bluuebunny/crossref_metadata_2025 huggingface dataset:
HVMNE, a novel lymphocryptovirus related to Epstein-Barr virus, induces lymphoma in New Zealand White rabbits
Authors: Ferrari Maria G. , Rivadeneira Emilia D. , Jarrett Ruth , Stevceva Liljana , Takemoto Shigeki , Markham Phil , Franchini Genoveffa
Published: July 2002

HVMNE is a novel Epstein-Barr (EBV)–like virus isolated from a Macaca nemestrina with CD8+ T-cell mycosis fungoides–cutaneous T-cell lymphoma. Here it is demonstrated that intravenous inoculation of irradiated HVMNE-infected T cells or cell-free virus from the J94356PBMC cell line in New Zealand White rabbits results in seroconversion to the viral capsid antigen (VCA) of EBV; all animals that seroconverted to VCA developed malignant lymphoma within months of inoculation. In contrast, control rabbits, inoculated with heat-inactivated culture supernatants from the same cell line, failed to seroconvert to VCA and did not develop disease. Disseminated lymphoma cells of mixed origin were detected in most vital organs, including the spleen, liver, lungs, kidneys, and heart of the affected rabbits. Neoplastic infiltrates were also observed in lymph nodes, thymus, skin, and subcutaneous tissues. HVMNE DNA and EBV-like RNA expression was demonstrated in the lymphomatous organs and in 2 transformed T-cell lines, one established from the lymph node and the other from the blood of the 2 lymphomatous animals. Analysis of one of these T-cell lines demonstrated the persistence of HVMNEDNA, expression of an LMP1-like protein, and acquisition of interleukin-2 independence, and constitutive activation of the Jak/STAT pathway. Thus, HVMNE in rabbits provides a valuable animal model for human T-cell lymphoma whereby genetic determinants for T-cell transformation by this EBV-like animal virus can be studied.
Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice
Authors: Yanagi Shigeru , Inatome Ryoko , Ding Junyi , Kitaguchi Hironori , Tybulewicz Victor L. J. , Yamamura Hirohei
Published: July 2002

Mice deficient in the Syk tyrosine kinase showed severe petechiae in utero and died shortly after birth. The mechanism of this bleeding, however, remains unknown. Here it is shown that this bleeding is caused by morphologic defects of Syk-deficient endothelial cells during embryogenesis. Immunoblot and reverse transcriptase–polymerase chain reaction Northern blot analysis indicated that Syk is expressed in several endothelial cell lines. Immunocytochemical analysis also confirmed that Syk is expressed in the normal embryonic endothelial cells and is absent in Syk-deficient mice. Furthermore, electron microscopic analysis of Syk-deficient mice revealed an abnormal morphogenesis and a decreased number of endothelial cells. The results indicate a critical role for Syk in endothelial cell function and in maintaining vascular integrity in vivo.
Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins
Authors: Lorentz Axel , Schuppan Detlef , Gebert Andreas , Manns Michael P. , Bischoff Stephan C.
Published: July 2002

Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% ± 12% of mast cells) and to denatured collagens (40% ± 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by β1 integrins, and most cells expressed the ECM-binding integrins α2β1, α3β1, α4β1, α5β1, and αVβ3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 β1 epitope, which is associated with an activated conformation of β1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.
Midcareer Satisfaction and Likelihood of Leaving Current Position of Former Career Development Awardees
Authors: Jagsi Reshma , Griffith Kent A. , Paradis Kelly C. , Santos Patricia Mae G. , Torres Mylin A. , Jones Rochelle D. , Kerr Eve A.
Published: July 2024

This study assesses career satisfaction, discrepancies between ideal and expected careers, and likelihood of leaving current positions among former K awardees.
Statins for Primary Prevention of Cardiovascular Disease—With PREVENT, What’s a Clinician to Do?
Authors: Khan Sadiya S. , Lloyd-Jones Donald M.
Published: July 2024

This Viewpoint explores decision thresholds and the evidence that informs them as well as how clinicians may respond to an updated risk estimation model, such as the Predicting Risk of cardiovascular disease EVENTs equations.
The CREATE TRUST Communication Framework for Patient Messaging Services
Authors: Allen Matthew R. , Schillinger Dean , Ayers John W.
Published: July 2024

This Viewpoint proposes a messaging framework called CREATE TRUST to improve written communication with patients.
Prenatal Maternal Occupation and Child Epigenetic Age Acceleration in an Agricultural Region
Authors: Daredia Saher , Bozack Anne K. , Riddell Corinne A. , Gunier Robert , Harley Kim G. , Bradman Asa , Eskenazi Brenda , Holland Nina , Deardorff Julianna , Cardenas Andres
Published: July 2024

Importance

Research on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility.

Objective

To examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community.

Design, Setting, and Participants

This cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California’s Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks’ gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023.

Exposures

Prenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery.

Main Outcomes and Measures

Child EAA at 7, 9, and 14 years of age was estimated using DNA methylation–based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure.

Results

Analyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy.

Conclusions and Relevance

In this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children’s health.
Essential Nutrients, Added Sugar Intake, and Epigenetic Age in Midlife Black and White Women
Authors: Chiu Dorothy T. , Hamlat Elissa June , Zhang Joshua , Epel Elissa S. , Laraia Barbara A.
Published: July 2024

Importance

Nutritive compounds play critical roles in DNA replication, maintenance, and repair, and also serve as antioxidant and anti-inflammatory agents. Sufficient dietary intakes support genomic stability and preserve health.

Objective

To investigate the associations of dietary patterns, including intakes of essential nutrients and added sugar, and diet quality scores of established and new nutrient indices with epigenetic age in a diverse cohort of Black and White women at midlife.

Design, Setting, and Participants

This cross-sectional study included analyses (2021-2023) of past women participants of the 1987-1997 National Heart, Lung, and Blood Institute Growth and Health Study (NGHS), which examined cardiovascular health in a community cohort of Black and White females aged between 9 and 19 years. Of these participants who were recruited between 2015 and 2019 from NGHS’s California site, 342 females had valid completed diet and epigenetic assessments. The data were analyzed from October 2021 to November 2023.

Exposure

Diet quality scores of established nutrient indices (Alternate Mediterranean Diet [aMED], Alternate Healthy Eating Index [AHEI]–2010); scores for a novel, a priori–developed Epigenetic Nutrient Index [ENI]; and mean added sugar intake amounts were derived from 3-day food records.

Main Outcomes and Measures

GrimAge2, a second-generation epigenetic clock marker, was calculated from salivary DNA. Hypotheses were formulated after data collection. Healthier diet indicators were hypothesized to be associated with younger epigenetic age.

Results

A total of 342 women composed the analytic sample (mean [SD] age, 39.2 [1.1] years; 171 [50.0%] Black and 171 [50.0%] White participants). In fully adjusted models, aMED (β, −0.41; 95% CI, −0.69 to −0.13), AHEI-2010 (β, −0.05; 95% CI, −0.08 to −0.01), and ENI (β, −0.17; 95% CI, −0.29 to −0.06) scores, and added sugar intake (β, 0.02; 95% CI, 0.01-0.04) were each significantly associated with GrimAge2 in expected directions. In combined analyses, the aforementioned results with GrimAge2 were preserved with the association estimates for aMED and added sugar intake retaining their statistical significance.

Conclusions and Relevance

In this cross-sectional study, independent associations were observed for both healthy diet and added sugar intake with epigenetic age. To our knowledge, these are among the first findings to demonstrate associations between added sugar intake and epigenetic aging using second-generation epigenetic clocks and one of the first to extend analyses to a diverse population of Black and White women at midlife. Promoting diets aligned with chronic disease prevention recommendations and replete with antioxidant or anti-inflammatory and pro-epigenetic health nutrients while emphasizing low added sugar consumption may support slower cellular aging relative to chronological age, although longitudinal analyses are needed.
Advancing Health Disparities Science Through Social Epigenomics Research
Authors: Gillman Arielle S. , Pérez-Stable Eliseo J. , Das Rina
Published: July 2024

Importance

Although scientific and technological discoveries have improved the health of the US population overall, racial and ethnic minority (American Indian and Alaska Native, Asian, Black or African American, Hispanic or Latino, or Native Hawaiian and Pacific Islander persons) and socioeconomically disadvantaged populations continue to experience a disproportionate burden of disease and other adverse health conditions. To better understand and address the drivers of health disparities and inform the development of effective interventions, integrative mechanistic studies examining the dynamic interplay of multiple factors across the life course and even between generations are needed. The emerging field of social epigenomics, which seeks to link social stressors and protective factors to health status through the examination of epigenomic modifications of various biological pathways, is one promising area of research contributing to this need.

Observations

This thematic issue of JAMA Network Open highlights new findings from the grantees of the National Institutes of Health (NIH) Social Epigenomics Program. These findings, taken together, examine the associations of a variety of social, behavioral, and structural factors throughout the life course with epigenomic and other biological changes among populations experiencing health disparities. The studies link early-life exposures, structural inequities, and behavioral factors and interventions to epigenetic changes, and in some studies, later health outcomes. While there is still more work to be done to fully characterize the mechanistic pathways linking social exposures to epigenetic changes and health outcomes, the body of work presented in this special issue represents solid progress toward this goal.

Conclusions and Relevance

The studies highlighted in this special issue demonstrate important scientific progress in the complex integration of social determinants of health and health disparities with biological pathways and health outcomes to improve understanding of the mechanisms underlying health disparities among various underserved populations. Continued progress remains important in integrating different disciplines to transform the field of health disparities research.
Drug Repurposing Via the Best Pharmaceuticals for Children Act
Authors: Liu Ian T. T. , Kesselheim Aaron S.
Published: July 2024

This Viewpoint discusses the benefits and impediments of drug repurposing in the US and how the Best Pharmaceuticals for Children Act may serve as a successful legislative model to stimulate greater drug repurposing.
Disparities in HPV Vaccination Among Adolescents by Health Care Facility Type
Authors: Nair Mrudula , Fokom Domgue Joël , Joseph Christine L. M. , Alleman Elizabeth R. , Williams Amy M. , Abouelella Dina K. , Babatunde Oluwole A. , Osazuwa-Peters Nosayaba , Adjei Boakye Eric
Published: July 2024

Importance

Approximately 31 000 cases of human papillomavirus (HPV)–associated cancers are diagnosed annually in the US. The HPV vaccine can prevent more than 90% of these cancers, yet national uptake remains lower than the Healthy People 2030 target of 80% completion. To devise targeted interventions to increase the uptake of HPV vaccines, it is crucial to understand the vaccination rates across various health care settings.

Objective

To examine the association between health care facility type and adolescent HPV vaccine uptake and clinician recommendation for the vaccine in the US.

Design, Setting, and Participants

This cross-sectional study uses a complex sampling design of data from the 2020 National Immunization Survey–Teen. The study included adolescents aged 13 to 17 years. The data analysis was completed between March 1 and May 31, 2022.

Exposure

Health care facility type classified as public, hospital-based, private, mixed (more than 1 type), and other facilities (eg, military health care facility; Women, Infants, and Children clinic; school-based health center; pharmacy).

Main Outcomes and Measures

Initiation of HPV vaccination was defined as the receipt of at least 1 dose of the HPV vaccine and completion as receipt of at least 2 or 3 doses, depending on age of initiation. Parent or guardian self-reported clinician recommendation was categorized as yes or no. Weighted, multivariable logistic regression models were used to estimate the odds of initiating and completing the HPV vaccine series and receiving clinician recommendation by health care facility type adjusted for adolescent and maternal characteristics.

Results

A total of 20 162 adolescents (mean [SD] age, 14.9 [1.4] years; 51.0% male) were included. Clinician recommendation for the HPV vaccine was received by 81.4% of adolescents, and 75.1% initiated and 58.6% completed the HPV vaccine series. In the adjusted analyses, adolescents who received recommended vaccinations at public facilities had lower odds of initiating (adjusted odds ratio [AOR], 0.71; 95% CI, 0.58-0.88) and completing (AOR, 0.62; 95% CI, 0.51-0.76) HPV vaccination compared with those who received recommended vaccinations at private facilities. Similarly, adolescents who received recommended vaccinations at public facilities (AOR, 0.62; 95% CI, 0.51-0.77) had lower odds of receiving a clinician recommendation for the HPV vaccine compared with those who received recommended vaccinations at private facilities.

Conclusions and Relevance

These findings reveal health disparities in HPV vaccination among adolescent populations served by public health care facilities, suggesting that a greater focus is needed on vaccine recommendations and uptake in public facilities.
Maternal Obesity and Risk of Sudden Unexpected Infant Death
Authors: Tanner Darren , Ramirez Jan-Marino , Weeks William B. , Lavista Ferres Juan M. , Mitchell Edwin A.
Published: July 2024

Importance

Rates of maternal obesity are increasing in the US. Although obesity is a well-documented risk factor for numerous poor pregnancy outcomes, it is not currently a recognized risk factor for sudden unexpected infant death (SUID).

Objective

To determine whether maternal obesity is a risk factor for SUID and the proportion of SUID cases attributable to maternal obesity.

Design, Setting, and Participants

This was a US nationwide cohort study using Centers for Disease Control and Prevention National Center for Health Statistics linked birth–infant death records for birth cohorts in 2015 through 2019. All US live births for the study years occurring at 28 weeks’ gestation or later from complete reporting areas were eligible; SUID cases were deaths occurring at 7 to 364 days after birth with International Statistical Classification of Diseases, Tenth Revision cause of death code R95 (sudden infant death syndrome), R99 (ill-defined and unknown causes), or W75 (accidental suffocation and strangulation in bed). Data were analyzed from October 1 through November 15, 2023.

Exposure

Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared).

Main Outcome and Measure

SUID.

Results

Of 18 857 694 live births eligible for analysis (median [IQR] age: maternal, 29 [9] years; paternal, 31 [9] years; gestational, 39 [2] weeks), 16 545 died of SUID (SUID rate, 0.88/1000 live births). After confounder adjustment, compared with mothers with normal BMI (BMI 18.5-24.9), infants born to mothers with obesity had a higher SUID risk that increased with increasing obesity severity. Infants of mothers with class I obesity (BMI 30.0-34.9) were at increased SUID risk (adjusted odds ratio [aOR], 1.10; 95% CI, 1.05-1.16); with class II obesity (BMI 35.0-39.9), a higher risk (aOR, 1.20; 95% CI, 1.13-1.27); and class III obesity (BMI ≥40.0), an even higher risk (aOR, 1.39; 95% CI, 1.31-1.47). A generalized additive model showed that increased BMI was monotonically associated with increased SUID risk, with an acceleration of risk for BMIs greater than approximately 25 to 30. Approximately 5.4% of SUID cases were attributable to maternal obesity.

Conclusions and Relevance

The findings suggest that infants born to mothers with obesity are at increased risk of SUID, with a dose-dependent association between increasing maternal BMI and SUID risk. Maternal obesity should be added to the list of known risk factors for SUID. With maternal obesity rates increasing, research should identify potential causal mechanisms for this association.
Pattern of Buprenorphine Treatment Retention Among Youth Aged 10 to 18 Years—US, 2015 to 2021
Authors: Connolly Sarah , Terranella Andrew , Guy Gery P. , Mikosz Christina A.
Published: July 2024

This cohort study investigates patterns of buprenorphine treatment retention among US youth aged 10 to 18 years from 2015 to 2021.
Human CKAP2L shows a cell cycle‐dependent expression pattern and exhibits microtubule‐stabilizing properties
Authors: Kwon Hyerim , Joh Jonathan Y. , Hong Kyung U.
Published: July 2024

Cytoskeleton‐associated protein 2‐like (CKAP2L) is a paralogue of cytoskeleton‐associated protein 2 (CKAP2). We characterized the expression pattern, subcellular localization, and microtubule‐stabilizing properties of human CKAP2L. The levels of both CKAP2L transcript and protein were cell cycle phase‐dependent, peaking during the G2/M phase and relatively high in certain human tissues, including testis, intestine, and spleen. CKAP2L protein was detectable in all human cancer cell lines we tested. CKAP2L localized to the mitotic spindle apparatus during mitosis, as reported previously. During interphase, however, CKAP2L localized mainly to the nucleus. Ectopic overexpression of CKAP2L resulted in ‘microtubule bundling’, and, consequently, an elevated CKAP2L level led to prolonged mitosis. These findings support the mitotic role of CKAP2L during the human cell cycle.
XAI is in trouble
Authors: Weber Rosina O , Johs Adam J , Goel Prateek , Silva João Marques
Published: July 2024

Researchers focusing on how artificial intelligence (AI) methods explain their decisions often discuss controversies and limitations. Some even assert that most publications offer little to no valuable contributions. In this article, we substantiate the claim that explainable AI (XAI) is in trouble by describing and illustrating four problems: the disagreements on the scope of XAI, the lack of definitional cohesion, precision, and adoption, the issues with motivations for XAI research, and limited and inconsistent evaluations. As we delve into their potential underlying sources, our analysis finds these problems seem to originate from AI researchers succumbing to the pitfalls of interdisciplinarity or from insufficient scientific rigor. Analyzing these potential factors, we discuss the literature at times coming across unexplored research questions. Hoping to alleviate existing problems, we make recommendations on precautions against the challenges of interdisciplinarity and propose directions in support of scientific rigor.
Applying the six‐sigma methodology to determine the limits of quality control (QC) tests for a specific linear accelerator
Authors: Ma Min , Li Minghui , Zhang Ke , Ma Pan , Hu Zhihui , Yan Hui , Men Kuo , Dai Jianrong
Published: July 2024

Purpose

We aimed to show the framework of the six‐sigma methodology (SSM) that can be used to determine the limits of QC tests for the linear accelerator (Linac). Limits for QC tests are individually determined using the SSM.

Methods and Materials

The SSM is based on the define‐measure‐analyze‐improve‐control (DMAIC) stages to improve the process. In the “define” stage, the limits of QC tests were determined. In the “measure” stage, a retrospective collection of daily QC data using a Machine Performance Check platform was performed from January 2020 to December 2022. In the “analyze” stage, the process of determining the limits was proposed using statistical analyses and process capability indices. In the “improve” stage, the capability index was used to calculate the action limits. The tolerance limit was established using the larger one of the control limits in the individual control chart (I‐chart). In the “control” stage, daily QC data were collected prospectively from January 2023 to May 2023 to monitor the effect of action limits and tolerance limits.

Results

A total of 798 sets of QC data including beam, isocenter, collimation, couch, and gantry tests were collected and analyzed. The Collimation Rotation offset test had the min‐Cp, min‐Cpk, min‐Pp, and min‐Ppk at 2.53, 1.99, 1.59, and 1.25, respectively. The Couch Rtn test had the max‐Cp, max‐Cpk, max‐Pp, and max‐Ppk at 31.5, 29.9, 23.4, and 22.2, respectively. There are three QC tests with higher action limits than the original tolerance. Some data on the I‐chart of the beam output change, isocenter KV offset, and jaw X1 exceeded the lower tolerance and action limit, which indicated that a system deviation occurred and reminded the physicist to take action to improve the process.

Conclusions

The SSM is an excellent framework to use in determining the limits of QC tests. The process capability index is an important parameter that provides quantitative information on determining the limits of QC tests.
Analyzing post‐endovascular treatment stroke prognosis with transcranial Doppler and quantitative electroencephalography
Authors: Qi Yajie , Xing Yingqi , Wang Qingduo , Cao Yanting , Chen Hongxiu , Chen Ying
Published: July 2024

Objective

Despite successful recanalization following acute ischemic stroke, patients may have a poor prognosis. We investigated whether transcranial Doppler combined with quantitative electroencephalography can identify patients with a poor prognosis at an early stage.

Methods

Prospectively recruited patients with successful recanalization after endovascular treatment for acute ischemic stroke were assessed for prognosis at 90 days using the modified Rankin Scale. Clinical information and National Institute of Health Stroke Scale scores were recorded. Transcranial Doppler combined with quantitative electroencephalography was used to evaluate brain function.

Results

Of the 37 patients (63.5 ± 11.7 years) studied, 18 had a poor prognosis at 90 days (modified Rankin Scale >3). Multivariable analysis revealed that transcranial Doppler indicators of the pulsatility index of the unaffected side, quantitative electroencephalography indicators of the pairwise‐derived Brain Symmetry Index, and National Institute of Health Stroke Scale score were independent prognostic indicators. Modeling indicated that combining these independent predictors yielded superior accuracy and net clinical benefit to any single variable. With the final predictive model presented as a nomogram, internal validation by bootstrap resampling showed good discrimination with a concordance index of 0.961. The calibration curve displayed good agreement of predicted and actual probabilities.

Interpretation

The nomogram prediction model combining transcranial Doppler with quantitative electroencephalography and National Institute of Health Stroke Scale scores can provide guidance for individualized risk prediction in patients with acute ischemic stroke after revascularization.
Corticospinal premotor fibers facilitate complex motor control after stroke
Authors: Paul Theresa , Cieslak Matthew , Hensel Lukas , Wiemer Valerie M. , Tscherpel Caroline , Grefkes Christian , Grafton Scott T. , Fink Gereon R. , Volz Lukas J.
Published: July 2024

Objective

The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post‐stroke motor control remains poorly understood.

Methods

We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single‐joint muscle synergies and strength) and complex motor control (involving inter‐joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients.

Results

While M1 sub‐tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub‐tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub‐tract integrity and basal motor control.

Interpretation

While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post‐stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery.
The clinical relevance of MOG antibody testing in cerebrospinal fluid
Authors: Reynolds Molly , Tan Irene , Nguyen Kristy , Merheb Vera , Lee Fiona X. Z. , Trewin Benjamin P , Lerch Magdalena , Shah Snehal , Wolfe Nigel , Buzzard Katherine , Lechner‐Scott Jeannette , Fabis‐Pedrini Marzena , Fok Anthony , John Nevin , Kneebone Chris , Yiannikas Con , Brown David A. , Kermode Allan G. , Reddel Stephen , Dale Russell C. , Brilot Fabienne , Ramanathan Sudarshini ,   the Australasian MOGAD Study Group
Published: July 2024

Myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) is diagnosed by serum MOG‐immunoglobulin G (MOG‐IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG‐IgG. Only 7/1016 (0.7%) seronegative patients had CSF‐restricted MOG‐IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF‐restricted MOG‐IgG had a low sensitivity (2.63%, 95%CI 0.55–7.50%) and low positive predictive value (1.97%, 95%CI 0.45–8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF‐restricted MOG‐IgG in patients without clinico‐radiological features consistent with MOGAD.
Association Between Frailty Status and Readmissions in Hospitalized Patients With Systemic Lupus Erythematosus
Authors: Leung Christopher , Tahir Waqas , Rosli Yenny , Lieber Sarah B. , Makris Una E. , Lee Jiha , Ali Hammad , Goulabchand Radjiv , Singh Siddharth , Singh Namrata
Published: July 2024

Objective

The objective of this study was to evaluate the association between frailty status and risk of readmissions, inpatient death, and cost of admission among patients with systemic lupus erythematosus (SLE).

Methods

We conducted a retrospective cohort study using the National Readmissions Database. Using International Statistical Classification of Diseases, Tenth Revision codes, we identified individuals >18 years of age who had a primary or secondary diagnosis of SLE and were hospitalized between January and June 2018. Using the validated claims‐based Hospital Frailty Risk Score, we categorized individuals as frail (score ≥ 5) or nonfrail (score < 5) at the time of index hospitalization. Our primary outcome was readmission rates post discharge from index hospitalization. Secondary outcomes were rates of inpatient mortality and the total cost of hospitalizations. Cox proportional hazard models were used to estimate the association between frailty and risk of readmissions, with adjustment for age, sex, insurance type, household income, and Elixhauser Comorbidity Index score.

Results

A total of 39,738 patients with SLE met eligibility criteria. Over a median follow‐up of eight months, frail patients with SLE (n = 18,385) had higher Elixhauser Comorbidity Index scores and longer length of stay compared to nonfrail patients with SLE (n = 21,353). Frail patients with SLE had higher readmission rates, a higher proportion of prolonged hospitalizations, and higher costs per hospitalization. Frailty was independently associated with a 10% higher risk of readmission after adjustment for covariates.

Conclusion

Among hospitalized adults with SLE, presence of frailty was associated with higher readmission and inpatient mortality rates. Our results highlight that frailty status can help risk stratify patients with SLE at increased risk for readmissions and other adverse health outcomes.
Oscillating‐to‐Continuous Combustion Transition in Mesoparticle Composites Through Manipulation of Heat Feedback
Authors: Wang Yujie , Chowdhury Mahbub , Zhou Yuxin , Issac Paul George , Shi Keren , Zachariah Michael R.
Published: July 2024

In this study, free‐standing composites consisting of 90 wt% nanoenergetic mesoparticles are fabricated and their combustion characteristics are investigated. The findings reveal that the integrity of the mesoparticles remains intact during the printing process and a reduction in sintering is observed for the composite of mesoparticles compared to the physical mixture. However, the composite of mesoparticles exhibits noncontinuous and oscillating propagation behavior at a steady frequency of ≈5 Hz. This is attributed to insufficient heat feedback from the flame to the unburnt material. To address this issue, carbon fiber (C.F.) is introduced into the composite to enhance heat feedback to the reaction front by intercepting hot agglomerates near the burning surface. Incorporating C.F. leads to steady propagation of the composite. Agglomerate residence time and characteristic heat transfer time analysis near the burning surface indicate that while the composite without C.F. has agglomerate residence time on the same order of magnitude as the characteristic heat transfer time, the composite with C.F. has significantly increased overall agglomerate residence time compared to the characteristic heat transfer time. This confirms the enhanced heat feedback through C.F. inclusion. This study demonstrates the crucial role of heat feedback in the combustion behavior of energetic composites.
Photoactive Dye‐Loaded Polymer Materials: A New Cutting Edge for Antibacterial Photodynamic Therapy
Authors: Elian Christine , Méallet Rachel , Versace Davy‐Louis
Published: July 2024

Healthcare‐associated infections remain a significant health concern, particularly with the emergence of antibiotic resistance. While these antibiotics have saved countless lives, their overuse reduces their efficacy promoting the emergence of multidrug‐resistant (MDR) bacteria. This prompts researchers to explore new alternatives for treating bacteria proliferation. In this context, antibacterial photodynamic therapy (aPDT) has emerged as a promising approach for treating localized infections. It utilizes reactive oxygen species (ROS) as oxidative stress agents, thereby minimizing the risk of developing MDR. The success of aPDT significantly hinges on the careful selection of photosensitizers (PSs) and polymer matrices for the synthesis of polymer‐based photoactive materials. Various light‐absorbing PSs are therefore designed for enhancing ROS production and antimicrobial efficacy. By incorporating PSs into polymer matrices, these materials can harness the light power to generate ROS, destroying bacterial cells upon irradiation. This review aims to provide a comprehensive overview of advancements in this field, specifically focusing on the use of polymer‐based materials. The mechanism of the four main ROS generated in aPDT, the methods used for their detection, and their mode of action against bacteria has been outlined. The recent improvement in polymer‐based aPDT materials and their antibacterial efficacy have been also addressed.
Carbon Nanotubes/Graphene‐Skinned Glass Fiber Fabric with 3D Hierarchical Electrically and Thermally Conductive Network
Authors: Liu Mengxiong , Yang Yuyao , Liu Ruojuan , Wang Kun , Cheng Shuting , Yuan Hao , Huang Kewen , Liang Fushun , Yang Fan , Zheng Kangyi , Liu Longfei , Tu Ce , Wang Jingnan , Gai Xuzhao , Qiao Wang , Wang Xiaobai , Qi Yue , Liu Zhongfan
Published: July 2024

Graphene‐skinned fiber fabric is prepared by chemical vapor deposition (CVD) of continuous graphene on fabric, which enables conformal graphene coverage on fibers and inherits high electrical and thermal conductivity of graphene. However, in the fabric‐shaped configuration, high electrical and thermal contact resistances between fibers, and the lack of conductive and thermal pathways along radial direction of fibers limit the improvement of electrical and thermal conductivity. Herein, carbon nanotubes (CNTs), due to the 1D structure with excellent electrical and thermal conductivity, are introduced to build rich “bridges” to connect the isolated fibers to build new electron and phonon transport channels. Thus, the conceptual design of CNT/graphene‐skinned glass fiber fabric (CNT/GGFF) is creatively proposed and realized by a carefully designed CVD. Constructing the 3D electrically and thermally conductive network in CNT/GGFF leads to >90% decrease of sheet resistance, 4.5 times increase of tensile strength, and >70% decrease of thermal resistance compared with GGFF, making it promising for applications in composite materials, heat dissipation, and de‐icing. Moreover, the thermal resistance of CNT/GGFF exhibits temperature‐independent, extending applications to aviation and space because changes in thermal conductivity of traditional materials with environmental temperatures can adversely affect the thermal stability, reliability, and lifetime of aircrafts.
Inducing One‐Step Dehydrogenation of Magnesium Borohydride via Confinement in Robust Dodecahedral Nitrogen‐Doped Porous Carbon Scaffold
Authors: Jia Yuxiao , Han Bo , Wang Jianchuan , Yuan Sicheng , Tang Lin , Zhang Zheyu , Zou Yongjin , Sun Lixian , Du Yong , Chen Lixin , Xiao Xuezhang
Published: July 2024

A dodecahedral activated N‐doped porous carbon scaffold is synthesized and used for the nanoconfinement of Mg(BH4)2. The optimized mesoporous scaffold possesses an accumulated pore width of 2.65 nm, high specific surface area (3955.9 m2 g−1), and large pore volume (2.15 cm3 g−1), providing ample space for the confinement of Mg(BH4)2 particles and numerous surface active sites for interactions with the same. The confined Mg(BH4)2 system features a dehydrogenation onset temperature of 81.5 °C, an extremely high capacity of 10.2 wt% H2, and an almost single‐step dehydrogenation profile. Moreover, the system exhibits superior capacity retention of 82.7% after 20 cycles at a moderate temperature of 250 °C. Precise activation control enables a transformation from microporous carbon materials to mesoporous ones, and hence the efficient nanoconfinement of Mg(BH4)2 and realization of one‐step dehydrogenation. The evolution of borohydride intermediates is systematically revealed throughout the cycling process. Density functional theory calculations demonstrate defective N heteroatoms within the scaffold are vital in reducing the strength of B─H bonds, and the N‐doped carbon can facilitate decomposition of the irreversible MgB12H12 intermediate. This study opens up new avenues for designing robust carbon scaffolds doped with heteroatoms and analyzing intermediate evolution in nanoconfined Mg‐based borohydride systems.
Fully Degradable Polyphosphoester Cubosomes for Sustainable Agrochemical Delivery
Authors: Azhdari Suna , Linders Jürgen , Coban Deniz , Stank Tim Julian , Dargel Carina , Gojzewski Hubert , Hellweg Thomas , Gröschel André H. , Wurm Frederik R.
Published: July 2024

Microplastic pollution and the urgent need for sustainable agriculture have raised interest in developing degradable carriers for controlled agrochemical release. Porous polymeric particles are particularly promising due to their unique release profiles compared to solid or core‐shell carriers. However, creating degradable, mesoporous (2–50 nm) microparticles is challenging, and their potential for agrochemical delivery is largely unexplored.
A straightforward self‐assembly method is demonstrated for fully degradable porous polymer cubosomes (PCs), showcasing their ability to load and release agrochemicals. Using fully degradable block copolymers (BCPs), poly(ethyl ethylene phosphate)‐b‐polylactide (PEEP‐b‐PLA), PCs are synthesized in water with high inner order and open pores averaging 19 ± 3 nm in diameter. During the self‐assembly process in the presence of the hydrophobic fungicide tebuconazole, polymersomes transform into PCs by enriching the hydrophobic polymer domain and altering the BCP packing parameter. After self‐assemby, highly porous and fungicide‐loaded PCs are obtained.
Fungicide‐loaded PCs show high antimycotic activity against Botrytis cinerea (grey mold), adhere to Vitis vinifera Riesling leaves even after simulated rain, and release the fungicide continuously over several days with different release‐kinetics compared to solid particles. PCs hydrolyze completely into lactic acid and phosphate derivatives, highlighting their potential as microplastic‐free agrochemical delivery systems for sustainable agriculture.
Extracellular Vesicles from Nanomedicine‐Trained Intestinal Microbiota Substitute for Fecal Microbiota Transplant in Treating Ulcerative Colitis
Authors: Zu Menghang , Liu Ga , Xu Haiting , Zhu Zhenhua , Zhen Junfeng , Li Baoyi , Shi Xiaoxiao , Shahbazi Mohammad‐Ali , Reis Rui L. , Kundu Subhas C. , Nie Guangjun , Xiao Bo
Published: July 2024

The biosafety concerns associated with fecal microbiota transplant (FMT) limit their clinical application in treating ulcerative colitis (UC). Gut microbiota secrete abundant extracellular vesicles (Gm‐EVs), which play a critical role in bacteria‐to‐bacteria and bacteria‐to‐host communications. Herein, intestinal microbiota are trained using tea leaf lipid/pluronic F127‐coated curcumin nanocrystals (CN@Lp127s), which can maintain stability during transit through the gastrointestinal tract. Compared with FMT, Gm‐EVs derived from healthy mice significantly improve treatment outcomes against UC by reducing colonic inflammatory responses, restoring colonic barrier function, and rebalancing intestinal microbiota. Strikingly, Gm‐EVs obtained from CN@Lp127‐trained healthy mice exhibit a superior therapeutic effect on UC compared to groups receiving FMT from healthy mice, Gm‐EVs from healthy mice, and FMT from CN@Lp127‐trained healthy mice. Oral administration of Gm‐EVs from CN@Lp127‐trained healthy mice not only alleviates colonic inflammation, promotes mucosal repair, and regulates gut microbiota but also regulates purine metabolism to decrease the uric acid level, resulting in a robust improvement in the UC. This study demonstrates the UC therapeutic efficacy of Gm‐EVs derived from nanomedicine‐trained gut microbiota in regulating the immune microenvironment, microbiota, and purine metabolism of the colon. These EVs provide an alternative platform to replace FMT as a treatment for UC.
Autophagy Deficiency Induced by SAT1 Potentiates Tumor Progression in Triple‐Negative Breast Cancer
Authors: Tian Wenwen , Zhu Lewei , Luo Yongzhou , Tang Yuhui , Tan Qingjian , Zou Yutian , Chen Kun , Deng Xinpei , Tang Hailin , Li Hongsheng , Cai Manbo , Xie Xiaoming , Ye Feng
Published: July 2024

Aggressive triple‐negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role of SAT1 (Spermidine/Spermine N1‐acetyltransferase 1) in cancer, which needs to be further elucidated in breast cancer. In this study, highly expressed SAT1 in TNBC signified worse patient prognoses. And SAT1 knockdown effectively inhibited the proliferation and migration abilities of TNBC cells in vitro and in vivo. In terms of mechanism, the transcription factor JUN enhanced SAT1 transcriptional activity by binding to its promoter region. Then, SAT1 protein in the cytoplasm engaged in directly binding with YBX1 for sustaining YBX1 protein stability via deubiquitylation mediated by the E3 ligase HERC5. Further, SAT1 was found to suppress autophagy remarkably via stabilization of mTOR mRNA with the accumulation of YBX1‐mediated methyl‐5‐cytosine (m5C) modification. These findings proved that SAT1 drives TNBC progression through the SAT1/YBX1/mTOR axis, which may provide a potential candidate for targeted therapy in advanced TNBC.
A Senomorphlytic Three‐Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan
Authors: Wang Jiqun , Liu Wenwen , Huang Yunyuan , Wang Guangwei , Guo Xiaobo , Shi Donglei , Sun Tianyue , Xiao Chaojiang , Zhang Chao , Jiang Bei , Guo Yuan , Li Jian
Published: July 2024

The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti‐aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan‐extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence‐accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti‐aging therapies.
Population affinities in pre‐colonial West Africa: The case of the burial cave Iroungou (Gabon, 14th–15th century CE)
Authors: Mounier Aurélien , Villotte Sébastien , Kacki Sacha , Mora Pascal , Espinasse Loic , Dempawo Jules Zamke , Gerin Christian , Meunier Quentin , Oslisly Richard
Published: July 2024

Introduction

Our knowledge of the populations of sub‐Saharan Africa in the periods before European colonization is limited. Few archeological sites containing human remains have been identified, and written sources for these periods are rare. The discovery in 2018 of the Iroungou sepulchral cave (Gabon), whose use predates the arrival of the Portuguese (14th–15th centuries CE), is an exceptional source of information: at least 28 individuals associated with numerous metal artifacts were found there. The anthropobiological remains were left in situ, but the eight best preserved crania were digitized.

Objectives

This study focuses on the population affinities of these crania, whose morphology was described using 237 landmarks.

Materials and Methods

Geometric morphometric analyses were used to compare the eight Iroungou specimens with 154 individuals representing 12 well‐defined African populations. After alignment (Generalized Procrustes Analysis), morphological affinity was assessed using Euclidean and Mahalanobis distances, and posterior probabilities of population membership (discriminant analysis).

Results

Results indicate that the eight Iroungou crania have, on average, more affinity with Bayaka Pygmy, followed by Central African Bantu. Nevertheless, individually, the Iroungou specimens show an important morphological variation and the eight crania can be separated into different affinity groups: Bayaka and Central African Bantu, KhoeSan, and East‐African Bantu. Finally, one individual presents strong affinity with Somalis.

Conclusion

This phenetic mapping of the Iroungou sample raises questions about the profile of the individuals deposited in the cave in a geographical area known for the Loango pre‐colonial kingdom, which ruling class seemed to have had privileged relationships with the Pygmy populations.