bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between white matter alterations and contamination subgroup in obsessive compulsive disorder: A diffusion tensor imaging study
Authors: Azarvand Damirichi Mahvash , Karimi Moridani Mohammad , Mohammadi Seyyed Erfan 
Published: March 2023

AbstractApproximately 2%–3% of the world population suffers from obsessive–compulsive disorder (OCD). Several brain regions have been involved in the pathophysiology of OCD, but brain volumes in OCD may vary depending on specific OCD symptom dimensions. The study aims to explore how white matter structure changes in particular OCD symptom dimensions. Prior studies attempt to find the correlation between Y‐BOCS scores and OCD patients. However, in this study, we separated the contamination subgroup in OCD and compared directly to healthy control to find regions that exactly related to contamination symptoms. To evaluate structural alterations, diffusion tensor imaging was acquired from 30 OCD patients and 34 demographically matched healthy controls. Data were processed using tract‐based spatial statistics (TBSS) analysis. First, by comparing all OCD to healthy controls, significant fractional anisotropy (FA) decreased in the right anterior thalamic radiation, right corticospinal tract, and forceps minor observed. Then by comparing the contamination subgroup to healthy control, FA decreases in the forceps minor region. Consequently, forceps minor plays a central role in the pathophysiology of contamination behaviors. Finally, other subgroups were compared to healthy control and discovered that FA in the right corticospinal tract and right anterior thalamic radiation is reduced.
Identifying individuals with attention‐deficit/hyperactivity disorder based on multisite resting‐state functional magnetic resonance imaging: A radiomics analysis
Authors: Liu Guanlu , Lu Weizhao , Qiu Jianfeng , Shi Liting 
Published: March 2023

AbstractAttention‐deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by symptoms of age‐inappropriate inattention, hyperactivity, and impulsivity. Apart from behavioral symptoms investigated by psychiatric methods, there is no standard biological test to diagnose ADHD. This study aimed to explore whether the radiomics features based on resting‐state functional magnetic resonance (rs‐fMRI) have more discriminative power for the diagnosis of ADHD. The rs‐fMRI of 187 subjects with ADHD and 187 healthy controls were collected from 5 sites of ADHD‐200 Consortium. A total of four preprocessed rs‐fMRI images including regional homogeneity (ReHo), amplitude of low‐frequency fluctuation (ALFF), voxel‐mirrored homotopic connectivity (VMHC) and network degree centrality (DC) were used in this study. From each of the four images, we extracted 93 radiomics features within each of 116 automated anatomical labeling brain areas, resulting in a total of 43,152 features for each subject. After dimension reduction and feature selection, 19 radiomics features were retained (5 from ALFF, 9 from ReHo, 3 from VMHC and 2 from DC). By training and optimizing a support vector machine model using the retained features of training dataset, we achieved the accuracy of 76.3% and 77.0% (areas under curve = 0.811 and 0.797) in the training and testing datasets, respectively. Our findings demonstrate that radiomics can be a novel strategy for fully utilizing rs‐fMRI information to distinguish ADHD from healthy controls. The rs‐fMRI‐based radiomics features have the potential to be neuroimaging biomarkers for ADHD.
Mechanisms of mGluR‐dependent plasticity in hippocampal area CA2
Authors: Samadi Mahsa , Hales Claire A. , Lustberg Daniel J. , Farris Shannon , Ross Madeleine R. , Zhao Meilan , Hepler John R. , Harbin Nicholas H. , Robinson Emma S. J. , Banks Paul J. , Bashir Zafar I. , Dudek Serena M. 
Published: March 2023

AbstractPyramidal cells in hippocampal area CA2 have synaptic properties that are distinct from the other CA subregions. Notably, this includes a lack of typical long‐term potentiation of stratum radiatum synapses. CA2 neurons express high levels of several known and potential regulators of metabotropic glutamate receptor (mGluR)‐dependent signaling including Striatal‐Enriched Tyrosine Phosphatase (STEP) and several Regulator of G‐protein Signaling (RGS) proteins, yet the functions of these proteins in regulating mGluR‐dependent synaptic plasticity in CA2 are completely unknown. Thus, the aim of this study was to examine mGluR‐dependent synaptic depression and to determine whether STEP and the RGS proteins RGS4 and RGS14 are involved. Using whole cell voltage‐clamp recordings from mouse pyramidal cells, we found that mGluR agonist‐induced long‐term depression (mGluR‐LTD) is more pronounced in CA2 compared with that observed in CA1. This mGluR‐LTD in CA2 was found to be protein synthesis and STEP dependent, suggesting that CA2 mGluR‐LTD shares mechanistic processes with those seen in CA1, but in addition, RGS14, but not RGS4, was essential for mGluR‐LTD in CA2. In addition, we found that exogenous application of STEP could rescue mGluR‐LTD in RGS14 KO slices. Supporting a role for CA2 synaptic plasticity in social cognition, we found that RGS14 KO mice had impaired social recognition memory as assessed in a social discrimination task. These results highlight possible roles for mGluRs, RGS14, and STEP in CA2‐dependent behaviors, perhaps by biasing the dominant form of synaptic plasticity away from LTP and toward LTD in CA2.
Evaluating the effectiveness of land use management as a natural flood management intervention in reducing the impact of flooding for an upland catchment
Authors: Kingsbury‐Smith Lorna , Willis Thomas , Smith Mark , Boisgontier Hélène , Turner Daniel , Hirst Jack , Kirkby Michael , Klaar Megan 
Published: March 2023

AbstractNatural flood management (NFM) is a method for reducing flooding by using a catchment‐based approach to managing flood risk. Understanding and quantifying the impact of implementing NFM at the catchment scale remains ambiguous with a clear need for robust empirical evidence. A combination of fieldwork, laboratory analysis and modelling was applied to quantify the impacts of land use management changes on catchment flood hazard. Soil hydraulic conductivity was measured under varying land management regimes and used to parameterize a physically based spatially distributed hydrological model (SD‐TOPMODEL). A suite of stakeholder informed land management scenarios was modelled, permitting the quantification of the impact of NFM interventions on the timing and the intensity of the peak discharge at the catchment outlet. The findings support the implementation of NFM interventions as a means of reducing flood hazard within a rural upland catchment. Improved soil infiltration provided the greatest reduction in the intensity and delayed timing of the flood peak for a 10‐year occurrence storm event (7% reduction in peak runoff and 8% increase in lag time) with similar reductions observed for a 100‐year storm event. Catchment wide woodland planting reduced peak flow by 11% during the 100‐year event but was not effective during the 10‐year event. Riparian buffer strips provided consistent reductions in peak flow and in the timing of the peak across both storm events with no significant differences relating to vegetation age. Critically, we observed that the effect of implementing multiple NFM interventions was not additive and that efficiencies can be made in using this modelling approach to prioritize the most effective outcomes.
Bone marrow stromal cell‐derived exosomes improve oxidative stress and pyroptosis in doxorubicin‐induced myocardial injury in vitro by regulating the transcription of GSDMD through the PI3K‐AKT‐Foxo1 pathway
Authors: Zeng Hong , Yang Yong , Tou Fangfang , Zhan Yuliang , Liu Songtao , Zou Pengtao , Chen Yanmei , Shao Liang 
Published: March 2023

AbstractObjectivesDoxorubicin (DOX) can contribute to severe myocardial injury, and bone marrow stromal cells (BMSC)‐exosomes (Exos) improves acute myocardial infarction. Hence, this research investigated whether BMSC‐Exos alleviated DOX‐induced myocardial injury.MethodsBMSC‐derived Exos were isolated and identified, and the optimal concentration of DOX was confirmed. H9C2 cells were treated with DOX and BMSC‐Exos or in combination with the protein kinase B (AKT) inhibitor. Reactive oxygen species (ROS) and JC‐1 were detected to assess oxidative stress (OS) and mitochondrial membrane damage, respectively. In addition, the expression of pyroptosis‐related molecules was measured. The expression of phosphatidylinositol 3 kinase (PI3K)‐AKT pathway‐related proteins and the phosphorylation and acetylation of forkhead box O1 (Foxo1) in the cell nucleus and cytoplasm were tested. Last, interactions between Foxo1 and gasdermin D (GSDMD) were assessed.ResultsBMSC‐Exo treatment increased viability and mitochondrial membrane potential and reduced lactic dehydrogenase release and ROS levels in DOX‐treated H9C2 cells. Furthermore, the addition of BMSC‐Exos suppressed DOX‐induced activation and upregulation of NLRP3 and apoptosis‐associated speck‐like protein containing A CARD (ASC) and in vitro cleavage of caspase‐1, GSDMD, interleukin (IL)‐1β, and IL‐18 proteins. Additionally, BMSC‐Exo treatment enhanced the expression of phosphorylated (p)‐PI3K, p‐AKT, and p‐mTOR in DOX‐treated H9C2 cells and the levels of phosphorylated Foxo1 in the cytoplasm of DOX‐treated H9C2 cells. Foxo1 was enriched in the promoter region of GSDMD. Moreover, the AKT inhibitor API‐2 annulled the effects of BMSC‐Exos on OS, pyroptosis, and Foxo1 phosphorylation in DOX‐treated H9C2 cells.ConclusionsBMSC‐Exos phosphorylated Foxo1 and inactivated Foxo1 transcription via the PI3K‐AKT pathway to diminish GSDMD expression, thus restraining DOX‐induced pyroptosis and OS of myocardial cells.
FSCN1 as a new druggable target in adrenocortical carcinoma
Authors: Ruggiero Carmen , Tamburello Mariangela , Rossini Elisa , Zini Silvia , Durand Nelly , Cantini Giulia , Cioppi Francesca , Hantel Constanze , Kiseljak‐Vassiliades Katja , Wierman Margaret E. , Landwehr Laura‐Sophie , Weigand Isabel , Kurlbaum Max , Zizioli Daniela , Turtoi Andrei , Yang Shengyu , Berruti Alfredo , Luconi Michaela , Sigala Sandra , Lalli Enzo 
Published: March 2023

AbstractAdrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatic spread. The actin‐bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with VAV2, a guanine nucleotide exchange factor for the Rho/Rac GTPase family, to enhance the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC zebrafish model. Here, we showed that FSCN1 is a transcriptional target for β‐catenin in H295R ACC cells and that its inactivation resulted in defects in cell attachment and proliferation. FSCN1 knock‐out modulated the expression of genes involved in cytoskeleton dynamics and cell adhesion. When Steroidogenic Factor‐1 (SF‐1) dosage was upregulated in H295R cells, activating their invasive capacities, FSCN1 knock‐out reduced the number of filopodia, lamellipodia/ruffles and focal adhesions, while decreasing cell invasion in Matrigel. Similar effects were produced by the FSCN1 inhibitor G2‐044, which also diminished the invasion of other ACC cell lines expressing lower levels of FSCN1 than H295R. In the zebrafish model, metastases formation was significantly reduced in FSCN1 knock‐out cells and G2‐044 significantly reduced the number of metastases formed by ACC cells. Our results indicate that FSCN1 is a new druggable target for ACC and provide the rationale for future clinical trials with FSCN1 inhibitors in patients with ACC.
Molecular imaging for cancer immunotherapy
Authors: Yu Jing , Gao Bo 
Published: March 2023

AbstractThe success of immune checkpoint blockade has reaffirmed the importance of the immune system in cancer treatment. Immunotherapy enables the body's own immune system to fight tumor cells. However, the complex tumor microenvironment and its interaction with the immune system remain a mystery. The efficacy of immunotherapy is often affected by tumor heterogeneity. Molecular imaging techniques, such as single photon emission computed tomography and positron emission tomography, enable noninvasive whole‐body imaging of tumor and immune cell signatures. Noninvasive molecular imaging can also be used to monitor the treatment response of tumors, thereby achieving personalized response assessment, which may ultimately lead to improved clinical management, development of individualized treatments, and reliable prognosis. This article reviews recent research in immunotherapy response assessment, immune T‐cell imaging, immune checkpoint imaging, and radiomics/radiogenomics in immunotherapy. To date, these studies have primarily comprised exploratory preclinical imaging with preliminary results indicating that biomarker molecular imaging may have a role to play in the assessment of immunotherapy. Therefore, the principle of selecting patients for immunotherapy based on imaging results is feasible.
Hypocalcemia Risk of Denosumab Across the Spectrum of Kidney Disease: A Population-Based Cohort Study
Authors: Cowan Andrea , Jeyakumar Nivethika , McArthur Eric , Fleet Jamie L , Kanagalingam Tharsan , Karp Igor , Khan Tayyab , Muanda Flory Tsobo , Nash Danielle M , Silver Samuel A , Thain Jenny , Weir Matthew A , Garg Amit X , Clemens Kristin K 
Published: March 2023

ABSTRACT
Denosumab can be used in patients with chronic kidney disease (CKD) but has been linked with cases of severe hypocalcemia. The incidence of and risk factors for hypocalcemia after denosumab use are not well established. Using linked health care databases at ICES, we conducted a population-based cohort study of adults &gt;65 years old with a new prescription for denosumab or a bisphosphonate between 2012 and 2020. We assessed incidence of hypocalcemia within 180 days of drug dispensing and stratified results by estimated glomerular filtration rate (eGFR in mL/min/1.73 m2). We used Cox proportional hazards to assess risk factors for hypocalcemia. There were 59,151 and 56,847 new denosumab and oral bisphosphonate users, respectively. Of the denosumab users, 29% had serum calcium measured in the year before their prescription, and one-third had their serum calcium checked within 180 days after their prescription. Mild hypocalcemia (albumin corrected calcium &lt;2.00 mmol/L) occurred in 0.6% (95% confidence interval [CI] 0.6, 0.7) of new denosumab users and severe hypocalcemia (&lt;1.8 mmol/L) in 0.2% (95% CI 0.2, 0.3). In those with an eGFR &lt;15 or receiving maintenance dialysis, the incidence of mild and severe hypocalcemia was 24.1% (95% CI 18.1, 30.7) and 14.9% (95% CI 10.1, 20.7), respectively. In this group, kidney function and baseline serum calcium were strong predictors of hypocalcemia. We did not have information on over-the-counter vitamin D or calcium supplementation. In new bisphosphonate users, the incidence of mild hypocalcemia was 0.3% (95% CI 0.3, 0.3) with an incidence of 4.7% (95% CI 1.5, 10.8) in those with an eGFR &lt;15 or receiving maintenance dialysis. In this large population-based cohort, we found that the overall risk of hypocalcemia with new denosumab use was low but increased substantially in those with eGFR &lt;15 mL/min/1.73 m2. Future studies should investigate strategies to mitigate hypocalcemia. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Hip Fracture Risk Assessment in Elderly and Diabetic Patients: Combining Autonomous Finite Element Analysis and Machine Learning
Authors: Yosibash Zohar , Trabelsi Nir , Buchnik Itay , Myers Kent W , Salai Moshe , Eshed Iris , Barash Yiftach , Klang Eyal , Tripto-Shkolnik Liana 
Published: March 2023

ABSTRACT
Autonomous finite element analyses (AFE) based on CT scans predict the biomechanical response of femurs during stance and sidewise fall positions. We combine AFE with patient data via a machine learning (ML) algorithm to predict the risk of hip fracture. An opportunistic retrospective clinical study of CT scans is presented, aimed at developing a ML algorithm with AFE for hip fracture risk assessment in type 2 diabetic mellitus (T2DM) and non-T2DM patients.
Abdominal/pelvis CT scans of patients who experienced a hip fracture within 2 years after an index CT scan were retrieved from a tertiary medical center database. A control group of patients without a known hip fracture for at least 5 years after an index CT scan was retrieved. Scans belonging to patients with/without T2DM were identified from coded diagnoses. All femurs underwent an AFE under three physiological loads. AFE results, patient's age, weight, and height were input to the ML algorithm (support vector machine [SVM]), trained by 80% of the known fracture outcomes, with cross-validation, and verified by the other 20%.
In total, 45% of available abdominal/pelvic CT scans were appropriate for AFE (at least 1/4 of the proximal femur was visible in the scan). The AFE success rate in automatically analyzing CT scans was 91%: 836 femurs we successfully analyzed, and the results were processed by the SVM algorithm. A total of 282 T2DM femurs (118 intact and 164 fractured) and 554 non-T2DM (314 intact and 240 fractured) were identified. Among T2DM patients, the outcome was: Sensitivity 92%, Specificity 88% (cross-validation area under the curve [AUC] 0.92) and for the non-T2DM patients: Sensitivity 83%, Specificity 84% (cross-validation AUC 0.84).
Combining AFE data with a ML algorithm provides an unprecedented prediction accuracy for the risk of hip fracture in T2DM and non-T2DM populations. The fully autonomous algorithm can be applied as an opportunistic process for hip fracture risk assessment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Inverse design of ligands using a deep generative model semi‐supervised by a data‐driven ligand field strength metric
Authors: Lee Zhi‐Hang , Lin Po Chuan , Yang Tzuhsiung 
Published: March 2023

AbstractTransition metal (TM) complexes exhibit diverse structural and electronic properties. The properties of a TM complex can be tuned by modulating the ligand field strength (LFS) inflicted by its ligands. Current quantification of the LFS of a ligand is mainly derived from experimental measurements on a subset of highly symmetrical TM complexes and is limited in ligand scope. Herein, we report a data‐driven method to quantify the LFS of ligands assigned from experimental crystal structures of TM complexes. We first show that the experimental metal–ligand bond lengths of over 4,000 mononuclear Fe, Co, and Mn complexes form bimodal distributions. Using Gaussian fits on the bimodal distributions, each TM complex is assigned a spin state (SS) label. These SS labels can then be used to calculate the LFS of the ligands of the complexes. Using the obtained data‐driven LFS metric, we establish that a semi‐supervised deep generative model, junction tree variational autoencoder (JTVAE), can be employed to predict LFS values. Our model exhibits a mean absolute error (MAE) of 0.047 and root mean squared error of 0.072 on the training set. The model also allows the generation of novel ligands with desirable LFS values.
Hemogram‐based decision tree models for discriminating COVID‐19 from RSV in infants
Authors: Dobrijević Dejan , Andrijević Ljiljana , Antić Jelena , Rakić Goran , Pastor Kristian 
Published: March 2023

AbstractObjectiveDecision trees are efficient and reliable decision‐making algorithms, and medicine has reached its peak of interest in these methods during the current pandemic. Herein, we reported several decision tree algorithms for a rapid discrimination between coronavirus disease (COVID‐19) and respiratory syncytial virus (RSV) infection in infants.MethodsA cross‐sectional study was conducted on 77 infants: 33 infants with novel betacoronavirus (SARS‐CoV‐2) infection and 44 infants with RSV infection. In total, 23 hemogram‐based instances were used to construct the decision tree models via 10‐fold cross‐validation method.ResultsThe Random forest model showed the highest accuracy (81.8%), while in terms of sensitivity (72.7%), specificity (88.6%), positive predictive value (82.8%), and negative predictive value (81.3%), the optimized forest model was the most superior one.ConclusionRandom forest and optimized forest models might have significant clinical applications, helping to speed up decision‐making when SARS‐CoV‐2 and RSV are suspected, prior to molecular genome sequencing and/or antigen testing.
Childhood exposure to parental threatening behaviors and anxiety in emerging adulthood: Indirect effects of perceived stress
Authors: Trent Erika S. , Viana Andres G. , Raines Elizabeth M. , Busch Haley E. Conroy , Silva Karina , Storch Eric A. , Zvolensky Michael J. 
Published: March 2023

AbstractBackgroundAlthough childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress—a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self‐efficacy (confidence in one's ability to manage stressors)—is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults.MethodsParticipants (N = 855; Mage = 18.75 years, SD = 1.05, range 18−24; 70.8% female) were recruited from a large state university and administered a battery of self‐report questionnaires assessing constructs of interest.ResultsStructural equation modeling (SEM) analyses indicated that only greater childhood exposure to maternal threatening behaviors was directly associated with greater feelings of helplessness and lower self‐efficacy. Furthermore, only childhood exposure to maternal threatening behaviors was indirectly associated with anxiety severity through greater feelings of helplessness and lower self‐efficacy. In contrast, childhood exposure to paternal threatening behaviors was neither directly nor indirectly associated with anxiety severity.LimitationsLimitations include a cross‐sectional design, use of self‐report measures, and a nonclinical sample. Replicating these findings in a clinical sample and testing the hypothesized model in a longitudinal design is necessary.ConclusionsFindings underscore the need for intervention efforts that screen for and target perceived stress in emerging adults exposed to negative maternal parenting behaviors.