bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep multimodal predictome for studying mental disorders
Authors: Rahaman Md Abdur , Chen Jiayu , Fu Zening , Lewis Noah , Iraji Armin , van Erp Theo G. M. , Calhoun Vince D. 
Published: September 2022

AbstractCharacterizing neuropsychiatric disorders is challenging due to heterogeneity in the population. We propose combining structural and functional neuroimaging and genomic data in a multimodal classification framework to leverage their complementary information. Our objectives are two‐fold (i) to improve the classification of disorders and (ii) to introspect the concepts learned to explore underlying neural and biological mechanisms linked to mental disorders. Previous multimodal studies have focused on naïve neural networks, mostly perceptron, to learn modality‐wise features and often assume equal contribution from each modality. Our focus is on the development of neural networks for feature learning and implementing an adaptive control unit for the fusion phase. Our mid fusion with attention model includes a multilayer feed‐forward network, an autoencoder, a bi‐directional long short‐term memory unit with attention as the features extractor, and a linear attention module for controlling modality‐specific influence. The proposed model acquired 92% (p < .0001) accuracy in schizophrenia prediction, outperforming several other state‐of‐the‐art models applied to unimodal or multimodal data. Post hoc feature analyses uncovered critical neural features and genes/biological pathways associated with schizophrenia. The proposed model effectively combines multimodal neuroimaging and genomics data for predicting mental disorders. Interpreting salient features identified by the model may advance our understanding of their underlying etiological mechanisms.
Self‐reported involvement in road traffic crashes in Kenya: A cross‐sectional survey of a nationally representative sample
Authors: Shaikh Masood Ali , Lule Herman , Bärnighausen Till , Lowery Wilson Michael , Abio Anne 
Published: September 2022

AbstractBackgroundRoad traffic crashes (RTCs) are a global public health burden whose resulting morbidity and mortality disproportionately impact low‐ and middle‐income countries with stressed health systems. There is a paucity of published studies that evaluate the sociodemographic distribution of RTCs using nationally representative samples from the African region.AimTo examine population‐wide associations between sociodemographic factors and involvement in RTCs in Kenya.MethodsData were obtained from the 2014 Kenyan Demographic Health Survey, representing all 47 counties in Kenya, from May to October of 2014. We estimated the prevalence of RTCs and utilized logistic regression for bivariate and multivariable analyses to determine the sociodemographic factors associated with RTCs. Study variables included age, place of residence, household wealth index, educational attainment, and history of alcohol consumption. We computed odds ratios (ORs) and their corresponding 95% confidence intervals (CIs).ResultsA higher prevalence was reported among men (8.76%) versus women (3.22%). The risk factors among men included being 20−34 years of age, living in a rural area (OR 1.38, 95% CI 1.09, 1.74), drinking alcohol (OR 1.33, 95% CI 1.11, 1.59), and having not higher than a primary (OR 1.90, 95% CI 1.19, 3.03) or secondary (OR 1.68, 95% CI 1.04, 2.71) education. The strongest risk factors for women included the being aged 45−49 (OR 2.30, 95% CI 1.44, 3.67) and 20−24 years (OR 1.81, 95% 1.17, 2.79) as well as being in the fourth wealth quintile (OR 1.83, 95% CI 1.15, 2.91).ConclusionMen and the most economically productive age groups were more likely to report being involved in RTCs. Strategies to reduce the occurrences of RTCs should prioritize the most vulnerable sociodemographic groups.
Associations between early‐life and in utero infections and cytomegalovirus‐positive acute lymphoblastic leukemia in children
Authors: Gallant Rachel E. , Arroyo Katti , Metayer Catherine , Kang Alice Y. , de Smith Adam J. , Wiemels Joseph L. 
Published: September 2022

AbstractChildhood infections and cytomegalovirus (CMV) are associated with pediatric acute lymphoblastic leukemia (ALL). CMV dysregulates the host immune system and alters the immune response to subsequent antigenic exposures. We suspect that this immune dysregulation contributes to increased numbers of symptomatic infections in childhood allowing for expansion of pre‐leukemic clones. We explored the association between childhood infections, maternal infections during pregnancy and CMV‐positive ALL. Using a droplet digital PCR assay, we screened diagnostic ALL bone marrow samples from the California Childhood Leukemia Study (1995‐2015) for the presence of CMV DNA identifying CMV‐positive and CMV‐negative cases. We performed a case‐only analysis (n = 524) comparing the number and types of childhood infections and maternal infections during pregnancy between CMV‐positive and CMV‐negative ALL cases using logistic regression. With increasing numbers of infections in the first 12 months of life, children were more likely to classify to the highest tertile of CMV DNA in the bone marrow at diagnosis (OR: 1.04, 95% CI: 1.01‐1.08). Specifically, those reporting cough or flu in the first 12 months were more likely to be CMV‐positive at ALL diagnosis (OR: 2.15, 95% CI: 1.06‐4.37 and OR: 2.06, 95% CI: 1.17‐3.63 respectively). Furthermore, those with a history of maternal infection during pregnancy were more likely to be CMV‐positive (OR: 2.12, 95% CI: 1.24‐3.62). We hypothesize that children with underlying immune dysregulation develop more symptomatic infections in childhood and ultimately CMV‐positive ALL; this underlying immune dysregulation may be due to early immune system alterations via CMV exposure (in utero or early infancy) proposing a potential link between CMV and ALL etiology.
iTRAQ‐based proteomic analysis of 17β‐Estradiol‐induced anti‐proliferation and apoptosis in mouse thymic epithelial cells by disturbing ribosomal biogenesis
Authors: Liu Yameng , Li Zilong , Guo Dongguang , Ma Yongjiang , Li Yugu 
Published: September 2022

AbstractMany evidences have suggested that estrogen was associated with thymic atrophy and suppressed thymocyte functions. Thymic epithelial cells (TECs), as a crucial constituent of thymic stroma support a unique microenvironment for thymocyte maturation, but the effects of estrogen on TECs were poorly understood. In our study, we found that 17β‐Estradiol (17β‐E2), one of the primary estrogens, could significantly inhibit cell proliferation, and cause cell cycle arrest in G2/M phase and apoptosis in mouse thymic epithelial cell line 1 (MTEC1 cells) with time‐ and dose‐ dependent. Above all, we provided the systemic and sufficient proteomic profiling of 17β‐E2 (50 nmol/L) acting on MTEC1 cells through isobaric tags for relative and absolute quantitation and LC–MS/MS (Liquid Chromatography Mass Spectrometry/Mass Spectrometry). A total of 71 differentially expressed proteins were identified, of which 61 were up‐regulated and 10 were down‐regulated. Particularly, the differential expression of abundant ribosomal proteins (RPs) was drawing our attention, including RPL3, RPL4, RPS11, RPL17, RPL5, RPS9, RPL13, RPL23A, RPLP2, RPS15A, and RPL29. Most of these proteins have been widely reported exerting extra‐ribosomal function associated with the proliferation and apoptosis of distinct cell types, but not yet observed in TECs. Moreover, bioinformatics analysis revealed that disturbance of ribosomal biogenesis was closely related to the anti‐proliferation and apoptosis in MTEC1 cells upon 17β‐E2. These data highlighted the possible mechanisms of 17β‐E2 on MTEC1 cells through showing adequate differential protein expression profiles. We inferred that 17β‐E2 induced anti‐proliferation and apoptosis in MTEC1 cells in response to alterations of ribosome biogenesis and RPs expression, which will contribute to gaining insight into the internal mechanism of thymic degeneration and exploiting to treat autoimmune diseases in the future.
Mechanical stress‐caused chondrocyte dysfunction and cartilage injury can be attenuated by dioscin via activating sirtuin1/forkhead box O1
Authors: Jiang Shilin , Zhang Chengyuan , Lu Ye , Yuan Feng 
Published: September 2022

AbstractSirtuin1 (Sirt1)/forkhead box O1 (FoxO1) axis has been reported as a crucial regulator involved in chondral homeostasis of healthy or osteoarthritis (OA) cartilage. In our study, the aim is to investigate whether dioscin functions as an activator of Sirt1/FoxO1 to protect against mechanical stress‐induced chondrocyte dysfunction in vitro and in vivo models. HERB and PubChem databases were implemented to predict dioscin‐related gene targets. Cell and mouse models of OA were established to determine the pharmacological value of dioscin, a steroidal saponin. Cartilage loss in the knee joint was detected by Safranin O staining. Phosphorylation and nucleocytoplasmic shuttling of FoxO1 was observed in mechanical stress‐stimulated chondrocyte and anterior cruciate ligament transection‐induced cartilage injury. However, dioscin treatment repressed FoxO1 phosphorylation and cytoplasmic transfer and elevated Sirt1 protein expression. Dioscin treatment reversed mechanical stress‐induced growth inhibition and apoptosis of chondrocytes and improved cartilage degradation and bone loss in the epiphysis of the distal femur. Moreover, dioscin could maintain the normal phenotype of chondrocytes via mediating multiple gene expressions. Dioscin inhibited apoptosis and metabolic disorders in OA‐like chondrocytes via maintaining the transcriptional activity of FoxO1 and enhancing Sirt1 expression. Dioscin might be a potential Sirt1 activator providing a novel therapeutic schedule for the treatment of OA.
Therapeutic properties and molecular docking study of some phenolic compounds as anti‐human lung cancer potential: A biochemical approach
Authors: Wen Hongqing , Wang Lei , Morsy Kareem , Hamdi Hamida , El‐Kenawy Ayman E. , El‐kott Attalla F. 
Published: September 2022

AbstractChloroxine (5,7‐dichloro‐8‐hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate compounds on the 3‐hydroxy‐3‐methylglutaryl coenzyme‐A (HMG‐CoA Reductase) and urease enzymes. We have obtained results for the HMG‐CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and Methyl 3,4,5‐trihydroxybenzoate on HMG‐CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds (1 and 2) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6‐31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7‐dichloro‐8‐hydroxyquinoline and methyl 3,4,5‐trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC50 of them were 54.28 and 48.05 µM.
Maternal–Fetal Drug Development: An Industry Perspective
Authors: Burnham Janelle , Darsey Edress 
Published: September 2022

AbstractMedicines and vaccines prescribed to pregnant women often have not had pregnant women or lactating women included in clinical trials and products are often not approved by regulatory agencies for use in pregnant women. As a result, practitioners may need to prescribe medicines and give vaccines to this special population with limited drug efficacy and safety information available. Multiple regulatory guidance documents regarding the development of medications for pregnant and lactating women have been developed to encourage drug development and the investigation of medicines and vaccines used in this population. However, clinical, regulatory, ethical, and drug development challenges are encountered when designing clinical trials that include pregnant women and their fetuses, in which innovative methods and trial designs are essential. This article provides an overview of an industry perspective on maternal–fetal drug development that includes a review of the regulatory landscape for developing medicines for pregnant women and their fetuses, trial designs that include pregnant women, identification of gaps and challenges, and strategies for potential maternal–fetal drug development considerations for the future development of medicines and vaccines for pregnant women. Early involvement and discussion of drug and vaccine products with multiple stakeholders, including therapeutic experts, patients, physicians, and regulators, is encouraged to optimize the development of safe and effective medicines and vaccines for pregnant women and their fetuses.
Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI‐FDA Meeting)
Authors: Herzeg Akos , Almeida‐Porada Graça , Charo R. Alta , David Anna L. , Gonzalez‐Velez Juan , Gupta Nalin , Lapteva Larissa , Lianoglou Billie , Peranteau William , Porada Christopher , Sanders Stephan J. , Sparks Teresa N. , Stitelman David H. , Struble Evi , Sumner Charlotte J. , MacKenzie Tippi C. 
Published: September 2022

AbstractWe are living in a golden age of medicine in which the availability of prenatal diagnosis, fetal therapy, and gene therapy/editing make it theoretically possible to repair almost any defect in the genetic code. Furthermore, the ability to diagnose genetic disorders before birth and the presence of established surgical techniques enable these therapies to be delivered safely to the fetus. Prenatal therapies are generally used in the second or early third trimester for severe, life‐threatening disorders for which there is a clear rationale for intervening before birth. While there has been promising work for prenatal gene therapy in preclinical models, the path to a clinical prenatal gene therapy approach is complex. We recently held a conference with the University of California, San Francisco–Stanford Center of Excellence in Regulatory Science and Innovation, researchers, patient advocates, regulatory (members of the Food and Drug Administration), and other stakeholders to review the scientific background and rationale for prenatal somatic cell gene therapy for severe monogenic diseases and initiate a dialogue toward a safe regulatory path for phase 1 clinical trials. This review represents a summary of the considerations and discussions from these conversations.
Engineering graduate students' critical events as catalysts of attrition
Authors: Zerbe Ellen , Sallai Gabriella M. , Shanachilubwa Kanembe , Berdanier Catherine G. P. 
Published: September 2022

AbstractBackgroundWhile attrition from the PhD has been attributed to many high‐level causal factors, such as funding, advisor relationship, and “fit” into a department, few studies have closely examined the mechanisms of attrition or why and how graduate engineering students begin to consider attrition from their doctoral programs.Design/MethodThis study analyzed interviews with current and former doctoral engineering students at research universities across the United States, collected through two closely‐related studies on graduate engineering experiences and attrition consideration. We used critical event analysis as a methodological approach to understand the experiences of a subset of 13 participants, who, at some point in their graduate career, experienced a singular event that caused them to question whether to persist in their PhD program.Purpose/HypothesisThe purpose of the present paper is to investigate how graduate engineering students begin to question whether they should remain in their PhD programs of study.ResultsWe categorized the environments in which critical events occurred into four quadrants along the lines of University and Nonuniversity Settings and Routine versus Unexpected Contexts, mapping critical events and supporting events to themes from prior literature. The findings demonstrate how seemingly mundane experiences for faculty can be cataclysmic in the eyes of the student; how critical events serve to magnify other issues that had been accumulating over time; and how students may not self‐reflect on their rationale for pursuing a PhD until a critical juncture occurs.ConclusionsCritical events are one mechanism by which students may begin considering departure from their engineering PhD programs. Some critical events masquerade within mundane contexts, like conversations or conferences (although, in retrospect, students can identify other relevant features contributing to dissatisfaction). From this work, we provide implications geared toward administrators, advisors, and graduate students on how to address and potentially mitigate critical events or their effects, including engaging in conversations about leaving.
Lung Ultrasound in the Evaluation of Neonatal Respiratory Distress Syndrome
Authors: Xin Hua , Wang Lijun , Hao Wei , Hu Haiyang , Li Hecui , Liu Bin 
Published: September 2022

ObjectiveThe purpose of this study is to examine the impact of bedside lung ultrasound (LUS) and LUS scores in the evaluating and grading of neonatal respiratory distress syndrome (NRDS).MethodsWe performed a prospective study on 80 children with suspected NRDS. Infants with a PaO2‐to‐FiO2 ratio of <200, 200–300, and >300 mmHg were categorized as the “severe‐NRDS group,” “mild‐NRDS group,” and “non‐NRDS group,” respectively. Left and right lungs were divided into six areas, respectively. For each lung area, a 0‐ to 3‐point score was given.ResultsThe most common ultrasonic signs of NRDS include bilateral coalescent B‐lines, thickened pleural line, and white lung without spared areas. Moreover, different LUS scores among non‐NRDS, mild‐NRDS, and severe‐NRDS groups were identified (6.00 ± 4.033, 25.82 ± 3.778 and 27.90 ± 4.071, respectively; P < .05). When the cutoff value of LUS score was selected as 13 for the differentiation of non‐NRDS from NRDS, the sensitivity and specificity were 96.9% and 93.3%, respectively, and the area under the curve (AUC) of receiver operating characteristics (ROC) was 0.938 (95% confidence interval [CI], 0.84–1.00). With a cutoff value of 26.5 for the differentiation between mild‐ and severe‐ARDS, the AUC of ROC curve of the LUS score was 0.707 (95% CI, 0.58–0.83). Similar results were revealed as those with chest X‐ray.ConclusionThis study showed that LUS and LUS scores complement each other, and are highly reliable and efficient in bedside radiological diagnostic investigations in newborns with NRDS.
Proportion of Malignancy and Evaluation of Sonographic Features of Thyroid Nodules Classified as Highly Suspicious Using ACR TI‐RADS Criteria
Authors: Hussain Najia , Goldstein Michael B. , Zakher Mariam , Katz Douglas S. , Brandler Tamar C. , Islam Shahidul , Rothberger Gary D. 
Published: September 2022

ObjectivesThe reported malignancy rate of highly suspicious thyroid nodules based on the ACR TI‐RADS criteria (TI‐RADS category 5 [TR5]) varies widely. The objective of our study was to determine the rate of malignancy of TR5 nodules at our institution. We also aimed to determine the predictive values of individual sonographic features, as well as the correlation of total points assigned to a nodule and rate of malignancy.MethodsOur single‐institution retrospective study evaluated 450 TR5 nodules that had cytology results available, in 399 patients over a 1‐year period. Sonographic features and total TI‐RADS points were determined by the interpreting radiologist. Statistical analyses included logistic regression models to find factors associated with increased odds of malignancy, and computing sensitivity, specificity, positive and negative predictive values of various individual sonographic features.ResultsOf the 450 nodules, 95 (21.1%, 95% exact confidence interval 17.4–25.2%) were malignant. Each additional TI‐RADS point increased the odds of malignancy (adjusted odds ratio 1.35, 95% confidence interval 1.13–1.60, P < .001). “Very hypoechoic" was the sonographic feature with the highest specificity and positive predictive value for malignancy (95.5 and 44.8%, respectively), while “punctate echogenic foci” had the lowest positive predictive value (20.0%).ConclusionsThe rate of malignancy of TR5 nodules at our institution was 21.1%, which is lower than other malignancy rates reported in the literature. The total number of points assigned on the basis of the TI‐RADS criteria was positively associated with malignancy, which indicates that TR5 should be viewed as a spectrum of risk.
Giant congenital melanocytic naevus caused by NRAS Q61K mosaicism
Authors: Thielmann Carl M. , Kampmeier Antje , Küchler Alma , Zenker Martin , Wieland Ilse , Matull Johanna , Krefting Frederik , Griewank Klaus , Hadaschik Eva 
Published: September 2022

AbstractGiant congenital melanocytic naevi (CMN) are large melanocytic lesions commonly associated with neurologic abnormalities. Patients diagnosed with giant melanocytic naevi are at an increased risk of developing melanoma compared to patients with smaller congenital naevi. If patients develop central nervous system (CNS) lesions and exhibit certain characteristic facial features, then the diagnosis of CMN syndrome can be made. We here present the case of a 24‐year‐old female who presented with multiple melanocytic naevi, which had been apparent since birth, and was diagnosed with giant melanocytic naevi caused by NRAS Q61K mosaicism. Both close follow‐up of imaging and clinical study is important so as not to miss cutaneous malignancy and CNS lesions.
Hierarchical Self‐Assembly of Triphilic Main‐Chain‐Type Semifluorinated Alternating Graft Copolymers in Aqueous Solution
Authors: Cheng Jiannan , Yu Qing , Tu Kai , Wang Jinying , Zhang Lifen , Cheng Zhenping 
Published: September 2022

AbstractFluorinated copolymers can self‐assemble in solution and form micelles with rare properties due to the peculiar behavior of fluorinated groups. However, the process description of the self‐assembly is still largely phenomenological and difficult to explain due to the tendency of the fluorinated segments to segregate from both the hydrophilic and lipophilic segments, which can result in various morphologies. Herein, the controlled formation of ellipsoidal micelles, disklike micelles, and sheets by hierarchical self‐assembly of triphilic main‐chain‐type semifluorinated alternating graft copolymers (AB)nA‐g‐mOEG is presented (where A represents unit of α,ω‐diiodoperfluoroalkane, B represents the unit of α,ω‐unconjugated diene, and mOEG represents methoxy oligo(ethylene glycol)), which are synthesized by step transfer‐addition and radical‐termination (START) polymerization and azide‐alkyne click chemistry. Furthermore, the possible self‐assembly mechanism of these micron‐level aggregates is proposed, which is ascribed to the hierarchical self‐assembly, crowding effect of hydrophilic chains and the interfacial tension between the fluoroalkane and alkane segments. This study can provide a facile and highly efficient approach to the synthesis of main‐chain‐type fluorinated graft copolymers and expand the research field for the solution self‐assembly of fluorinated copolymers.