bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in PDGFRA D842V-Mutant Gastrointestinal Stromal Tumor
Authors: Rossi Ferdinand , Liu Mengyuan , Tieniber Andrew , Etherington Mark S. , Hanna Andrew , Vitiello Gerardo A. , Param Nesteene J. , Do Kevin , Wang Laura , Antonescu Cristina R. , Zeng Shan , Zhang Jennifer Q. , DeMatteo Ronald P. 
Published: March 2023

Abstract

Purpose:
To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy.

Experimental Design:
We created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light-chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro. Human GIST specimens were analyzed for MYLK expression.

Results:
The PDX was minimally responsive to imatinib but sensitive to avapritinib. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. ML-7 induced apoptosis and disrupted actin filaments in short-term cultures of PDX cells and decreased survival in GIST T1 cells in combination with imatinib or avapritinib. Combined therapy with ML-7 improved the antitumor effects of low-dose avapritinib in vivo. Furthermore, MYLK was expressed in human GIST specimens.

Conclusions:
MYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects.
Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet 
Published: March 2023

Abstract

Multiple studies have identified metabolic changes within the tumor and its microenvironment during carcinogenesis. Yet, the mechanisms by which tumors affect the host metabolism are unclear. We find that systemic inflammation induced by cancer leads to liver infiltration of myeloid cells at early extrahepatic carcinogenesis. The infiltrating immune cells via IL6–pSTAT3 immune–hepatocyte cross-talk cause the depletion of a master metabolic regulator, HNF4α, consequently leading to systemic metabolic changes that promote breast and pancreatic cancer proliferation and a worse outcome. Preserving HNF4α levels maintains liver metabolism and restricts carcinogenesis. Standard liver biochemical tests can identify early metabolic changes and predict patients’ outcomes and weight loss. Thus, the tumor induces early metabolic changes in its macroenvironment with diagnostic and potentially therapeutic implications for the host.

Significance:
Cancer growth requires a permanent nutrient supply starting from early disease stages. We find that the tumor extends its effect to the host's liver to obtain nutrients and rewires the systemic and tissue-specific metabolism early during carcinogenesis. Preserving liver metabolism restricts tumor growth and improves cancer outcomes.
This article is highlighted in the In This Issue feature, p. 1501
High frequency isolated bidirectional dual active bridge DC-DC converters and its application to distributed energy systems: an overview
Authors: Bathala Kiran , Kishan Dharavath , Harischandrappa Nagendrappa 
Published: March 2023

Among the DC-DC converters, an isolated bidirectional dual active bridge converter is a core circuit for high-frequency power converters in distributed energy system applications. These high-frequency power conversion systems attract academia and industry due to various advantages, such as high-power density, less weight, reduced noise, high efficiency, low cost and high reliability. First, the importance of power electronic converters in modern-day life is introduced. Second, a topological overview of voltage-fed and current-fed isolated bidirectional dual active bridge converters is presented with their importance in integrating hybrid power sources. Third, switching modes of isolated bidirectional DC-DC converters are also presented with a degree of freedom of control. Forth, performance evaluation of voltage-fed and current-fed isolated bidirectional converters has been presented with an example. Their suitability in integrating fuel cells and photovoltaics with energy storage systems in low to medium-power applications is presented.
Transcranial Direct-Current Stimulation in Subacute Aphasia: A Randomized Controlled Trial
Authors: Stockbridge Melissa D. , Elm Jordan , Breining Bonnie L. , Tippett Donna C. , Sebastian Rajani , Cassarly Christy , Teklehaimanot Abeba , Spell Leigh Ann , Sheppard Shannon M. , Vitti Emilia , Ruch Kristina , Goldberg Emily B. , Kelly Catherine , Keator Lynsey M. , Fridriksson Julius , Hillis Argye E. 
Published: March 2023

Background:
Transcranial direct-current stimulation (tDCS) is a promising adjunct to therapy for chronic aphasia.

Methods:
This single-center, randomized, double-blind, sham-controlled efficacy trial tested the hypothesis that anodal tDCS augments language therapy in subacute aphasia. Secondarily, we compared the effect of tDCS on discourse measures and quality of life and compared the effects on naming to previous findings in chronic stroke. Right-handed English speakers with aphasia <3 months after left hemisphere ischemic stroke were included, unless they had prior neurological or psychiatric disease or injury or were taking certain medications (34 excluded; final sample, 58). Participants were randomized 1:1, controlling for age, aphasia type, and severity, to receive 20 minutes of tDCS (1 mA) or sham-tDCS in addition to fifteen 45-minute sessions of naming treatment (plus standard care). The primary outcome variable was change in naming accuracy of untrained pictures pretreatment to 1-week posttreatment.

Results:
Baseline characteristics were similar between the tDCS (N=30) and sham (N=28) groups: patients were 65 years old, 53% male, and 2 months from stroke onset on average. In intent-to-treat analysis, the adjusted mean change from baseline to 1-week posttreatment in picture naming was 22.3 (95% CI, 13.5–31.2) for tDCS and 18.5 (9.6–27.4) for sham and was not significantly different. Content and efficiency of picture description improved more with tDCS than sham. Groups did not differ in quality of life improvement. No patients were withdrawn due to adverse events.

Conclusions:
tDCS did not improve recovery of picture naming but did improve recovery of discourse. Discourse skills are critical to participation. Future research should examine tDCS in a larger sample with richer functional outcomes.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02674490.
Cerebrovascular Reactivity Has Negligible Contribution to Hemodynamic Lag After Stroke: Implications for Functional Magnetic Resonance Imaging Studies
Authors: Braban Andra , Leech Robert , Murphy Kevin , Geranmayeh Fatemeh 
Published: March 2023

Background:
Functional magnetic resonance imaging (fMRI) is ubiquitously used to study poststroke recovery. However, the fMRI–derived hemodynamic responses are vulnerable to vascular insult which can result in reduced magnitude and temporal delays (lag) in the hemodynamic response function (HRF). The cause of HRF lag remains controversial, and a better understanding of it is required to ensure accurate interpretation of poststroke fMRI studies. In this longitudinal study, we investigate the relationship between hemodynamic lag and cerebrovascular reactivity (CVR) following stroke.

Methods:
Voxel-wise lag maps were calculated relative to a mean gray matter reference signal for 27 healthy controls and 59 patients with stroke across 2 time points (≈2 weeks and ≈4 months poststroke) and 2 conditions: resting-state and breath-holding. The breath-holding condition was additionally used to calculate CVR in response to hypercapnia. HRF lag was computed for both conditions across tissue compartments: lesion, perilesional tissue, unaffected tissue of the lesioned hemisphere, and their homolog regions in the unaffected hemisphere. CVR and lag maps were correlated. Group, condition, and time effects were assessed using ANOVA analyses.

Results:

Compared with the average gray matter signal, a relative hemodynamic lead was observed in the primary sensorimotor cortices in resting-state and bilateral inferior parietal cortices in the breath-holding condition. Whole-brain hemodynamic lag was significantly correlated across conditions irrespective of group, with regional differences across conditions suggestive of a neural network pattern. Patients showed relative lag in the lesioned hemisphere which significantly reduced over time. Breath-hold derived lag and CVR had no significant voxel-wise correlation in controls, or patients within the lesioned hemisphere or the homologous regions of the lesion and perilesional tissue in the right hemisphere (mean
r
<0.1).

Conclusions:
The contribution of altered CVR to HRF lag was negligible. We suggest that HRF lag is largely independent of CVR, and could partly reflect intrinsic neural network dynamics among other factors.
Distinct Roles of Cyclones and Anticyclones in Setting the Midwinter Minimum of the North Pacific Eddy Activity: A Lagrangian Perspective
Authors: Okajima Satoru , Nakamura Hisashi , Kaspi Yohai 
Published: March 2023

Abstract
The North Pacific storm-track activity is suppressed substantially under the excessively strong westerlies to form a distinct minimum in midwinter, which seems inconsistent with linear baroclinic instability theory. This “midwinter minimum” of the storm-track activity has been intensively investigated for decades as a test case for storm-track dynamics. However, the mechanisms controlling it are yet to be fully unveiled and are still under debate. Here we investigate the detailed seasonal evolution of the climatological density of surface migratory anticyclones over the North Pacific, in comparison with its counterpart for cyclones, based on a Lagrangian tracking algorithm. We demonstrate that the frequency of surface cyclones over the North Pacific maximizes in midwinter, whereas that of anticyclones exhibits a distinct midwinter minimum under the upstream influence, especially from the Japan Sea region. In midwinter, it is only on such a rare occasion that prominent weakening of the East Asian winter monsoon allows a migratory surface anticyclone to form over the Japan Sea, despite the unfavorable climatological-mean conditions due to persistent monsoonal cold-air outbreaks and the excessively strong upper-tropospheric westerlies. The midwinter minimum of the North Pacific anticyclone density suggests that anticyclones are likely the key to understanding the midwinter minimum of the North Pacific storm-track activity as measured by Eulerian eddy statistics.
The Association Between Resiliency Factors and Suicide Indicators Among American Indian/Alaska Native Middle School Students in New Mexico: A Strength-Based Analysis
Authors: Parshall Carolyn , Qeadan Fares , Espinoza Judith , English Kevin 
Published: March 2023

Objective: Suicide is a leading cause of death among American Indian/Alaska Native (AI/AN) young people aged 10-19 years in the United States, but data collection and reporting in this population are lacking. We examined results of an oversample project in New Mexico to determine the association between resiliency factors and suicide-related behaviors among AI/AN middle school students. Methods: We conducted analyses using data from the 2019 New Mexico Youth Risk and Resiliency Survey for students in grades 6 through 8. An oversampling method was used to increase the sample size of AI/AN students. We used logistic regression to determine the association between resiliency factors and suicide indicators among AI/AN students, stratified by sex. Results: Among female AI/AN students, community support had the strongest protective effect against having seriously thought about suicide (adjusted odds ratio [aOR] = 0.23; 95% CI, 0.14-0.38), while family support was significantly associated with the lowest odds of having made a suicide plan (aOR = 0.15; 95% CI, 0.08-0.28) and having attempted suicide (aOR = 0.21; 95% CI, 0.13-0.34) ( P < .001 for all). Among male AI/AN students, school support had the strongest protective effect against all 3 outcomes: seriously thought about suicide (aOR = 0.34; 95% CI, 0.19-0.62; P < .001), having made a suicide plan (aOR = 0.19; 95% CI, 0.09-0.39; P < .001), and having attempted suicide (aOR = 0.27; 95% CI, 0.12-0.65; P = .003). Conclusions: Oversampling AI/AN young people can help accurately quantify and understand health risk behaviors and strengths of this population, leading to improved health and wellness. Family, community, and school-based support should be considered in interventions geared toward suicide prevention among AI/AN young people.
Comparison of anterior cervical discectomy and fusion versus anterior cervical corpectomy and fusion in the treatment of localized ossification of the posterior longitudinal ligament
Authors: Chen Tangyiheng , Wang Yujie , Zhou Hong , Lin Cheng , Li Xuefeng , Yang Huilin , Liu Yijie , Jiang Weimin 
Published: March 2023

Background The retrospective study was conducted to compare the efficacy of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) for localized ossification of the posterior longitudinal ligament (OPLL) by evaluating clinical and radiologic outcomes. Methods We reviewed 151 patients to assess the effects of treatment for one or two levels localized OPLL. Perioperative parameters, such as blood loss, operation time and complications, were recorded. Radiologic outcomes, such as the occupying ratio (OR), fusion status, cervical lordosis angle, segmental angle, disc space height, T1 slope, and C2–C7 sagittal vertical axis (SVA), were assessed. Clinical indices, such as the JOA scores and VAS scores, were investigated to compare the two surgical options. Results There were no significant differences in the JOA scores or VAS scores between the two groups ( p > 0.05). The operation time, volume of blood loss and incidence of dysphagia were significantly less in the ACDF group than in the ACCF group ( p < 0.05). In addition, cervical lordosis, segmental angle and disc space height were significantly different from their preoperative evaluations. No adjacent segment degenerated in the ACDF group. The subsidence rates of implants were 5.2% in the ACDF group and 28.4% in the ACCF group. The degeneration of the ACCF group was 4.1%. The incidence of CSF leaks was 7.8% in the ACDF group and 13.5% in the ACCF group. All the patients ultimately achieved successful fusion. Conclusion Although both options achieved satisfactory primary clinical and radiographic efficacies, ACDF was associated with a shorter surgical procedure, less intraoperative blood loss, better radiologic outcomes, and lower incidence of dysphagia than ACCF.
Qualitative Findings From a Survey on Patient Experiences and Satisfaction with Lung Cancer Screening
Authors: Pérez-Morales Jaileene , Pathak Rashmi , Reyes Monica , Tolbert Haley , Tirbene Rajwantee , Gray Jhanelle E. , Simmons Vani N. , Schabath Matthew B. , Quinn Gwendolyn P. 
Published: March 2023

Background To reveal successes and potential limitations of the lung cancer screening program, we conducted a survey that included both quantitative and open-ended questions to measure patient experiences and satisfaction with screening. Methods We report on the five open-ended items related to barriers to returning for screening, experience with other cancer prevention screenings, positive and negative experiences, and suggestions for improving future appointments. The open-ended responses were analyzed using constant comparison method and inductive content analysis. Results Respondents (182 patients, 86% response rate for open-ended questions) provided generally positive comments about their lung cancer screening experience. Negative comments were related to desire for more information about results, long wait times for results, and billing issues. Suggestions for improvements included: scheduling on-line appointments and text or email reminders, lower costs, and responding to uncertainty about eligibility criteria. Conclusion Findings provide insights about patient experiences and satisfaction with lung cancer screening which is important given low uptake. Ongoing patient-centered feedback may improve the lung cancer screening experience and increase follow-up screening rates.
A Longitudinal Study of Thrombosis and Bleeding Outcomes With Thromboprophylaxis in Pregnant Women at Intermediate and High Risk of VTE
Authors: Schapkaitz E. , Libhaber E. , Gerber A. , Rhemtula H. , Zamparini J. , Jacobson B.F , Büller H.R 
Published: March 2023

Background The efficacy and safety of thromboprophylaxis in pregnancy at intermediate to high risk of venous thrombo-embolism (VTE) is an area of ongoing research. Aim This study aimed to assess thrombosis and bleeding outcomes associated with thromboprophylaxis in women at risk of VTE. Methods A cohort of 129 pregnancies, who received thromboprophylaxis for the prevention of VTE, were identified from a specialist obstetric clinic in Johannesburg, South Africa. Intermediate-risk pregnancies, with medical comorbidities or multiple low risks, were managed with fixed low-dose enoxaparin antepartum and for a median (interquartile range) of 4 (4) weeks postpartum. High-risk pregnancies, with a history of previous VTE, were managed with anti-Xa adjusted enoxaparin antepartum and for a median of 6 (0) weeks postpartum. Pregnancy-related VTE was objectively confirmed. Major bleeding, clinically relevant nonmajor bleeding (CRNMB) and minor bleeding were defined according to the International Society on Thrombosis and Hemostasis Scientific Subcommittee. Results Venous thrombo-embolism occurred antepartum in 1.4% (95% CI: 0.04-7.7) of intermediate and 3.4% (95% CI: 0.4-11.7) of high-risk pregnancies. Bleeding events occurred in 7.1% (95% CI: 2.4-15.9) of intermediate and 8.5% (95% CI: 2.8-18.7) of high-risk pregnancies. Of these bleeding events, 3.1% (95% CI: 1.0-8.0) were classified as major bleeding. On univariate analysis, no independent predictors of bleeding were identified. Conclusion The rates of thrombosis and bleeding in this predominantly African population were consistent with similar studies and can be used to inform pregnant women of the benefits of anticoagulation and the risks of potential bleeding.
COVID-19 Infection Risk Among Previously Uninfected Adults: Development of a Prognostic Model
Authors: Sloane Richard , Pieper Carl F , Faldowski Richard , Wixted Douglas , Neighbors Coralei E , Woods Christopher W , Kristin Newby L 
Published: March 2023

Background Few models exist that incorporate measures from an array of individual characteristics to predict the risk of COVID-19 infection in the general population. The aim was to develop a prognostic model for COVID-19 using readily obtainable clinical variables. Methods Over 74 weeks surveys were periodically administered to a cohort of 1381 participants previously uninfected with COVID-19 (June 2020 to December 2021). Candidate predictors of incident infection during follow-up included demographics, living situation, financial status, physical activity, health conditions, flu vaccination history, COVID-19 vaccine intention, work/employment status, and use of COVID-19 mitigation behaviors. The final logistic regression model was created using a penalized regression method known as the least absolute shrinkage and selection operator. Model performance was assessed by discrimination and calibration. Internal validation was performed via bootstrapping, and results were adjusted for overoptimism. Results Of the 1381 participants, 154 (11.2%) had an incident COVID-19 infection during the follow-up period. The final model included six variables: health insurance, race, household size, and the frequency of practicing three mitigation behavior (working at home, avoiding high-risk situations, and using facemasks). The c-statistic of the final model was 0.631 (0.617 after bootstrapped optimism-correction). A calibration plot suggested that with this sample the model shows modest concordance with incident infection at the lowest risk. Conclusion This prognostic model can help identify which community-dwelling older adults are at the highest risk for incident COVID-19 infection and may inform medical provider counseling of their patients about the risk of incident COVID-19 infection.
In vitro and in vivo study on the anticancer effects of anethole-loaded bovine serum albumin nanoparticles surface decorated with chitosan and folic acid
Authors: Sadeghzadeh Farzaneh , Nasiraei Haghighi Hasti , Ghiyamati Mahdiyeh , Hajizadenadaf Fateme , Homayouni Tabrizi Masoud 
Published: March 2023

AbstractAnethole (Ant) is a herbal compound with unique properties, which is limited in its clinical use due to its low solubility in aqueous solutions. Therefore, in this study, albumin nanocarrier modified with chitosan-folate was used to transfer Ant to cancer cells and its anticancer effects were evaluated. First, Ant was loaded on albumin nanoparticles by desolvation method and then the surface of nanoparticles was covered with chitosan bound to folate. After characterization, the amount of Ant loading in nanoparticles was measured by the absorption method and then its toxicity effects on breast cancer cell lines, colon, and normal cells were evaluated by the MTT method. The real-time QPCR method was used to investigate the expression changes of apoptosis-related genes in the treated cells compared to the control cells, and finally, the antitumor effects of nanoparticles were evaluated in the mouse model carrying breast cancer. The results of this investigation showed the presence of nanoparticles with dimensions of 252 nm, a dispersion index of 0.28 mV, and a surface charge of 27.14 mV, which are trapped in about 88% of ATL. The toxicity effect of nanoparticles was shown on breast, colon, and normal cancer cells, respectively. In addition, the examination of the gene profile under investigation showed an increase in the expression of BAX and caspase-3 and -9 along with a decrease in the expression of the Bcl-2 gene, which confirms the activation of the internal pathway of apoptosis. The decrease in the volume of tumors and the presence of apoptotic areas in the tissue sections confirmed the antitumor effects of nanoparticles in the in vivo model. The inhibition percentage of free Ant and nanoparticles with a concentration of 25 and 50 mg/kg/tumor volume was reported as 36.9%, 56.6%, and 64.9%, respectively, during 15 days of treatment. These results showed the effectiveness of the formulation in inhibiting cancer cells both in vitro and in vivo.