bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fate of Costochondral Grafts for Micrognathia: 3D Analysis of Postoperative Length, Position, and Graft Take
Authors: Kono Hikaru , Hikosaka Makoto , Kaneko Tsuyoshi , Baba Yoshiyuki 
Published: September 2022

Purpose:
Costochondral grafting is performed in the reconstruction of severe micrognathia. In this study, we report our experience with graft take, as well as unique findings that have not been focused on in the past literature such as postoperative position and changes in the shape of the graft and thinning of the skull base in contact with the graft.

Methods:
Between 2002 and 2019, costochondral grafting was performed on 15 sides of 10 patients with micrognathia. Graft take and other detailed findings such as growth, position, and changes in the shape of the grafts and skull base in contact with the grafts were evaluated using computed tomography images.

Results:
Graft take was obtained in all cases, and subsequent distraction could be performed in 8 of 10 graft sites as planned. Six of 15 grafts were displaced anterior to the preoperative planned position. However, there were no cases with complications due to deviation such as trismus. Concave deformity of the skull base in contact with the graft was observed in 9 graft sites. The thinning and bending deformation were observed in 2 grafts.

Conclusions:
Costochondral grafting was considered a reasonable method for first-line treatment of severe micrognathia. Several unique findings that have not been focused on in the past literature were observed. These should be kept in mind when performing costochondral grafting. Several modifications to the present protocol are suggested to improve the quality of graft take.
Disentangling the roles of trauma and genetics in psychiatric disorders using an Electronic Health Records-based approach
Authors: Marchese Shelby , Cuddleston Winston , Seah Carina , Johnson Jessica , Huckins Laura M. 
Published: September 2022

AbstractPosttraumatic stress disorder (PTSD) requires an exposure to trauma for diagnosis by the DSM-V. Despite this, there is no documented linear relationship between degree of trauma and severity/chronicity of PTSD.To determine whether traumatic and stressful life events (TSLEs) collected from Electronic Health Records (EHR) interact with PTSD genetics to better define individual risk of developing PTSD. We collected trauma information from patient records in the Mount Sinai BioMe™ biobank population-based cohort and tested for associations with PTSD. We generated a TSLE risk score (TRS), tested its association with PTSD, and for interactions with a polygenic risk score (PRS) of PTSD and a GWAS of PTSD using our biobank population.We used the Mount Sinai BioMe™ biobank patient population of 31,704 individuals with matched genotype and EHR data, which has been enrolling patients since 2006. Patient enrollment in BioMe™ is unrestricted, resulting in high diversity. Our study includes 1,990 individuals with PTSD and 28,478 individuals without PTSD from the Mount Sinai BioMe™ biobank.A total of 1,990 individuals with PTSD and 28,478 controls were analyzed (average age 42-78 years, 58.7% women). We identified a total of 22 EHR-derived TSLEs that were associated with PTSD (β> 0.029, p<1.61×10−3). TSLEs interacted with each other to increase the risk of developing PTSD, with the most significant interaction between being female (as a proxy for experiencing sexism) and being HIV+ (β=0.013, p=8.9×10−11). PRS of PTSD and lead SNPS from GWAS interacted with TSLEs and our TRS to increase PTSD risk. In addition to TRS interactions, we found significant interactions between PTSD PRS and domestic violence, and sexual assault in European Americans (β>207.74, p<1.80×10−3). rs113282988 and rs189796944 variants reached genome-wide significance in interactions with TRS (β>0.056, p<9.04×10−9), and rs189796944 in an interaction with Physical Survival TSLEs (β>0.127, p<4×10−8).In conclusion, quantification of trauma type, severity, and magnitude—alone and in concert with genetics—provides better prediction of PTSD risk than PRS alone. Understanding who is at risk of developing PTSD allows for timely clinical intervention and possible prevention.
Knowledge Attitude and Practice towards Cutaneous Leishmaniasis in Sodo District Southern Ethiopia
Authors: Gazu Lina , Nkosi Zerish Zethu , Kebede Nigatu 
Published: September 2022

AbstractBackgroundIn Ethiopia, Cutaneous Leishmaniasis (CL) is a common infectious disease. However, existing knowledge on community awareness is scarce.ObjectiveObjectives is to access knowledge, attitude, and practices about CL in Sodo District.MethodsPrimary quantitative method using a cross-sectional descriptive approach was applied. Data were collected from face-to-face interviews held with 423 households between January to April 2018. Knowledge, attitude, and practice scores were obtained by aggregating responses to questions. Levels of these outcomes were determined by dichotomizing the generated scores using their mean vales. Percentages, frequency and mean values were used to descriptively understand the data. Logistic regression was used to model the binary outcomes. R Package Version 3.02 was used to conduct the statistical analysis.ResultsOf 423 participants 263 (61.9%), 226 (53.4%), and 213 (50.4%) have satisfactory knowledge, favourable attitude, and good practice about leishmaniasis. Majority are unable to identify leishmaniasis and unaware of its cause and transmission. Sandfly is considered “important biting and blood-sucking insect” by 210 (49.6%) but knowledge on biting time and breeding place was unsatisfactory. Most believed CL can be treated, is a serious problem and have a disfiguring outcome. However, most (59.3%, n=251) prefer use of traditional medication. Concerning practice, 288 (68.1%) have bed nets but personal protective measures are rarely used.ConclusionThe level of overall knowledge and attitudes and practice in the current study was not adequate. This finding implies that there is a need for intensified education regarding CL.
The Natural History of Untreated Pulmonary Tuberculosis in Adults: A Systematic Review and Meta-Analysis
Authors: Sossen Bianca , Richards Alexandra , Heinsohn Torben , Frascella Beatrice , Balzarini Federica , Oradini-Alacreu Aurea , Odone Anna , Rogozińska Ewelina , Häcker Brit , Cobelens Frank , Kranzer Katharina , Houben Rein MGJ , Esmail Hanif 
Published: September 2022

ABSTRACTBACKGROUNDKey stages in TB disease can be delineated by radiology, microbiology and symptoms, but transition between relevant stages remains unclear. We sought to quantify progression and regression across the spectrum of TB disease by systematically reviewing studies of individuals with untreated TB undergoing follow up.METHODSWe searched PubMED, EMBASE and Web of Science until December 31st 1960, the Index Medicus between 1895 and 1945, and extensive investigator collections without date restriction - in English and German. Eligible studies were observational cohorts and clinical trials, presenting adults/adolescents with TB or recent TB exposure, undergoing follow-up for at least 12 months without therapeutic intervention. Two authors independently reviewed titles/abstracts and full texts for inclusion. Quality was assessed with a modified Newcastle-Ottawa Score, excluding highly biased studies. Summary estimates were extracted to align with TB disease transitions in a conceptual model, and we used meta-analysis of proportions with random-effects to synthesise the extracted data. This study is registered with PROSPERO (CRD42019152585).FINDINGS10477 titles were screened and 1648 full texts reviewed. 223 met inclusion criteria. 109 were excluded for high risk of bias and 90 did not have extractable data. 24 studies (34 cohorts) were included. Progression from microbiologically negative to positive disease in those with radiographic TB evidence occurred at an annualized rate of 9.71% (95% CI:6.17-13.34) with “active” TB imaging, and 1.06% (95% CI:0.31-1.82) with “inactive” TB imaging. Reversion from microbiologically-positive to -undetectable in prospective cohorts occurred at an annualized rate of 12.40% (95% CI: 6.81-17.99). Studies reported symptoms poorly not allowing for direct estimation of transitions for subclinical (asymptomatic, culture positive) disease.INTERPRETATIONWe present the risk of progression in those with radiographic evidence of disease and the rate of self-cure for microbiologically positive disease to inform global disease burden estimates, clinical guidelines and policy decisions.
Polygenic risk scores for asthma and allergic disease associate with COVID-19 severity in 9/11 responders
Authors: Waszczuk Monika A. , Morozova Olga , Lhuillier Elizabeth , Docherty Anna R. , Shabalin Andrey A. , Yang Xiaohua , Carr Melissa A. , Clouston Sean A. P. , Kotov Roman , Luft Benjamin J. 
Published: September 2022

AbstractBackgroundGenetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals.MethodsParticipants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection=56.06; 93.4% male; 82.7% European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category; 306 (31.1%) reported at least one post-acute COVID-19 symptom at 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates.FindingsThe asthma PRS was associated with severe COVID-19 category (odds ratio [OR]=1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β=.09,p=.01), independently of respiratory disease diagnosis. Severe COVID-19 category was also associated with the allergic disease PRS (OR=1.97, [1.26-3.07]) and the PRS for COVID-19 hospitalization (OR=1.35, [1.01-1.82]). PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity.ConclusionRecently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population.
Long-term spatial patterns in COVID-19 booster vaccine uptake
Authors: Wood A.J. , MacKintosh A.M. , Stead M. , Kao R.R. 
Published: September 2022

AbstractVaccination is a critical tool for controlling infectious diseases, with its use to protect against COVID-19 being a prime example. Where a disease is highly transmissible, even a small proportion of unprotected individuals can have substantial implications for disease burdens and compromise disease control. As socio-demographic factors such as deprivation and ethnicity have been shown to influence uptake rates, identifying how uptake varies with socio-demographic indicators is a critical step for reducing hesitancy and issues of access, and identifying plausible future uptake patterns.Here, we analyse the numbers of COVID-19 booster vaccinations subdivided by age, sex, dose and location. We use publicly available socio-demographic data, and use Random Forest models to capture patterns of first booster uptake at high spatial resolution, with systematic variation restricted to∼1km in urban areas. We introduce a novel method to predict future distributions using our first booster model, assuming existing trends with respect to deprivation will persist. This provides a quantitative estimate of the impact of changing motivations and efforts to increase uptake.While age and sex have the greatest impact on the model fit, there is a substantial influence of community deprivation and the proportion of residents belonging to a black or minority ethnicity. Changes in patterns from first to second boosters suggest in the longer-term that the impact of deprivation is likely to increase, furthering the disproportionate impact of COVID-19 on deprived communities. Our analysis is based solely on publicly available socio-demographic data and readily recorded vaccination data, and would be easily adaptable to uptake data from countries where data recording is similar, and for aiding vaccination campaigns against other infectious diseases.
Data augmentation for imbalanced blood cell image classification
Authors: Rana Priyanka , Sowmya Arcot , Meijering Erik , Song Yang 
Published: September 2022

ABSTRACTDue to progression in cell-cycle or duration of storage, classification of morphological changes in human blood cells is important for correct and effective clinical decisions. Automated classification systems help avoid subjective outcomes and are more efficient. Deep learning and more specifically Convolutional Neural Networks have achieved state-of-the-art performance on various biomedical image classification problems. However, real-world data often suffers from the data imbalance problem, owing to which the trained classifier is biased towards the majority classes and does not perform well on the minority classes. This study presents an imbalanced blood cells classification method that utilises Wasserstein divergence GAN, mixup and novel nonlinear mixup for data augmentation to achieve oversampling of the minority classes. We also present a minority class focussed sampling strategy, which allows effective representation of minority class samples produced by all three data augmentation techniques and contributes to the classification performance. The method was evaluated on two publicly available datasets of immortalised human T-lymphocyte cells and Red Blood Cells. Classification performance evaluated using F1-score shows that our proposed approach outperforms existing methods on the same datasets.
Profound lipid dysregulation in mutant TDP-43 mice is ameliorated by the glucocerebrosidase 2 inhibitor ambroxol
Authors: Luikinga Sophia , Henriques Alexandre , Ngo Shyuan T. , Rapasinghe Thusi , Loeffler Jean-Philippe , Spedding Michael , Turner Bradley J. 
Published: September 2022

AbstractThe importance of dyslipidemia in amyotrophic lateral sclerosis (ALS) patients is increasingly recognised as a potential key mechanism driving disease onset, progression and survival. Evidence in familial ALS models suggests that lipid composition is significantly affected, however clinically relevant models have yet to be investigated. Using a powerful lipidomic approach, we uncover significant dysregulation of glycosphingolipid (GSL) metabolism in both the spinal cord and skeletal muscles of transgenic TDP-43Q331K mice. Treatment with the selective glucocerebrosidase 2 (GBA2) inhibitor ambroxol at symptom onset significantly improved motor and gait functions in TDP-43Q331K mice. Ambroxol treatment preserved motor neurons and neuromuscular junctions which was associated with modulation of GSL metabolism. Our study establishes significant lipid dysregulation in a clinically relevant model of ALS. Importantly, we show positive therapeutic outcomes in a mouse model of TDP-43 proteinopathy, suggesting that ambroxol may be a promising candidate to treat underlying dyslipidemia and symptoms of ALS.
ACAT1/SOAT1 Blockade Suppresses LPS-Mediated Neuroinflammation by Modulating the Fate of Toll-Like Receptor 4 in Microglia
Authors: Li Haibo , Huynh Thao N. , Duong Michael Tran , Gow James G. , Chang Catherine C.Y. , Chang Ta-Yuan 
Published: September 2022

AbstractBackgroundCholesterol is essential for growth and maintenance of mammalian cells. It is stored as cholesteryl esters by the enzymes acyl-CoA:cholesterol acyltransferases 1 & 2 (ACAT 1 & 2) (Sterol O-acyltransferase 1 & 2; SOATs in GenBank). ACAT1 blockade (A1B) in macrophages ameliorates various pro-inflammatory responses elicited by lipopolysaccharides (LPS) or by cholesterol loading. In mouse and human brains, Acat1 expression dominates over Acat2 and Acat1 is elevated in many neurodegenerative diseases and in acute neuroinflammation. However, the possible effects of ACAT1 blockade in neuroinflammation, regulated by mediators such as Toll-Like Receptor 4 (TLR4), has not been studied.MethodsWe conducted LPS-induced acute neuroinflammation experiments in control vs myeloid specific or neuron specific Acat1 knockout (KO) mice. Furthermore, we evaluated LPS-induced neuroinflammation in the microglial cell line N9 with or without pre-treatment of the small molecule ACAT1-specific inhibitor K-604. Biochemical and microscopy assays were used to monitor inflammatory responses and the fate of TLR4.ResultsIn vivo studies revealed that Acat1 inactivation in myeloid cell lineage, but not in neurons, markedly attenuated LPS-induced activation of various pro-inflammatory response genes in hippocampus and cortex. Studies in cell culture showed that pre-incubating cells with K-604 significantly ameliorated the pro-inflammatory responses induced by LPS. In cells acutely treated with LPS (for 30 min), pre-incubation with K-604 significantly increased the endocytosis of TLR4, the major transmembrane signaling receptor that mediates LPS-dependent acute neuroinflammation. In cells chronically treated with LPS (for 24-48 hrs), pre-incubation with K-604 significantly decreased the total TLR4 protein content, presumably due to enhanced trafficking of TLR4 to the lysosomes for degradation. For ex vivo evidence, we isolated microglia from adult mice, and found that in mice without LPS stimulation, myeloid Acat1 inactivation altered cellular distribution of TLR4; in mice with LPS stimulation, myeloid Acat1 inactivation decreased the cellular content of TLR4.ConclusionBlocking ACAT1 in mouse microglia alters the fate of TLR4 and suppresses its ability to participate in pro-inflammatory signaling cascade in response to LPS.
Spatial analysis of the metastatic brain tumor immune and extracellular matrix microenvironment
Authors: Widodo Samuel S. , Dinevska Marija , Cuzcano Lucero , Papanicolaou Michael , Cox Thomas R. , Stylli Stanley S. , Mantamadiotis Theo 
Published: September 2022

AbstractMetastatic cancer is responsible for the overwhelming majority of cancer-related deaths with metastatic tumors being the most common neoplasms affecting the central nervous system. One of the major factors regulating tumor biology is the tumor microenvironment. However, little is known about the cellular and non-cellular composition of metastatic brain tumors and how tumor cell ontogeny influences the metastatic brain tumor microenvironment. By integrating multiplex immunohistochemistry and histopathological analysis to investigate composition and the spatial relationship between neoplastic cells, infiltrating and brain resident immune cells and the extracellular matrix, we demonstrate that metastatic brain tumors exhibit differences in ECM deposition, compared with the most common primary brain tumor type, glioblastoma, and that the dominant immune cell types in metastatic brain tumors are immunosuppressive macrophages, which preferentially localize to ECM-rich stromal regions.
COVID-19 disruptions of food systems and nutrition services in Ethiopia: Evidence of the impacts and policy responses
Authors: McCann Juliet , Sinno Lea , Ramadhan Eki , Assefa Nega , Berhane Hanna Y. , Madzorera Isabel , Fawzi Wafaie 
Published: September 2022

AbstractBackgroundSince its first case of COVID-19 on March 13, 2020 and Ethiopia has exerted efforts to curb the spread of the Coronavirus disease 2019 (COVID-19) without imposing a nationwide lockdown. Globally, COVID-19 related disruptions and mitigation measures have impacted livelihoods and food systems, nutrition, as well as access and use of health services.ObjectiveTo develop a comprehensive understanding of the impacts of the COVID-19 pandemic on food security and maternal and child nutrition and health services and to synthesize lessons from policy responses to the COVID-19 pandemic in Ethiopia.MethodsWe conducted a review of literature and 8 key informant interviews across government agencies, donors, and non-governmental organizations (NGOs), to map the impacts of the COVID-19 pandemic on the food and health systems in Ethiopia. We summarized policy responses and identified recommendations for future actions related to the COVID-19 pandemic and other future emergencies.ResultsThe impacts of the COVID-19 pandemic were felt across the food system. Disruptions were noted in inputs supply due to travel restrictions and closed borders restricting trade, reduced in-person support by agriculture extension workers, income losses, increases in food prices, and the reduction in food security and consumption of less diverse diets. Maternal and child health services were disrupted due to fear of contacting COVID-19, diversion of resources, and lack of personal protective equipment. Disruptions eased over time due to the expansion of social protection, through the Productive Safety Net Program, and the increased outreach and home service provision by the health extension workers.ConclusionEthiopia experienced disruptions to food systems and expanded existing social protection and public health infrastructure and leveraged partnerships with non-state actors. Nevertheless, vulnerabilities and gaps remain and there is a need for a long-term strategy that considers the cyclical nature of COVID-19 cases.
A clinical stage LMW-DS drug inhibits infection of human cells by Dengue, Zika and Yellow Fever viruses
Authors: Logan Ann , Mazzon Michela , Bruce Lars , Barnes Nicholas M. 
Published: September 2022

AbstractThe flavivirus family are responsible for the most abundant arboviral diseases of humans in terms of geographical distribution, morbidity and mortality; at least 2.5 billion people are at risk with, for example, an estimated 100-400 million Dengue infections a year. However, for infections by Dengue, Zika or Yellow Fever virus there are no effective anti-infective drug treatments nor for Dengue or Zika virus a safe effective vaccine and prevention at present focusses on vector (mosquito) control. Whilst symptoms from Dengue, Zika and Yellow Fever virus infection may be mild for some, they are very serious and life threatening for others. For instance, severe Dengue is a leading cause of hospitalisation and death among children and adults in Asian and Latin American countries. Likewise, Zika infection can have catastrophic consequences for pregnant women following the passing of the virus to their foetus with arising miscarriage or birth defects including microcephaly that can be fatal. The aim of the present study was to evaluate the potential of a unique low molecular weight dextran sulphate (LMW-DS) clinical stage drug, ILB®, to inhibit infection of human cells by four serotypes of Dengue virus (DENV1-4), two strains of Zika virus (African and Asian) and Yellow Fever virus (vaccine strain YF17D) assessed by immunofluorescence of viral particles. ILB® potently inhibited infection by all the strains of Dengue, Zika and Yellow Fever virus in a concentration-dependent manner with IC50 for ILB® ranging from 31 to 343 μg/ml. In conclusion, given the safety profile of ILB® established in a number of Phase I and Phase II clinical trials, these results highlight the potential of ILB® to treat patients infected with Dengue, Zika or Yellow Fever virus with the opportunity to translate the findings quickly by clinical investigation.