coronal suture.
Assessing Long-Term Postoperative Resorption in Mandibular Block Cortical Grafts for Facial Asymmetry Correction: A Retrospective Investigation
Authors: Pang Wanyu , Chen Kai , Wu Guomin
Published: August 2024

Objective:

To evaluate the long-term postoperative resorption of the graft mandibular block cortical graft and identify the resorption site following free transplantation into the contralateral mandible.

Methods:

In this study, individuals aged 18 years or older with facial asymmetry deformity who underwent free grafting of the mandibular block cortical graft were included. Postoperative computed tomography (CT) data were collected at predetermined intervals. The degree of graft bone absorption postoperatively was quantitatively evaluated using the equation Absorptivity=(VTn-VT0)/VT0 ×100%. The resorption site was qualitatively assessed through a color-coded distance map.

Results:

Postoperative analysis revealed partial absorption of the transplanted mandibular block cortical graft in the contralateral mandible, predominantly at the lower and posterior mandibular margins. The average decrease of 29.9±6.37% (paired t test, P<0.01).

Conclusion:

The utilization of mandibular block cortical grafts in correcting facial asymmetry results in a low absorption rate and a stable absorption situation, rendering it a safe and effective technique.
Simulation as Proof of Concept to Assess the Feasibility and Address Uncertainties Regarding Cardiopulmonary Resuscitation in an Adolescent Patient With Viral Hemorrhagic Fever
Authors: Nawathe Pooja , Garland Jennifer , Cuzzolina Jennifer , Salinas Nancy , Dodd Brett , Grein Jonathan
Published: August 2024

Introduction

While general management guidelines exist for patients with viral hemorrhagic fevers (VHF), uncertainty surrounds the extent to which critical care interventions should be provided. There has been significant concern in providing cardiopulmonary resuscitation (CPR) to a patient with VHF due to concerns regarding CPR efficiency and the safety of the healthcare team. However, data on CPR feasibility, efficiency, and latent safety threats (LSTs) to the healthcare team in patients with VHF needing CPR are lacking. Our team proactively studied this in the simulation environment as the first step to guiding evidence-based and ethically informed decisions about CPR for these patients.

Methods

We studied CPR metrics, times to critical interventions, and LSTs using systems-focused debriefing in an adolescent patient with VHF who had pulseless electrical activity. This exercise included 3 members inside the patient room in full PPE and special pathogens team members in modified PPE outside the room.

Results

We found that CPR is feasible in full PPE. The chest compression fraction was 72%, with an average manual rate of 129 compressions per minute and an average manual depth of 2.1 inches. We identified multiple LSTs in the debriefing and video analysis.

Conclusions

This simulation study showed that CPR in a patient with VHF is possible in full PPE with a minimum of 3 team members. However, we identified physical and psychological LSTs with the systems-focused debriefing. Therefore, refining roles and responsibilities would be necessary to improve the safety of the healthcare team and improve the quality of CPR.
DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women
Authors: Al-darsani Zeinah , Banack Hailey R. , Ziegler Mallory N. , Rapp Stephen R. , Corrada Maria M. , Odegaard Andrew O.
Published: August 2024

Background:

This study extends prior research from the MRI substudy of the Women’s Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat.

Methods:

The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.6]) enrolled in WHIMS-MRI who had undergone DXA scans. DXA scans were completed at years 0, 3, and 6, and MRI scans were conducted ~8 years after baseline. Adjusted linear regression models were used to analyze the association between adiposity averaged across the 3-time points and volumes of brain regions previously linked to dementia.

Results:

Higher levels of total body fat, TAT, VAT, SAT, gynoid, and overall leg fat were associated with larger hippocampal volume (β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12], respectively). No other significant associations were observed.

Conclusion:

Higher levels of adiposity were positively associated with hippocampal volume. Additional research with larger sample sizes is needed to ascertain the significance of this association.
MRI for the diagnosis of limb girdle muscular dystrophies
Authors: Bolano-Díaz Carla , Verdú-Díaz José , Díaz-Manera Jordi
Published: August 2024

Purpose of review

In the last 30 years, there have many publications describing the pattern of muscle involvement of different neuromuscular diseases leading to an increase in the information available for diagnosis. A high degree of expertise is needed to remember all the patterns described. Some attempts to use artificial intelligence or analysing muscle MRIs have been developed. We review the main patterns of involvement in limb girdle muscular dystrophies (LGMDs) and summarize the strategies for using artificial intelligence tools in this field.

Recent findings

The most frequent LGMDs have a widely described pattern of muscle involvement; however, for those rarer diseases, there is still not too much information available. patients. Most of the articles still include only pelvic and lower limbs muscles, which provide an incomplete picture of the diseases. AI tools have efficiently demonstrated to predict diagnosis of a limited number of disease with high accuracy.

Muscle MRI continues being a useful tool supporting the diagnosis of patients with LGMD and other neuromuscular diseases. However, the huge variety of patterns described makes their use in clinics a complicated task. Artificial intelligence tools are helping in that regard and there are already some accessible machine learning algorithms that can be used by the global medical community.
Towards multimodal cognition-based treatment for cognitive impairment in Parkinson's disease: drugs, exercise, non-invasive brain stimulation and technologies
Authors: Mantovani Elisa , Bressan Miriana Maria , Tinazzi Michele , Tamburin Stefano
Published: August 2024

Purpose of review

Cognitive impairment is one of the most challenging non-motor symptoms of Parkinson's disease (PD) and may occur during all PD stages. There are no established pharmacological treatments for PD-related cognitive impairment, which may be improved by cognition-based interventions (i.e., cognitive stimulation, cognitive training, cognitive rehabilitation). Multimodal cognition-based interventions by adjunctive drugs, exercise, non-invasive brain stimulation and technologies may be effective in PD.

Recent findings

Exercise combined with cognitive training may enhance global, memory, visuospatial and executive functioning, transcranial direct current stimulation delivered alongside cognitive training may improve attention and executive functioning, and exergames, semi-immersive virtual reality (VR) and telerehabilitation plus non-immersive VR combined with cognitive training may ameliorate global and executive functioning in PD patients.

The evidence reviewed here, despite preliminary, is very encouraging and suggests strong rationale for combining pharmacological and non-pharmacological interventions with cognition-based treatments in PD. To overcome limitations of current studies, we propose some recommendations for future trials on drugs, exercise, non-invasive brain stimulation and technologies combined with cognition-based treatments for cognitive impairment in PD.
Overall constitutive properties of stratified lattices with alternating chirality
Authors: Bacigalupo Andrea , Badino Paolo , Diana Vito , Gambarotta Luigi
Published: August 2024

The present research focuses on a continuum description of stratified metamaterials achieved through the superposition of layers with alternating chirality. Each layer is constructed as a periodic assembly of centre-symmetric periodic cells, formed by a recurring arrangement of rigid circular discs connected by elastic ligaments. The layers are interconnected through elastic pins passing through the centres of aligned discs, allowing for either restrained or free relative rotation. A micropolar continuum model is used to describe each individual layer. The overall response of the metamaterials to in-plane forces is derived using a multi-field non-local model, expressed in terms of the average and difference of displacement and rotational fields. The overall micropolar and standard (Cauchy) constitutive tensors have been determined in closed form. The validity of the equivalent generalized micropolar model has been confirmed through comparison with discrete Lagrangian solutions of representative examples. In addition, a detailed analysis of a pseudo-indentation test has been carried out.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 2)’.
Local-to-non-local transition laws for stiffness-tuneable monoatomic chains preserving springs mass
Authors: Guarracino Flavia , Fraldi Massimiliano , Pugno Nicola M.
Published: August 2024

Recently, non-local configurations have been proposed by adding beyond nearest neighbour couplings among elements in lattices to obtain roton-like dispersion relations and phase and group velocities with opposite signs. Even though the introduction of non-local elastic links in metamaterials has unlocked unprecedented possibilities, literature models and prototypes seem neither to provide criteria to compare local and non-local lattices nor to discuss any related rules governing the transition between the two configurations. A physically reasonable principle that monoatomic one-dimensional chains must obey to pass from single- to multi-connected systems is here proposed through a mass conservation law for elastic springs thereby introducing a suitable real dimensionless parameter

α

to tune stiffness distribution. Therefore, the dispersion relations as a function of

α

and of the
degree of non-locality

P

are derived analytically, demonstrating that the proposed principle can be rather interpreted as a general mechanical consistency condition to preserve proper dynamics, involving the spring-to-bead mass ratio. Finally, after discussing qualitative results and deriving some useful inequalities, numerical simulations and two-dimensional FFTs are performed for some paradigmatic examples to highlight key dynamics features exhibited by chains with finite length as the parameters

α

and

P

vary.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 2)’.
Current developments in elastic and acoustic metamaterials science
Authors: Failla Giuseppe , Marzani Alessandro , Palermo Antonio , Russillo Andrea Francesco , Colquitt Daniel
Published: August 2024

The concept of metamaterial recently emerged as a new frontier of scientific research, encompassing physics, materials science and engineering. In a broad sense, a metamaterial indicates an engineered material with exotic properties not found in nature, obtained by appropriate architecture either at macro-scale or at micro-/nano-scales. The architecture of metamaterials can be tailored to open unforeseen opportunities for mechanical and acoustic applications, as demonstrated by an impressive and increasing number of studies. Building on this knowledge, this theme issue aims to gather cutting-edge theoretical, computational and experimental studies on elastic and acoustic metamaterials, with the purpose of offering a wide perspective on recent achievements and future challenges.

This article is part of the theme issue, ‘Current developments in elastic and acoustic metamaterials science (Part 2)’.
Selective dynamic band gap tuning in metamaterials using graded photoresponsive resonator arrays
Authors: Dal Poggetto V. F. , Urban D. , Nistri F. , Beoletto P. H. , Descrovi E. , Miniaci M. , Pugno N. M. , Bosia F. , Gliozzi A. S.
Published: August 2024

The introduction of metamaterials has provided new possibilities to manipulate the propagation of waves in different fields of physics, ranging from electromagnetism to acoustics. However, despite the variety of configurations proposed so far, most solutions lack dynamic tunability, i.e. their functionality cannot be altered post-fabrication. Our work overcomes this limitation by employing a photo-responsive polymer to fabricate a simple metamaterial structure and enable tuning of its elastic properties using visible light. The structure of the metamaterial consists of graded resonators in the form of an array of pillars, each giving rise to different resonances and transmission band gaps. Selective laser illumination can then tune the resonances and their frequencies individually or collectively, thus yielding many degrees of freedom in the tunability of the filtered or transmitted wave frequencies, similar to playing a keyboard, where illuminating each pillar corresponds to playing a different note. This concept can be used to realize low-power active devices for elastic wave control, including beam splitters, switches and filters.

This article is part of the theme issue ‘Current developments in elastic and acoustic metamaterials science (Part 2)’.
YTHDF1 mediates translational control by m6A mRNA methylation in adaptation to environmental challenges
Authors: Shi Zhuoyue , Wen Kailong , Zou Zhongyu , Fu Wenqin , Guo Kathryn , Sammudin Nabilah H , Ruan Xiangbin , Sullere Shivang , Wang Shuai , Zhang Xiaochang , Thinakaran Gopal , He Chuan , Zhuang Xiaoxi
Published: August 2024

Animals adapt to environmental challenges with long-term changes at the behavioral, circuit, cellular, and synaptic levels which often require new protein synthesis. The discovery of reversible N6-methyladenosine (m6A) modifications of mRNA has revealed an important layer of post-transcriptional regulation which affects almost every phase of mRNA metabolism and therefore translational control. Manyin vitroandin vivostudies have demonstrated the significant role of m6A in cell differentiation and survival, but its role in adult neurons is understudied. We used cell-type specific gene deletion ofMettl14,which encodes one of the subunits of the m6A methyltransferase, andYthdf1, which encodes one of the cytoplasmic m6A reader proteins, in dopamine D1 receptor expressing or D2 receptor expressing neurons.Mettl14orYthdf1deficiency blunted responses to environmental challenges at the behavioral, cellular, and molecular levels. In three different behavioral paradigms, gene deletion of eitherMettl14orYthdf1in D1 neurons impaired D1-dependent learning, whereas gene deletion of eitherMettl14orYthdf1in D2 neurons impaired D2-dependent learning. At the cellular level, modulation of D1 and D2 neuron firing in response to changes in environments was blunted in all three behavioral paradigms in mutant mice.Ythdf1deletion resembled impairment caused byMettl14deletion in a cell type-specific manner, suggesting YTHDF1 is the main mediator of the functional consequences of m6A mRNA methylation in the striatum. At the molecular level, while striatal neurons in control mice responded to elevated cAMP by increasingde novoprotein synthesis, striatal neurons inYthdf1knockout mice didn’t. Finally, boosting dopamine release by cocaine drastically increased YTHDF1 binding to many mRNA targets in the striatum, especially those that encode structural proteins, suggesting the initiation of long-term neuronal and/or synaptic structural changes. While the m6A-YTHDF1 pathway has similar functional significance at cellular level, its cell type specific deficiency in D1 and D2 neurons often resulted in contrasting behavioral phenotypes, allowing us to cleanly dissociate the opposing yet cooperative roles of D1 and D2 neurons.
Exploring the molecular basis of the genetic correlation between body mass index and brain morphological traits
Authors: Fusco Daniela , Marinelli Camilla , André Mathilde , Troiani Lucia , Noè Martina , Pizzagalli Fabrizio , Marnetto Davide , Provero Paolo
Published: August 2024

Several studies have demonstrated significant phenotypic and genetic correlations between body mass index (BMI) and brain morphological traits derived from structural magnetic resonance imaging (sMRI). We use the sMRI, BMI, and genetic data collected by the UK Biobank to systematically compute the genetic correlations between area, volume, and thickness measurements of hundreds of brain structures on one hand, and BMI on the other. In agreement with previous literature, we find many such measurements to have negative genetic correlation with BMI. We then dissect the molecular mechanisms underlying such correlations using brain eQTL data and summary-based Mendelian randomization, thus producing an atlas of genes whose genetically regulated expression in brain tissues pleiotropically affects brain morphology and BMI. Fine-mapping followed by colocalization analysis allows, in several cases, the identification of credible sets of variants likely to be causal for both the macroscopic phenotypes and for gene expression. In particular, epigenetic fine mapping identifies variant rs7187776 in the 5′ UTR of theTUFMgene as likely to be causal of increased BMI and decreased caudate volume, possibly through the creation, by the alternate allele, of an ETS binding site leading to increased chromatin accessibility, specifically in microglial cells.
Machine Learning to Predict-Then-Optimize Elective Orthopaedic Surgery Scheduling Improves Operating Room Utilization
Authors: Lex Johnathan R. , Mosseri Jacob , Toor Jay , Abbas Aazad , Simone Michael , Ravi Bheeshma , Whyne Cari , Khalil Elias B.
Published: August 2024

Objective

To determine the potential for improving elective surgery scheduling for total knee and hip arthroplasty (TKA and THA, respectively) by utilizing a two-stage approach that incorporates machine learning (ML) prediction of the duration of surgery (DOS) with scheduling optimization.

Materials and Methods

Two ML models (for TKA and THA) were trained to predict DOS using patient factors based on 302,490 and 196,942 examples, respectively, from a large international database. Three optimization formulations based on varying surgeon flexibility were compared: Any: surgeons could operate in any operating room at any time, Split: limitation of two surgeons per operating room per day and MSSP: limit of one surgeon per operating room per day. Two years of daily scheduling simulations were performed for each optimization problem using ML-prediction or mean DOS over a range of schedule parameters. Constraints and resources were based on a high-volume arthroplasty hospital in Canada.

Results

The Any scheduling formulation performed significantly worse than the Split and MSSP formulations with respect to overtime and underutilization (p<0.001). The latter two problems performed similarly (p>0.05) over most schedule parameters. The ML-prediction schedules outperformed those generated using a mean DOS over all schedule parameters, with overtime reduced on average by 300 to 500 minutes per week. Using a 15-minute schedule granularity with a wait list pool of minimum 1 month generated the best schedules.

Conclusion

Assuming a full waiting list, optimizing an individual surgeon’s elective operating room time using an ML-assisted predict-then-optimize scheduling system improves overall operating room efficiency, significantly decreasing overtime.

Highlights

-

A new approach for elective surgery scheduling was developed combining machine learning prediction of duration of surgery with integer linear programming optimization.

-

Models developed on six years of prospective multi-institution data and prediction results were used to generate two years of weekly simulated operating room schedules.

-

Three optimization models with varying levels of surgeon constraint were compared, and the model that optimized an individual surgeon’s wait list performed the best.

-

Using this approach reduced overtime by 300-500 minutes per week across five operating rooms.
Extended-spectrum beta-lactamases resistance inKlebsiella pneumoniaein sub-Saharan Africa: a systematic review and meta-analysis
Authors: Olaitan Morufat Oluwatosin , Orababa Oluwatosin Qawiyy , Shittu Bushola Rukayya , Oyediran Adams Alabi , Obunukwu Gift Maureen , Arowolo Margaret Toluwalayo , Kade Ayomikun Emmanuel , Yahaya Khalid Ibrahim , Yusuff Rildwan Alaba
Published: August 2024

Background

Extended-spectrum beta-lactamase (ESBL)-producingKlebsiella pneumoniaeis a critical priority pathogen for which there is a need for new antimicrobials and poses a great public health threat to many parts of the world including sub-Saharan Africa (SSA). This study aims to determine the prevalence of ESBL-resistantK. pneumoniaein SSA and the predominant ESBL genes in the region.

Methods

Databases such as PubMed, Scopus, Web of Science, Africa Journal Online, and Google Scholar were searched for eligible articles based on preset eligibility criteria. After screening of titles, abstracts, and full texts, a meta-analysis using a random-effect model was conducted on the eligible studies to determine the overall and subgroup prevalence of ESBL-producingK. pneumoniaein SSA.

Findings

This meta-analysis included 119 eligible studies from 25 SSA countries in all SSA subregions. The overall prevalence of ESBL-resistantK. pneumoniaein SSA is estimated to be 8·6% [95% CI: 6·4-11]. South Africa (18·5%) and Central Africa (4·6%) subregions have the highest and lowest prevalence of ESBL-producingK. pneumoniaein the region, respectively. Additionally, South Africa (23·3%), Kenya (23%), and Nigeria (11·1%) are countries with the top three prevalence of ESBL-resistantK. pneumoniaein the region. Animal samples were also seen to have the highest prevalence compared to clinical and environmental samples in this study. Lastly, CTX-M-15 was the most reported ESBL gene in SSA.

Interpretation

Although this study reports a low pooled prevalence of ESBL-resistantK. pneumoniaein SSA, some countries in the region have a high burden of this drug-resistant strain. Additionally, some countries in the region lack data on this drug-resistant strain, thus putting other parts of the region at risk due to the porous borders and immigration between the countries in the region.

Funding

There was no funding for this study
Mycobacterium tuberculosisinfection in pregnancy: a systematic review
Authors: Morton Alison J. , Mitchell Alexandra Roddy , Melville Richard E. , Hui Lisa , Tong Steven YC , Dunstan Sarah J. , Denholm Justin T.
Published: August 2024

Pregnancy may be associated with risk of developing tuberculosis (TB) in those infected withMycobacterium tuberculosis(Mtb). The perinatal period could provide opportunities for targeted screening and treatment. This study aims to synthesise published literature onMtbinfection in pregnancy, relating to prevalence, natural history, test performance, cascade of care, and treatment. We searched Ovid MEDLINE, Embase+Embase Classic, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) on October 3, 2023, and 47 studies met the inclusion criteria. The prevalence ofMtbinfection was up to 57.0% in some populations, with rates increasing with maternal age and in women from high TB-incidence settings. Five studies quantified perinatal progression fromMtbinfection to active TB disease, with two demonstrating increased risk compared to non-pregnant populations (IRR 1.3-1.4 during pregnancy and IRR 1.9-2 postpartum). Concordance between Tuberculin Skin Test (TST) and Interferon Gamma-Release Assay (IGRA) ranged from 49.4%-96.3%, with k-values of 0.19-0.56. High screening adherence was reported, with 62.0-100.0% completing antenatal TST and 81.0-100.0% having chest radiograph. Four studies of TB preventative treatment (TPT) did not find a significant association with serious adverse events. The antenatal period could provide opportunities for contextualisedMtbinfection screening and treatment. As women with increased age and from high TB-incidence settings demonstrate higher prevalence and risk of disease, this cohort should be prioritised. TPT appears safe and feasible; however, further studies are needed to optimise algorithms, ensuring pregnant and postpartum women can make evidence-informed decisions for effective TB prevention.
Estimation of age and sex specific Glomerular Filtration Rate in the Abu Dhabi population and its association with mortality and Atherosclerotic cardiovascular outcome. A Retrospective Cohort Study
Authors: AlKetbi Latifa Baynouna , Boobes Yousef , Nagelkerke Nico , Aleissaee Hamda , AlShamsi Noura , AlMansoori Mohammed , Hemaid Ahmed , AlDobaee Muna Jalal , AlAlawi Noura , AlKetbi Rudina Mubarak , Fahmawee Toqa , AlHashaikeh Basil , AlAzeezi AlYazia , Shuaib Fatima , Alnuaimi Jawaher , Mahmoud Esraa , AlAhbabi Nayla , Afandi Bachar
Published: August 2024

The impact of abnormal Glomerular Filtration Rate (eGFR) on various adverse outcomes has been well studied; however, the United Arab Emirates (UAE), like many other regions in the world, remains understudied in this area.

Method

This retrospective cohort study estimates the age and sex-specific Glomerular Filtration Rate (eGFR) in the Abu Dhabi population and its association with mortality and Atherosclerotic cardiovascular (ASCVD) outcomes. The cohort of 8699 participants in a national cardiovascular disease screening from 2011 to 2013. The cohort was reevaluated in 2023 for mortality and cardiovascular outcomes. Reference eGFR percentiles were estimated from subjects without comorbidities using the LMS method.

Results

The reference percentiles of normal eGFR values showed a marked decrease with age, with small sex differences in the reference percentile distribution. A prognostic definition of renal hyperfiltration (RH) is suggested by the observation that subjects in the 97th percentile had a significantly higher incidence of ASCVD, although not statistically significant, in terms of mortality rate.

Older age, female sex, history of ASCVD, history of hypertension, being treated for hypertension, lower diastolic blood pressure, higher systolic blood pressure, lower HDL, higher HA1C, and higher vitamin D were significantly associated with lower eGFR percentiles. Subjects in the two categories within the RH range, the 95th and 97th percentiles, had a significantly higher prevalence of diabetes; they are older smokers with higher BMI, higher HA1C, higher HDL, lower vitamin D, and more likely to be males, with higher physical activity and have a lower prevalence of CHD.

Conclusion

The distribution of eGFR by age and sex is valuable for clinical decision-making in Abu Dhabi and likely for the Arab population in general. Although the 95th percentile of eGFR in this cohort showed a higher but nonsignificant risk, the 97th percentile is significantly associated with ASCVD, even more than subjects in the less than 10th eGFR percentile. This study provides important insights into the prevalence and risk factors associated with different eGFR percentiles in the Abu Dhabi population. The findings underscore the need for targeted interventions to address modifiable risk factors and prevent the progression of renal damage in this high-risk population.
Genome-wide association studies foundCCDC7andITGB1associated with diabetic retinopathy
Authors: Cai Tengda , Pan Qi , Tao Yiwen , Yang Luning , Nangia Charvi , Rajendrakumar Aravind L , Huang Yu , Shao Yongqing , Ye Yunyan , Dottorini Tania , Haque Mainul , Palmer Colin NA , Meng Weihua
Published: August 2024

Purpose

Diabetic retinopathy (DR), a complication affecting the eyes, is associated with diabetes. This study aims to identify genetic variants associated with DR in patients with type 1 diabetes in the UK Biobank cohort (n = 1,004).

Methods

A genome-wide association study (GWAS) was conducted to identify significant genetic variants of DR in type 1 diabetes. The findings are set to undergo validation during the replication and meta-analysis stages by using six cohorts: African American, European, FinnGen, GoSHARE, GoDARTS and Caucasian Australians.

Results

In a locus, top single nucleotide polymorphism (SNP) rs184619214 inCCDC7reached a GWAS significance level (p= 6.38 x 10−9) and rs79853754 inITGB1(p= 3.24 x 10−8), with both genes being adjacent to each other. The SNP-based heritability was estimated to be 31.09%. Rs184619214 was replicated and reached statistical significance (p< 5.0 x 10−8) in the meta-analysis stage. Pathway analysis revealed that ITGB1 is involved in the generation of biomolecules that impact the progression of DR. PheWAS analysis revealed that osteoarthritis (OA) of the hip was significantly associated with most of the SNPs of the locus. Mendelian Randomization further confirmed an association between OA and DR.

Conclusions

Our study has identified a novel genomic risk locus associated with DR in type 1 diabetes, located in the intergenic region between theCCDC7andITGB1genes, providing insights for DR researchers.
Cardiotoxicity in Pediatric Cancer Survivorship: Patterns, Predictors, and Implications for Long-term Care
Authors: Mansoor Masab A.
Published: August 2024

Background

Improved survival rates in pediatric cancer have shifted focus to long-term effects of treatment, with cardiovascular complications emerging as a leading cause of morbidity and mortality. Understanding the patterns and predictors of cardiotoxicity is crucial for risk stratification, treatment optimization, and long-term care planning.

Objective

This study aimed to investigate the prevalence, incidence, and risk factors of cardiotoxicity in pediatric cancer survivors using data from the Childhood Cancer Survivor Study (CCSS).

Methods

We conducted a retrospective cohort study of 24,938 five-year survivors of childhood cancer diagnosed between 1970 and 1999. Cardiovascular complications, including cardiomyopathy, coronary artery disease, valvular heart disease, and arrhythmias, were assessed through self-reported questionnaires and medical record review. Cox proportional hazards models were used to evaluate risk factors, and a prediction model was developed using multivariable logistic regression.

Results

The cumulative incidence of any cardiovascular complication by 30 years post-diagnosis was 18.7% (95% CI: 17.9%-19.5%). Significant risk factors included anthracycline exposure (HR 2.31, 95% CI: 2.09-2.55 for doses ≥250 mg/m2), chest radiation (HR 1.84, 95% CI: 1.66-2.05 for doses ≥20 Gy), older age at diagnosis, male sex, and obesity. A risk prediction model demonstrated good discrimination (C-statistic: 0.78, 95% CI: 0.76-0.80). Survivors had a significantly higher risk of cardiovascular complications compared to sibling controls (OR 3.7, 95% CI: 3.2-4.2).

Conclusions

Childhood cancer survivors face a substantial and persistent risk of cardiovascular complications. The identified risk factors and prediction model can guide personalized follow-up strategies and interventions. These findings underscore the need for lifelong cardiovascular monitoring and care in this population.
B cells targeting parasites capture spatially linked antigens to secure T cell help
Authors: Gao Xin , McNamara Hayley A. , Lee Jiwon , Lo Adrian F. , Chatterjee Deepyan , Spensberger Dominik , Fernandez-Ruiz Daniel , Walz Kevin , Wang Ke , Kelly Hannah G. , Pohl Kai , Carreira Patricia E. , Do Andrea , Xiong Le , Beattie Lynette , Spencer Alexandra J. , Gray Daniel H.D. , Frischknecht Friedrich , Rug Melanie , Cockburn Ian A.
Published: August 2024

Our understanding of T-cell-dependent humoral responses has been largely shaped by studies involving model antigens such as recombinant proteins and viruses1,2. In these contexts, B cells internalize the entire antigen or pathogen, and present a range of antigens to helper CD4+T cells to initiate the humoral response. However, this model does not account for large pathogens (such as parasites) that are too large to be taken up by individual B cells, and the mechanisms by which B cells acquire and present antigens from large complex pathogens to T cells remain poorly understood. Here we usedPlasmodium, the causative parasite of malaria, as a model to investigate the requirements for T cell help for B cells targeting thePlasmodiumsurface circumsporozoite protein (CSP). UponPlasmodiumsporozoite (SPZ) immunization, CSP-specific B cells can form a synapse-like structure with SPZs and take up CSP and non-CSP surface antigens. As a result, CSP-specific B cells can receive help from CD4+T cells specific to antigens that are located on the surface but not cytosol of thePlasmodiumSPZ. Therefore, B cells can obtain help, not only from T cells with the same protein specificity, but also from T cells specific for spatially linked antigens. This flexibility in T cell help may enhance the initiation and maintenance of humoral immune responses to complex pathogens.