bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Systematic review of nonsyndromic craniosynostosis: genomic alterations and impacted signaling pathways.”
Authors: Albaugh Shaley L. , Diaz Ashley , Wang Esther , Shen Timothy C. , Williams Lydia , He Tong-Chuan , Reid Russell R. 
Published: April 2023

Background:
Genetic research in nonsyndromic craniosynostosis remains limited compared to syndromic craniosynostosis. This systematic review aimed to comprehensively summarize the genetic literature of nonsyndromic craniosynostosis and highlight key signaling pathways.

Methods:
The authors performed a systematic literature search of PubMed, Ovid, and Google Scholar databases from inception until December 2021 using search terms related to nonsyndromic craniosynostosis and genetics. Two reviewers screened titles and abstract for relevance, and three reviewers independently extracted study characteristics and genetic data. Gene networks were constructed using STRING11 analysis.

Results:
Thirty-three articles published between 2001 and 2020 met inclusion criteria. Studies were further classified into candidate gene screening and variant identification studies (16), genetic expression studies (13) and common and rare variant association studies (4). Most studies were good quality. Using our curated list of one-hundred and sixteen genes extracted from the studies, 2 main networks were constructed.

Conclusions:
This systematic review concerns the genetics of nonsyndromic craniosynostosis, with network construction revealing TGF-β/BMP, Wnt, and NF-kB/RANKL as important signaling pathways. Future studies should focus on rare rather than common variants to examine the missing heritability in this defect and going forward, adopt a standard definition.
Performance of a modified fracture risk assessment tool for fragility fracture prediction among older veterans living with HIV
Authors: Womack Julie A. , Murphy Terrence E. , Leo-Summers Linda , Kidwai-Khan Farah , Skanderson Melissa , Gill Thomas M. , Gulanski Barbara , Rodriguez-Barradas Maria C. , Tien Phyllis C. , Yin Michael T. , Hsieh Evelyn 
Published: April 2023

Objective:
Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a ‘modified FRAX’ identifies PAH at risk for fractures in a contemporary HIV cohort.

Design:
Cohort study.

Methods:
We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to us: age, sex, BMI, history of previous fracture, glucocorticoid use, rheumatoid arthritis, alcohol use, and smoking status. These predictor values were then used to estimate participant risk for each of two types of fractures (major osteoporotic and hip) over the subsequent 10 years in strata defined by race/ethnicity using multivariable logistic regression.

Results:
Discrimination for major osteoporotic fracture was modest [Blacks: area under the curve (AUC) 0.62; 95% confidence interval (CI) 0.62, 0.63; Whites: AUC 0.61; 95% CI 0.60, 0.61; Hispanic: AUC 0.63; 95% CI 0.62, 0.65]. For hip fractures, discrimination was modest to good (Blacks: AUC 0.70; 95% CI 0.69, 0.71; Whites: AUC 0.68; 95% CI 0.67, 0.69]. Calibration was good in all models across all racial/ethnic groups.

Conclusion:
Our ‘modified FRAX’ exhibited modest discrimination for predicting major osteoporotic fracture and slightly better discrimination for hip fracture. Future studies should explore whether augmentation of this subset of FRAX predictors results in enhanced prediction of fractures among PAH.
Experiencing homelessness and progression through the HIV cascade of care among people who use drugs
Authors: Reddon Hudson , Fairbairn Nadia , Grant Cameron , Milloy M-J 
Published: April 2023

Objective:
To investigate the longitudinal association between periods of homelessness and progression through the HIV cascade of care among people who use drugs (PWUD) with universal access to no-cost HIV treatment and care.

Design:
Prospective cohort study.

Methods:
Data were analysed from the ACCESS study, including systematic HIV clinical monitoring and a confidential linkage to comprehensive antiretroviral therapy (ART) dispensation records. We used cumulative link mixed-effects models to estimate the longitudinal relationship between periods of homelessness and progression though the HIV cascade of care.

Results:
Between 2005 and 2019, 947 people living with HIV were enrolled in the ACCESS study and 304 (32.1%) reported being homeless at baseline. Homelessness was negatively associated with overall progression through the HIV cascade of care [adjusted partial proportional odds ratio (APPO) = 0.56, 95% confidence interval (CI): 0.49–0.63]. Homelessness was significantly associated with lower odds of progressing to each subsequent stage of the HIV care cascade, with the exception of initial linkage to care.

Conclusions:
Homelessness was associated with a 44% decrease in the odds of overall progression through the HIV cascade of care, and a 41–54% decrease in the odds of receiving ART, being adherent to ART and achieving viral load suppression. These findings support calls for the integration of services to address intersecting challenges of HIV, substance use and homelessness among marginalized populations such as PWUD.
Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV
Authors: Rubin Leah H. , Du Yong , Sweeney Shannon Eileen , O’Toole Riley , Harrington Courtney K. , Jenkins Katelyn , Lesniak Wojciech G. , Veenhuis Rebecca T. , Dastgheyb Raha , Severson Joan , Fan Hong , Holt Daniel P. , Hall Andrew W. , Dannals Robert F. , Horti Andrew G. , Pomper Martin G. , Coughlin Jennifer M. 
Published: April 2023

Objective:
Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target.

Design:
[11C]CPPC, 5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxaminde, is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [11C]CPPC PET in virally-suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH.

Methods:
Sixteen VS-PWH and 15 HIV-uninfected individuals completed [11C]CPPC PET. [11C]CPPC binding (VT) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups.

Results:
Regional [11C]CPPC VT did not significantly differ between groups after age- and sex- adjustment [unstandardized beta coefficient (B) = 1.84, standard error (SE) = 1.18, P = 0.13]. The effect size was moderate [Cohen's d = 0.56, 95% confidence interval (CI) −0.16, 1.28), with strongest trend of higher VT in VS-PWH in striatum and parietal cortex (each P = 0.04; Cohen's d = 0.71 and 0.72, respectively).

Conclusions:
A group difference in [11C]CPPC VT was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.
Stunted Growth Is Associated With Dyslipidemia in Young Adults With Perinatal HIV Infection
Authors: Lesiapeto Maemo , Shults Justine , Mmunyane Mogakolodi , Matshaba Mogomotsi , Lowenthal Elizabeth D. 
Published: April 2023

Background:
HIV increases the risk of atherosclerosis and cardiovascular diseases (CVD). This risk maybe even higher in adult survivors of perinatal HIV infection because of prolonged exposure to HIV and its treatments. Nutritional deprivation in early life may further increase CVD risk.

Setting:
Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone.

Methods:
This study examined dyslipidemia in 18- to 24-year olds with perinatally-acquired HIV with and without linear growth retardation (“stunting”). Anthropometry and lipid profiles were measured following a minimum 8-hour fast. Stunting was defined by a height-for-age z-score of <2 SDs below the mean. Dyslipidemia was defined by non–high-density lipoprotein cholesterol (HDL-C) of ≥130 mg/dL, low-density lipoprotein cholesterol (LDL-C) of ≥100 mg/dL, or HDL of <40 mg/dL for male subjects and <50 mg/dL for female subjects. We used logistic regression to determine whether dyslipidemia was associated with stunting while adjusting for demographic and HIV treatment variables.

Results:
Of 107 young adults (46 males; 61 females) enrolled, 36 (33.6%) were stunted. Prevalence of dyslipidemia was 11.2%, 24.3%, and 65.4% for high non-HDL-C, high LDL-C, and low HDL-C, respectively. In univariable analysis, being stunted was associated with elevated LDL-C (odds ratio [OR], 2.52; 95% confidence interval [CI] =1.02 to 6.25) but not with elevated non-HDL-C (OR = 2.17; 95% CI: = 0.65 to 7.28) or with low HDL-C (OR = 0.75; 95% CI: = 0.33 to 1.73). The association between stunting and elevated LDL-C (OR = 4.40; 95% CI: = 1.49 to 12.98) remained significant after controlling for measured confounders.

Conclusion:
Dyslipidemia was common among perinatally HIV-infected youth and those with evidence of early nutritional deprivation who were more likely to have elevated LDL-C.
ALTERED LEVELS OF H3K9AC, H3K4ME3, AND H3K27ME3 IN PROMOTERS OF DIFFERENTIALLY EXPRESSED GENES RELATED TO INNATE IMMUNE RESPONSE IN SEPTIC PATIENTS WITH DIFFERENT CLINICAL OUTCOMES
Authors: Falcão-Holanda Renata Brito , Leite Giuseppe Gianini Figueirêdo , Brunialti Milena Karina Colo , Jasiulionis Miriam Galvonas , Salomão Reinaldo 
Published: April 2023

ABSTRACT
Sepsis is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients. These results were compared with public transcriptome data of the target genes and epigenetic enzymes that modulate the histone modifications. We used peripheral blood mononuclear cell from surviving and nonsurviving septic patients, and healthy volunteers to evaluate the expression of genes involved in innate immune response and the enrichment of H3K9ac, H3K4me3, and H3K27me3 in their promoters, by RT-qPCR and ChIP, respectively. Finally, we used transcriptome data sets to validate our findings. We found alterations in the chromatin enrichment of different genes, with an increase in H3K9ac in the anti-inflammatory cytokine IL-10 and the antimicrobial gene FPR1, as well as an increase in H3K27me3 in the IL-10 and HLA-DR promoter in nonsurvivors septic patients when compared with survivors. These alterations were partially associated with the gene expression profile. In addition, we found moderate to strong correlation between gene transcription and the enzymes that modulate these histone modifications in the transcriptome data sets. Our study, one of the pioneering by evaluating septic patients’ samples, suggests that epigenetic enzymes modulate the prevalent histone marks in promoters of genes involved in the immune-inflammatory response, altering the transcription of these specific genes during sepsis. Furthermore, nonsurviving sepsis patients have a more pronounced epigenetic dysregulation compared with survivors, suggesting a more dysfunctional response.
Two artificial tears outbreak-associated cases of XDRPseudomonas aeruginosadetected through whole genome sequencing-based surveillance
Authors: Sundermann Alexander J. , Srinivasa Vatsala Rangachar , Mills Emma G. , Griffith Marissa P. , Waggle Kady D. , Ayres Ashley M. , Pless Lora , Snyder Graham M. , Harrison Lee H. , Van Tyne Daria 
Published: April 2023

ABSTRACTWe describe two cases of XDRPseudomonas aeruginosainfection caused by a strain of public health concern recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from one of the case isolates from our center and examined the mobile elements encodingblaVIM-80andblaGES-9carbapenemases. We then used publicly availableP. aeruginosagenomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain.
Exploring non-linear associations of maternal pre-pregnant body mass index with risk of stillbirth, infant and neonatal mortality in over 21 million US births
Authors: Thornton Hannah V , Cornish Rosie P , Lawlor Deborah A 
Published: April 2023

AbstractBackgroundHigher maternal pre-pregnancy body mass index (BMI) has been associated with higher risk of stillbirth, infant and neonatal mortality. Few studies have explored associations of underweight, with those that have varying in their conclusions. Our aim was to examine the risk of stillbirth, infant and neonatal mortality across the pre-pregnancy BMI distribution and establish a likely healthy BMI range.MethodsWe used publicly available birth, infant death and fetal death datasets from the US National Center for Health Statistics National Vital Statistics System, 2014–2020. Fractional polynomial multivariable logistic regression was used to examine the nature of associations between maternal pre-pregnant BMI and stillbirth (birth with no signs of life at ≥24 weeks), infant mortality (death of a live born baby aged <365 days) and neonatal mortality (death of a live born baby aged <28 days).FindingsThere were 56,376/21,437,556 (0.26%) stillbirths, 108,413/24,742,273 (0.44%) infant deaths and 66,801/24,742,273 (0.27%) neonatal deaths among complete cases. Mean BMI was 27.0 kg/m2. We found non-linear associations between pre-pregnant BMI and all three outcomes - risk was elevated at both low and high BMIs although, for stillbirth, the increased risk at low BMI was less marked than for infant and neonatal mortality. The lowest risk was at a BMI of 21 kg/m2for infant and neonatal mortality and, for stillbirth, at 18 kg/m2.InterpretationPublic health messaging for preconception and postnatal care should focus on healthy weight to maximise maternal and child health, and not focus solely on maternal overweight or obesity.
Nowcasting and Forecasting the 2022 U.S. Mpox Outbreak: Support for Public Health Decision Making and Lessons Learned
Authors: Charniga Kelly , Madewell Zachary J. , Masters Nina B. , Asher Jason , Nakazawa Yoshinori , Spicknall Ian H. 
Published: April 2023

AbstractIn June of 2022, the U.S. Centers for Disease Control and Prevention (CDC) Mpox Response wanted timely answers to important epidemiological questions which can now be answered more effectively through infectious disease modeling. Infectious disease models have shown to be valuable tool for decision making during outbreaks; however, model complexity often makes communicating the results and limitations of models to decision makers difficult. We performed nowcasting and forecasting for the 2022 mpox outbreak in the United States using the R package EpiNow2. We generated nowcasts/forecasts at the national level, by Census region, and for jurisdictions reporting the greatest number of mpox cases. Modeling results were shared for situational awareness within the CDC Mpox Response and publicly on the CDC website. We retrospectively evaluated forecast predictions at four key phases during the outbreak using three metrics, the weighted interval score, mean absolute error, and prediction interval coverage. We compared the performance of EpiNow2 with a naïve Bayesian generalized linear model (GLM). The EpiNow2 model had less probabilistic error than the GLM during every outbreak phase except for the early phase. We share our experiences with an existing tool for nowcasting/forecasting and highlight areas of improvement for the development of future tools. We also reflect on lessons learned regarding data quality issues and adapting modeling results for different audiences.
Interference between Venus-A Valve and Anterior Mitral Valve Leaflets after Transcatheter Aortic Valve Replacement: Insight from FEops HEARTguide simulation
Authors: Wang Yong , Liu Ting , Zeng Ying , Debusschere Nic , Rocatello Giorgia , Cheng Sihang , Li Ping , Qian Dehui , Yu Shiyong , Jin Jun 
Published: April 2023

AbstractBackgroundScarce data exist regarding the occurrence of mitral valve interference after transcatheter aortic valve replacement (TAVR) with Venus-A valve implantation. Several case reports have noted that the anterior mitral leaflet (AML) is mechanically affected by the prosthesis frame, particularly when implanted in a low position. This study aimed to investigate the potential factors influencing the clinical outcomes of AML interference after Venus-A valve implantation.MethodsWe retrospectively included 20 severe aortic valve stenosis patients who had undergone TAVR and had been implanted with the Venus-A valve at our hospital between October 2020 and June 2021. Pre- and post-procedural CT scans were used for the FEops HEARTguide simulation. Anatomically influencing factors were measured using the 3mensio software and derived from the FEops HEARTguide. The prosthesis-AML interference (PAI) was defined when it met both of two criteria:1) significant interference and limited AML movement shown by transthoracic or transoesophageal echocardiography, and 2) more than half cell intersection between the simulated Venus-A valve and the reconstructed AML revealed by the FEops HEARTguide. Anatomical factors and clinical outcomes were compared between the PAI and non-PAI groups.ResultsNine PAI patients and 11 non-PAI cases were identified. PAI was associated with shorter mitral-aortic annulus distance (2.7±1.7 mm vs 5.0±2.2 mm,P= 0.019), larger prosthesis valve size (P= 0.013), deeper implantation (12.2±3.3 mm vs 6.2±2.9 mm at non-coronary cusp side,P< 0.001) and less calcification of non-coronary cusp (median calcification score, 52.2 mm3vs 156.0 mm3,P= 0.046). Regarding the clinical impact, PAI was associated with a higher rate of moderate or severe perivalvular leakage before discharge than those associated with the absence of PAI, with no difference in haemodynamic parameters and incidence of adverse events at the 30-day and 12-month follow-ups between the groups.ConclusionsInterference between the Venus-A prosthesis valve and AML after TAVR was associated with a shorter mitral-aortic annulus distance, larger prosthesis usage, greater implantation depth, and less calcification of the non-coronary cusp. However, further studies are required to explore its long-term clinical impact.
Aspergillus SUMOylation mutants have normal dynein function but exhibit chromatin bridges
Authors: Zhang Jun , Qiu Rongde , Bieger Baronger D. , Oakley C. Elizabeth , Oakley Berl R. , Egan Martin J. , Xiang Xin 
Published: April 2023

AbstractFunctions of protein SUMOylation remain incompletely understood in different cell types. The budding yeast SUMOylation machinery interacts with LIS1, a protein critical for dynein activation, but dynein-pathway components were not identified as SUMO-targets in the filamentous fungusAspergillus nidulans. ViaA. nidulansforward genetics, here we identifiedubaBQ247*, a loss-of-function mutation in a SUMO-activation enzyme UbaB. Colonies of theubaBQ247*, ΔubaBand ΔsumOmutants looked similar and less healthy than the wild-type colony. In these mutants, about 10% of nuclei are connected by abnormal chromatin bridges, indicating the importance of SUMOylation in the completion of chromosome segregation. Nuclei connected by chromatin bridges are mostly in interphase, suggesting that these bridges do not prevent cell-cycle progression. UbaB-GFP localizes to interphase nuclei just like the previously studied SumO-GFP, but the nuclear signals disappear during mitosis when the nuclear pores are partially open, and the signals reappear after mitosis. The nuclear localization is consistent with many SUMO-targets being nuclear proteins, for example, topoisomerase II whose SUMOylation defect gives rise to chromatin bridges in mammalian cells. Unlike in mammalian cells, however, loss of SUMOylation inA. nidulansdoes not apparently affect the metaphase-to-anaphase transition, further highlighting differences in the requirements of SUMOylation in different cell types. Finally, loss of UbaB or SumO does not affect dynein-and LIS1-mediated early-endosome transport, indicating that SUMOylation is unnecessary for dynein or LIS1 function inA. nidulans.
An explainable graph neural framework to identify cancer-associated intratumoral microbial communities
Authors: Liu Zhaoqian , Sun Yuhan , Ma Anjun , Wang Xiaoying , Xu Dong , Spakowics Daniel , Ma Qin , Liu Bingqiang 
Published: April 2023

ABSTRACTMicrobes are extensively present among various cancer tissues and play a vital role in cancer prevention and treatment responses. However, the underlying relationships between intratumoral microbes and tumors are still not well understood. Here, we developed a MIcrobial Cancer-association Analysis using a Heterogeneous graph transformer (MICAH) to identify intratumoral cancer-associated microbial communities. MICAH integrates metabolic and phylogenetic relationships among microbes into a heterogeneous graph representation. It uses a graph attention transformer to holistically capture the relationships between intratumoral microbes and cancer tissues, which improves the explainability of the association between identified microbial communities and cancer. We applied MICAH to intratumoral microbiome data across five cancer types and demonstrated its good generalizability and reproducibility. We believe this graph neural network framework can provide novel insights into cancer pathogenesis associated with the intratumoral microbiome.