bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of hormone therapy with blood pressure control in postmenopausal women with hypertension: a secondary analysis of the Women's Health Initiative clinical trials
Authors: Jiang Xuezhi , Aragaki Aaron K. , Nudy Matthew , Manson JoAnn E. , Shadyab Aladdin H. , Wild Robert A. , Valdiviezo Carolina , Gass Margery , Martin Lisa Warsinger , Pan Kathy , Stefanick Marcia L. , Robbins John A. , Schnatz Peter F. 
Published: October 2022

Abstract

Objective
The objective of this study was to assess the effect of menopausal hormone therapy (HT) on blood pressure control in postmenopausal women with hypertension.

Methods
The Women's Health Initiative HT clinical trials were double-blinded, randomized, placebo-controlled studies of women aged 50 to 79 years testing the effects of HT (conjugated equine estrogens [CEE, 0.625 mg/d] or CEE + medroxyprogesterone acetate [MPA; 2.5 mg/d]) on risks for coronary heart disease and invasive breast cancer, the primary outcomes for efficacy and safety, respectively. This secondary analysis of the Women's Health Initiative HT trials examined a subsample of 9,332 women with hypertension (reported ever taking pills to treat hypertension or were taking antihypertensive medication) at baseline. Blood pressure was measured at baseline and up to 10 annual follow-up visits during the planned study phase. Antihypertensive medications were inventoried at baseline and years 1, 3, 6, and 9 during the study, and self-reported during extended follow-up: 2009-2010 and 2012-2013, which occurred median of 13 and 16 years after randomization, respectively. The intervention effect was estimated through year 6. Cumulative follow-up included all visits.

Results
Compared with placebo, CEE-alone had significantly (P = 0.02) higher systolic blood pressure (SBP) by mean (95% confidene interval [CI]) = 0.9 (0.2-1.5) mm Hg during the intervention phase. For cumulative follow-up, the CEE arm was associated with increased SBP by mean (95% CI) = 0.8 (0.1-1.4) mm Hg (P = 0.02). Furthermore, CEE + MPA relative to placebo was associated with increased SBP by mean (95% CI) = 1.8 (1.2-2.5) mm Hg during the intervention phase (P < 0.001). For cumulative follow-up, the CEE + MPA arm was associated with increased SBP by mean (95% CI) = 1.6 (1.0-2.3) mm Hg (P < 0.001). The mean number of antihypertensive medications taken at each follow-up visit did not differ between randomization groups during the intervention or long-term extended follow-up of 16 years.

Conclusion
There was a small but statistically significant increase in SBP in both CEE-alone and CEE + MPA arms compared with placebo during both the intervention and cumulative follow-up phases among postmenopausal women with hypertension at baseline. However, this increase in SBP was not associated with an increased antihypertensive medication use over time among women randomized to HT compared with placebo.
Corneal Stromal Densitometry Evolution in a Clinical Model of Cellular Therapy for Advanced Keratoconus
Authors: El Zarif Mona , Alió del Barrio Jorge L. , Mingo David , A Jawad Karim , Alió Jorge L. 
Published: October 2022

Purpose:
The aim of this study was to report the corneal densitometry (CD) evolution studied by Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT), and confocal microscopy changes, in patients with advanced keratoconus included in a clinical experience of advanced cell therapy using autologous humans adipose-derived adult stem cells (ADASCs) and corneal decellularized and ADASCs-recellularized human donor corneal laminas.

Methods:
This study is an interventional prospective, consecutive, randomized, comparative series of cases. Fourteen patients with keratoconus were randomly distributed into 3 groups for 3 types of surgical interventions: group 1 (G-1), autologous ADASC implantation (n = 5); group 2 (G-2), decellularized human corneal stroma (n = 5); and group 3 (G-3), autologous ADASCs + decellularized human corneal stroma (n = 4). Participants were assessed with Scheimpflug-based Oculus Pentacam CD module, AS-OCT (Visante; Carl Zeiss), and confocal microscopy (HRT3 RCM Heidelberg).

Results:
A significant improvement of 1 to 2 logMAR lines in all visual parameters in the 3 groups was obtained. The central and total CD were statistically significantly higher in G-2 compared with G-1 and G-3 compared with G-1 at the studied annular zones centered on the corneal apex (0–2, 2–6, and 6–10 mm). There was statistical significance higher in G-3 compared with G-2 at the central corneal stroma at 0–2 and 2–6 mm. The confocal microscopy findings and the AS-OCT reflected the densitometry changes.

Conclusions:
The intrastromal implantation of ADASCs produced very subtle changes in CD at the level of the central corneal stroma. However, the intrastromal implantation of decellularized corneal laminas increases it slightly, but with lower values than the implantation of recellularized laminas with ADASCs.
Glucose Metabolism in Midlife Is Associated With Preceding 30-Year Employment Trajectories
Authors: Varanka-Ruuska Tuulia , Rautio Nina , Sebert Sylvain , Ala-Mursula Leena 
Published: October 2022

ObjectiveThe aim of the study is to evaluate how glucose metabolism in midlife is related to preceding 30-year-long employment trajectories.MethodsIn the Northern Finland Birth Cohort 1966, we compared glucose metabolism at 46 to employment trajectories (previously defined for men and women and named as high-educated, traditional, self-employed, delayed, and floundering;n= 6399).ResultsCompared with individuals in high-educated trajectories, odds ratios for type 2 diabetes (T2D, 95% confidence interval) in traditional and floundering trajectories in men were 1.65 (1.02–2.68) and 2.42 (1.38–4.23) and in women 1.89 (1.04–3.43) and 2.60 (1.46–4.62), respectively. In self-employed trajectory in women, odds ratios for prediabetes and T2D were 1.66 (1.09–2.51) and 2.47 (1.21–5.04).ConclusionsThe highest risks for T2D in midlife were associated after traditional and floundering trajectories in men and women and after self-employment trajectory in women.
18F-MFBG PET/CT Is an Effective Alternative of 68Ga-DOTATATE PET/CT in the Evaluation of Metastatic Pheochromocytoma and Paraganglioma
Authors: Wang Peipei , Li Tuo , Cui Yuying , Zhuang Hongming , Li Fang , Tong Anli , Jing Hongli 
Published: October 2022

Purpose
The current guidelines state that the functional imaging choice in the evaluation of metastatic pheochromocytoma and paraganglioma (PPGL) is 68Ga-DOTATATE PET/CT. 18F–meta-fluorobenzylguanidine (18F-MFBG) is a new PET tracer and an analog of meta-iodobenzylguanidine (MIBG). This study aimed to compare 18F-MFBG and 68Ga-DOTATATE PET/CT in patients with metastatic PPGL.

Patients and Methods
Twenty-eight patients with known metastatic PPGL were prospectively recruited for this study. All patients underwent both 18F-MFBG and 68Ga-DOTATATE PET/CT studies within 1 week. Lesion numbers detected were compared between these 2 studies.

Results

18F-MFBG PET/CT was positive for detecting metastases in all patients, whereas positive results of 68Ga-DOTATATE PET/CT were in 27 (96.4%) patients. A total of 686 foci of metastatic lesions were detected by both 18F-MFBG and 68Ga-DOTATATE imaging. In addition, 33 foci of abnormal activity were only detected by 18F-MFBG, whereas 16 foci were only shown on 68Ga-DOTATATE PET/CT.

Conclusions
Our data suggest that 18F-MFBG PET/CT is an effective imaging method in the evaluation of metastatic PPGL and could be alternative of 68Ga-DOTATATE PET/CT in this clinical setting.
Warthin-Like Papillary Thyroid Microcarcinoma With Coincidental Ipsilateral Warthin Tumor of the Parotid Gland Detected on 131I-SPECT/US and 18F-PET/US Fusion Imaging
Authors: Werner Anke , Freesmeyer Martin , Bensch Claudia , Eszlinger Markus , Seifert Philipp 
Published: October 2022

Abstract
A 66-year-old woman was referred with an incidental finding of a bilateral papillary thyroid microcarcinoma after thyroidectomy. On the right side, a Warthin-like variant was observed. After radioiodine therapy, whole-body scan revealed an unclear iodine uptake on the right-sided neck. For further clarification, 131I-SPECT/US and 18F-PET/US fusion imaging were performed, unambiguously revealing iodine and glucose uptake within a hypoechoic lesion located in the parenchyma of the right parotid gland. Surgical excision confirmed a Warthin tumor ipsilateral to the Warthin-like variant of the papillary thyroid microcarcinoma. Because the extensive imaging, targeted minimal-invasive surgery was possible.
C-peptide Targets and Patient-centered Outcomes of Relevance to Cellular Transplantation for Diabetes
Authors: Verhoeff Kevin , Marfil-Garza Braulio A. , Dajani Khaled , Bigam David L. , Anderson Blaire , Kin Tatsuya , Lam Anna , O’Gorman Doug , Senior Peter A. , Shapiro A. M. James 
Published: October 2022

Background
C-peptide levels are a key measure of beta-cell mass following islet transplantation, but threshold values required to achieve clinically relevant patient-centered outcomes are not yet established.

Methods.
We conducted a cross-sectional retrospective cohort study evaluating patients undergoing islet transplantation at a single center from 1999 to 2018. Cohorts included patients achieving insulin independence without hypoglycemia, those with insulin dependence without hypoglycemia, and those with recurrent symptomatic hypoglycemia. Primary outcome was fasting C-peptide levels at 6 to 12 mo postfirst transplant; secondary outcomes included stimulated C-peptide levels and BETA-2 scores. Fasting and stimulated C-peptide and BETA-2 cutoff values for determination of hypoglycemic freedom and insulin independence were evaluated using receiver operating characteristic curves.

Results.
We analyzed 192 patients, with 122 (63.5%) being insulin independent without hypoglycemia, 61 (31.8%) being insulin dependent without hypoglycemia, and 9 (4.7%) experiencing recurrent symptomatic hypoglycemia. Patients with insulin independence had a median (interquartile range) fasting C-peptide level of 0.66 nmol/L (0.34 nmol/L), compared with 0.49 nmol/L (0.25 nmol/L) for those being insulin dependent without hypoglycemia and 0.07 nmol/L (0.05 nmol/L) for patients experiencing hypoglycemia (P < 0.001). Optimal fasting C-peptide cutoffs for insulin independence and hypoglycemia were ≥0.50 nmol/L and ≥0.12 nmol/L, respectively. Cutoffs for insulin independence and freedom of hypoglycemia using stimulated C-peptide were ≥1.2 nmol/L and ≥0.68 nmol/L, respectively, whereas optimal cutoff BETA-2 scores were ≥16.4 and ≥5.2.

Conclusions.
We define C-peptide levels and BETA-2 scores associated with patient-centered outcomes. Characterizing these values will enable evaluation of ongoing clinical trials with islet or stem cell therapies.
Comparison of Idiopathic Intracranial Hypertension Patients With and Without Anemia
Authors: Sverdlichenko Irina , Yu Caberry W. , Margolin Edward , Micieli Jonathan A. 
Published: October 2022

Background:
Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure without an identifiable cause. It mostly affects young obese women but has been reported in individuals newly diagnosed with anemia or with chronic anemia. The relationship between anemia and IIH is not well elucidated. This study aims to characterize the course of IIH in anemic patients.

Methods:
Consecutive patients with IIH were recruited from neuro-ophthalmology clinics. Subsequent retrospective chart review obtained information on symptoms, complete blood counts (CBCs), visual acuity, visual fields, and optic disc edema at baseline and follow-up. Anemia was diagnosed by hemoglobin <120 g/L (women) and <130 g/L (men).

Results:
One hundred twenty-three patients with IIH were recruited for this study, and 22.8% (28/123) had anemia. More anemic individuals had mild-to-moderate visual acuity impairment (logarithm of minimum angle of resolution 0.3–1, P = 0.01) and worse automated mean deviation (P = 0.048). The median follow-up time was 47.4 weeks (interquartile range:20.1–91.8). Fifteen of 28 patients with anemia received anemia treatment and showed a trend toward increased hemoglobin. At follow-up, there were no differences in the visual acuity, but patients with anemia had worse automated mean deviation on visual fields (P = 0.045).

Conclusions:
IIH patients with anemia had worse visual function at presentation and worse final visual field parameters. This suggests that CBCs should be obtained for patients with papilledema because it may influence final visual outcome.
Normative Sex Differences in Cognition and Morphometric Brain Connectivity: Evidence from 30,000+ UK Biobank Participants
Authors: Yang Crystal C. , Totzek Jana F. , Lepage Martin , Lavigne Katie M. 
Published: October 2022

AbstractThere is robust evidence for sex differences in domain-specific cognitive performance in the general population, where females typically show an advantage for verbal memory (VM), while males tend to perform better on tasks of spatial memory (SM). Sex differences in brain structure and connectivity are also well-documented and may provide insight into sex differences in cognition. In this study, we examined sex differences in cognition and morphometric brain connectivity of a large healthy sample (N = 31,180) from the UK Biobank dataset. Using T1-weighted magnetic resonance imaging (MRI) scans and regional cortical thickness values, we applied jackknife bias estimation and graph theory to obtain subject-specific measures of morphometric brain connectivity, hypothesizing that sex-related differences in brain network global efficiency, or overall connectivity, would underlie observed cognitive differences. As predicted, females demonstrated better VM performance and males showed an advantage in SM. Females also demonstrated faster processing speed, with no observed sex difference in executive functioning. Males tended to have higher global efficiency, as well as higher regional connectivity (nodal strengths) in both the left and right hemispheres relative to females.Furthermore, higher global efficiency in males was found to mediate observed sex differences in cognition, predicting poorer verbal memory performance, better spatial memory, and slower processing speed in males. These findings contribute to an improved understanding of the way biological sex and differences in cognitive performance are related to morphometric brain connectivity as derived from graph-theoretic methods.
Not just with the natives, but phylogenetic relationship between stages of the invasion process determines invasion success of alien plant species
Authors: Banerjee Achyut Kumar , Feng Hui , Liang Xinru , Tan Fengxiao , Wang Jiakai , Lin Yuting , Yin Minghui , Peng Hao , Guo Wuxia , Zhang Nannan , Huang Yelin 
Published: October 2022

AbstractDarwin proposed two alternate hypotheses on the invasion success of alien plant species based on their close or distant phylogenetic relationship with the natives. Here we tested these hypotheses along the invasion process at large spatio-temporal scale. Using two abundance-based phylogenetic metrics for the native and alien flora of China, our study showed that invasion success of alien plant species is influenced by the phylogenetic relationship with native and alien species of different invasion stages. Phylogenetic similarity with the native species helps the alien ones to introduce and naturalize, but phylogenetic dissimilarity with the natives facilitates invasion success. The co-occurrence of invasive and naturalized aliens also formed more clustered assemblages, showed specialized responses to environmental stress, and provided temporal stability to the phylogenetic measures. The native-alien phylogenetic relationship is dynamic across spatial, environmental, and taxonomic scales. Therefore, assessing Darwin’s naturalization conundrum at different gradients of community assembly process is important.
Computational Speed-Up of Large-Scale, Single-Cell Model Simulations Via a Fully-Integrated SBML-Based Format
Authors: Mutsuddy Arnab , Erdem Cemal , Huggins Jonah R. , Salim Michael , Cook Daniel , Hobbs Nicole , Feltus F. Alex , Birtwistle Marc R. 
Published: October 2022

AbstractSummaryLarge-scale and whole-cell modeling has multiple challenges, including scalable model building and module communication bottlenecks (e.g. between metabolism, gene expression, signaling, etc). We previously developed an open-source, scalable format for a large-scale mechanistic model of proliferation and death signaling dynamics, but communication bottlenecks between gene expression and protein biochemistry modules remained. Here, we developed two solutions to communication bottlenecks that speed up simulation by ~4-fold for hybrid stochastic-deterministic simulations and by over 100-fold for fully deterministic simulations.Availability and ImplementationSource code is freely available athttps://github.com/birtwistlelab/SPARCED/releases/tag/v1.1.0implemented in python, and supported on Linux, Windows, and MacOS (via Docker).ContactMarc Birtwistlembirtwi@clemson.eduSupplementary informationN/A
The role of non-additive gene action on gene expression variation in plant domestication
Authors: Díaz-Valenzuela Erik , Hernández-Ríos Daniel , Cibrián-Jaramillo Angélica 
Published: October 2022

AbstractBackgroundPlant domestication is a remarkable example of rapid phenotypic transformation of polygenic traits such as organ size. Evidence from a handful of study cases suggests this transformation is due to gene regulatory changes that result in non-additive phenotypes. Employing data from published genetic crosses, we estimated the role of non-additive gene action in the modulation of transcriptional landscapes in three domesticated plants: maize, sunflower, and chili pepper. Using A.thaliana, we assessed the correlation between gene regulatory network (GRN) connectivity properties, transcript abundance variation, and gene action. Finally, we investigated the propagation of non-additive gene action in GRNs.ResultsWe compared crosses between domesticated plants and their wild relatives to a set of control crosses that included a pair of subspecies evolving under natural selection and a set of inbred lines evolving under domestication. We found abundance differences on a higher portion of transcripts in crosses between domesticated-wild plants relative to the control crosses. These transcripts showed non-additive gene action more often in crosses of domesticated-wild plants than in our control crosses. This pattern was strong for genes associated with cell cycle and cell fate determination, which control organ size. We found weak but significant negative correlations between the number of targets of trans-acting genes (Out-degree) and both the magnitude of transcript abundance differences a well as the absolute degree of dominance. Likewise, we found that the number of regulators that control a gene’s expression (In-degree) is weakly but negatively correlated with the magnitude of transcript abundance differences. We observed that dominant-recessive gene action is highly propagable through GRNs. Finally, we found that transgressive gene action is driven by trans-acting regulators showing additive gene action.ConclusionsOur study highlights the role of non-additive gene action on modulating domestication-related traits such as organ size via regulatory divergence. We propose that GRNs are shaped by regulatory changes at genes with modest connectivity, which reduces the effects of antagonistic pleiotropy. Finally, we provide empirical evidence of the propagation of non-additive gene action in GRNs, which suggests a transcriptional epistatic model for the control of polygenic traits such as organ size.
Reflective multi-immersion microscope objectives inspired by the Schmidt telescope
Authors: Voigt Fabian F. , Reuss Anna Maria , Naert Thomas , Hildebrand Sven , Schaettin Martina , Hotz Adriana L. , Whitehead Lachlan , Bahl Armin , Neuhauss Stephan C. F. , Roebroeck Alard , Stoeckli Esther T. , Lienkamp Soeren S. , Aguzzi Adriano , Helmchen Fritjof 
Published: October 2022

AbstractRapid advances in tissue clearing protocols have begun to outpace the capabilities of existing microscope objectives: High-resolution imaging inside cm-sized cleared samples is often not possible as it requires multi-immersion objectives with high numerical aperture (NA > 0.7), long working distance (WD > 10 mm) and a large field-of-view (FOV > 1 mm). Here, we introduce a novel mirror-based optical design, the “Schmidt objective”, which meets all these criteria despite containing only two optical elements. It consists of a spherical mirror in contact with the immersion medium and an aspherical correction plate. We showcase a multi-photon variant of a Schmidt objective that reaches NA 1.08 at an refractive index of 1.56 and demonstrate its versatility by imaging fixed samples in a wide range of immersion media ranging from air and water to BABB, DBE, and ECI. In addition, we demonstrate in vivo imaging by recording neuronal activity in larval zebrafish.
Identification of potent anti-fibrinolytic compounds against plasminogen and tissue-type plasminogen activator using computational approaches
Authors: Banerjee Suparna , M Yeshwanth , Prabhu Dhamodharan , Sekar Kanagaraj , Sen Prosenjit 
Published: October 2022

AbstractThe zymogen protease Plasminogen (Plg) and its active form plasmin (Plm) carry out important functions in the blood clot disintegration (breakdown of fibrin fibres) process. Inhibition of plasmin effectively reduces fibrinolysis to circumvent heavy bleeding. Currently, available Plm inhibitor tranexamic acid (TXA) that is used to treat severe hemorrhages is associated with an increased incidence of seizures which in turn were traced to gamma-aminobutyric acid antagonistic activity (GABAa) in addition to having multiple side effects. Fibrinolysis can be suppressed by targeting the three important protein domains: kringle-1 and serine protease domain of plasminogen and kringle-2 domain of tissue plasminogen activator. In the present study, combined approaches of structure-based virtual screening and molecular docking using Schrödinger Glide, AutoDock Vina, and ParDock/BAPPL+ were employed to identify potential hits from the ZINC database. Thereafter, the drug-likeness properties of the top three leads for each protein target were evaluated using Discovery Studio. Subsequently, a molecular dynamics simulation of 200ns for each protein-ligand complex was performed in GROMACS. The identified ligands are found to impart higher rigidity and stability to the protein-ligand complexes. Furthermore, the results were validated by performing the principal component analysis (PCA), and calculation of binding free energy using the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach. The identified ligands occupy smaller phase space, form stable clusters and exhibit stronger non-bonded interactions. Thus, our findings can be useful for the development of promising anti-fibrinolytic agents.Graphical Abstract