bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus
Authors: Lake Jordan E. , Wang Ruibin , Barrett Benjamin W. , Bowman Emily , Hyatt Ana N. , Debroy Paula , Candelario Jury , Teplin Linda , Bodnar Kaitlin , McKay Heather , Plankey Michael , Brown Todd T. , Funderburg Nicholas , Currier Judith S. 
Published: August 2022

Background:
Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW).

Methods:
TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations.

Results:
TW (HIV+ n = 75, HIV− n = 47) and CM (HIV+ n = 40, HIV− n = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P < 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1.

Conclusions:
Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV.
A randomized study of intensified antiretroviral treatment monitoring versus standard-of-care for prevention of drug resistance and antiretroviral treatment switch
Authors: Hermans Lucas E. , Ter Heine Rob , Schuurman Rob , Tempelman Hugo A. , Burger David M. , Vervoort Sigrid C.J.M. , Deville Walter L.J.M. , De Jong Dorien , Venter Willem D.F. , Nijhuis Monique , Wensing Annemarie M.J. 
Published: August 2022

Introduction:
Standard-of-care antiretroviral treatment (ART) monitoring in low and middle-income countries consists of annual determination of HIV-RNA viral load with confirmatory viral load testing in case of viral rebound. We evaluated an intensified monitoring strategy of three-monthly viral load testing with additional drug exposure and drug resistance testing in case of viral rebound.

Methods:
We performed an open-label randomized controlled trial (RCT) at a rural South African healthcare clinic, enrolling adults already receiving or newly initiating first-line ART. During 96 weeks follow-up, intervention participants received three-monthly viral load testing and sequential point-of-care drug exposure testing and DBS-based drug resistance testing in case of rebound above 1000 copies/ml. Control participants received standard-of-care monitoring according to the WHO guidelines.

Results:
Five hundred one participants were included, of whom 416 (83.0%) were randomized at 24 weeks. Four hundred one participants were available for intention-to-treat analysis. Viral rebound occurred in 9.0% (18/199) of intervention participants and in 11.9% (24/202) of controls (P = 0.445). Time to detection of rebound was 375 days [interquartile range (IQR): 348–515] in intervention participants and 360 days [IQR: 338–464] in controls [hazard ratio: 0.88 (95% confidence interval (95% CI): 0.46–1.66]; P = 0.683]. Duration of viral rebound was 87 days [IQR: 70–110] in intervention participants and 101 days [IQR: 78–213] in controls (P = 0.423). In the control arm, three patients with confirmed failure were switched to second-line ART. In the intervention arm, of three patients with confirmed failure, switch could initially be avoided in two cases.

Conclusion:
Three-monthly viral load testing did not significantly reduce the duration of viraemia when compared with standard-of-care annual viral load testing, providing randomized trial evidence in support of annual viral load monitoring.
Early Recurrence After Resection of Locally Advanced Pancreatic Cancer Following Induction Therapy
Authors: Seelen Leonard W.F. , Floortje van Oosten Anne , Brada Lilly J.H. , Groot Vincent P. , Daamen Lois A. , Walma Marieke S. , van der Lek Bastiaan F. , Liem Mike S.L. , Patijn Gijs A. , Stommel Martijn W.J. , van Dam Ronald M. , Koerkamp Bas Groot , Busch Olivier R. , de Hingh Ignace H.J.T. , van Eijck Casper H.J. , Besselink Marc G. , Burkhart Richard A. , Borel Rinkes Inne H.M. , Wolfgang Christopher L. , Molenaar Izaak Quintus , He Jin , van Santvoort Hjalmar C. 
Published: August 2022

Objective:
To establish an evidence-based cutoff and predictors for early recurrence in patients with resected locally advanced pancreatic cancer (LAPC).

Background:
It is unclear how many and which patients develop early recurrence after LAPC resection. Surgery in these patients is probably of little benefit.

Methods:
We analyzed all consecutive patients undergoing resection of LAPC after induction chemotherapy who were included in prospective databases in The Netherlands (2015–2019) and the Johns Hopkins Hospital (2016–2018). The optimal definition for “early recurrence” was determined by the post-recurrence survival (PRS). Patients were compared for overall survival (OS). Predictors for early recurrence were evaluated using logistic regression analysis.

Results:
Overall, 168 patients were included. After a median follow-up of 28 months, recurrence was observed in 118 patients (70.2%). The optimal cutoff for recurrence-free survival to differentiate between early (n=52) and late recurrence (n=66) was 6 months (P<0.001). OS was 8.4 months [95% confidence interval (CI): 7.3–9.6] in the early recurrence group (n=52) versus 31.1 months (95% CI: 25.7–36.4) in the late/no recurrence group (n=116) (P<0.001). A preoperative predictor for early recurrence was postinduction therapy carbohydrate antigen (CA) 19-9≥100 U/mL [odds ratio (OR)=4.15, 95% CI: 1.75–9.84, P=0.001]. Postoperative predictors were poor tumor differentiation (OR=4.67, 95% CI: 1.83–11.90, P=0.001) and no adjuvant chemotherapy (OR=6.04, 95% CI: 2.43–16.55, P<0.001).

Conclusions:
Early recurrence was observed in one third of patients after LAPC resection and was associated with poor survival. Patients with post-induction therapy CA 19-9 ≥100 U/mL, poor tumor differentiation and no adjuvant therapy were especially at risk. This information is valuable for patient counseling before and after resection of LAPC.
Racial and Ethnic Differences in Elective Versus Emergency Surgery for Colorectal Cancer
Authors: Howard Ryan , Hendren Samantha , Patel Minal , Gunaseelan Vidhya , Wixson Matthew , Waljee Jennifer , Englesbe Michael , Bicket Mark C. 
Published: August 2022

Objective:
To evaluate differences in presentation and outcomes of surgery for colorectal cancer.

Background:
Although racial and socioeconomic disparities in colorectal cancer outcomes are well documented, disparities in access affecting disease presentation are less clear.

Methods:
We conducted a statewide retrospective study of patients who underwent resection for colorectal cancer between January 1, 2015, and April 30, 2021. The primary outcome was undergoing emergency surgery. Secondary outcomes included preoperative evaluation and postoperative outcomes. Covariates of interest included race/ethnicity, social deprivation index, and insurance type.

Results:
A total of 4869 patients underwent surgery for colorectal cancer, of whom 1122 (23.0%) underwent emergency surgery. Overall, 28.1% of Black non-Hispanic patients and 22.5% of White non-Hispanic patients underwent emergency surgery. On multivariable logistic regression, Black non-Hispanic race was independently associated with a 5.8 (95% CI, 0.3–11.3) percentage point increased risk of emergency surgery compared with White non-Hispanic race. Patients who underwent emergency surgery were significantly less likely to have preoperative carcinoembryonic antigen measurement, staging for rectal cancer, and wound/ostomy consultation. Patients who underwent emergency surgery had a higher incidence of 30-day mortality (5.5% vs 1.0%, P<0.001), positive surgical margins (11.1% vs 4.9%, P<0.001), complications (29.2% vs 16.0%, P<0.001), readmissions (12.5% vs 9.6%, P=0.005), and reoperations (12.2% vs 8.2%, P<0.001).

Conclusions:
Among patients with colorectal cancer, Black non-Hispanic patients were more likely to undergo emergency surgery than White non-Hispanic patients, suggesting they may face barriers to timely screening and evaluation. Undergoing emergency surgery was associated with incomplete oncologic evaluation, increased incidence of postoperative complications including mortality, and increased surgical margin positivity. These results suggest that racial and ethnic differences in the diagnosis and treatment of colorectal cancer impact near-term and long-term outcomes.
Segmental Versus Diffuse Main Duct Intraductal Papillary Mucinous Neoplasm
Authors: Ecker Brett L. , Dickinson Shannan M. , Saadat Lily V. , Tao Alice J. , Pulvirenti Alessandra , Balachandran Vinod P. , D’Angelica Michael I. , Drebin Jeffrey A. , Kingham T.P. , Jarnagin William R. , Wei Alice C. , Gonen Mithat , Soares Kevin C. 
Published: August 2022

Objective:
To determine whether the morphologic features of the main pancreatic duct (MPD) of main-duct-involved-intraductal papillary mucinous neoplasm (IPMN) (ie, main duct or mixed main duct/side branch) have implications for the risk of malignancy and extent of resection.

Background:
International consensus guidelines acknowledge the presence of various MPD morphologies (ie, diffuse vs segmental main-duct-involved-IPMN) without a precise definition of each entity and with limited data to guide treatment strategy.

Methods:
All consecutive main-duct-involved-IPMN patients (2005–2019) with a MPD diameter ≥5 mm by cross-sectional imaging were reviewed from a prospective institutional database. Morphologic features of the MPD were correlated with the identification of high-grade dysplasia or pancreatic ductal adenocarcinoma (HGD/PDAC) by logistic regression modeling. In patients who underwent partial pancreatectomy, preoperative MPD morphologic features were correlated with the future development of HGD/PDAC in the pancreatic remnant by Cox hazards modeling.

Results:
In a cohort of 214 main-duct-involved-IPMN patients, the overall rate of HGD/PDAC was 54.2%. MPD morphologic characteristics associated with HGD/PDAC included: maximal MPD diameter (5–10 mm: 29.8%; 10–14 mm: 59.0%; 15–19 mm: 78.6%; ≥20 mm: 95.8%; P<0.001), segmental extent of maximal dilation (<25%: 28.2%; 25%–49%: 54.9%; 50%–74%: 63.1%; ≥75%: 67.9%; P=0.002), and nonsegmental MPD diameter (<5 mm: 21.5% vs ≥5 mm: 78.5%, P<0.001). Diffuse MPD dilation involving ≥90% extent was rare (5.6%). After a median follow-up of 50 months, 7 (7.2%) patients who underwent partial pancreatectomy for IPMN without associated PDAC developed HGD/PDAC in the pancreatic remnant. Maximal MPD diameter, segmental extent of maximal dilation, or nonsegmental MPD diameter were not associated with the development of HGD/PDAC in the pancreatic remnant. However, a mural nodule on preoperative imaging was associated with the development of HGD/PDAC in the pancreatic remnant.

Conclusions:
“Diffuse” involvement with homogenous dilation of the MPD was rare. For the majority of patients with segmental main-duct-involved-IPMN, the MPD morphology conferred malignancy risk. Duct morphology was not predictive for the development of HGD or invasive disease in the pancreatic remnant, implying the safety of limited pancreatic resection for initial surgical management.
Cloud-controlled microscopy enables remote project-based biology education in Latinx communities in the United States and Latin America
Authors: Baudin Pierre V. , Sacksteder Raina E. , Worthington Atesh K. , Voitiuk Kateryna , Ly Victoria T. , Hoffman Ryan N. , Elliott Matthew A.T. , Parks David F. , Ward Rebecca , Torres-Montoya Sebastian , Amend Finn , Montellano Duran Natalia , Vargas Paola A. , Martinez Guadalupe , Alvarado-Arnez Lucia Elena , Ehrlich Drew , Rosen Yohei M. , Breevoort Arnar , Schouten Tallulah , Kurniawan Sri , Haussler David , Teodorescu Mircea , Mostajo-Radji Mohammed A. 
Published: August 2022

AbstractProject-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment allowing simultaneous interaction by many students worldwide. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeat standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were executed in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments’ conclusion, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.
The Impact of Population Stratification on the Analysis of Multimodal Neuroimaging Derived Measures
Authors: Huang Tzu Hsuan , Loughnan Robert , Thompson Wesley K , Fan Chun Chieh 
Published: August 2022

AbstractMagnetic resonance imaging (MRI) studies of the human brain are now attaining larger sample sizes with more diverse samples. However, population stratification, a key factor driving heterogeneity and confounding of associations, is seldom accounted for in neuroimaging analyses. To investigate this issue, we assessed the impact of population stratification on multimodal imaging measures using baseline data from the Adolescent Brain Cognitive Development (ABCD) StudySM (n = 10,748). Given this sociodemographically diverse sample, which broadly reflects the population composition of the United States, we performed a thorough evaluation of the impact of population stratification on derived neuroimaging metrics across five different imaging modalities: task functional MRI (task fMRI), resting state functional MRI (rsMRI), diffusion tensor images (DTI), restricted spectrum images (RSI), and structural T1 MRI (sMRI). We used parental income level as an example to highlight the impact of population stratification in confounding brain-wide associations. We show that derived metrics from structural images have up to three times more signal related to population stratification than do functional images. Controlling for population stratification in statistical models leads to a substantial reduction in the association strength between variables of interests and imaging measures, indicating the scale of potential bias. Moreover, because of unequal access to resources (such as income) across ancestral groups in United States, population stratification effects on imaging features may bias associations between parental income levels and imaging features, as we demonstrate. Our results provide a guide for researchers to critically examine the impact of population stratification and to assist in avoiding spurious brain-behavior associations.HighlightsHere, we conduct a comprehensive survey of the confounding impact of population stratification in large-scale imaging studies.Morphological features from structural imaging appear to be more susceptible to the confounding effects of population stratification than do functional imaging features.The population stratification tends to inflates the association strengths between the variable of interest and imaging features.When the variable of interest is highly colinear with the population stratification, such as income levels, brain associations cannot be differentiated and may be misattributed as mediating effects.It is critical to account for population stratification in imaging analyses.
“METAVIR score Ultrasound” – Pictorial Essay of Anatomy / Ultrasound / Elastography / Histology
Authors: de Oliveira Andrade Luís Jesuino , de Oliveira Luís Matos , Matos de Oliveira Gabriela Correia 
Published: August 2022

AbstractThe METAVIR score was specifically elaborated and evaluated in chronic hepatitis C, is scoring system for evaluation the inflammatory activity and fibrosis on liver biopsies, although it ultrasound may indicate the fibrosis degree.ObjectiveTo present a pictorial essay by composing histological, ultrasound and elastography images of the METAVIR score of fibrosis.MethodUsing software for image composition, based on the sonographic image of the liver with degrees of fibrosis, secondary to hepatitis C, we adapted the corresponding histological image (METAVIR) and presented a pictorial essay.ResultsThe correlation of the anatomical image with the sonographic image and of the histological image with the corresponding sonographic image and elastography image are demonstrated.ConclusionUltrasonographic features and elastography in evaluation hepatic fibrosis present in hepatitis C can correlate with histological features METAVIR score.
HSPA8 chaperone complex drives chaperone-mediated autophagy regulation in acute promyelocytic leukemia differentiation
Authors: Rafiq Sreoshee , Mungure Irene , Niklaus Nicolas J. , Müller Stefan , Jacquel Arnaud , Robert Guillaume , Auberger Patrick , Torbett Bruce E. , Muller Sylviane , Tschan Mario P. , Humbert Magali 
Published: August 2022

AbstractAcute myeloid leukemia (AML) is a cancer of the hematopoietic system characterized by the hyperproliferation of undifferentiated cells of the myeloid lineage. While most of AML therapy are focusing on tumor debulking, all-trans retinoic acid (ATRA) induces differentiation in acute promeylocytic leukemia (APL) a particular subtype. Macroautophagy has been extensively investigated in the context of various cancers and is often dysregulated in AML where it can have context-dependent pro- or anti-leukemogenic effects. On the contrary, the implications of chaperone-mediated autophagy (CMA) on the pathophysiology of diseases are still being explored and its role in AML has remained elusive. To answer our questions we took advantages of human AML primary samples and databases. Furthermore, we used ATRA-sensitive (NB4) and –resistant (NB4-R1) cells to further dissect a potential function for CMA in ATRA-mediated neutrophil differentiation. NB4-R1 cells are unique in that they do respond to retinoic acid transcriptionally, but do not mature in response to retinoid signaling alone unless maturation is triggered by adding cAMP. Here, we report that CMA related mRNA transcripts are higher expressed in immature hematopoietic cells as compared to neutrophils. In line, lysosomal degradation of mCherry-KFERQ CMA reporter decreases during ATRA-induced differentiation of APL cells. On the other hand, using NB4-R1 cells we found that macroautophagy flux primed the ATRA resistant NB4-R1 cells to differentiate upon ATRA treatment, but reduced association of LAMP-2A and HSPA8 is necessary for complete neutrophil maturation. Accordingly, depletion of HSPA8 attenuated CMA activity and facilitated APL differentiation. In contrast, maintaining high CMA activity by ectopic expression of LAMP-2A impeded APL differentiation. Overall, our findings demonstrate that both normal and APL neutrophil differentiation require CMA downregulation and this pathway is predominantly dependent on HSPA8 assisted by other co-chaperones.
Fusarium oxysporum Effector Clustering version 2 (FoEC2): an updated pipeline to infer host range
Authors: Brenes Guallar Megan A. , Fokkens Like , Rep Martijn , Berke Lidija , van Dam Peter 
Published: August 2022

1AbstractThe fungus Fusarium oxysporum is infamous for its devastating effects on economically important crops worldwide. F. oxysporum isolates are grouped into formae speciales based on their ability to cause disease on different hosts. Assigning F. oxysporum strains to formae speciales using non-experimental procedures has proven to be challenging due to their genetic heterogeneity and polyphyletic nature. However, genetically diverse isolates of the same forma specialis encode similar repertoires of effectors, proteins that are secreted by the fungus and contribute to the establishment of compatibility with the host. Based on this observation, we previously designed the F. oxysporum Effector Clustering (FoEC) pipeline which is able to classify F. oxysporum strains by forma specialis based on hierarchical clustering of the presence of predicted putative effector sequences, solely using genome assemblies as input. Here we present the updated FoEC2 pipeline which is more user friendly, customizable and, due to multithreading, has improved scalability. It is designed as a Snakemake pipeline and incorporates a new interactive visualization app. We showcase FoEC2 by clustering 537 publicly available F. oxysporum genomes and further analysis of putative effector families as multiple sequence alignments. We confirm classification of isolates into formae speciales and are able to further identify their subtypes. The pipeline is available on github: https://github.com/pvdam3/FoEC2.
The effects of ethnoracial-related stressors during pregnancy on the developing offspring brain
Authors: Spann Marisa N. , Alleyne Kiarra , Holland Cristin M. , Davids Antonette , Pierre-Louis Arline , Bang Claire , Oyeneye Victoria , Kiflom Rebecca , Shea Eileen , Cheng Bin , Peterson Bradley S. , Monk Catherine , Scheinost Dustin 
Published: August 2022

AbstractWe are increasingly aware of the effects of ethnoracial stress on health, with emerging interest in the potential for intergenerational transmission before birth. Here, we investigate the effect of maternal prenatal discrimination and acculturation experiences on fetal growth, birth outcomes, and functional connectivity in the infant brain. In pregnant adolescent women, we collected self-report measures of acculturation (tailored to an adolescent and Latinx population), discrimination, and maternal distress (i.e., stress and depressive symptoms; n=165). Fetal growth were obtained via electronic health records (n=92), and infant amygdala seed connectivity was assessed using functional magnetic resonance imaging (n=38). We found that greater maternal prenatal assimilation to the host culture was associated with slower fetal growth, lower gestational age at birth, and weaker amygdala-fusiform connectivity. Maternal prenatal discrimination was associated with weaker amygdala-prefrontal connectivity. Together, these results suggest intergenerational effects of ethnoracial stressors on the growth and neural development of future generations.