bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding autism diagnosis in primary care: Rates of diagnosis from 2004 to 2019 and child age at diagnosis
Authors: Smith Jessica V , Menezes Michelle , Brunt Sophie , Pappagianopoulos Jessica , Sadikova Eleonora , O Mazurek Micah 
Published: March 2024

The capacity of the workforce lags behind the current demand for timely autism diagnostic assessment. Primary care providers (PCPs) are well-positioned to diagnose autism at earlier ages than providers from other disciplines. Thus, bolstering PCPs’ diagnostic capabilities has been the focus of many recent capacity-building initiatives. Using data from the National Survey of Children’s Health, this study aimed to evaluate whether diagnosis of autism in primary care has changed over time and whether diagnosis in primary care relates to age at autism diagnosis. Results indicated that the likelihood of being diagnosed with autism by a PCP decreased by about 2% with every passing year from 2004 to 2019 when controlling for demographic characteristics. PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychiatrists and psychologists), which supports the critical role PCPs can play in timely diagnosis. Further research is needed to understand why the proportion of children diagnosed by PCPs has decreased over time; however, these findings suggest that capacity-building initiatives have not yet reached community practice. Future research should focus on the dissemination and implementation of training initiatives in community-based primary care practices. Lay abstract The current demand for autism diagnostic services exceeds the ability of the workforce to assess and diagnose children in a timely manner. One solution may be to equip primary care providers (PCPs) with the tools and expertise needed to diagnose autism within their practice. PCPs are often trusted professionals who have many touchpoints with children during early development, in which they can identify early signs of autism. Recent initiatives have focused on bolstering PCPs’ diagnostic capabilities; however, no studies have examined how the rates of autism diagnosis in primary care have changed over time. We aimed to evaluate whether autism diagnosis in primary care has changed over time and how diagnosis in primary care relates to a child’s age at the time of diagnosis. We found that the likelihood of a child being diagnosed by a PCP decreased by about 2% with every passing year from 2004 to 2019 when accounting for demographic characteristics. In our sample, PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychologists and psychiatrists). Further research is needed to understand why the proportion of children diagnosed by PCPs decreases over time. However, this decrease suggests more work is needed to get capacity-building initiatives into community primary care practice. Though we must continue to find effective ways to build community PCPs’ ability to diagnose autism, the present findings support the crucial role PCPs can play in early autism diagnosis.
AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization
Authors: Lu Guangshuang , Xiao Shaobo , Meng Fanchao , Zhang Leyi , Chang Yan , Zhao Jinjing , Gao Nan , Su Wenjie , Guo Xinghao , Liu Yingyuan , Li Chenhao , Tang Wenjing , Zou Liping , Yu Shengyuan , Liu Ruozhuo 
Published: March 2024

Abstract
Background
Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM.

Methods
Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention.

Results
Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway.

Conclusions
AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.
Efficient and scalable gene delivery method with easily generated cationic carbon dots
Authors: Algarra Manuel , Gonzalez-Muñoz Elena 
Published: March 2024

AbstractGene delivery is a complex process with several challenges when attempting to incorporate genetic material efficiently and safely into target cells. Some of the key challenges include not only efficient cellular uptake and endosomal escape to ensure that the genetic material can exert its effect but also minimizing the toxicity of the delivery system, which is vital for safe gene delivery. Of importance, if gene delivery systems are intended for biomedical applications or clinical use, they must be scalable and easy and affordable to manufacture to meet the demand. Here, we show an efficient gene delivery method using a combination of carbon dots coated by PEI through electrostatic binding to easily generate cationic carbon dots. We show a biofunctional approach to generate optimal cationic carbon dots (CCDs) that can be scaled up to meet specific transfection demands. CCDs improve cell viability and increase transfection efficiency four times over the standard of PEI polyplexes. Generated CCDs enabled the challenging transfection protocol to produce retroviral vectors via cell cotransfection of three different plasmids into packing cells, showing not only high efficiency but also functionality of the gene delivery, tested as the capacity to produce infective retroviral particles.
Comparative analysis of the organelle genomes of Aconitum carmichaelii revealed structural and sequence differences and phylogenetic relationships
Authors: Zhang Rongxiang , Xiang Niyan , Qian Changjiang , Liu Shuwen , Zhao Yuemei , Zhang Guiyu , Wei Pei , Li Jianfeng , Yuan Tao 
Published: March 2024

AbstractIn this study, we conducted an assembly and analysis of the organelle genomes of Aconitum carmichaelii. Our investigation encompassed the examination of organelle genome structures, gene transfer events, and the environmental selection pressures affecting A. carmichaelii. The results revealed distinct evolutionary patterns in the organelle genomes of A. carmichaelii. Especially, the plastome exhibited a more conserved structure but a higher nucleotide substitution rate (NSR), while the mitogenome displayed a more complex structure with a slower NSR. Through homology analysis, we identified several instances of unidirectional protein-coding genes (PCGs) transferring from the plastome to the mitogenome. However, we did not observe any events which genes moved from the mitogenome to the plastome. Additionally, we observed multiple transposable element (TE) fragments in the organelle genomes, with both organelles showing different preferences for the type of nuclear TE insertion. Divergence time estimation suggested that rapid differentiation occurred in Aconitum species approximately 7.96 million years ago (Mya). This divergence might be associated with the reduction in CO2 levels and the significant uplift of the Qinghai-Tibet Plateau (QTP) during the late Miocene. Selection pressure analysis indicated that the dN/dS values of both organelles were less than 1, suggested that organelle PCGs were subject to purification selection. However, we did not detect any positively selected genes (PSGs) in Subg. Aconitum and Subg. Lycoctonum. This observation further supports the idea that stronger negative selection pressure on organelle genes in Aconitum results in a more conserved amino acid sequence. In conclusion, this study contributes to a deeper understanding of organelle evolution in Aconitum species and provides a foundation for future research on the genetic mechanisms underlying the structure and function of the Aconitum plastome and mitogenome.
Using the Super Learner algorithm to predict risk of major adverse cardiovascular events after percutaneous coronary intervention in patients with myocardial infarction
Authors: Zhu Xiang , Zhang Pin , Jiang Han , Kuang Jie , Wu Lei 
Published: March 2024

Abstract
Background
The primary treatment for patients with myocardial infarction (MI) is percutaneous coronary intervention (PCI). Despite this, the incidence of major adverse cardiovascular events (MACEs) remains a significant concern. Our study seeks to optimize PCI predictive modeling by employing an ensemble learning approach to identify the most effective combination of predictive variables.

Methods and results
We conducted a retrospective, non-interventional analysis of MI patient data from 2018 to 2021, focusing on those who underwent PCI. Our principal metric was the occurrence of 1-year postoperative MACEs. Variable selection was performed using lasso regression, and predictive models were developed using the Super Learner (SL) algorithm. Model performance was appraised by the area under the receiver operating characteristic curve (AUC) and the average precision (AP) score. Our cohort included 3,880 PCI patients, with 475 (12.2%) experiencing MACEs within one year. The SL model exhibited superior discriminative performance, achieving a validated AUC of 0.982 and an AP of 0.971, which markedly surpassed the traditional logistic regression models (AUC: 0.826, AP: 0.626) in the test cohort. Thirteen variables were significantly associated with the occurrence of 1-year MACEs.

Conclusion
Implementing the Super Learner algorithm has substantially enhanced the predictive accuracy for the risk of MACEs in MI patients. This advancement presents a promising tool for clinicians to craft individualized, data-driven interventions to better patient outcomes.
The minimal important difference of patient-reported outcome measures related to female urinary incontinence: a systematic review
Authors: Barbosa-Silva Jordana , Calixtre Letícia Bojikian , Von Piekartz Daniela , Driusso Patricia , Armijo-Olivo Susan 
Published: March 2024

Abstract
Background
The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making.

Objectives
To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods.

Methods
This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved.

Results
Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires.

Conclusions
There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited.
Artificial intelligence in tongue diagnosis: classification of tongue lesions and normal tongue images using deep convolutional neural network
Authors: Tiryaki Burcu , Torenek-Agirman Kubra , Miloglu Ozkan , Korkmaz Berfin , Ozbek İbrahim Yucel , Oral Emin Argun 
Published: March 2024

Abstract
Objective
This study aims to classify tongue lesion types using tongue images utilizing Deep Convolutional Neural Networks (DCNNs).

Methods
A dataset consisting of five classes, four tongue lesion classes (coated, geographical, fissured tongue, and median rhomboid glossitis), and one healthy/normal tongue class, was constructed using tongue images of 623 patients who were admitted to our clinic. Classification performance was evaluated on VGG19, ResNet50, ResNet101, and GoogLeNet networks using fusion based majority voting (FBMV) approach for the first time in the literature.

Results
In the binary classification problem (normal vs. tongue lesion), the highest classification accuracy performance of 93,53% was achieved utilizing ResNet101, and this rate was increased to 95,15% with the application of the FBMV approach. In the five-class classification problem of tongue lesion types, the VGG19 network yielded the best accuracy rate of 83.93%, and the fusion approach improved this rate to 88.76%.

Conclusion
The obtained test results showed that tongue lesions could be identified with a high accuracy by applying DCNNs. Further improvement of these results has the potential for the use of the proposed method in clinic applications.
Predictors of birth weight in pregnant women with malaria: a prospective cohort facility-based study in Webuye-Kenya
Authors: Mukala Joseph , Mogere Dominic , Kirira Peter , Kanoi Bernard N. , Akisa Violet , Kobia Francis , Waweru Harrison , Gitaka Jesse 
Published: March 2024

AbstractIn sub-Saharan Africa, malaria, which remains a major public health burden, has a prevalence of 9 to 28% and malaria in pregnancy is associated with severe adverse outcomes for the mother and her baby. Here, we sought to determine the predictors of birth weight in a cohort of 140 women with malaria in pregnancy, who were recruited at the Webuye County hospital in Western Kenya. All study participants underwent malaria diagnosis through microscopic examination of blood smear samples and were grouped into the malaria-positive and malaria-negative groups. Both groups were followed up beginning at the first antenatal visit (March 2022) until delivery (December 2022) and various data, including demographic, parity, gravidity, socioeconomic, maternal and fetal outcomes were collected. Data analyses were done using SPSS version 27. Chi-square and Fisher’s Exact tests were used for bivariate and relative risk analyses at a p-value of ≤0.05 (95%) confidence level. Most of the participants were aged 18–25 years, were primigravidas and married, had secondary school-level education, earned 20﻿–30 thousand Kenya shillings, resided in rural areas, and were in the second trimester. There were 6 (4.6%) cases of low birth weight, 3 (4.5%) in the malaria-negative group and 3 (4.7%) in the malaria-positive group. During pregnancy, 41 (31.5%) were anaemic, 5 (3.8%) were HIV-positive, 5 (3.8%) had preeclampsia, and 2 (1.5%) had gestational diabetes. Our analyses show that confounding factors like anaemia, HIV, pre-eclampsia and gestational diabetes did not influence birthweight (p ≥ 0.923). The malaria-positive and malaria-negative groups did not differ significantly with regard to the low birth weight (relative risk: 0.999, 95% confidence interval: 0.926–1.077). Marital status, gestational age, and area of residence were associated with malaria p ≤ 0.001, ≤ 0.001 and 0.028 respectively. In both groups, 124 of the ﻿140 deliveries had normal birth weights and of these 63 (95.4%, n =﻿ 70) were in the malaria-negative group, whereas 61 (95.3%, n = 70) belonged to the malaria-positive group.
The first pineoblastoma case report of a patient with Sotos syndrome harboring NSD1 germline mutation
Authors: Yue Xizan , Liu Bo , Han Tiantian , Guo Didi , Ding Ran , Wang Guangyu 
Published: March 2024

AbstractGermline mutations of NSD1 are associated with Sotos syndrome, characterized by distinctive facial features, overgrowth, and developmental delay. Approximately 3% of individuals with Sotos syndrome develop tumors. In this study, we describe an infant in pineoblastoma with facial anomalies, learning disability and mild autism at 1 years diagnosed as Sotos syndrome owing to carrying a novel mutation de novo germline NSD1 likely pathogenic variant. This patient expands both the mutation and phenotype spectrum of the Sotos Syndrome and provides new clinical insights into the potential mechanism of underlying pinealoblastoma pathology.
Association between textual and pictorial warnings on tumbac (waterpipe tobacco) boxes and motivation to quit waterpipe smoking among Lebanese and Iraqi adolescents
Authors: Malaeb Diana , Hassan Bassam Abdul Rasool , Mohammed Ali Haider , Farhan Sinan Subhi , Al-Ani Omar Abdulwahid , Sarray El Dine Abir , Fekih-Romdhane Feten , Obeid Sahar , Hallit Souheil 
Published: March 2024

Abstract
Background
Waterpipe tobacco smoking has increased tremendously at a global level among all age groups, particularly young people. Previous studies have examined the impact of waterpipe tobacco pictorial health warnings on adults but scarce studies were done on adolescents. The aim of this study was to assess the association of textual versus pictorial warnings on tumbac boxes and the motivation to quit waterpipe smoking among adolescents located in two Eastern Mediterranean countries Lebanon and Iraq.

Methods
A cross-sectional study was conducted between May and November 2022, involving 294 adolescents waterpipe smokers from Lebanon and Iraq. The questionnaire included the Lebanese Waterpipe Dependence Smoking-11, the Depression, Anxiety and Stress Scale, the Waterpipe Harm Perception Scale, Waterpipe Knowledge Scale, Waterpipe Attitude Scale, the Fagerstrom Test for Nicotine Dependence, and the Motivation to Stop Scale.

Results
When adjusting the results over confounding variables, the results showed that compared to finding the warnings to stop smoking not efficacious at all, adolescents who find the warnings moderately (aOR = 2.83) and very (aOR = 6.64) efficacious had higher motivation to quit. Compared to finding the warnings not increasing their curiosity for information about how to stop waterpipe smoking at all, participants who confessed that warnings increased their curiosity a little (aOR = 2.59), moderately (aOR = 3.34) and very (aOR = 3.58) had higher motivation to quit. Compared to not considering changing the tumbac brand if the company uses pictorial warnings, adolescents who would consider changing the tumbac brand (aOR = 2.15) had higher motivation to quit.

Conclusion
Pictorial and textual warnings on waterpipe packs were associated with higher motivation to stop waterpipe smoking. Public health education programs for this purpose seem warranted.
An Integrated Care Pathway for depression in adolescents: protocol for a Type 1 Hybrid Effectiveness-implementation, Non-randomized, Cluster Controlled Trial
Authors: Courtney Darren B. , Barwick Melanie , Amani Bahar , Greenblatt Andrea T. , Aitken Madison , Krause Karolin R. , Andrade Brendan F. , Bennett Kathryn , Cleverley Kristin , Uliaszek Amanda A. , de Oliveira Claire , Hawke Lisa D. , Henderson Jo , Wang Wei , Watson Priya , Gajaria Amy , Newton Amanda S. , Ameis Stephanie , Relihan Jacqueline , Prebeg Matthew , Chen Sheng , Szatmari Peter 
Published: March 2024

Abstract
Introduction
Our group developed an Integrated Care Pathway to facilitate the delivery of evidence-based care for adolescents experiencing depression called CARIBOU-2 (Care for Adolescents who Receive Information ‘Bout OUtcomes, 2nd iteration). The core pathway components are assessment, psychoeducation, psychotherapy options, medication options, caregiver support, measurement-based care team reviews and graduation. We aim to test the clinical and implementation effectiveness of the CARIBOU-2 pathway relative to treatment-as-usual (TAU) in community mental health settings.

Methods and analysis
We will use a Type 1 Hybrid Effectiveness-Implementation, Non-randomized Cluster Controlled Trial Design. Primary participants will be adolescents (planned n = 300, aged 13–18 years) with depressive symptoms, presenting to one of six community mental health agencies. All sites will begin in the TAU condition and transition to the CARIBOU-2 intervention after enrolling 25 adolescents. The primary clinical outcome is the rate of change of depressive symptoms from baseline to the 24-week endpoint using the Childhood Depression Rating Scale—Revised (CDRS-R). Generalized mixed effects modelling will be conducted to compare this outcome between intervention types. Our primary hypothesis is that there will be a greater rate of reduction in depressive symptoms in the group receiving the CARIBOU-2 intervention relative to TAU over 24 weeks as per the CDRS-R. Implementation outcomes will also be examined, including clinician fidelity to the pathway and its components, and cost-effectiveness.

Ethics and dissemination
Research ethics board approvals have been obtained. Should our results support our hypotheses, systematic implementation of the CARIBOU-2 intervention in other community mental health agencies would be indicated.