bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotyping peripheral neuropathies with and without pruritus: a cross-sectional multicenter study
Authors: Baka Panoraia , Segelcke Daniel , Birklein Frank , Pogatzki-Zahn Esther M. , Bigalke Stephan , Süer Ayşenur , Dugas Martin , Steenken Livia , Sommer Claudia , Papagianni Aikaterini
Published: July 2024

Pruritus often escapes physicians' attention in patients with peripheral neuropathy (PNP). Here we aimed to characterize neuropathic pruritus in a cohort of 191 patients with PNP (large, mixed, or small fiber) and 57 control subjects with deep phenotyping in a multicenter cross-sectional observational study at 3 German sites. All participants underwent thorough neurological examination, nerve conduction studies, quantitative sensory testing, and skin biopsies to assess intraepidermal nerve fiber density. Patients filled in a set of questionnaires assessing the characteristics of pruritus and pain, the presence of depression and anxiety, and quality of life. Based on the severity of pruritus and pain, patients were grouped into 4 groups: “pruritus,” “pain,” “pruritus and pain,” and “no pruritus/no pain.” Although 11% (21/191) of patients reported pruritus as their only symptom, further 34.6% (66/191) reported pruritus and pain. Patients with pain (with or without pruritus) were more affected by anxiety, depression, and reduced quality of life than control subjects. Patients with pruritus (with and without pain) had increases in cold detection threshold, showing Aδ-fiber dysfunction. The pruritus group had lower intraepidermal nerve fiber density at the thigh, concomitant with a more proximal distribution of symptoms compared with the other PNP groups. Stratification of patients with PNP by using cross-sectional datasets and multinominal logistic regression analysis revealed distinct patterns for the patient groups. Together, our study sheds light on the presence of neuropathic pruritus in patients with PNP and its relationship with neuropathic pain, outlines the sensory and structural abnormalities associated with neuropathic pruritus, and highlights its impact on anxiety levels.
The effect of balance training using touch controller-based fully immersive virtual reality devices on balance and walking ability in patients with stroke: A pilot randomized controlled trial
Authors: Kwak Ho-Dong , Chung Eunjung , Lee Byoung-Hee
Published: July 2024

Background:

Fully immersive virtual reality (FIVR) removes information from the real world and replaces it with computer-generated data, creating the impression of being in a genuine virtual world.

Objective:

To evaluate the effects of balance training using touch controller-based FIVR devices on balance and walking abilities in patients with stroke.

Methods:

The participants were randomly categorized into the FIVR group (n = 18) and control group (n = 18). The control group received conventional therapy for 5 sessions, 30 minutes per week, for 5 weeks. The FIVR group practiced additional touch controller-based FIVR balance training for 3 sessions of 30 minutes per week for 5 weeks and changes in balance and walking ability were measured for both groups.

Results:

Touch controller-based FIVR balance training significantly improved the Berg Balance Scale (BBS) and, timed up-and-go (TUG) test results (P < .01). There was also significant improvement in gait abilities, including gait velocity, step length of the affected side, stride length, and single limb support of the affected side (P < .01).

Conclusion:

Touch controller-based FIVR balance training improved balance and gait in patients with stroke. These results indicate that touch controller-based FIVR balance training is feasible and suitable for patients with stroke, providing a promising avenue for rehabilitation.
Antimicrobial management of dental infections: Updated review
Authors: Abdullah Faraj Mohammed , Hatim Qais Y. , Oraibi Amjad I. , Alsafar Thamir Hani , Alsandook Tahani Abdulaziz , Lutfi Wael , Al-Hussaniy Hany A.
Published: July 2024

Dental infections, which include anything from severe periodontal illnesses and abscess forms to routine tooth caries, are a major public health risk. This review article focuses on the pathophysiology and treatment of dental infections. A narrative review was conducted based on several published articles, relevant journals, and books in Google Scholar PubMed using the keywords dental caries, periodontal disease, gingivitis, and related diseases; we excluded duplicated information. Our review illustrated the types of dental infections and the proper antimicrobial drug that is suitable for this disease. Drawing from recent research findings and clinical evidence, we explore the spectrum of bacteria commonly associated with dental infections and their susceptibility profiles to various antibiotics. Emphasis is placed on understanding the mechanisms of antibiotic action and resistance in the context of dental pathogens, shedding light on optimal treatment regimens and potential challenges in clinical management. Additionally, we go over the clinical consequences of antibiotic therapy in dentistry, taking into account factors like patient selection, dose guidelines, and side effects. The management of dental infections through antimicrobial strategies has undergone significant advancements, as evidenced by this updated review. Besides the normal methods, emerging technologies such as 3D printing for drug delivery of antibiotics and disinfectants hold promise in enhancing treatment efficacy and patient outcomes. By leveraging the precision and customization afforded by 3D printing, dentistry can tailor antimicrobial interventions to individual patient needs, optimizing therapeutic outcomes while minimizing adverse effects.
Intestinal microbiota and tuberculosis: Insights from Mendelian randomization
Authors: Liu Peijun , Luo Yaomei , Zhang Minghua
Published: July 2024

Respiratory tuberculosis (RTB), a global health concern affecting millions of people, has been observationally linked to the gut microbiota, but the depth and nature of this association remain elusive. Despite these findings, the underlying causal relationship is still uncertain. Consequently, we used the Mendelian randomization (MR) method to further investigate this potential causal connection. We sourced data on the gut microbiota from a comprehensive genome-wide association study (GWAS) conducted by the MiBioGen Consortium (7686 cases, and 115,893 controls). For RTB, we procured 2 distinct datasets, labeled the Fingen R9 TBC RESP and Fingen R9 AB1 RESP, from the Finnish Genetic Consortium. To decipher the potential relationship between the gut microbiota and RTB, we employed MR on both datasets. Our primary mode of analysis was the inverse variance weighting (IVW) method. To ensure robustness and mitigate potential confounders, we meticulously evaluated the heterogeneity and potential pleiotropy of the outcomes. In the TBC RESP (RTB1) dataset related to the gut microbiota, the IVW methodology revealed 7 microbial taxa that were significantly associated with RTB. In a parallel vein, the AB1 RESP (RTB2) dataset highlighted 4 microbial taxa with notable links. Notably, Lachnospiraceae UCG010 was consistently identified across both datasets. This correlation was especially evident in the data segments designated Fingen R9 TBC RESP (OR = 1.799, 95% CI = 1.243−2.604) and Finngen R9 AB1 RESP (OR = 2.131, 95% CI = 1.088−4.172). Our study identified a causal relationship between particular gut microbiota and RTB at the level of prediction based on genetics. This discovery sheds new light on the mechanisms of RTB development, which are mediated by the gut microbiota.
Evaluation of the risk factors of metastasis to central cervical lymph nodes in patients with papillary thyroid carcinoma
Authors: Parsa Hossein , Haji Maghsoudi Leila , Delghandi Mojtaba
Published: July 2024

Background:

Papillary thyroid cancer, comprising 80% of thyroid malignancies in iodine-sufficient areas, can be effectively treated if detected early before metastasis. Cervical lymph nodes are a common site of metastasis, prompting some surgeons to suggest prophylactic dissection in all patients. To minimize potential side effects, this study aims to identify patients benefiting from this procedure by assessing risk factors for central lymph node metastasis.

Methods and materials:

This descriptive-analytical study was conducted on 150 patients with papillary thyroid cancer. The samples included cases in which central lymph node involvement was ruled out clinically and radiologically. After proving papillary cancer in the pathology sample, the variables of age, sex, frequency of central lymph node involvement, tumor size, location of thyroid involvement, multi-centric involvement, multi-focal involvement, presence of microcalcification, capsular invasion, lymphovascular invasion, and pathology were analyzed. The results were presented with descriptive statistics.

Results:

The percentage of central lymph node involvement in this study was reported as 9.3%. In the analysis, capsular invasion (P=0.01), lymphovascular invasion (P=0.0001) and involvement of the upper thyroid pole (P=0.001) were identified as risk factors for central lymph node involvement. There was no significant relationship between the variables of age, sex, tumor size, pathology, multi-centricity and multifocality and central lymph node involvement.

Conclusion:

Involvement of central lymph nodes in patients with capsular invasion, lymphovascular invasion, and involvement of the upper thyroid bridge is far more common than in other patients, and central lymph node dissection is recommended in patients with several of the above risk factors.
Prompt Engineering for Nurse Educators
Authors: Sun Grace H.
Published: July 2024

Background:

The integration of generative artificial intelligence (AI) tools like OpenAI’s ChatGPT into nursing education marks a transformative advance in personalized learning and interactive engagement.

Problem:

Variability in faculty’s experience with AI outputs highlights the need for well-crafted prompts that align with educational objectives, maximize learning outcomes, and ensure contextual relevance. Effective prompting is a key to eliciting accurate, relevant responses from AI, fostering a dynamic learning environment that bolsters student comprehension of complex topics.

Approach:

This article examines the critical role of prompt engineering in optimizing AI-generated content’s effectiveness within academic settings. With a detailed guide and strategies specifically designed for nursing education, the article prepares faculty to proficiently use generative AI.

Conclusions:

By mastering prompt engineering, educators can leverage AI tools as powerful aids, potentially significantly enhancing teaching effectiveness, work efficiency, and student learning outcomes.
Pharmacodynamic characteristics, safety profile, and interactions of CDK4/6 inhibitors (CDK4/6i) in HR+/HER2– advanced/metastatic breast cancer
Authors: Savvidou Antria , Kitiri Stavroula , Zacharia Lefteris , Constantinidou Anastasia , Petrou Christos C.
Published: July 2024

Targeted therapies such as cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6i) have improved the prognosis of hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+)/(HER2–) advanced/metastatic breast cancer (a/mBC) by combating the resistance observed with traditional endocrine therapy. Currently, palbociclib, ribociclib, and abemaciclib are the three medicinal products authorized by the European Medicines Agency and the Food and Drug Administration. In addition to their overall similarities, related to their primary molecular mechanism of action through CDK4/6 inhibition, they also exhibit significant pharmacodynamic differences that affect their efficacy and safety profile, which may, through further research, help in understanding predicted toxicity, safety, and interactions and assist in adjusting dosing regimens in daily clinical practice. This review article will examine the pharmacodynamic profile of CDK4/6 inhibitors, their efficacy and safety in the treatment of HR+/HER2– a/mBC.
Successful Management of Cherubism Patient With Staged Bone Grafting and Fat Grafting
Authors: Butts Jonathan , Dadireddy Kalyan , Ching Jessica A.
Published: July 2024

Cherubism is a rare hereditary dysplasia of the craniofacial skeleton with unpredictable course and controversial management. The authors report a case managed at the onset with limited mandibular resection and primary autogenous bone grafting, as well as staged secondary fat grafting for contour definition. Over 5 years, the patient demonstrated no recurrence of deformity except for mild hypoplasia, which was improved with fat grafting. The advantages of this early treatment were the ability to address the social stigma and anxiety at a young age versus conservative management strategies with minimal comorbidity.
Use of Machine Perfusion to Increase the Number of Expanded Criteria Deceased Donor Kidney Transplants: A Pharmacoeconomic Analysis
Authors: Tedesco Silva Helio , Ramos Teresa Raquel de Moraes , Carvalho Deise De Boni Monteiro de , Ferreira Gustavo Fernandes , de Andrade João Marcelo Medeiros , de Andrade Luis Gustavo Modelli , Abbud-Filho Mario , Foresto Renato Demarchi , Manfro Roberto Ceratti , Esmeraldo Ronaldo de Matos , Freitas Tainá Veras de Sandes , Garcia Valter Duro , Pestana José Medina , Fonseca Marcelo Cunio Machado
Published: July 2024

Background.

The discard of expanded criteria donor (ECD) kidneys is unacceptably high, considering the growing demand for transplantation. Using machine perfusion may reduce the discard rate, increase the number of transplants, and reduce mortality on the waiting list.

Methods.

We developed a 5-y Markov model to simulate incorporating the pulsatile perfusion machine into the current government-funded healthcare system. The model compared the universal use of static cold storage for all kidneys with the selective use of machine perfusion for ECD kidneys. Real-life data were used to compose the cohort characteristics in this model. This pharmacoeconomic analysis aimed to determine the cost-effectiveness and budgetary impact of using machine perfusion to preserve ECD kidneys.

Results.

Compared with the universal use of static cold storage, the use of machine perfusion for ECD kidneys was associated with an increase in the number of kidney transplants (n = 1123), a decrease in the number of patients on the waiting list (n = 815), and decrease in mortality (n = 120), with a cost difference of US dollar 4 486  009 in the period. The budget impact analysis revealed an additional cost of US dollar 4 453 749 >5 y. The budget impact analysis demonstrated a progressive reduction in costs, becoming cost-saving during the last year of the analysis.

Conclusions.

This stochastic model showed that incorporating machine perfusion for ECD kidneys is most often a dominant or cost-effective technology associated with an increase in the number of transplants and a reduction in the number of patients on the waiting list, reducing mortality on the waiting list.
Propofol ameliorates cognitive deficits following splenectomy in aged rats by inhibiting ferroptosis via the SIRT1/Nrf2/GPX4 pathway
Authors: Wen Yadong , Zhang Weihua , Wang Dingran , Lu Meijing
Published: July 2024

The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function.
Successful Electroconvulsive Therapy in a Patient With Catatonia and Maternal Duplication 15q11-13 Syndrome
Authors: Homiack Damek R. , Yan Lulu E. , Petry Luke G. , Lloyd Jenifer R. , Najjar Fedra , Cook Edwin H.
Published: July 2024

The 15q11-q13 chromosomal region contains genes encoding for GABA-A receptor subunits and is a known region of epigenetic modification associated with the development of neurodevelopmental disorders. The presence of at least one additional copy of the maternal 15q11-q13 results in a syndrome (maternal dup15q) characterized by intellectual disability, autism spectrum disorder, mood disorders, and epilepsy. Catatonia is a serious syndrome of behavioral and motor dysfunction, which occurs across a variety of psychiatric, neurologic, and general medical conditions, which has successfully been treated with benzodiazepines and electroconvulsive therapy. In this case report, we describe the treatment course of a patient with established maternal dup 15q with comorbid intellectual disability, autism spectrum disorder, bipolar mood disorder, and juvenile epilepsy who developed hypokinetic catatonia refractory to high-dose benzodiazepine therapy. In contrast with benzodiazepine treatment, electroconvulsive therapy resulted in rapid improvement in catatonic symptoms and return to premorbid baseline. This case suggests that electroconvulsive therapy can be safely delivered for some patients with maternal dup 15q and may be rapidly effective when benzodiazepine treatment results in inadequate symptom improvement.
Intranasal administration of DSM 32444 Bacillus subtilis spores: safety and tolerability
Authors: Ho Yen-Linh Thi , Hynes Daniel , Martina Yuri , Love Bill , Horwell Ed , Xu Rong , Kadioglu Aras , Vo Linh , Hong Huynh A. , Nguyen Linh Hanh , Cutting Simon M.
Published: July 2024

Introduction. Administered nasally, spores of the Gram-positive bacterium Bacillus subtilis have been shown to be able to induce innate immunity sufficient to confer protection to influenza and respiratory syncytial virus.

Hypothesis. Although members of the aerobiome, intranasal delivery of high numbers of live spores carries potential safety issues.

Aim. To address the potential safety risk of using live spores, we assessed the safety of spores that had been completely inactivated using heat sterilization.

Methodology. Using autoclaved, and therefore killed, spores of a generally recognized as safe-notified B. subtilis strain (DSM 32444), safety was assessed in vitro (biotype, genome and cell based cytoxicity) and in vivo, using intranasal administration in rodent models and lastly in human volunteers.

Results. Using a 15-day, repeat-dose, regimen in a rodent model, no indication of toxicity was observed. In a registered human study (NCT05984004), a formulated preparation of inactivated DSM 32444 spores referred to as SPEROVID was developed, and tolerance in human volunteers was assessed following 7 days of nasal dosing (2–4 times/day).

Conclusion. Our study demonstrated that in humans an intranasal dose of up to 3×108 killed spores was safe and well tolerated.
Unravelling a diversity of cellular structures and aggregation dynamics during the early development ofMyxococcus xanthus
Authors: Rivera-Yoshida Natsuko , Arzola Alejandro V. , Benítez Mariana
Published: July 2024

Aggregation underlies collective dynamics of a diversity of organisms, enabling the formation of complex structures and emergent behaviours in interaction with the environment.Myxococcus xanthus, a social bacterium, is a valuable model for studying aggregation, particularly in the development and evolution of multicellularity. While the collective behaviour ofM. xanthushas been largely studied under very crowded, ideal, conditions, there is a lack of understanding at not crowded or sparse conditions. In this work, we study the early stages of emergent collective behaviour ofM. xanthusunder nutrient-poor and low density conditions, uncovering the formation of diverse cellular structures with different shapes and sizes, ranging from individual cells to networks comprising thousands of cells. We study their motility patterns and their prevalence along development, and argue over their cross-scale role on the population’s exploratory dynamics. This work contributes to understanding key, yet largely understudied, aspects in the early stages of multicellular development in myxobacteria, shedding light on the dynamics underlying aggregative processes in this and other taxa and study systems.
MYBPHLnonsense mutations have poor sarcomere binding, are degraded, and cause abnormal contraction
Authors: Alvarez-Arce Alejandro , Fritzmann Geena E , Burnham Hope V , Araujo Kelly N , Pena Alexandra , Wittenkeller Lucas , Barefield David Y.
Published: July 2024

Heart function depends on the cardiomyocyte contractile apparatus and proper sarcomere protein expression. Mutations in sarcomere genes cause inherited forms of cardiomyopathy and arrhythmias, including atrial fibrillation (AF). Recently, a novel sarcomere component, myosin binding protein-H like (MyBP-HL) was identified. MyBP-HL is mainly expressed in cardiac atria and shares homology to the last three C-terminal domains of cardiac myosin binding protein-C (cMyBP-C). TheMYBPHLR255X mutation has been linked to atrial enlargement, dilated cardiomyopathy, and atrial and ventricular arrhythmias. Similar nonsense mutations inMYBPC3result in no myofilament incorporation and a rapid degradation of the truncated protein and are highly associated with development of hypertrophic cardiomyopathy. However, theMYBPHLR255X mutation occurs too frequently in the human population to be highly pathogenic. We sought to determine whether allMYBPHLnonsense mutations lead to impaired MyBP-HL sarcomere integration and degradation of the mutant protein, or if theMYBPHLR255X mutation has a different consequence. We mimicked humanMYBPHLnonsense mutations in the mouseMybphlcDNA sequence and tested their sarcomere incorporation in neonatal rat cardiomyocytes. We demonstrated that wild type MyBP-HL overexpression showed the expected C-zone sarcomere incorporation, like cMyBP-C. Nonsense mutations showed defective sarcomere incorporation. We demonstrated that wild type MyBP-HL and MyBP-HL nonsense mutations were degraded by both proteasome and calpain mechanisms. Additionally, we observed changes in contraction kinetics and calcium transients in cells transfected with MyBP-HL nonsense mutations compared to MyBP-HL full length. Together, these data support the hypothesis thatMYBPHLnonsense mutations are largely similar.

Short summary

Premature stop mutations in myosin binding protein H-like prevent sarcomere incorporation of the translated protein. Overexpression of truncating mutants causes contractile defects in neonatal rat cardiomyocytes. These effects occur regardless of the location of the premature stop along the protein.
Kinetic modeling of18F-PI-2620 binding in the brain using an image-derived input function with total-body PET
Authors: Bhattarai Anjan , Holy Emily Nicole , Wang Yiran , Spencer Benjamin A. , Wang Guobao , DeCarli Charles , Fan Audrey P.
Published: July 2024

Accurate quantification of tau binding from18F-PI-2620 PET requires kinetic modeling and an input function. Here, we implemented a non-invasive Image-derived input function (IDIF) derived using the state-of-the-art total-body uEXPLORER PET/CT scanner to quantify tau binding and tracer delivery rate from18F-PI-2620 in the brain. Additionally, we explored the impact of scan duration on the quantification of kinetic parameters. Total-body PET dynamic data from 15 elderly participants were acquired. Time-activity curves from the grey matter regions of interest (ROIs) were fitted to the two-tissue compartmental model (2TCM) using a subject-specific IDIF derived from the descending aorta. ROI-specific kinetic parameters were estimated for different scan durations ranging from 10 to 90 minutes. Logan graphical analysis was also used to estimate the total distribution volume (VT). Differences in kinetic parameters were observed between ROIs, including significant reduction in tracer delivery rate (K1) in the medial temporal lobe. All kinetic parameters remained relatively stable after the 60-minute scan window across all ROIs, with K1showing high stability after 30 minutes of scan duration. Excellent correlation was observed between VTestimated using 2TCM and Logan plot analysis. This study demonstrated the utility of IDIF with total-body PET in investigating18F-PI-2620 kinetics in the brain.
Policies, practices, opportunities, and challenges for TB screening – A survey of sixty National TB Programmes
Authors: Macpherson L , Miller C , Hamada Y , Rangaka MX , Ruhwald M , Falzon D , Kik S.V. , Esmail H
Published: July 2024

Background

To meet incidence reduction goals, the Global Plan to End TB 2023-30 emphasises for the first time that detection of subclinical TB is a priority. WHO Systematic Screening guidelines (2021) have stressed the importance of CXR as a screening tool to achieve this including recommending the use of Computer Aided Detection (CAD) technology.

Methods

We conducted a cross-sectional survey of National TB Programmes who reported >1000 TB cases annually. The questions aligned with 2021 WHO screening guidelines and aimed to understand country’s practices, policies, and challenges when screening for TB disease.

Results

Sixty of 123 invited countries responded representing 82% of the global TB burden. Only 66% carried out all 6 WHO-recommended steps to implement screening and 39% collected all 7 of the WHO-recommended datapoints for monitoring activity. Although most countries had a policy for using CXR and increasing CXR-based screening (77% and 68% respectively), 90% reported at least one significant barrier to implementing this and 92% reported at least one barrier to implementing CAD technology.

Conclusion

Many countries do not carry out all recommended steps for implementation and monitoring of TB screening and although CXR and CAD use are expanding and hold promise as tools to find people with TB, many programmes do not have adequate access to them. While global policy is in place that recommends the use of these tools more efforts should be made to support countries in tackling the barriers that prohibit implementation to make sure that we can close the TB case finding gap.

What is already known on this topic

Since the publication of the updated WHO TB screening guidelines there are limited published data on how countries carry out screening for TB disease and what the perceived challenges are for implementing screening from a country perspective.

What this study adds

This study provides data on current and planned screening practices and policies within countries as well as the common challenges being faced to implement screening effectively.

How this study might affect research, practice, or policy

This information will help developers, policymakers, funding agencies, and academics to better plan and support the roll-out of appropriate screening interventions.
Predicting Autism Spectrum Disorder: Transformer-Based Deep Learning Ensemble Framework Using Health Administrative & Birth Registry Data
Authors: Dick Kevin , Kaczmarek Emily , Ducharme Robin , Bowie Alexa C. , Dingwall-Harvey Alysha L.J. , Howley Heather , Hawken Steven , Walker Mark C. , Armour Christine M.
Published: July 2024

Background

Early diagnosis and access to resources, support and therapy are critical for improving long-term outcomes for children with autism spectrum disorder (ASD). ASD is typically detected using a case-finding approach based on symptoms and family history, resulting in many delayed or missed diagnoses. While population-based screening would be ideal for early identification, available screening tools have limited accuracy. This study aims to determine whether machine learning models applied to health administrative and birth registry data can identify young children (aged 18 months to 5 years) who are at increased likelihood of developing ASD.

Methods

We assembled the study cohort using individually linked maternal-newborn data from the Better Outcomes Registry and Network (BORN) Ontario database. The cohort included all live births in Ontario, Canada between April 1st, 2006, and March 31st, 2018, linked to datasets from Newborn Screening Ontario (NSO), Prenatal Screening Ontario (PSO), and Canadian Institute for Health Information (CIHI) (Discharge Abstract Database (DAD) and National Ambulatory Care Reporting System (NACRS)). The NSO and PSO datasets provided screening biomarker values and outcomes, while DAD and NACRS contained diagnosis codes and intervention codes for mothers and offspring. Extreme Gradient Boosting models and large-scale ensembled Transformer deep learning models were developed to predict ASD diagnosis between 18 and 60 months of age. Leveraging explainable artificial intelligence methods, we determined the impactful factors that contribute to increased likelihood of ASD at both an individual- and population-level.

Results

The final study cohort included 703,894 mother-offspring pairs, with 10,964 identified cases of ASD. The best-performing ensemble of Transformer models achieved an area under the receiver operating characteristic curve of 69.6% for predicting ASD diagnosis, a sensitivity of 70.9%, a specificity of 56.9%. We determine that our model can be used to identify an enriched pool of children with the greatest likelihood of developing ASD, demonstrating the feasibility of this approach.

Conclusions

This study highlights the feasibility of employing machine learning models and routinely collected health data to systematically identify young children at high likelihood of developing ASD. Ensemble transformer models applied to health administrative and birth registry data offer a promising avenue for universal ASD screening. Such early detection enables targeted and formal assessment for timely diagnosis and early access to resources, support, or therapy.
Cardi-Ankle Vascular Index Optimizes Ischemic Heart disease Diagnosis
Authors: Marzoog Basheer Abdullah , Gognieva Daria , Chomakhidze Peter , Kopylov Philipp
Published: July 2024

Background

Ischemic heart disease (IHD) has the highest mortality rate in the globe in between the other cardiovascular diseases (CVD). This returns to the poor diagnostic and therapeutic strategies including the primary prevention techniques.

Aims

To assess the changes in the cardio-ankle vascular index (CAVI) in patients with vs without IHD confirmed by stress computed tomography myocardial perfusion (CTP) imaging with vasodilatation stress-test (Adenosine triphosphate).

Objectives

IHD often has preventable risk factors and causes that lead to the appearance of the disease. However, the lack of appropriate diagnostic and prevention tools remains a global challenge in or era despite current scientific advances.

Material and methods

A single center observational study included 80 participants from Moscow. The participants aged ≥ 40 years and given a written consent to participate in the study. Both groups, G1=31 with vs. G2 = 49 without post stress induced myocardial perfusion defect, received cardiologist’s consultation, anthropometric measurements, blood pressure and pulse rate, echocardiography, CAVI and performing bicycle ergometry. For statistical analysis, descriptive statistics, t-test independent by groups and dependent by numerical variables for repeated analysis for the same patients, Pearson’s correlation coefficient, multivariate ANOVA test, and for clarification purposes, diagrams and bar figures were used. For performing the statistical analysis, used the Statistica 12 programme (StatSoft, Inc. (2014). STATISTICA (data analysis software system), version 12.www.statsoft.com.) and the IBM SPSS Statistics, version 28.0.1.1 (14).

Results

The mean age of the participants 56.28, standard deviation (Std.Dev. ± 10.601). Mean CAVI in the IHD group 8.509677 (Std.Dev. ± 0.975057208) vs 7.994898 (Std.Dev. ± 1.48990509) in the non-IHD group. The mean estimated biological age of the arteries according to the results of the CAVI in the first group 61.2258 years vs 53.5102 years in the second group. The Mean brachial-ankle pulse (Tba) in the IHD group 82.0968 vs 89.0102 in the second group. The mean heart-ankle pulse wave velocity (haPWV; m/s) in the IHD group was 0.9533 vs 0.8860 in the second group. Regression analysis demonstrated that the dependent variable, the CAVI parameter, have no significant effect on the development of stress-induced myocardial perfusion defect, regression coefficient 95.316, p>0.05. The CAVI showed 64 % diagnostic accuracy for the IHD.

Conclusion

The CAVI parameter showed no statistical difference between the participants with IHD vs without. The CAVI parameter can be used as an axillary method for improving the diagnosis of IHD.

Other

Additional indicators associated with IHD include the Tba and haPWV parameters, higher in patients with IHD.

Graphical abstract
Reevaluation of the Bicycle Ergometry in the Diagnosis of Ischemic Heart Disease
Authors: Marzoog Basheer Abdullah , Chomakhidze Peter , Kopylov Philipp
Published: July 2024

Background

Ischemic heart disease (IHD) and related complications and outcomes remain the most frequently reported cardiovascular events. However, the diagnosis and prevention of ischemic heart disease primary depends on the clinical manifestations and electrocardiography changes.

Objectives

Patients with IHD are victims of the poor diagnostic methods and the prevention strategies.

Aims

To assess the diagnostic accuracy of the used bicycle ergometry in the diagnosis of ischemic heart disease based on the results of the stress computed myocardial perfusion (CTP) imaging with vasodilator test (adenosine triphosphate).

Materials and methods

A single center prospective, and non-randomized study included participations aged ≥ 40. The study included 38 participants with vs without IHD confirmed by CTP. The participants done bicycle ergometry following Bruce protocol then performed CTP. For statistical analysis used the descriptive statistics, Pearson Correlation test, Student test. The Statistica 12 program used for the statistical test.

Results

The study included 38 participants included 19 (50 %) patients with positive stress induced myocardial perfusion defect on the CTP and 19 (50 %) with negative results. The mean age of the participants 58,77 years (std. div. ± 9,664). The bicycle ergometry specificity and sensitivity 61.11%, 57.89%, respectively. The diagnostic accuracy of the bicycle ergometry 59.46%.

Conclusions

The bicycle ergometry test characterized by severe limitations in terms of the IHD diagnosis.

Others

Recommended to combine additional diagnostic methods with the bicycle ergometry to improve it is diagnostic accuracy, such as single channel electrocardiography and exhaled breath analysis.
High Mortality Associated with Chikungunya Epidemic in Southeast Brazil, 2023
Authors: Freitas Andre Ricardo Ribas , Lima Neto Antonio Silva , Oliveira Erneson Alves , Andrade José Soares , Cavalcanti Luciano Pamplona
Published: July 2024

The chikungunya virus (CHIKV) was first detected in Brazil in 2014 with two lineages, North Asia and ECSA (East/Central/South Africa). The ECSA lineage dominated, causing significant outbreaks, especially in densely populated areas. The co-circulation of dengue and chikungunya has complicated diagnosis and treatment. The 2023 chikungunya epidemic in Minas Gerais, Southeast Brazil, prompted an assessment of associated mortality using WHO methodologies.

The study used epidemiological data from the laboratory surveillance, disease notification and mortality systems of the Brazilian Ministry of Health. The North and Northeast Health Macroregions of Minas Gerais, with 2.5 million inhabitants, were analyzed. A Poisson regression model, excluding critical periods of COVID-19 and the chikungunya epidemic, estimated expected mortality. Excess deaths were calculated by comparing observed deaths with model estimates during the epidemic period.

During the epidemic, there were 890 excess deaths attributed to chikungunya, translating into a mortality rate of 35.1/100,000 inhabitants. The excess mortality rate was significantly 60 times higher than the deaths reported by surveillance, with only 15 deaths confirmed. The correlation between excess deaths and laboratory-confirmed chikungunya cases was strong, while the correlation with dengue and COVID-19 was negligible. The results highlighted the serious underestimation of chikungunya mortality by epidemiological surveillance.

We estimate that there were 890 excess deaths in the 2023 chikungunya epidemic in just one affected area of Minas Gerais, Brazil (2.5 million inhabitants). During the same year, only 420 chikungunya deaths were reported by all PAHO member countries. Epidemiological surveillance has underestimated the impact of this disease. Excess mortality is a crucial measure for understanding the impact of epidemics, as demonstrated by COVID-19 and influenza pandemics. The study highlights the need for complementary tools to traditional surveillance to better assess impacts on morbidity and mortality. Underreporting of chikungunya deaths has significant implications for public health responses and resource allocation. This study supports the importance of accurately quantifying mortality from emerging viruses to inform risk assessments and priority setting in public health interventions.
Cross-validating the electrophysiological markers of early face categorization
Authors: Yildirim-Keles Fazilet Zeynep , Stacchi Lisa , Caldara Roberto
Published: July 2024

Human face categorization has been widely studied using electroencephalogram (EEG) and event related potentials (ERP). Within this context, the N170 ERP component has emerged as the earliest and most robust neural marker of face categorization, documented in thousands of studies conducted over nearly three decades. However, in the last decade there has been a surge in research using the fast periodic visual stimulation (FPVS) methodology to investigate face categorization. FPVS studies have consistently reported robust bilateral face categorization responses over the occipitotemporal cortex with a right hemispheric dominance, closely mirroring the N170 scalp topography. Yet, the question remains whether the neural response elicited in FPVS can be considered a proxy for the N170 or if it might be driven by different components. To address this issue, we recorded the electrophysiological signals of human observers who viewed natural images of faces and non-face objects during FPVS and three different ERP paradigms. We quantified the FPVS response in the frequency domain and extracted ERP visual components, including the P1, N170 and P2 in response to face stimuli, from both the ERP paradigms as well as the time domain of the FPVS response. Our results revealed little relationship between any single ERP component and the FPVS frequency response. Across methodologies, only the peak-to-peak differences between N170 and P2 components significantly and consistently explained the FPVS frequency response. Our data show that the FPVS frequency response is not singularly contingent on any isolated ERP component, such as the N170, but rather reflects a later complex neural integration. These findings raise crucial methodological and theoretical considerations on the relationship between FPVS and ERP responses, urging caution when interpreting the neurofunctional role of both electrophysiological signals. While both markers are indicative of human face categorization, they appear to capture different stages in this cognitive process.
Taxonomy, nomenclature, and identification of the giant hummingbirds (Patagona spp.) (Aves: Trochilidae)
Authors: Williamson Jessie L. , Gadek Chauncey R. , Robinson Bryce W. , Bautista Emil , Bauernfeind Selina M. , Baumann Matthew J. , Gyllenhaal Ethan F. , Marra Peter P. , Ricote Natalia , Singh Nadia D. , Valqui Thomas , Witt Christopher C.
Published: July 2024

Giant hummingbirds (Patagonaspp.) are extraordinarily large hummingbirds whose taxonomy has been muddled for two centuries.Patagonasystematics were recently redefined in a study of migration, physiology, and genomics, revealing two species: the Southern Giant Hummingbird and Northern Giant Hummingbird. Here, we re-evaluate taxonomy and nomenclature of the genus in light of its newly-clarified biology and species limits, analyzing data from 608 specimens and wild-caught individuals spanning 1864–2023. The formsgigasandperuvianawere both described based on multiple syntypes. No adequate syntypes forP. gigasare extant, so we designate a neotype for this taxon. We then critically consider the identity and usage ofgigasandperuviana, respectively, and examine identification challenges that have fostered taxonomic uncertainty. We endorse the namesPatagona gigasfor the Southern Giant Hummingbird andP. peruvianafor the Northern Giant Hummingbird. The genetic identity of theperuvianalectotype remains untested, but its plumage appears to match the northern species. We found that ∼33% ofPatagona gigasspecimens in major museum collections are misidentified asperuviana; we provide this list to correct the historical record. To facilitate identification and future study of these two cryptic species, we provide comprehensive information on plumage, measurements, and seasonal ranges.
Acoustic monitoring for tropical insect conservation
Authors: Riede Klaus , Balakrishnan Rohini
Published: July 2024

Monitoring the species-specific sounds produced by insects could provide us with a rapid, reliable, non-invasive measure of tropical ecosystem health and biodiversity. Although acoustic biodiversity monitoring has made rapid progress over the past decade, the focus has been mostly on vertebrates, even though insects far outnumber them, and tropical soundscapes are dominated by insect sounds. Here we provide an overview of song features for the major sound-producing insect groups, identify technological milestones and describe impediments for analyzing tropical soundscapes and insect communities. We review some promising best-practices using singing insects for non-invasive acoustic profiling and tracking of diversity in rainforest ecosystems under threat. We suggest a roadmap for joint research efforts to accelerate acoustic assessments of singing insects based on re-using the wealth of existing data from Passive Acoustic Monitoring (PAM) in combination with curated multimedia repositories and citizen science.
Intercellular adhesion boots collective cell migration through elevated membrane tension
Authors: Bijonowski Brent M. , Park Jongkwon , Bergert Martin , Teubert Christina , Diz-Muñoz Alba , Galic Milos , Wegner Seraphine V.
Published: July 2024

In multicellular systems, the migration pattern of individual cells critically relies on the interactions with neighboring cells. Depending on the strength of these interactions, cells either move as a collective, as observed during morphogenesis and wound healing, or migrate individually, as it is the case for immune cells and fibroblasts. Transducers of cell-cell adhesions, such as cadherins coordinate collective dynamics by linking the cytoskeleton of neighboring cells. However, whether intercellular binding alone triggers signals that originate from within the plasma membrane itself, remains unclear. To address this question, we designed photoswitchable cell-cell adhesions that selectively connect adjacent plasma membranes without linking directly to cytoskeletal elements. We find that these intercellular adhesions are sufficient to achieve collective cell migration. Here, linking adjacent cells increases membrane tension, which activates the enzyme phospholipase D2. The resulting increase in phosphatidic acid, in turn, stimulates the mammalian target of rapamycin, a known actuator of collective cell migration. Collectively, these findings introduce a membrane-based signaling axis as promotor of collective cell dynamics, which is independent of the direct coupling of cell-cell adhesions to the cytoskeleton.
Identifying Alzheimer’s disease-related pathways based on whole-genome sequencing data
Authors: Wang Yongheng , Liu Taihang , He Yijie , Tang Yaqin , Tan Pengcheng , Huang Lin , Huang Dongyu , Wen Tong , Shao Lizhen , Wang Jia , Wang Yingxiong , Han Zhijie
Published: July 2024

Alzheimer’s disease (AD) is a highly inheritable neurodegenerative disorder for which pathway-specific genetic profiling provides insights into its key biological mechanisms and potential treatment targets. Traditional disease-pathway analyses for AD have certain limitations, such as environmental interference and arbitrary sample division. We present a comprehensive framework that starts with genome data, avoiding these drawbacks and offering intrinsic pathway-specific genetic profiling for AD. Whole genome sequencing data from 173 individuals were used to quantify transcriptomes in 14 brain regions, estimate individual-level pathway variant scores, and analyze AD risk for each patient. These results were combined to identify AD-related pathways and quantify their interactions. The predicted expression levels were consistent with previous findings, and the estimated AD risk showed a significant correlation with Braak/Thal scores. A total of 3,798 pathways were identified as potentially associated with AD, with about 19.7% previously reported. Key pathways, including NF-κB signaling and GSK3β activation, were linked to AD pathogenesis. The interactions among pathways highlighted shared gene functions in AD. In summary, we provided an effective framework for disease-pathway analysis, revealing the interdependence or compensatory effects of pathways in AD.