bluuebunny/crossref_metadata_2025_split huggingface dataset:
When to sleep and consume caffeine to boost alertness
Authors: Vital-Lopez Francisco G , Doty Tracy J , Reifman Jaques 
Published: June 2024

Abstract

Study Objectives
Sleep loss can cause cognitive impairments that increase the risk of mistakes and accidents. However, existing guidelines to counteract the effects of sleep loss are generic and are not designed to address individual-specific conditions, leading to suboptimal alertness levels. Here, we developed an optimization algorithm that automatically identifies sleep schedules and caffeine-dosing strategies to minimize alertness impairment due to sleep loss for desired times of the day.

Methods
We combined our previous algorithms that separately optimize sleep or caffeine to simultaneously identify the best sleep schedules and caffeine doses that minimize alertness impairment at desired times. The optimization algorithm uses the predictions of the well-validated Unified Model of Performance to estimate the effectiveness and physiological feasibility of a large number of possible solutions and identify the best one. To assess the optimization algorithm, we used it to identify the best sleep schedules and caffeine-dosing strategies for four studies that exemplify common sleep-loss conditions and compared the predicted alertness-impairment reduction achieved by using the algorithm’s recommendations against that achieved by following the U.S. Army caffeine guidelines.

Results
Compared to the alertness-impairment levels in the original studies, the algorithm’s recommendations reduced alertness impairment on average by 63%, an improvement of 24 percentage points over the U.S. Army caffeine guidelines.

Conclusions
We provide an optimization algorithm that simultaneously identifies effective and safe sleep schedules and caffeine-dosing strategies to minimize alertness impairment at user-specified times.
Adipose Kiss1 controls aerobic exercise‐related adaptive responses in adipose tissue energy homeostasis
Authors: Liang Chunyu , Li Xuehan , Song Ge , Schmidt Søren Fisker , Sun Lingyu , Chen Jianhao , Pan Xinliang , Zhao Haotian , Yan Yi 
Published: June 2024

AbstractKisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose‐specific Kiss1 knockout (Kiss1adipoq−/−) and adeno‐associated virus‐induced adipose tissue Kiss1‐overexpressing (Kiss1adipoq over) mice. We found that adipose‐derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex‐dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator‐activated receptor gamma co‐activator 1 alpha (PGC‐1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.
The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila
Authors: Dai Yuting , Wang Yixuan , Kang Qian , Wu Yifan , Liu Yongqi , Su Yun , Wang Xinhua , Xiu Minghui , He Jianzheng 
Published: June 2024

AbstractOxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1‐GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative‐related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aβ42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aβ‐induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.
Andragogic Improvements in Radiation Safety Training
Authors: Cotton Chandler , Wilson Charles , Heath Robert , Caffrey Emily 
Published: June 2024

Abstract
At the University of Alabama at Birmingham (UAB), many diagnostic and therapeutic procedures involving radioactive materials or radiation-producing machines are performed daily. A growing number of minor but preventable incidents related to radiation safety have brought up concerns related to the effectiveness of the training program. A comprehensive literature review was performed to summarize post-COVID insights into andragogic online training practices, statistical analyses, and overall retention competencies in radiation safety. Andragogic research shows that the best method of training adult learners is controlled simulation that tests critical thinking and problem-solving capabilities, drawing upon previous knowledge or experiences. A new training curriculum based on these andragogic principles was designed and administered to a subgroup of UAB radiation workers. Scores from pre-testing and post-testing were collected and analyzed. An ANCOVA was used to account for differences in the pre-test scores between the control and experimental groups, which was found to be statistically significant (p = 0.018), suggesting that small changes in a radiation safety training program can have significant impacts in retention of key information.
The Effect of Medicare Annual Wellness Visits on Breast Cancer Screening and Diagnosis
Authors: Hamer Mika K. , Bradley Cathy J. , Lindrooth Richard , Perraillon Marcelo C. 
Published: June 2024

Objective:
The Medicare Annual Wellness Visit (AWV)—a prevention-focused annual check-up—has been available to beneficiaries with Part B coverage since 2011. The objective of this study was to estimate the effect of Medicare AWVs on breast cancer screening and diagnosis.

Data Sources and Study Setting:
The National Cancer Institute’s Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims (SEER-Medicare), HRSA’s Area Health Resources Files, the FDA’s Mammography Facilities database, and CMS “Mapping Medicare Disparities” utilization data from 2013 to 2015.

Study Design:
Using an instrumental variables approach, we estimated the effect of AWV utilization on breast cancer screening and diagnosis, using county Welcome to Medicare Visit (WMV) rates as the instrument.

Data Collection/Extraction Methods:
66,088 person-year observations from 49,769 unique female beneficiaries.

Principal Findings:
For every 1-percentage point increase in county WMV rate, the probability of AWV increased by 1.7 percentage points. Having an AWV was associated with a 22.4-percentage point increase in the probability of receiving a screening mammogram within 6 months (P<0.001). There was no statistically significant increase in the probability of breast cancer diagnosis (overall or early stage) within 6 months of an AWV. Findings were robust to multiple model specifications.

Conclusions:
Performing routine cancer screening is an evidence-based practice for diagnosing earlier-stage, more treatable cancers. The AWV effectively increases breast cancer screening and may lead to more timely screening. Continued investment in Annual Wellness Visits supports breast cancer screening completion by women who are most likely to benefit, thus reducing the risk of overscreening and overdiagnosis.
Clinical Relevance of Cancerization of Ducts in Resected Pancreatic Ductal Adenocarcinoma
Authors: Kinny-Köster Benedict , Ahmad Yembur , Pflüger Michael J. , Habib Joseph R. , Fujikura Kohei , Hutchings Danielle , Cameron John L. , Shubert Christopher R. , Lafaro Kelly J. , Burkhart Richard A. , Burns William R. , Javed Ammar A. , Yu Jun , Hruban Ralph H. , Wood Laura D. , Thompson Elizabeth D. , He Jin 
Published: June 2024

Objectives
Although prevalent in 50%–90% of pancreatic ductal adenocarcinomas, the clinical relevance of “cancerization of ducts” (COD) remains unknown.

Methods
Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry.

Results
Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS.

Conclusions
Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact.
Mandibular third-molar germectomy: case report
Authors: Ouaabbou Hajar , Hakkou Fouzia , Chbicheb Saliha 
Published: June 2024

Introduction and importance:
Third molars are often removed in order to prevent complications and various other problems associated with impacted teeth.

Case presentation:
A healthy 17-year-old girl with no history was referred to the Department of Oral Surgery by her orthodontist to remove mandibular third-molar germs. Panoramic radiography showed the presence of impacted mandibular third-molar germs, vertically positioned, with incomplete root formation. The tooth germs (48, 38) were extracted under local-regional anesthesia. The postoperative period was uneventful.

Clinical discussion:
Germectomy is still relevant in the management of mandibular third molars (MTM). It is a surgical removal of the dental germ at a particularly specific developmental period. However, the need to extract the MTM germs is still controversial.

Conclusion:
Germectomy is well justified in light of clinical symptomatology and/or a suspicious radiographic image. Nonetheless, in asymptomatic MTM, it is important to assess the procedure’s cost-benefit ratio.
Electrocardiogram (EKG) knowledge and interpretation proficiency among healthcare professionals in Pakistan: a prospective cross-sectional study
Authors: Hassan Zair , Kumari Usha , Waseem Maria , Yaqoob Uzair , Sahito Moiz , Zehra Syeda Arshia , Reddy Nikhil , Jan Muneeb Ullah , Surani Salim , Khan Aarash 
Published: June 2024

Background:
Electrocardiogram (EKG) is a commonly used diagnostic tool for the evaluation of the electrical activity of the heart. The purpose of this study was to assess the knowledge and interpretation proficiency of EKG among healthcare professionals (HCPs) in Pakistan.

Methods:
This prospective cross-sectional study was conducted among HCPs working in different healthcare settings. A structured questionnaire was used to assess the participants’ theoretical knowledge and ability to interpret EKG findings. The data were analyzed using descriptive statistics and χ2 tests. The study indicates that EKG knowledge and interpretation proficiency among HCPs in Pakistan is unsatisfactory. The inadequacy of training periods of EKG training sessions and insufficient participation of HCPs in offered training opportunities put forward the need for the formation and introduction of better structured and efficient EKG training programmes.

Results:
A total of 511 HCPs participated in the study, 28% of whom reportedly had received formal training for EKG interpretation. About 80% of the participants correctly identified theoretical questions pertaining to EKG, while 58% of the participants were able to accurately interpret EKG findings, and most HCPs (69.9%) read fewer than ten EKGs per week.

Conclusion:
This study demonstrates a lack of expertise and a poor understanding of EKG in HCPs of Pakistan. The low level of EKG knowledge and interpretation proficiency among HCPs may lead to diagnostic errors and poor patient outcomes. Therefore, efforts should be made to improve EKG education and training among HCPs in Pakistan.
Deconvoluted methylation profiles discriminate between closely related melanocytic nevi
Authors: Aldea Daniel , Macagno Nicolas , Marechal Elise , Moreno Mathias , Romanet Pauline , Pertuit Morgane , Garcia Jérémy , Degardin Nathalie , Mallet Stéphanie , James Isabelle , Captier Guillaume , Barlier Anne , Etchevers Heather C. 
Published: June 2024

SUMMARYCongenital melanocytic nevi (CMN) and common acquired melanocytic nevi (AMN) are melanoma-predisposing skin conditions presenting excessive numbers of melanocytes but arising at different times in life. Appropriately weighted whole-genome methylation analysis can be used as a basis for further research in dermatopathology and as applied here provides new insights into nevus biology.
Mistranslating tRNA variants have anticodon- and sex-specific impacts onDrosophila melanogaster
Authors: Isaacson Joshua R. , Berg Matthew D. , Jagiello Jessica , Yeung William , Charles Brendan , Villén Judit , Brandl Christopher J. , Moehring Amanda J. 
Published: June 2024

ABSTRACTTransfer RNAs (tRNAs) are vital in determining the specificity of translation. Mutations in tRNA genes can result in the misincorporation of amino acids into nascent polypeptides in a process known as mistranslation. Since mistranslation has different impacts, depending on the type of amino acid substitution, our goal here was to compare the impact of different mistranslating tRNAServariants on fly development, lifespan, and behaviour. We established two mistranslating fly lines, one with a tRNAServariant that misincorporates serine at valine codons (V➔S) and the other that misincorporates serine at threonine codons (TàS). While both mistranslating tRNAs increased development time and developmental lethality, the severity of the impacts differed depending on amino acid substitution and sex. The V➔S variant extended embryonic, larval, and pupal development whereas the T➔S only extended larval and pupal development. Females, but not males, containing either mistranslating tRNA presented with significantly more anatomical deformities than controls. Mistranslating females also experienced extended lifespan whereas mistranslating male lifespan was unaffected. In addition, mistranslating flies from both sexes showed improved locomotion as they aged, suggesting delayed neurodegeneration. Therefore, although mistranslation causes detrimental effects, we demonstrate that mistranslation also has positive effects on complex traits such as lifespan and locomotion. This has important implications for human health given the prevalence of tRNA variants in humans.PLAIN LANGUAGE SUMMARYMutant tRNA genes can cause mistranslation, the misincorporation of amino acids into proteins, and are associated with several human diseases. This study investigated the role of two tRNA variants that cause threonine-to-serine (T➔S) or valine-to-serine (V➔S) substitution. Both variants caused developmental delays and lethality in both sexes and increase prevalence of deformities in females. Surprisingly, female T➔S and V➔S flies experienced increased lifespan and mistranslating males and females showed improved locomotion. These results suggest that mistranslation has both positive and negative effects that depend on the tRNA variant and sex of the fly.
Combined effects of matrix stiffness and obesity-associated signaling directs progressive phenotype in PANC-1 pancreatic cancer cellsin vitro
Authors: Jones A.E. , Netto J.F. , Foote T.L. , Ruliffson B.N.K. , Whittington C.F. 
Published: June 2024

ABSTRACTObesity is a leading risk factor of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor disease prognosis and outcomes. Retrospective studies have identified this link, but interactions surrounding obesity and PDAC are still unclear. Research has shifted to contributions of fibrosis (desmoplasia) on malignancy, which involves increased deposition of collagens and other extracellular matrix (ECM) molecules and increased ECM crosslinking, all of which contribute to increased tissue stiffening. However, fibrotic stiffening is underrepresented as a model feature in current PDAC models. Fibrosis is shared between PDAC and obesity, and can be leveraged forin vitromodel design, as current animal obesity models of PDAC are limited in their ability to isolate individual components of fibrosis to study cell behavior. In the current study, methacrylated type I collagen (PhotoCol®) was photo-crosslinked to pathological stiffness levels to recapitulate fibrotic ECM stiffening. PANC-1 cells were encapsulated within PhotoCol®, and the tumor-tissue constructs were prepared to represent normal (healthy) (∼600 Pa) and pathological (∼2000 Pa) tissues. Separately, human mesenchymal stem cells were differentiated into adipocytes representing lean (2D differentiation) and obese fat tissue (3D collagen matrix differentiation), and conditioned media was applied to PANC-1 tumor-tissue constructs. Conditioned media from obese adipocytes showed increased vimentin expression, a hallmark of invasiveness and progression, that was not seen after exposure to media from lean adipocytes or control media. Characterization of the obese adipocyte secretome suggested that some PANC-1 differences may arise from increased interleukin-8 and -10 compared to lean adipocytes. Additionally, high matrix stiffness associated induced an amoeboid morphology in PANC-1 cells that was not present at low stiffness. Amoeboid morphology is an accessory to epithelial-to-mesenchymal transition and is used to navigate complex ECM environments. This plasticity has greater implications for treatment efficacy of metastatic cancers. Overall, this work 1) highlights the importance of investigating PDAC-obesity interactions to study the effects on disease progression and persistence, 2) establishes PhotoCol® as a matrix material that can be leveraged to study amoeboid morphology and invasion in PDAC, and 3) emphasizes the importance of integrating both biophysical and biochemical interactions associated within both pathologies forin vitroPDAC models.
Early transatlantic movement of horses and donkeys at Jamestown
Authors: Treal Taylor William Timothy , Delsol Nicolas , Oelze Vicky M. , Mitchell Peter , Stricker Leah , Lavin Michael , Ogundiran Akin , Hosek Lauren , Barrón-Ortiz Christina Isabelle , Ojediran Olumide , Quintero-Bisono Diana , Magoon Dane , Hill Matthew E. , Thomas Ariane E. , Waterman Anna , Peate David W. , Chauvey Lorelei , Schiavinato Stéphanie , Tonasso-Calvière Laure , Borges Luis , Brito-Mayor Aitor , Santana Jonathan , Kamenov George , Orlando Ludovic , Krigbaum John 
Published: June 2024

AbstractDomestic horses and donkeys played a key role in the initial colonization of the Atlantic seaboard of the Americas, a process partially chronicled by historical records. While Spanish colonists brought horses to the Caribbean and southern latitudes earlier, the transport of domestic horses to the English colony at Jamestown, Virginia in 1606 was among the first dispersals to the eastern seaboard. Archaeozoological analysis, isotope analysis, and radiocarbon dating of identifiable domestic equid remains from two contexts associated with the initial occupation of Jamestown demonstrate intense processing and consumption of the first Jamestown horses during the “Starving Time” winter of 1609, while paleopathological data show evidence of their use in transport. Osteological, genetic, and isotopic study of these equid remains reveal the presence of at least one adult domestic donkey with mixed European and West African ancestry, possibly supplied through undocumented exchange during a trans-Atlantic stopover. These results reveal the importance of equids in the survival of early European settlers and the global connectivity of early trans-Atlantic exchange in horses and donkeys, showing Caribbean and African links in the founding livestock populations and pointing towards an important and ecologically-anchored role for donkeys in the early colonial lifeways along the Eastern seaboard.