bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher Adherence to the Mediterranean Dietary Pattern Is Inversely Associated With Severity of COVID-19 and Related Symptoms: A Cross-Sectional Study
Authors: Zargarzadeh Nikan , Tadbir Vajargah Kiana , Ebrahimzadeh Armin , Mousavi Seyed Mohammad , Khodaveisi Hamidreza , Akhgarjand Camellia , Toyos Fernando M. P. , Cerqueira Henrique S. , Santos Heitor O. , Taghizadeh Mohsen , Milajerdi Alireza 
Published: July 2022

Background and AimsAdherence to the Mediterranean diet (MD) has been associated with a decreased risk of developing a variety of chronic diseases that are comorbidities in COVID-19 patients. However, its association to the severity and symptoms of COVID-19 are still unknown. This study aimed to examine the association between adherence to the MD pattern and COVID-19 severity and symptoms in Iranian hospitalized patients.MethodsIn this cross-sectional study, 250 COVID-19 patients aged 18 to 65 were examined. We employed a food frequency questionnaire (FFQ) to obtain data on dietary intake of participants in the year prior to their COVID-19 diagnosis. COVID-19 severity was determined using the National Institutes of Health's Coronavirus Disease 2019 report. Additionally, symptoms associated with COVID-19, inflammatory markers, and other variables were evaluated. The scoring method proposed by Trichopoulou et al. was used to assess adherence to the MD.ResultsThe participants' mean age was 44.1 ± 12.1 years, and 46% of them had severe COVID-19. Patients who adhered more closely to the MD had lower serum C-reactive protein levels (7.80 vs. 37.36 mg/l) and erythrocyte sedimentation rate (14.08 vs. 42.65 mm/h). Those with the highest MD score were 77% less likely to have severe COVID-19 after controlling for confounding variables. The MD score was also found to be inversely associated with COVID-19 symptoms, including dyspnea, cough, fever, chills, weakness, myalgia, nausea and vomiting, and sore throat.ConclusionHigher adherence to the MD was associated with a decreased likelihood of COVID-19 severity and symptoms, as well as a shorter duration of hospitalization and convalescence, and inflammatory biomarkers.
A rare case of arrhythmogenic right ventricular cardiomyopathy associated with LAMA2 mutation: A case report and literature review
Authors: Wang Yue , Fang Yibing , Zhang Dan , Li Yifei , Luo Shuhua 
Published: July 2022

BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the LAMA2 gene is reported here. The protein encoded by LAMA2 gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix. We explored the potential mechanism and the relationship between the mutation and ARVC.Case PresentationAt the age of 8, the patient developed syncope and palpitation after exercise. Dynamic electrocardiogram recorded continuous premature ventricular beats, and MRI showed the right ventricle was significantly enlarged and there were many localized distensions at the edge of the right ventricular wall. The patient was diagnosed with ARVC and received heart transplantation at the age of 14 due to severe heart dysfunction. The myocardial histological pathological staining revealed a large amount of fibrosis and adipose migration. Whole exome sequencing (WES) identified the heterozygous mutation in the LAMA2 gene [NM_000426.3: c.8842G &gt; A (p.G2948S)]. This is the first report of these variants. Analysis was performed on genetic disorders to reveal splice site changes and damage to protein structure. LAMA2 p.G2948S predicted unstable protein structure and impaired function. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were established. RNA-seq and the western blot were performed on IPSC-CMs to explore the ARVC-related signaling pathway.ConclusionThis is the first case report to describe an ARVC phenotype in patients possessing a novel LAMA2 c.8842G &gt; A (p.G2948S) mutation. Our results aid in understanding of the pathogenesis of ARVC. The molecular mechanism of LAMA2 leading to ARVC disease still needs further study.
Comorbid depressive symptoms can aggravate the functional changes of the pain matrix in patients with chronic back pain: A resting-state fMRI study
Authors: Zhang Guangfang , Ma Junqin , Lu Weirong , Zhan Hongrui , Zhang Xuefei , Wang Kangling , Hu Yingxuan , Wang Xianglong , Peng Weiwei , Yue Shouwei , Cai Qingxiang , Liang Wen , Wu Wen 
Published: July 2022

ObjectiveThe purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function.MethodsThirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations.ResultCompared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = −2.175, p = 0.034), gamma (t = −2.332, p = 0.023), and local efficiency (t = −2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = −3.581, p = 0.0007), and the network efficiency values (t = −2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores.ConclusionOur study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP.
Does Executive Function Influence Walking in Acutely Hospitalized Patients With Advanced Parkinson's Disease: A Quantitative Analysis
Authors: Geritz Johanna , Welzel Julius , Hansen Clint , Maetzler Corina , Hobert Markus A. , Elshehabi Morad , Sobczak Alexandra , Kudelka Jennifer , Stiel Christopher , Hieke Johanne , Alpes Annekathrin , Bunzeck Nico , Maetzler Walter 
Published: July 2022

IntroductionIt is well-known that, in Parkinson's disease (PD), executive function (EF) and motor deficits lead to reduced walking performance. As previous studies investigated mainly patients during the compensated phases of the disease, the aim of this study was to investigate the above associations in acutely hospitalized patients with PD.MethodsA total of seventy-four acutely hospitalized patients with PD were assessed with the delta Trail Making Test (ΔTMT, TMT-B minus TMT-A) and the Movement Disorder Society-revised version of the motor part of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS III). Walking performance was assessed with wearable sensors under single (ST; fast and normal pace) and dual-task (DT; walking and checking boxes as the motor secondary task and walking and subtracting seven consecutively from a given three-digit number as the cognitive secondary task) conditions over 20 m. Multiple linear regression and Bayes factor BF10 were performed for each walking parameter and their dual-task costs while walking (DTC) as dependent variables and also included ΔTMT, MDS-UPDRS III, age, and gender.ResultsUnder ST, significant negative effects of the use of a walking aid and MDS-UPDRS III on gait speed and at a fast pace on the number of steps were observed. Moreover, depending on the pace, the use of a walking aid, age, and gender affected step time variability. Under walking-cognitive DT, a resolved variance of 23% was observed in the overall model for step time variability DTC, driven mainly by age (β = 0.26, p = 0.09). Under DT, no other significant effects could be observed. ΔTMT showed no significant associations with any of the walking conditions.DiscussionThe results of this study suggest that, in acutely hospitalized patients with PD, reduced walking performance is mainly explained by the use of a walking aid, motor symptoms, age, and gender, and EF deficits surprisingly do not seem to play a significant role. However, these patients with PD should avoid walking-cognitive DT situations, as under this condition, especially step time variability, a parameter associated with the risk of falling in PD worsens.
Preoperative Non-Invasive Prediction of Breast Cancer Molecular Subtypes With a Deep Convolutional Neural Network on Ultrasound Images
Authors: Li Chunxiao , Huang Haibo , Chen Ying , Shao Sihui , Chen Jing , Wu Rong , Zhang Qi 
Published: July 2022

PurposeThis study aimed to develop a deep convolutional neural network (DCNN) model to classify molecular subtypes of breast cancer from ultrasound (US) images together with clinical information.MethodsA total of 1,012 breast cancer patients with 2,284 US images (center 1) were collected as the main cohort for training and internal testing. Another cohort of 117 breast cancer cases with 153 US images (center 2) was used as the external testing cohort. Patients were grouped according to thresholds of nodule sizes of 20 mm and age of 50 years. The DCNN models were constructed based on US images and the clinical information to predict the molecular subtypes of breast cancer. A Breast Imaging-Reporting and Data System (BI-RADS) lexicon model was built on the same data based on morphological and clinical description parameters for diagnostic performance comparison. The diagnostic performance was assessed through the accuracy, sensitivity, specificity, Youden’s index (YI), and area under the receiver operating characteristic curve (AUC).ResultsOur DCNN model achieved better diagnostic performance than the BI-RADS lexicon model in differentiating molecular subtypes of breast cancer in both the main cohort and external testing cohort (all p &lt; 0.001). In the main cohort, when classifying luminal A from non-luminal A subtypes, our model obtained an AUC of 0.776 (95% CI, 0.649–0.885) for patients older than 50 years and 0.818 (95% CI, 0.726–0.902) for those with tumor sizes ≤20 mm. For young patients ≤50 years, the AUC value of our model for detecting triple-negative breast cancer was 0.712 (95% CI, 0.538–0.874). In the external testing cohort, when classifying luminal A from non-luminal A subtypes for patients older than 50 years, our DCNN model achieved an AUC of 0.686 (95% CI, 0.567–0.806).ConclusionsWe employed a DCNN model to predict the molecular subtypes of breast cancer based on US images. Our model can be valuable depending on the patient’s age and nodule sizes.
Indoleamine 2,3-Dioxygenase Immune Status as a Potential Biomarker of Radioiodine Efficacy for Advanced Distant Metastatic Differentiated Thyroid Cancer
Authors: Shi Liang , Duan Rui , Jia Qiong , Wu Wenyu , Zhou Jianming , Li Shaohua , Zhang Hao , Xue Xue 
Published: July 2022

PurposeHost immunity influences the impact of cancer therapy but the effect of immune status in radioiodine (RAI)-treated differentiated thyroid cancer (DTC) remains obscure. Here we investigated indoleamine 2,3-dioxygenase (IDO) activity as a biomarker of response to RAI in patients with distant metastatic DTC (dmDTC).MethodsPatients with dmDTC receiving RAI were evaluated for serum IDO activity (kynurenine and kynurenine:tryptophan ratio) at baseline and 3 months after RAI. The optimal cut-off value for these biomarkers to predict response was established by receiver operating characteristic analysis. The relationship between disease outcomes, overall survival (OS) and progression-free survival (PFS), and IDO activity levels was studied.ResultsHigher baseline kynurenine:tryptophan ratio (&gt;2.46) was correlated with poorer RAI response as well as shorter median PFS (45 mo versus not reached, p=0.002) and OS (78 mo versus not reached, p=0.035). High baseline kynurenine:tryptophan ratio was also correlated with a reduced number of tumor-infiltrating lymphocytes. Higher post/pre-kynurenine ratio (&gt;1.69) was associated with survival endpoints: shorter median PFS (48 mo versus not reached, p=0.002) and OS (68 mo versus not reached, p=0.010). Favorable baseline and favorable change corresponded with better PFS and OS.ConclusionsOur results suggest that RAI also alters IDO activity in dmDTC patients. IDO activity could predict progression and survival outcomes for advanced dmDTC patients. Serum IDO biomarker levels could be used to select dmDTC likely to benefit from RAI therapy, although further studies are necessary.
Radiomic Features From Diffusion-Weighted MRI of Retroperitoneal Soft-Tissue Sarcomas Are Repeatable and Exhibit Change After Radiotherapy
Authors: Thrussell Imogen , Winfield Jessica M. , Orton Matthew R. , Miah Aisha B. , Zaidi Shane H. , Arthur Amani , Thway Khin , Strauss Dirk C. , Collins David J. , Koh Dow-Mu , Oelfke Uwe , Huang Paul H. , O’Connor James P. B. , Messiou Christina , Blackledge Matthew D. 
Published: July 2022

BackgroundSize-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test–retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT).Materials and MethodsThirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test–retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability.ResultsFor the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC &gt; 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (&gt;0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively).ConclusionsThe ADC-based radiomic analysis shows better test–retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change.
Apogossypolone Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition in Cervical Cancer via Activating DKK3
Authors: Li Yuling , Qu Jinfeng , Liu Lu , Sun Yu , Zhang Junhua , Han Sai , Zhang Youzhong 
Published: July 2022

Apogossypolone (ApoG2), a novel derivative of gossypol lacking of two aldehyde groups, exhibits anti-tumor effects. However, the mechanisms by which ApoG2 regulates cervical cancer (CC) cells remain unclear. In this study, we treated two CC cell lines (CaSki and HeLa) with an increasing concentration of ApoG2 for 24 h. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, flow cytometry and transwell invasion assay were utilized to detect cell proliferation, apoptosis and invasion in vitro. We first observed that ApoG2 inhibited cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT) process in CC cells, along with upregulation of Dickkopf Wnt signaling pathway inhibitor 3 (DKK3) in a dose-dependent manner. The immunohistochemistry confirmed the downregulation of DKK3 in tumor tissues. Moreover, DKK3 was correlated with FIGO stage and lymph node metastasis. Functionally, DKK3 overexpression significantly suppressed cell viability, colony formation and invasion, but promoted apoptosis in CaSki and HeLa cells. Overexpression of DKK3 upregulated the protein levels of cleaved caspase-3 and E-cadherin, but downregulated the protein levels of Bcl-2, N-cadherin and Vimentin. Furthermore, DKK3 knockdown reversed the suppressive effects of ApoG2 on CaSki cell proliferation, invasion and EMT markers, while DKK3 overexpression enhanced these effects. In addition, ApoG2 treatment inhibited CC xenograft tumor growth and upregulated the protein levels of DKK3, cleaved caspase-3 and E-cadherin. In conclusions, these findings suggested that ApoG2 could effectively inhibit the growth and invasion of CC cells at least partly by activating DKK3.
Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial
Authors: Sainz Talía , Casas Inmaculada , González-Esguevillas Mónica , Escosa-Garcia Luis , Muñoz-Fernández María Ángeles , Prieto Luis , Gosalbes María José , Jiménez-Hernández Nuria , Ramos José Tomas , Navarro María Luisa , Mellado María José , Serrano-Villar Sergio , Calvo Cristina 
Published: July 2022

AimsVaccine response is poor among children living with HIV. The gut microbiota has been identified as a potential target to improve vaccine immunogenicity, but data are scarce in the context of HIV infection.MethodsPilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected children were randomized to receive a mixture of symbiotics, omega-3/6 fatty acids, and amino acids or placebo for 4 weeks, each in combination with ART, and were then immunized against influenza. Vaccine response and safety of the nutritional supplementation were the primary outcomes.ResultsEighteen HIV-infected children completed the follow-up period (mean age 11.5 ± 4.14 years, 61% female). The nutritional supplement was safe but did not enhance the response to the influenza vaccine. A 4-fold rise in antibody titers was obtained in only 37.5% of participants in the intervention arm vs. 40% in the placebo. No immunological or inflammatory predictors of vaccine response were identified.ConclusionsIn this exploratory study, a 4-week course of symbiotics did not increase influenza vaccine immunogenicity in HIV-infected children. Larger studies are warranted to address the potential of modulating the microbiome in children living with HIV.
Associations Between Antithrombosis and Ventilator-Associated Events, ICU Stays, and Mortality Among Mechanically Ventilated Patients: A Registry-Based Cohort Study
Authors: Wang Mingqi , Wang Wen , Jia Xue , He Qiao , Zhu Shichao , Kang Yan , Zhang Rui , Ren Yan , Li Ling , Zou Kang , Zong Zhiyong , Sun Xin 
Published: July 2022

Background: The effect of thromboembolism prophylaxis on clinical outcomes, such as ventilator-associated events (VAEs), ICU stays, and mortality, remains controversial. This study was conducted to evaluate the effect of pharmacological thromboprophylaxis on VAEs, ICU stays, and ICU mortality among patients receiving mechanical ventilation (MV).Materials and Methods: A retrospective cohort study was conducted based on a well-established registry of healthcare-associated infections at ICUs in the West China Hospital system. Patients who consistently received MV for at least 4 days from 1 April 2015 to 31 December 2018 were included. Hazard ratios (HRs) were compared for three tiers of VAEs, ICU stays, and ICU mortality among patients receiving pharmacological thromboprophylaxis versus those without using the time-dependent Cox model. For the analyses of ICU stays and ICU mortality, we also used Fine-Gray models to disentangle the competing risks and outcomes of interest.Results: Overall, 6,140 patients were included. Of these, 3,805 received at least one prescription of antithrombosis agents. Treatments with antithrombosis agents were associated with lower risk of VAEs (HR: 0.87, 95% CI: 0.77, 0.98) and ICU mortality (HR: 0.72, 95% CI: 0.61, 0.86) than those without. Anticoagulants but not antiplatelet agents were associated with decreased risk of VAEs (HR: 0.86, 95% CI: 0.75, 0.98), ICU mortality (HR: 0.62, 95% CI: 0.51, 0.76), and less time to ICU discharge (HR: 1.15, 95% CI: 1.04, 1.28). Antithrombosis may be associated with decreased risk of VAEs in patients with D-dimer &gt;5 mg/LFEU (HR: 0.84, 95%CI: 0.72, 0.98).Conclusions: Pharmacological thromboprophylaxis was associated with lower risk of VAEs and ICU mortality. Similar effects were observed between unfractionated heparins versus low-molecular-weight heparins.
Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
Authors: Fan Linyuan , Liu Zhaohui , Zhang Zhan , Li Ting , Zong Xiaonan , Bai Huihui 
Published: July 2022

Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS), a Traditional Chinese Medicine (TCM) formulation, may short the course of the disease and reduce the occurrence of PID sequelae, but its pharmacological action and potential mechanism have not been fully elucidated. Here, we aimed to investigate the therapeutic effects and mechanism of KFXYS in rats with PID.Materials and Methods: A PID rat model was constructed through endometrial mechanical injury and pathogen infection. The rectal temperature was measured during the 14-days course of treatment, and the white blood cell (WBC) count in the blood and the levels of cytokines (IFN-γ, IL-1β, IL-4, TNF-α) in the serum were evaluated by ELISA. Hematoxylin and eosin (HE) staining was performed to analyze pathological changes, and transmission electron microscopy (TEM) was used to observe ultrastructural changes. The p-p65/p65 protein expression was evaluated by western blotting and the levels of MMP-2 and TGF-β in adhesion tissues were assessed by immunohistochemistry.Results: KFXYS lowered the rectal temperature and the WBC counts in the blood in the acute stage of PID and alleviated inflammatory cell infiltration of the uterus, especially when combined with levofloxacin. KFXYS significantly decreased the levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-4) and adhesion-related factors (TNF-α) and protected the ultrastructure of endometrial epithelial cells. Mechanistically, KFXYS inhibited the NF-κB activation by decreasing phosphorylation of p65, thus the alleviation of inflammation further reduced the expression of TGF-β and MMP-2, and inhibited the occurrence of uterine adhesions.Conclusion: These results revealed that KFXYS alleviated pelvic inflammation and effectively inhibits inflammation-associated adhesion, which indicated the potential role of KFXYS for treatment of PID and the prevention of PID sequelae.