bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical Activity and Progression of Coronary Artery Calcification in Men and Women
Authors: Shuval Kerem , Leonard David , DeFina Laura F. , Barlow Carolyn E. , Berry Jarett D. , Turlington William M. , Pavlovic Andjelka , Radford Nina B. , Gabriel Kelley Pettee , Khera Amit , Levine Benjamin D.
Published: May 2024

Importance

Prior cross-sectional studies have suggested that very high levels of physical activity (PA) are associated with a higher prevalence of coronary artery calcium (CAC). However, less is known regarding the association between high-volume PA and progression of CAC over time.

Objective

To explore the association between PA (measured at baseline and during follow-up) and the progression of CAC over time.

Design, Setting, and Participants

This cohort study included data from 8771 apparently healthy men and women 40 years and older who had multiple preventive medicine visits at the Cooper Clinic (Dallas, Texas), with a mean (SD) follow-up time of 7.8 (4.7) years between the first and last clinic visit. Participants with reported PA and CAC measurements at each visit during 1998 to 2019 were included in the study. Data were analyzed from March 2023 to February 2024.

Exposures

PA reported at baseline and follow-up, examined continuously per 500 metabolic equivalent of task minutes per week (MET-min/wk) and categorically: less than 1500, 1500 to 2999, 3000 or more MET-min/wk.

Main Outcomes and Measures

Negative binomial regression was used to estimate the rate of mean CAC progression between visits, with potential modification by PA volume, calculated as the mean of PA at baseline and follow-up. In addition, proportional hazards regression was used to estimate hazard ratios for baseline PA as a predictor of CAC progression to 100 or more Agatston units (AU).

Results

Among 8771 participants, the mean (SD) age at baseline was 50.2 (7.3) years for men and 51.1 (7.3) years for women. The rate of mean CAC progression per year from baseline was 28.5% in men and 32.1% in women, independent of mean PA during the same time period. That is, the difference in the rate of CAC progression per year was 0.0% per 500 MET-min/wk for men and women (men: 95% CI, −0.1% to 0.1%; women: 95% CI, −0.4% to 0.5%). Moreover, baseline PA was not associated with CAC progression to a clinically meaningful threshold of 100 AU or more over the follow-up period. The hazard ratio for a baseline PA value of 3000 or more MET-min/wk vs less than 1500 MET-min/wk to cross this threshold was 0.84 (95% CI, 0.66 to 1.08) in men and 1.16 (95% CI, 0.57 to 2.35) in women.

Conclusions and Relevance

This study found that PA volume was not associated with progression of CAC in a large cohort of healthy men and women who were initially free of overt cardiovascular disease.
Drug Reaction With Eosinophilia and Systemic Symptoms With Pustulosis
Authors: Hansen Emma , Kirven Rachel M. , Gallardo Matthew , Chung Catherine G. , Fisher Kristopher , Kaffenberger Benjamin H. , Korman Abraham M.
Published: May 2024

This cohort study examines patients with drug reaction with eosinophilia and systemic symptoms who also have pustules.
Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae
Authors: Caplan Avrom S. , Todd Gabrielle C. , Zhu YanChun , Sikora Michelle , Akoh Christine C. , Jakus Jeannette , Lipner Shari R. , Graber Kayla Babbush , Acker Karen P. , Morales Ayana E. , Rolón Rebecca M. Marrero , Westblade Lars F. , Fonseca Maira , Cline Abigail , Gold Jeremy A. W. , Lockhart Shawn R. , Smith Dallas J. , Chiller Tom , Greendyke William G. , Manjari Swati R. , Banavali Nilesh K. , Chaturvedi Sudha
Published: May 2024

Importance

Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission.

Objective

To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing.

Design, Setting, and Participants

This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers.

Main Outcome and Measure

Improvement or resolution at the last follow-up assessment.

Results

Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates.

Conclusion and Relevance

The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.
Multidimensional Approach to Exploring Neighborhood Determinants and Symptom Severity Among Individuals With Psychosis
Authors: Oluwoye Oladunni , Puzia Megan , Lissau Ari , Amram Ofer , Weeks Douglas L.
Published: May 2024

Importance

The impact of cumulative exposure to neighborhood factors on psychosis, depression, and anxiety symptom severity prior to specialized services for psychosis is unknown.

Objective

To identify latent neighborhood profiles based on unique combinations of social, economic, and environmental factors, and validate profiles by examining differences in symptom severity among individuals with first episode psychosis (FEP).

Design, Setting, and Participants

This cohort study used neighborhood demographic data and health outcome data for US individuals with FEP receiving services between January 2017 and August 2022. Eligible participants were between ages 14 and 40 years and enrolled in a state-level coordinated specialty care network. A 2-step approach was used to characterize neighborhood profiles using census-tract data and link profiles to mental health outcomes. Data were analyzed March 2023 through October 2023.

Exposures

Economic and social determinants of health; housing conditions; land use; urbanization; walkability; access to transportation, outdoor space, groceries, and health care; health outcomes; and environmental exposure.

Main Outcomes and Measures

Outcomes were Community Assessment of Psychic Experiences 15-item, Patient Health Questionnaire 9-item, and Generalized Anxiety Disorder 7-item scale.

Results

The total sample included 225 individuals aged 14 to 36 years (mean [SD] age, 20.7 [4.0] years; 152 men [69.1%]; 9 American Indian or Alaska Native [4.2%], 13 Asian or Pacific Islander [6.0%], 19 Black [8.9%], 118 White [55.1%]; 55 Hispanic ethnicity [26.2%]). Of the 3 distinct profiles identified, nearly half of participants (112 residents [49.8%]) lived in urban high-risk neighborhoods, 56 (24.9%) in urban low-risk neighborhoods, and 57 (25.3%) in rural neighborhoods. After controlling for individual characteristics, compared with individuals residing in rural neighborhoods, individuals residing in urban high-risk (mean estimate [SE], 0.17 [0.07]; P = .01) and urban low-risk neighborhoods (mean estimate [SE], 0.25 [0.12]; P = .04) presented with more severe psychotic symptoms. Individuals in urban high-risk neighborhoods reported more severe depression (mean estimate [SE], 1.97 [0.79]; P = .01) and anxiety (mean estimate [SE], 1.12 [0.53]; P = .04) than those in rural neighborhoods.

Conclusions and Relevance

This study found that in a cohort of individuals with FEP, baseline psychosis, depression, and anxiety symptom severity differed by distinct multidimensional neighborhood profiles that were associated with where individuals reside. Exploring the cumulative effect of neighborhood factors improves our understanding of social, economic, and environmental impacts on symptoms and psychosis risk which could potentially impact treatment outcomes.
Disparities in Patient Portal Engagement Among Patients With Hypertension Treated in Primary Care
Authors: Khatib Rasha , Glowacki Nicole , Chang Eva , Lauffenburger Julie , Pletcher Mark J. , Siddiqi Alvia
Published: May 2024

Importance

Patient portals are increasingly used for patient-clinician communication and to introduce interventions aimed at improving blood pressure control.

Objective

To characterize patient portal use among patients with hypertension managed in primary care.

Design, Settings, and Participants

This retrospective cohort study used electronic health records linked with patient portal log file data from a large, diverse Midwestern health care system. Patients with hypertension who had a primary care visit from January 1, 2021, to December 31, 2021, were included. The first visit in 2021 was considered the baseline visit; patient portal engagement was evaluated during the following year. Multivariate logistic regressions, presented as odds ratios (ORs) and 95% CIs, were used to evaluate associations between patient characteristics and patient portal engagement, adjusting for potential confounders.

Exposures

Primary exposures included 4 sociodemographic factors routinely collected in the electronic health record: race and ethnicity, insurance, preferred language, and smoking status.

Main Outcomes and Measures

Indicators of patient engagement with the patient portal included accessing the patient portal at least once, accessing the portal within 7 days of at least 50.0% of primary care physician (PCP) visits, frequent logins (<28 vs ≥28), messaging (<2 vs ≥2), and sharing home blood pressure readings.

Results

Among 366 871 patients (mean [SD], 63.5 [12.6] years), 52.8% were female, 3.4% were Asian, 7.8% were Hispanic, 19.7% were non-Hispanic Black, 66.9% were non-Hispanic White, and 2.3% were of other race or ethnicity. During the 1-year study period starting in 2021, 70.5% accessed the patient portal at least once, 60.2% accessed around the time of their PCP visits, 35.7% accessed the portal frequently, 28.9% engaged in messaging, and 8.7% shared home blood pressure readings. Compared with White patients, non-Hispanic Black and Hispanic patients had lower odds of any access (Black: OR, 0.53; 95% CI, 0.52-0.54; Hispanic: OR, 0.66; 95% CI, 0.64-0.68), access around PCP visit time (Black: OR, 0.49; 95% CI, 0.48-0.50; Hispanic: OR, 0.62; 95% CI, 0.60-0.64), frequent access (Black: OR, 0.56; 95% CI, 0.55-0.57; Hispanic: OR, 0.71; 95% CI, 0.69-0.73), and messaging (Black: OR, 0.63; 95% CI, 0.61-0.64); Hispanic: OR, 0.71; 95% CI, 0.69-0.73).

Conclusions and Relevance

This cohort study of patients with hypertension found clear sociodemographic disparities in patient portal engagement among those treated in primary care. Without special efforts to engage patients with portals, interventions that use patient portals to target hypertension may exacerbate disparities.
Outcomes of Conversion Surgery for Patients With Low-Risk Papillary Thyroid Carcinoma
Authors: Levyn Helena , Scholfield Daniel W. , Eagan Alana , Boe Lillian A. , Shaha Ashok R. , Wong Richard J. , Shah Jatin P. , Ganly Ian , Morris Luc G. T. , Tuttle R. Michael
Published: May 2024

Importance

The outcomes of patients with low-risk thyroid cancer who undergo surgery following a period of active surveillance (AS) are not well-defined.

Objective

To evaluate surgical, pathologic, and oncologic outcomes among patients undergoing conversion surgery (CS) following AS for low-risk papillary thyroid carcinoma.

Design, Setting, and Participants

In this cohort study, patients who underwent CS for disease progression were compared with patients who underwent CS without disease progression and with a propensity score–matched cohort of patients who underwent initial surgery (IS). The median (IQR) postsurgical follow-up time was 40.3 (18.0-59.0) months. Patients were treated at a quaternary cancer referral center in the United States.

Exposures

Surgery.

Main Outcomes and Measures

Surgical complications, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS).

Results

Of 550 patients who underwent AS, 55 (10.0%) had CS, of whom 39 (7.1%) had surgery due to suspected disease progression (median [IQR] age, 48 [39-56] years; 32 [82.1%] female). There were no clinically meaningful differences in rates of surgical sequalae between the progression CS group (12 of 39 [30.7%]) and the nonprogression CS group (7 of 16 [43.8%]) (Cramer V, 0.2; 95% CI, 0.01-0.5). The 5-year OS was 100% (95% CI, 100%-100%) in both the disease-progression CS cohort and the IS cohort. Although the cohort of patients undergoing CS after disease progression was by definition a subset with more aggressive tumor behavior, no clinically meaningful differences were observed in the rates of regional recurrence (2 of 39 [5.1%] vs 0 of 39 patients with IS), local recurrence (0 patients), distant metastasis (0 patients), or disease-specific mortality (0 patients) when compared with the matched IS group. Five-year RFS rates were similar: 100% in the IS group and 86% (95% CI, 70%-100%) in the CS group.

Conclusions and Relevance

In this cohort study, CS for suspected disease progression was associated with surgical and oncologic outcomes similar to IS, supporting the feasibility and safety of AS for patients with low-risk papillary thyroid carcinoma.
Pediatric Trauma Center Access, Regional Injury Burden, and Socioeconomic Disadvantage
Authors: Hur Dong G. , Ren Alexander L. , Yue Tiffany M. , Spain David A. , Choi Jeff
Published: May 2024

This cross-sectional study assesses whether populations in socioeconomically disadvantaged regions in the US lack timely access to pediatric trauma centers.
Pressure‐Dependent Superconductivity in Topological Dirac Semimetal SrCuBi
Authors: Lee Nahyun , Pei Cuiying , Koo Jahyun , Qi Yanpeng , Kim Sung Wng
Published: May 2024

The discovery of superconducting states in diverse topological materials generates a burgeoning interest to explore a topological superconductor and to realize a fault‐tolerant topological quantum computation. A variety of routes to realize topological superconductors are proposed, and many types of topological materials are developed. However, a pristine topological material with a natural superconducting state is relatively rare as compared to topological materials with artificially induced superconductivity. Here, it is reported that the planar honeycomb structured 3D topological Dirac semimetal (TDS) SrCuBi, which is the Zintl phase, shows a natural surface superconductivity at 2.1 K under ambient pressure. It is clearly identified from theoretical calculations that a topologically nontrivial state exists on the (100) surface. Further, its superconducting transition temperature (Tc) increases by applying pressure, exhibiting a maximal Tc of 4.8 K under 6.2 GPa. It is believed that this discovery opens up a new possibility of exploring exotic Majorana fermions at the surface of 3D TDS superconductors.
Nanogalvanic Cells Release Highly Reactive Electrons in Tumors to Effectively Eliminate Tumors
Authors: Huang Wei‐Qiang , Zhu Ya‐Qi , Gao Fan , You Wei , Chen Guang , Nie Xuan , Xia Lei , Wang Long‐Hai , Hong Chun‐Yan , Zhang Ze , Wang Fei , Yu Yue , You Ye‐Zi
Published: May 2024

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.
A Review: Active Tunable Terahertz Metamaterials
Authors: Li Jining , Chen Jiyue , Yan Dexian , Fan Fei , Chen Kai , Zhong Kai , Wang Yuye , Tian Zhen , Xu Degang
Published: May 2024

The diversity and practicability of terahertz metamaterials have experienced rapid development in the past decade due to the increasing demand for various devices. This topic has attracted significant interest from researchers. Among the key functional devices in terahertz metamaterial systems, the active control ability of terahertz metamaterials is highly valuable and captivating. This implies that the electromagnetic properties of metamaterials can be modulated over a wide dynamic range by external stimuli. This review categorizes the different types of tunable terahertz metamaterials based on the external stimuli to which they respond, namely, mechanical modulation, electrical modulation, magnetic modulation, and optical modulation. Mechanically modulated devices offer simple yet efficient modulation, while electrical and magnetic modulation provide effective active modulation through electrical mechanisms. Optical modulation, in contrast, focuses on incorporating various materials to achieve active modulation.
Dual‐Comb Interferometry for Coherence Analysis of Tightly Locked Mid‐Infrared Quantum Cascade Laser Frequency Combs
Authors: Parriaux Alexandre , Komagata Kenichi N. , Bertrand Mathieu , Wittwer Valentin J. , Faist Jérôme , Südmeyer Thomas
Published: May 2024

Frequency combs are powerful tools for many applications and high performances are achieved by stabilizing these lasers. For operation in the mid‐infrared, quantum cascade lasers (QCL) are ideal candidates as they present numerous advantages. However, stabilized QCL‐combs lack a detailed characterization of their noise properties due to the sensitivity limits of current analyzing techniques. To overcome these challenges, what is believed to be the first tightly locked dual QCL‐comb system is developed. Its use is twofold. First, phase noise analysis of the dual‐comb signal shows residual phase noise below 600 mrad for all comb lines, and the comb coherence as well as the performances of the repetition frequency locking mechanism is characterized. Second, coherent averaging with a 7 × 105 Hz1/2 figure‐of‐merit system is demonstrated, which is compatible with high‐precision spectroscopy.
Economic value of Brangus cattle traits in Argentina
Authors: Gatti Nicolas , Funes Victor , Amaro Ignacio Benito
Published: May 2024

Starting in the early 2000s, a boom in demand for agricultural commodities displaced cattle ranching out of the most productive areas of the Pampas' prairie. The crossbreeds between Angus and Hereford with Brahman, that is, Brangus and Braford, have been successfully adopted across Argentina. However, little is known about the specific bulls' traits that drive the demand for genetic selection of cattle outside the Pampas. Obtaining the economic value of traits would help to identify the demand for adapting livestock production to different ecosystems while preserving the meat quality of Angus and Hereford cattle. We estimated hedonic price models using Brangus bull sales data from two cattle breeding ranches in the north of Cordoba province. We find that cattle ranchers prefer observed traits such as weight, coat color, and age, while genetic indicators such as Expected Progeny Differences (EPDs) have secondary importance. We argue that stronger preferences for red‐coated bulls, as opposed to black‐coated bulls, could be associated with the demand for reducing heat stress. In addition, the relatively weak association between EPDs and prices may be related to unobservable variables such as ranchers' characteristics, and that the value of genetics is implicit in the studs' reputation. [EconLit Citations: Q12, Q13, Q16].
Design Methodology for a 3D Printable Multi‐Degree of Freedom Soft Actuator Using Geometric Origami Patterns
Authors: Mak Yoeko X. , Dijkshoorn Alexander , Abayazid Momen
Published: May 2024

Soft pneumatic actuators (SPAs) have applications in various domains due to their compliance, low cost, and lightweight characteristics. Herein, a geometric origami design for 3‐degree of freedom (DoF) SPAs is presented, which enables manufacturing using 3D printing at one go without any support structure. The proposed method uses a general design parameterization that works for multiple types of cylindrical origami patterns (Kresling, cylindrical Miura, Yoshimura, and Accordion). It is shown that a 3‐DoF pneumatic actuator capable of bending and extension can be constructed by superimposing two cylindrical origami patterns to create a separation of chambers inside of the module. In addition, the design parameters are chosen to reduce the strain during deformation and maximize the output forces of the origami actuator. The actuator is manufactured, and its motion and force profiles are experimentally characterized. The designed origami actuator can bend from to and the length during operation can vary between and of the initial length.
Overshoot‐Suppressed Memristor Array with AlN Oxygen Barrier for Low‐Power Operation in the Intelligent Neuromorphic Systems
Authors: Kim Sungjoon , Hong Kyungho , Kim Hyungjin , Kim Min‐Hwi , Choi Woo Young
Published: May 2024

As the demand for bio‐inspired neuromorphic systems grows, memristor has emerged as a pivotal component in artificial synaptic devices. This study delves into the advantages and limitations of the one‐transistor‐one‐resistor (1T‐1R) and 0T‐1R architectures for memory array configurations. A significant enhancement in the memristor's on/off ratio, surpassing 103, achieved by integrating both an overshoot suppression layer (OSL) and an ultra‐thin AlN oxygen barrier layer (OBL) is also reported. The concurrent insertion of an AlOx OSL is essential for manifesting the self‐compliance attribute in 4F2 memristor arrays. Evaluations of a 24 × 24 array embedded with OSL and OBL reveal a substantial reduction in retention variation. In terms of functionality, a 7.13‐fold decline in vector‐matrix multiplication error is observed, accentuating the potential of this approach for neural network synapse applications. The analog reset characteristics of the OBL memristor facilitate over 25 multilevel states. Furthermore, the adoption of nonnegative weights presents an avenue to potentially double synaptic integration density. Through simulation program with integrated circuit emphasis simulations, the necessity of nonnegative and 16‐level quantized conductance in balancing power consumption without accuracy loss at the image classification is validated.
ClassyPose: A Machine‐Learning Classification Model for Ligand Pose Selection Applied to Virtual Screening in Drug Discovery
Authors: Tran‐Nguyen Viet‐Khoa , Camproux Anne‐Claude , Taboureau Olivier
Published: May 2024

Determining the target‐bound conformation of a drug‐like molecule is a crucial step in drug design, as it affects the outcome of virtual screening (VS), and paves the way for hit‐to‐lead and lead optimization. While most docking programs usually manage to produce at least a near‐native pose for a bioactive molecule inside its binding pocket, their integrated classical scoring functions (SFs) generally fail to prioritize this pose. Many studies have been carried out to tackle this SF problem, offering multiple pose refinement and/or classification methods, albeit with limitations. This study presents a new support vector machine model for pose classification, called “ClassyPose”, which predicts the probability that a receptor‐bound ligand conformation could be near‐native, without any additional pose optimization step. Trained on protein‐ligand extended connectivity features extracted from over 21 600 crystal and docking poses of diverse ligands, this model outperformed other machine‐learning algorithms and three existing SFs in terms of docking power, identifying the native ligand pose as top‐ranked solution for more than 90% of entries in two test sets. It also achieved high specificity (above 0.96), and improved VS performance when used for pose selection. This efficient, user‐friendly tool and all related data are available at https://github.com/vktrannguyen/Classy_Pose.
Clinical and molecular characteristics of hemophilia A affected individuals and carriers: A 24 years experience from three centers
Authors: Ho Stephanie K. L. , Ng Samuel Y. L. , Yung Tsz‐Kwai , Mok Myth T. S. , Yiu Wing‐Chung , Cheng Heidi H. Y. , Cheng Shirley S. W. , Luk Ho‐ming , Lo Ivan F. M. , Kan Anita S. Y.
Published: May 2024

Hemophilia A is a rare bleeding disorder with variable expressivity and allelic heterogeneity. Despite the advancement of prenatal diagnostics and molecular studies, the number of studies reviewing the reproductive choices of hemophilia A carriers and affected individuals remains limited. Through this retrospective review, we hope to gain a deeper understanding of hemophilia A‐affected individuals' clinical and molecular characteristics, as well as the reproductive choices of the at‐risk couples. A total of 122 individuals harboring likely causative F8 gene alterations from 64 apparently unrelated families attending three centers between 3/2000 and 3/2023 were included in this study. Their clinical and molecular findings as well as reproductive choices were gathered in a clinical setting and verified through the electronic medical record database of the public health system. Forty‐seven affected males and 75 female heterozygous carriers were included in the analysis. Among 64 apparently unrelated families, 36 distinct pathogenic/likely pathogenic variants were identified, of which 30.6% (11/36) of variants were novel. While the majority of clinical findings and genotype–phenotype correlations appear to be in accordance with existing literature, female carriers who had no fertility intention were significantly more likely to have affected sons than those who had fertility intention (5/19 vs. 4/5; p = 0.047). Through this retrospective review, we summarized the clinical and molecular characteristics of 122 individuals harboring pathogenic/likely pathogenic F8 variants, as well as their fertility intentions and reproductive outcomes. Further studies are required to look into the considerations involved in reproductive decision‐making.
Characterizing molecular and synaptic signatures in mouse models of late‐onset Alzheimer's disease independent of amyloid and tau pathology
Authors: Kotredes Kevin P. , Pandey Ravi S. , Persohn Scott , Elderidge Kierra , Burton Charles P , Miner Ethan W. , Haynes Kathryn A. , Santos Diogo Francisco S. , Williams Sean‐Paul , Heaton Nicholas , Ingraham Cynthia M. , Lloyd Christopher , Garceau Dylan , O'Rourke Rita , Herrick Sarah , Rangel‐Barajas Claudia , Maharjan Surendra , Wang Nian , Sasner Michael , Lamb Bruce T. , Territo Paul R. , Sukoff Rizzo Stacey J. , Carter Gregory W. , Howell Gareth R. , Oblak Adrian L.
Published: May 2024

INTRODUCTION

MODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late‐onset Alzheimer's disease (LOAD) more accurately.

METHODS

We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid‐beta (Aβ). Mice were subjected to a control diet or a high‐fat/high‐sugar diet (LOAD2+HFD). We assessed disease‐relevant outcome measures in plasma and brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, and multi‐omics.

RESULTS

By 18 months, LOAD2+HFD mice exhibited sex‐specific neuron loss, elevated insoluble brain Aβ42, increased plasma neurofilament light chain (NfL), and altered gene/protein expression related to lipid metabolism and synaptic function. Imaging showed reductions in brain volume and neurovascular uncoupling. Deficits in acquiring touchscreen‐based cognitive tasks were observed.

DISCUSSION

The comprehensive characterization of LOAD2+HFD mice reveals that this model is important for preclinical studies seeking to understand disease trajectory and progression of LOAD prior to or independent of amyloid plaques and tau tangles.

Highlights

By 18 months, unlike control mice (e.g., LOAD2 mice fed a control diet, CD), LOAD2+HFD mice presented subtle but significant loss of neurons in the cortex, elevated levels of insoluble Ab42 in the brain, and increased plasma neurofilament light chain (NfL).

Transcriptomics and proteomics showed changes in gene/proteins relating to a variety of disease‐relevant processes including lipid metabolism and synaptic function.

In vivo imaging revealed an age‐dependent reduction in brain region volume (MRI) and neurovascular uncoupling (PET/CT).

LOAD2+HFD mice also demonstrated deficits in acquisition of touchscreen‐based cognitive tasks.
Cognitive Trajectories and Alzheimer Disease Biomarkers: From Successful Cognitive Aging to Clinical Impairment
Authors: Harrison Theresa M. , Chadwick Trevor , Pezzoli Stefania , Lee JiaQie , Landau Susan M. , Jagust William J. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: May 2024

Objective

Cross‐sectional definitions of successful cognitive aging have been widely utilized, but longitudinal measurements can identify people who do not decline. We performed this study to contrast maintenance with declining trajectories, including clinical conversion.

Methods

We included baseline cognitively unimpaired Alzheimer's Disease Neuroimaging Initiative participants with 3 or more cognitive testing sessions (n = 539, follow‐up 6.1 ± 3.5 years) and calculated slopes of an episodic memory composite (MEM) to classify them into two groups: maintainers (slope ≥ 0) and decliners (slope < 0). Within decliners, we examined a subgroup of individuals who became clinically impaired during follow‐up. These groups were compared on baseline characteristics and cognitive performance, as well as both cross‐sectional and longitudinal Alzheimer disease (AD) biomarker measures (beta‐amyloid [Aβ], tau, and hippocampal volume).

Results

Forty‐one percent (n = 221) of the cohort were MEM maintainers, and 33% (n = 105) of decliners converted to clinical impairment during follow‐up. Compared to those with superior baseline scores, maintainers had lower education and were more likely to be male. Maintainers and decliners did not differ on baseline MEM scores, but maintainers did have higher non‐MEM cognitive scores. Maintainers had lower baseline global Aβ, lower tau pathology, and larger hippocampal volumes than decliners, even after removing converters. There were no differences in rates of change of any AD biomarkers between any cognitive trajectory groups except for a higher rate of hippocampal atrophy in clinical converters compared to maintainers.

Interpretation

Using longitudinal data to define cognitive trajectory groups reduces education and sex bias and reveals the prognostic importance of early onset of accumulation of AD pathology. ANN NEUROL 2024;96:378–389
Ionic Hydrogen Bond‐Assisted Catalytic Construction of Nitrogen Stereogenic Center via Formal Desymmetrization of Remote Diols
Authors: Luo Zhongfu , Liao Minghong , Li Wei , Zhao Sha , Tang Kun , Zheng Pengcheng , Chi Yonggui Robin , Zhang Xinglong , Wu Xingxing
Published: May 2024

The control of noncarbon stereogenic centers is of profound importance owing to their enormous interest in bioactive compounds and chiral catalyst or ligand design for enantioselective synthesis. Despite various elegant approaches have been achieved for construction of S‐, P‐, Si‐ and B‐stereocenters over the past decades, the catalyst‐controlled strategies to govern the formation of N‐stereogenic compounds have garnered less attention. Here, we disclose the first organocatalytic approach for efficient access to a wide range of nitrogen‐stereogenic compounds through a desymmetrization approach. Intriguingly, the pro‐chiral remote diols, which are previously not well addressed with enantiocontrol, are well differentiated by potent chiral carbene‐bound acyl azolium intermediates. Preliminary studies shed insights on the critical importance of the ionic hydrogen bond (IHB) formed between the dimer aggregate of diols to afford the chiral N‐oxide products that feature a tetrahedral nitrogen as the sole stereogenic element with good yields and excellent enantioselectivities. Notably, the chiral N‐oxide products could offer an attractive strategy for chiral ligand design and discovery of potential antibacterial agrochemicals.
Steric and temperature effects in unsymmetrical α‐diimine nickel‐catalyzed ethylene and 1‐octene polymerization
Authors: Shou Jinke , Li Pei , Tian Wanlu , Liu Yue , Zhang Shaojie , Wang Fuzhou , Tan Chen
Published: May 2024

In this contribution, a series of unsymmetric α‐diimine nickel complexes are synthesized. One side of these nickel complexes is the 2,4‐dimethyl‐6‐diphenylmethylaniline unit, and the steric effects are tuned by changing another aniline unit. These nickel complexes have high catalytic activities in ethylene (>106 g mol−1 h−1) and 1‐octene (104–105 g mol−1 h−1) polymerization, generating high‐molecular‐weight polyolefins (Mn > 104 g mol−1) with tunable branching densities (59–91/1000C). Steric effects and polymerization temperature can significantly affect the catalytic performance of the catalyst. Most importantly, catalysts with different steric hindrances have different temperature sensitivity. In general, catalysts with larger steric hindrances are more sensitive to temperature. This may be due to the fact that the rotation of some chemical bonds is blocked at low temperatures due to the larger volume of the substituents, resulting in more significant temperature sensitivity.
Cerium‐based metal–organic frameworks (MOFs) as a sustainable approach to mitigating environmental stress‐induced intestinal ulcers in earthworms
Authors: Abd El‐Aziz Fatma El‐Zahraa A. , Abdelhamid Hani Nasser
Published: May 2024

Exposure to environmental stresses such as heavy metal pollution, herbicides, and climate change may cause adverse effects on biological animals such as earthworms, leading to conditions including intestinal ulcers. This study outlines the potential of a cerium‐based metal–organic framework (Ce‐MOF) in healing alcohol‐induced ulcers in earthworms. The Ce‐MOF was synthesized via a solvothermal technique and analyzed using X‐ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Ce‐MOF exhibited a one‐dimensional channel and demonstrated multi‐enzyme‐like activity. It was examined on earthworms suffering from ulcers caused by alcohol use. Examinations at a macroscopic level, histological analysis, and transmission electron microscopy images showed significant harm to the intestinal lining in ulcerated worms. The ulcer treatment with Ce‐MOF substantially enhanced intestinal morphology, repaired the epithelial lining, and facilitated ulcer healing. Furthermore, Ce‐MOF decreased the death rate and enhanced the weight of earthworms in comparison to untreated groups. This study emphasizes the potential of Ce‐MOF as an innovative therapeutic agent for alcohol‐induced ulcers, emphasizing its prospective uses in regenerative medicine and tissue regeneration.
Facile and efficient fabrication of carbon nanotube reinforced epoxy vitrimers through dynamic crosslinking
Authors: Li Zixia , Liu Yunfeng , Ran Yin
Published: May 2024

Carbon nanotubes (CNT) is an ideal candidate for reinforced epoxy vitrimer composites, however, achieving a desirable improvement of the mechanical properties is a great challenge owing to CNT is extremely easy to aggregate. In this study, well‐dispersed CNT reinforced epoxy vitrimers, namely EVD/CNT, were prepared by combining ultrasonic dispersion and dynamic crosslinking techniques, using multiple wall carbon nanotube as reinforcement filler, sebacic acid as curing agent, diglycidyl ether of bisphenol A (DGEBA) as epoxy monomer, zinc acetylacetonate as transesterification catalyst, torque rheometer (internal mixer) as dynamic crosslinking equipment. The CNT reinforced epoxy vitrimers, namely EVS/CNT, were prepared using traditional static curing method. The structure and morphology, mechanical properties and stress relaxation behavior of EVS/CNT and EVD/CNT were comparatively investigated, and the influence of CNT content on the structure and properties of EVD/CNT prepared by dynamic crosslinking method were also studied. The results indicated that dynamic crosslinking technology can stably disperse CNT into epoxy vitrimer resin matrix under continuous shear force. However, CNT experienced severe secondary agglomeration during the static curing process. When the loading amount of CNT was 2 wt%, the tensile strength and elongation at break of EVD/CNT‐2 were 3.2 times and 2.2 times higher than those of EVS/CNT‐2, respectively. The Young's modulus and glass transition temperature (Tg) of EVD/CNT‐2 (6.43 ± 1.10 MPa, 29.6°C) were also higher than those of EVS/CNT‐2 (5.46 ± 0.31 MPa, 25.4°C). Moreover, dynamic crosslinking technology greatly shortened the reaction time of CNT reinforced epoxy vitrimers, improved production efficiency and reduced reaction energy consumption, and was expected to be used for large‐scale and industrial production.
Review of bioactive wax emulsified films
Authors: Tijani Abodunrin Tirmidhi , Ayodele Tawakalt , Liadi Musiliu , Clementson Clairmont , Hammed Ademola
Published: May 2024

Plastic packaging materials have caused significant environmental issues because they are nonrenewable and nonbiodegradable. Wax‐emulsified films from biomaterials, on the other hand, are renewable and biodegradable, making them promising packaging alternatives. The development of bioactive wax‐emulsified films (BWEFs) with antimicrobial and antioxidant properties has been a topic of extensive research. In this review, we provide an overview of wax emulsification, BWEF processing, and applications. BWEF contains several bioactive agents such as tannins, flavonoids, phenolic acids, and carotenes. The addition of emulsified wax and active agents to films not only enhances their antimicrobial and antioxidant properties but also reduces their hydrophilicity. Other reagents have been added to BWEF partially to increase hydrophobicity and mainly to improve mechanical properties. BWEFs prolong food shelf life, monitor wound healing, and control drug delivery. We have identified some research challenges that need to be solved to make BWEFs industrially attractive.
Fisher perceptions of catch and trade of sharks and rays in Angolan small‐scale fisheries
Authors: Soares Ana Lúcia Furtado , Jabado Rima W.
Published: May 2024

Small‐scale fisheries ensure food security and employment in Angolan coastal communities. These dynamic, widespread fisheries remain mostly unregulated, with limited data available despite their likely significant impact on marine megafauna. We used an interview‐based survey to investigate local fisher interactions with elasmobranchs (sharks and rays) and gather information on utilization, trade and perceptions. All fishers (n = 83) landed elasmobranchs. Most fishers considered sharks as bycatch (74.7%, n = 62), while 100% targeted rays (Order Myliobatiformes), and 62.8% (n = 52) targeted guitarfishes (Order Rhinopristiformes). Over 80% of fishers reported declining catches and sizes of elasmobranchs over the last 30 years, raising concerns about the sustainability of these fisheries. Utilization and trade routes varied depending on elasmobranch products, with exports to China (fins) and local market sales (meat). Specifically, 8.4% (n = 5) of fishers confirmed meat and fin exports to China (4.8%, n = 3). The protection of sharks was considered by 32.5% (n = 30) of respondents, while 21.7% (n = 18) believed only certain shark species should be protected. Most respondents reported that rays (80.5%, n = 67) and guitarfishes (61%, n = 51) should not be protected. Regarding the ban on fishing, none considered it for ray species, with only 6.1% (n = 5) supporting this idea for guitarfishes. We highlight the lack of elasmobranch‐specific conservation measures and the need for a multi‐pronged approach to inform policy. Considering the scale of these fisheries, management actions need to be urgently developed and implemented to ensure the sustainability of elasmobranch fisheries while securing the livelihoods of coastal communities.
Assessing Drinking Water Systems to Improve Performance and Capacity
Authors: Bell Emily V. , Hansen Katy , Mullin Megan
Published: May 2024

Key Takeaways

Fragmented data across state agencies and subagencies reduce the ability to assess a community water system's overall condition.

Identifying relationships among different dimensions of performance can help assess how well systems respond to challenges.

Balancing affordability with capacity for reliable drinking water delivery over time is an ongoing challenge for many utilities.

Focusing only on safe drinking water compliance in research and oversight may overlook systems with other critical vulnerabilities.
Cognitive ability or motivation, or both: An integrative path analysis of the interplay between two key factors in academic achievement
Authors: Dadandı İbrahim , Yazıcı Hikmet
Published: May 2024

While the individual roles of general cognitive ability and motivation in predicting academic achievement are well established, how they interact with one another and the extent of their combined effect on students' learning outcomes leave much to be explained. The present study investigates the relationships among general cognitive ability, selected motivational constructs (i.e., academic self‐efficacy, academic self‐concept, self‐esteem and student engagement) and academic achievement within a structural model. A total of 346 (M = 52%, F = 48%; Mage = 12.98 ± 0.98) middle school students completed Primary Abilities Test 6–8, Myself as A Learner Scale, Academic Self‐Efficacy Scale, School Short‐Form of the Coopersmith Self‐Esteem Inventory and Student Engagement Scale. Path analysis revealed that general cognitive ability had a direct effect on academic achievement and significant indirect effects on academic achievement through academic self‐efficacy, as well as on student engagement through both academic self‐efficacy and academic self‐concept. Moreover, academic self‐efficacy had significant direct effects on both academic achievement and student engagement. Additionally, self‐esteem and academic self‐concept had significant direct effects on student engagement, as well as indirect effects on both academic achievement and student engagement through academic self‐efficacy. The present study contributes to the understanding of dynamics between cognitive and motivational variables in shaping academic achievement and provides valuable insights for educators and policymakers to develop effective pedagogical designs and strategies for improving student learning outcomes.
Climate change and its impact on the mental health well‐being of Indigenous women in Western cities, Canada
Authors: Chapola Jebunnessa , Datta Ranjan , Waucaush‐Warn Jaime , Subroto Sujoy
Published: May 2024

This collaborative paper explores the interconnections between climate change and the mental health and well‐being of Indigenous women in Western Canada. As the impacts of climate change intensify globally, vulnerable populations, particularly Indigenous communities, face disproportionate and multifaceted challenges. Centering on Indigenous women in Western Canada, this study explores how the climate crisis magnifies Indigenous communities' mental health disparities. Drawing from the Indigenist feminist research approach, the investigation focuses on Indigenous women's lived experiences, perceptions, and land‐based coping strategies amidst climate challenges, while simultaneously addressing the unique social, cultural, and historical factors influencing their mental health vulnerabilities within the context of climate change. The findings shed light on the complex relationships between environmental degradation, ongoing colonial impacts on traditional practices, and the mental well‐being of Indigenous women. Concluding with implications for policy and community‐led interventions, this research contributes to the discourse on the intersectionality of climate change impacts and mental health, particularly focusing on Indigenous women in Western Canada.
Influence of drought stress and growth temperature during kernel development on physical and chemical starch characteristics of malting barley
Authors: Hör Stefan , Beer Thomas , Hoheneder Felix , Becker Thomas , Gastl Martina
Published: May 2024

Background and Objectives

Starch is the main component of malting barley (Hordeum vulgare L.), and its physical and chemical characteristics are particularly important in further processing in the beverage industry. This study investigates how the parameters (i) growing temperature (high/low) and (ii) water deficit (drought stress) during grain filling affect starch characteristics by cultivating nine different commonly used malting barley varieties in greenhouses under defined conditions. Particle size distribution of the starch granules, their phase transition characteristics (DSC), the pasting temperature (RVA), and the amylose/amylopectin (AM/AP) ratio were examined to assess starch characteristics.

Findings

Two‐way ANOVA analyses revealed that drought stress during the grain‐filling phase resulted in significantly smaller starch granules, lower onset, peak, and endset temperatures (DSC), and increased pasting temperature (PT) while not affecting the AM/AP ratio. 
High growth temperature during grain filling resulted in significantly higher onset, peak, and endset temperatures (DSC), lower phase transition enthalpies, significantly higher PTs, and lower AM/AP ratios.

Conclusions

Growth temperature during kernel development affected starch phase transition characteristics the most, while water availability was significantly associated with starch granule sizes.

Significance and Novelty

Climate change is increasing the events and severity of heat and drought in Europe. Agricultural practices and modern barley varieties must be adapted to these requirements to maintain processability for food production.