bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Definition to Identify Severe Opioid Overdoses Treated in Emergency Departments, 2019-2022
Authors: Liu Stephen J. , Smith Herschel , Krishnasamy Vikram , Gladden R. Matthew 
Published: September 2024

Background:
Existing surveillance systems monitor nonfatal and fatal opioid overdoses but do not monitor severe nonfatal overdoses that require intensive medical interventions.

Methods:
The Centers for Disease Control and Prevention’s Drug Overdose Surveillance and Epidemiology system was used to query emergency department data from local syndromic systems and the National Syndromic Surveillance Program from January 2019 to August 2022. Opioid overdoses were classified as not severe or severe using a definition from the patient’s chief complaint terms and discharge diagnosis codes. The percentage of opioid overdoses treated in emergency departments classified as severe was described by patient demographics, US Census region, and month.

Results:
Among 503 156 opioid overdoses in 29 states and Washington, DC, from January 2019 to August 2022, 17.4% were classified as severe. Common key terms found among severe opioid overdoses were hypoxia (34.8%), unresponsive (32.9%), and naloxone/Narcan (20.9%). The largest severity percentage was in the South Census region (19.6%). The trends of severe opioid overdoses remained stable during the study period.

Discussion:
Based on the severe opioid overdose definition, there was minimal change in the severity of opioid overdoses during the study period. This definition can help monitor trends of severe opioid overdoses, guiding public health action such as focusing on naloxone and fentanyl test strip distribution to areas of need.
The Impact of Blood Glucose Levels on the Prognosis of Diabetic Patients With Successful Recanalization After Mechanical Thrombectomy: A Single-Center Retrospective Study
Authors: Wang Yubo , Ren Hecheng , Ma Lin , Xiang Yi , Zhang Xiqiang , Luo Bin 
Published: September 2024

Objective:
To investigate the impact of postoperative fasting blood glucose monitoring on the prognosis of patients with acute intracranial large vessel occlusion (ALVO) after mechanical thrombectomy.

Methods:
A retrospective study was conducted on 328 diabetic patients diagnosed with acute ischemic stroke through MRI, confirmed to have intracranial large vessel occlusion through MRA or DSA, and treated with mechanical thrombectomy between June 2021 and June 2023 at Tianjin Huanhu Hospital. Based on the 90-day postonset prognosis (modified Rankin scale, 90d-mRS), 148 patients were categorized into the favorable prognosis group (90d-mRS score 0–2) and 180 into the poor prognosis group (90d-mRS 3–6). Clinical data between the 2 groups were compared. Factors with P<0.1 in univariate analysis were included in multivariate Logistic regression analysis to evaluate their impact on prognosis.

Results:
A total of 328 diabetic patients were included in the study, with a median age of 63 (56, 69) years; 240 males aged 60.88 (55, 68.75) years and 88 females aged 65.16 (60, 72) years. There were significant differences between the 2 groups in terms of gender, preoperative mRS, and fasting blood glucose within the first 3 days postoperation. Multivariate Logistic regression analysis indicated that gender, preoperative mRS score, and fasting blood glucose on the first postoperative day were independent risk factors for poor prognosis. Female diabetic patients had a 56.7% higher rate of poor prognosis compared with males patients (OR: 0.567, 95% CI: 0.326–0.986, P=0.044); the poor prognosis rate in the preoperative mRS 3 to 6 group was 2.101 times that of the preoperative mRS 0 to 2 group (OR: 2.101, 95% CI: 1.027–4.300, P=0.042); for every 1 mmol/L increase in fasting blood glucose on the first day post-thrombectomy was associated with a 10.2% increase in the rate of poor prognosis at 90 days (OR: 1.102, 95% CI: 1.023–1.189, P=0.011). The predictive power of fasting blood glucose on the first postoperative day for 90d-mRS was greater than that of gender and preoperative mRS, with sensitivity and specificity of 68.2% and 60.6%, respectively. Combined prediction using fasting blood glucose, gender, and preoperative mRS had similar effectiveness. Maintaining fasting blood glucose levels below 11.5 mmol/L on the first day post-thrombectomy could reduce the rate of poor prognosis in patients.

Conclusion:
Fasting blood glucose levels on the first day post-thrombectomy can be used as a prognostic indicator for diabetic patients with acute intracranial large vessel occlusion. Effective blood glucose control can significantly reduce the rate of poor prognosis in these patients.
Conservative Versus Radical Treatment of Ameloblastoma: A 14-Year Study in Kedah, Malaysia
Authors: Ling Xiao Feng , Ismail Sumairi bin , Zainal Abidin Marzuki bin , bt Amran Nurfitri Atirah , bin Abd Samad Mohammad Azrin , Tew Mei Mei , Awang Hasyim Noratikah binti 
Published: September 2024

Introduction:
Ameloblastoma is a slow-growing benign odontogenic tumor of the jaws. The objectives of this study were to evaluate the epidemiological data of ameloblastoma in Kedah, to identify the clinicopathological characteristics that predict the outcome of the treatment and recurrence rate.

Methodology:
A retrospective cohort study was conducted for patients who underwent treatment for ameloblastoma from 2007 to 2021. All patients with histopathologically proven ameloblastoma and underwent at least 2 years of follow-up were included in the study.

Results:
Fifty-one patients met the study’s inclusion criteria. The mean age was 39.8 +/− 18.8 years old, and the mean follow-up period was 80 +/− 51 months. A recurrence was observed in 10 patients out of 51 patients (19.6%). There was significant association between histologic pattern and tumor recurrence (P<0.05). Most of the recurrence cases showed mixed histologic subtypes with the predominant variant lead by acanthomatous-follicular subtypes.

Discussion:
The recurrence rate in our study, 19.6% was in line with other studies. (17.2%–24.0%) Conventional ameloblastoma with mixed acanthomatous and follicular subtypes were the most common histologic variant in recurrence cases of our study. In our study, the recurrence rate for enucleation with peripheral ostectomy was 26.7% in conventional ameloblastoma, which was lower than the reported rates, 33.3%.

Conclusions
Our data indicate that the conservative treatment can preserve the appearance and function well, at the same time keeping the risk of recurrence lower than currently published figures.
The Difference in Cognitive Profiles Between Patients With Alzheimer Dementia With and Without Psychosis
Authors: Carmel Jean-François , Clerc Doris , Couture Vincent , Reid Isabelle , Filali Ali , Villalpando Juan Manuel 
Published: September 2024

Background:
Psychosis in Alzheimer disease (AD) is a major burden for patients and their family. Identifying the characteristics of delusions and hallucinations in the AD population is key to understanding the interconnection between the psychiatric and cognitive symptoms in neurocognitive disorders. The aim of this study is to compare the cognitive profiles of AD patients with and without psychosis.

Methods:
We conducted a rapid review to explore the relationship between psychotic symptoms and cognitive performances in patients with AD. We used MEDLINE, Embase, and PsychINFO literature databases between January 2015 and January 2023. This rapid review was guided by the Cochrane Rapid Reviews Methods Group.

Results:
We identified 2909 records from the initial searches. After reviewing the titles, abstracts, and full texts, we selected 8 cross-sectional and 5 cohort studies for the qualitative analysis. Among them, 6 studies were included in the final quantitative analysis. Most studies suggested a correlation between general cognitive decline and the risk of presenting psychotic symptoms. Three studies found an association between hallucinations and deficits in the visuocognitive domains (visuospatial, visuoperceptual, and visuoconstructive skills). Two studies found a relationship between psychotic symptoms and executive dysfunction. Two studies also found a correlation between psychotic symptoms and language. Our results are in line with previous data in the literature, especially regarding the outcome of psychosis on executive function and visuocognitive abilities.

Conclusions:
There appears to be an association between cognitive deficits and psychotic symptoms in AD, but the direction of causality is still unclear, and further studies using longitudinal designs would give more insight into the pathophysiological process of psychosis in AD.
Transcriptome profiling of dopaminergic neurons derived from an ADHD induced pluripotent stem cell (iPSC) model
Authors: Namipashaki Atefeh , Arnatkeviciute Aurina , Hellyer Shane D. , Nowell Cameron J , Walsh Kevin , Polo Jose M. , Gregory Karen J , Bellgrove Mark A. , Hawi Ziarih 
Published: September 2024

AbstractThe most recent ADHD–GWAS meta–analysis highlighted the potential role of 76 genes enriched among genes expressed in early brain development and associated with midbrain dopaminergic neurons. However, the precise functional importance of the GWAS-identified single nucleotide polymorphisms (SNPs) remain unknown. In contrast to GWAS, transcriptome analysis directly investigates gene products by assessing the transcribed RNA. This allows one to gain functional insights into gene expression paving the way for a better understanding of the molecular risk mechanisms of conditions, such as ADHD. In this study, we performed transcriptome profiling of highly homogeneous dopamine neurons developed from induced pluripotent cells (iPSCs) that were derived from an individual with ADHD and a neurotypical comparison individual. Comparative gene expression analysis between the examined lines revealed that the top differentially expressed genes (DEGs) were predominantly associated with nervous system functions related to neuronal development and dopaminergic regulation. Notably, 29 of the DEGs overlapped with those identified by ADHD–GWAS meta- analysis. These genes are overrepresented in biological processes including developmental growth regulation, axonogenesis, and nervous system development. In addition, gene set analysis revealed significant enrichment for meta categories such as ion channel activity, synaptic function and assembly, neuronal development and cell differentiation. Further, we observed significantly reduced projections in the ADHD dopamine neurons at the mid–differentiation stage (day 14 in vitro), providing preliminary support for the delayed neuronal maturation hypotheses of ADHD. This study underscores the potential of using iPSC–derived cell type–specific models that integrate genome and transcriptome analyses for biological discovery in ADHD.
Dissecting the Reduced Penetrance of Putative Loss-of-Function Variants in Population-Scale Biobanks
Authors: Blair David R. , Risch Neil 
Published: September 2024

AbstractLoss-of-function variants (LoFs) disrupt the activity of their impacted gene. They are often associated with clinical phenotypes, including autosomal dominant diseases driven by haploinsufficiency. Recent analyses using biobanks have suggested that LoF penetrance for some haploinsufficient disorders may be low, an observation that has important implications for population genomic screening. However, biobanks are also rife with missing data, and the reliability of these findings remains uncertain. Here, we examine the penetrance of putative LoFs (pLoFs) using a cohort of ≈24,000 carriers derived from two population-scale biobanks: the UK Biobank and the All of Us Research Program. We investigate several possible etiologies for reduced pLoF penetrance, including biobank recruitment biases, annotation artifacts, missed diagnoses, and incomplete clinical records. Systematically accounting for these factors increased penetrance, but widespread reduced penetrance remained. Therefore, we hypothesized that other factors must be driving this phenomenon. To test this, we trained machine learning models to identify pLoFs with high penetrance using the genomic features specific to each variant. These models were predictive of penetrance across a range of diseases and pLoF types, including those with prior evidence for pathogenicity. This suggests that reduced pLoF penetrance is in fact common, and care should be taken when counseling asymptomatic carriers.
Longitudinal analysis of genetic and environmental interplay in human metabolic profiles and the implication for metabolic health
Authors: Wang Jing , Zenere Alberto , Wang Xingyue , Bergström Göran , Edfors Fredrik , Uhlén Mathias , Zhong Wen 
Published: September 2024

AbstractBackgroundUnderstanding how genetics and environmental factors shape human metabolic profiles is crucial for advancing metabolic health. Variability in metabolic profiles, influenced by genetic makeup, lifestyle, and environmental exposures, plays a critical role in disease susceptibility and progression.MethodsWe conducted a two-year longitudinal study involving 101 clinically healthy individuals aged 50 to 65, integrating genomics, metabolomics, lipidomics, proteomics, clinical measurements, and lifestyle questionnaire data from repeat sampling. We evaluated the influence of both external and internal factors, including genetic predispositions, lifestyle factors, and physiological conditions, on individual metabolic profiles. Additionally, we developed an integrative metabolite-protein network to analyze protein-metabolite associations under both genetic and environmental regulations.ResultsOur findings highlighted the significant role of genetics in determining metabolic variability, identifying 22 plasma metabolites as genetically predetermined. Environmental factors such as seasonal variation, weight management, smoking, and stress also significantly influenced metabolite levels. The integrative metabolite-protein network comprised 5,649 significant protein-metabolite pairs and identified 87 causal metabolite-protein associations under genetic regulation, validated by showing a high replication rate in an independent cohort. This network revealed stable and unique protein-metabolite profiles for each individual, emphasizing metabolic individuality. Notably, our results demonstrated the importance of plasma proteins in capturing individualized metabolic variabilities. Key proteins representing individual metabolic profiles were identified and validated in the UK Biobank, showing great potential for predicting metabolic diseases and metabolic risk assessment.ConclusionsOur study provides longitudinal insights into how genetic and environmental factors shape human metabolic profiles, revealing unique and stable individual metabolic profiles. Plasma proteins emerged as key indicators for capturing the variability in human metabolism and assessing metabolic risks. These findings offer valuable tools for personalized medicine and the development of diagnostics for metabolic diseases.
Beneficial vs harmful effects of pharmacological treatment of patent ductus arteriosus: A Bayesian meta-analysis
Authors: Villamor Eduardo , Galán-Henríquez Gloria , Bartoš František , Gonzalez-Luis Gema E 
Published: September 2024

AbstractBackgroundRandomized controlled trials (RCTs) have failed to demonstrate beneficial effects of the pharmacological treatment of patent ductus arteriosus (PDA) in preterm infants. We conducted a Bayesian model averaged (BMA) meta-analysis of RCTs comparing pharmacological treatment of PDA with placebo or expectant treatment.MethodsWe searched for RCTs including infants with gestational age (GA) ≤32 weeks and with a rate of open-label treatment of less than 25% in the control arm. Primary outcome was mortality and secondary outcomes included bronchopulmonary dysplasia (BPD). We calculated Bayes factors (BFs). The BF+/-is the ratio of the probability of the data under H+(pharmacological treatment is beneficial) over the probability of the data under H-(pharmacological treatment is harmful).ResultsFive RCTs were included (1341 infants). BMA showed strong evidence in favor of a harmful effect of medication for BPD (BF+/-=0.02) and BPD or death (BF+/-=0.03). When the two largest trials, which used early (<72 h) ibuprofen in infants with GA ≤28 weeks, were pooled, the BMA demonstrated moderate evidence in favor of higher mortality in the medication group (BF+/-=0.24).ConclusionsEarly ibuprofen treatment of a PDA in extremely preterm infants may result in more complications than clinical benefit.
Enhancing the Diagnostic Efficacy of Right-to-Left Shunt Using Robot-Assisted Transcranial Doppler: A Quality Improvement Project
Authors: Shah Ruchir , Devlin Christian , Gao Lan. , Ledford Samuel , Ramjee Vimal , Madan Vinay , Patterson Jennifer , Walden Lauren , Devlin Thomas 
Published: September 2024

ABSTRACTBackgroundStroke is the leading cause of adult disability worldwide, with approximately 30% of strokes remaining cryptogenic. One potential etiology is a patent foramen ovale (PFO), which may contribute to stroke through paradoxical thrombo-embolism or in situ thrombo-embolus formation. Recent advancements in robot-assisted transcranial Doppler (raTCD) have shown increased sensitivity in detecting right-to-left shunt (RLS) compared to transthoracic echocardiography (TTE), particularly in detecting large shunts, which are associated with a higher risk of stroke.MethodsWe conducted a retrospective quality improvement project at our regional stroke center to compare the performance of TTE and raTCD in identifying RLS in ischemic stroke patients. The study involved 148 patients admitted between February 2021 and February 2023. All patients underwent TTE and raTCD with agitated saline bubble contrast, with additional transesophageal echocardiography (TEE) at the treatment team’s discretion. The primary metrics analyzed included differences in overall RLS detection and large RLS detection rates for raTCD, TTE and TEE.ResultsraTCD detected RLS in 60.1% of patients compared to 37.2% with TTE (p = 0.00012), with a 42.6% detection rate for large shunts on raTCD versus 23.0% on TTE (p = 0.00053). The sensitivity and specificity of raTCD were 92% and 87.5%, respectively, compared to 78.57% and 71.43% for TTE, using TEE as the gold standard. Nine patients underwent PFO closure, all correctly identified with large shunts by raTCD, while TTE missed or underestimated the PFO size in 44% of the cases.ConclusionraTCD significantly outperforms TTE in detecting RLS and large shunts, suggesting its integration into standard PFO workup protocols may enhance secondary stroke prevention. These findings support the adoption of raTCD as a complementary diagnostic tool alongside TTE and TEE for more accurate PFO detection and risk stratification.
Hepatic mitochondrial respiration is crucial for euthermia in complex III-deficient mice with impaired brown adipose tissue thermogenesis
Authors: Banerjee Rishi , Upadhyay Divya , Zarybnický Tomáš , Kietz Christa , Kuure Satu , Fellman Vineta , Purhonen Janne , Kallijärvi Jukka 
Published: September 2024

AbstractLiver is the key hub of systemic energy metabolism and growth regulation, yet its roles in mitochondrial disease pathophysiology remain relatively understudied.Bcs1lp.S78Gknock-in mice, carrying a patient mutation causing respiratory complex III (CIII)-deficiency, present juvenile-onset liver and kidney disease, growth restriction, lipodystrophy, and early death. We restored CIII function in the hepatocytes of these mice using recombinant adeno-associated viral vectors (rAAVs) expressing wild-typeBcs1l. A single intraperitoneal injection of rAAVs into presymptomatic juvenile mice prevented liver disease, improved hypoglycemia and growth, normalized hepatic fuel utilization, and doubled the survival. The mutant mice showed hypothermia and brown adipose tissue (BAT) inflammation, and lacked BAT activation basally and upon acute cold challenge. Disrupted foot pad innervation suggested sensory neuropathy and impaired thermosensation as a contributor to the BAT inactivity. Surprisingly, the rAAV-treated mice maintained near-normal body temperature without significant effect on BAT. Increasing cellular respiration via transgenic alternative oxidase (AOX) was sufficient to prevent the hypothermia. The CIII-deficient mice did not reach euthermia until at an ambient temperature of 35°C, housing at which relieved metabolic stress and ameliorated hepatocyte senescence. We conclude that mitochondrial respiration in hepatocytes is essential for euthermia in mice. Our findings highlight the crucial role of the liver in thermoregulation, hypothermia as a consequence of mitochondrial dysfunction, and the therapeutic potential of rAAV-based gene delivery in a preclinical model of a multiorgan mitochondrial disease.Graphical abstract
dScaff – an automatic bioinformatics framework for scaffolding draftde novoassemblies based on reference genome data
Authors: Constantin Nicoleta-Denisa , Ionascu Adrian , Ratiu Attila Cristian 
Published: September 2024

AbstractRapid evolution of long-read sequencing technologies requires accurate, fast and user-friendly genome assembly and scaffolding tools. In this article we present Digital Scaffolding (dScaff), a bioinformatics tool that performs scaffolding ofde novogenome assemblies based on reference scaffolds or chromosomes. dScaff makes use of a series of bash and R scripts in order to create a minimal complete scaffold from a genome assembly, with future features to be implemented. Herein, we demonstrate the functionality of dScaff on a novel genome assembly pertaining to a recently sequenced local strain ofDrosophila suzukii.
Watch-breaker: establishment of a microwell array-based miniaturized thymic organoid model suitable for high throughput applications
Authors: Major Viktoria , Palmer Sam , Rouse Paul , Henderson Timothy , Hübscher Tania , Sweetman Joanna , Morys Jan , Bacon Andrea , Chengrui An , Guiyun Qiu , Wang Yu , Corsinotti Andrea , Cholewa-Waclaw Justyna , Chapman S. Jon , Lütolf Matthias P. , Anderson Graham , Blackburn C. Clare 
Published: September 2024

AbstractT-cell development depends critically on the thymic stroma, in particular the diverse array of functionally distinct thymic epithelial cell (TEC) types. However, a robustin vitrothymus model mimicking the native thymus and compatible with medium/high-throughput analyses is currently lacking. Here, we demonstrate a novel high-density microwell array-based miniaturized thymus organoid (mTO) model, that supports T-cell commitment and development, possesses key organizational characteristics of the native thymus and is compatible with live-imaging and medium/high-throughput applications. We establish the minimum cellular input required for functional mTO and show that mTO TEC phenotype and complexity closely mirrors the native thymus. Finally, we use mTO to probe the role of fetal thymic mesenchyme, revealing a requirement beyond maintenance ofFoxn1in differentiation/maintenance of mature TEC subpopulations. Collectively, mTO present a newin vitromodel of the native thymus adaptable to medium/high-throughput applications and validated for exploration of thymus- and thymus organoid-biology.