bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau
Authors: Balmik Abhishek Ankur , Sonawane Shweta Kishor , Chinnathambi Subashchandrabose 
Published: May 2021

AbstractBackgroundMicrotubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein.MethodsHere, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization.ResultsHDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3β increases without any change in total GSK-3β level.ConclusionsHDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.
Poorer mental health and sleep quality are associated with greater self-reported reward-related eating during pregnancy and postpartum: an observational cohort study
Authors: Betts Grace M. , Lipsky Leah M. , Temmen Chelsie D. , Siega-Riz Anna Maria , Faith Myles S. , Nansel Tonja R. 
Published: May 2021

Abstract
Background
Depression, stress, and poor-quality sleep are common during pregnancy and postpartum, but the relationship of these factors with reward-related eating is not well understood. This observational cohort study examines associations of depression, stress, and sleep quality with self-reported reward-related eating in pregnancy and postpartum.

Methods
Participants were enrolled at < 12 weeks gestation and followed through 1 year postpartum. Self-reported measures obtained at baseline and 23–31 weeks postpartum included the Edinburgh Postnatal Depression Scale, Perceived Stress Scale, Pittsburgh Sleep Quality Index; reward-related eating measures included the Power of Food Scale (assessing hedonic hunger), modified Yale Food Addiction Scale (assessing addictive-like eating), and frequency and intensity of cravings. Linear and logistic regression models estimated associations of depressive symptoms, stress, and sleep quality with reward-related eating during pregnancy and postpartum, as well as change in each predictor with change in outcome.

Results
During pregnancy, greater depressive symptoms (β ± SE = 0.03 ± 0.01, p < .01), higher stress (0.03 ± 0.01, p < .01), and worse sleep quality (0.03 ± 0.01, p = 0.03) were associated with greater hedonic hunger. Similarly, greater depressive symptoms (OR = 1.08, 95% CI: 1.02, 1.14, p = .01), higher stress (OR = 1.09, 95% CI: 1.04, 1.14, p = <.01), and worse sleep quality (OR = 1.09, 95% CI: 1.00, 1.18, p = .04) were associated with greater odds of addictive-like eating. These associations were also significant in postpartum except that sleep quality was not associated with hedonic hunger. Greater depressive symptoms (β ± SE = 0.06 ± 0.02, p < .01; 0.08 ± 0.02, p = <.01), higher stress (0.04 ± 0.01, p < .01; 0.06 ± 0.02, p < .01), and worse sleep quality (0.11 ± 0.03, p < .01; 0.13 ± 0.03, p < .01) during pregnancy were associated with stronger and more frequent cravings, respectively. Increased depressive symptoms from pregnancy to postpartum was associated with increased hedonic hunger (β ± SE = 1.17 ± 0.57, p = 0.01) and addictive-like eating (0.88 ± 0.33, p = 0.01), and increased stress was associated with increased hedonic hunger (1.71 ± 0.76, p = 0.02). Change in stress was not associated with change in addictive-like eating and change in sleep quality was not associated with change in either hedonic hunger or addictive-like eating.

Conclusions
Greater depressive symptoms, perceived stress, and poorer sleep quality are associated with greater self-reported reward-related eating during pregnancy and postpartum, suggesting that efforts to improve diet during and after pregnancy may benefit from addressing mental health and sleep.

Trial registration
Clinicaltrials.gov
Registration ID – NCT02217462.
Date of registration – August 13, 2014
Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway
Authors: Long Shiqi , Gu Yangzhuo , An Yuanyuan , Lin Xiaojin , Chen Xiaoqing , Wang Xianyao , Liao Chunxiang , Ouyang Weiwei , Wang Nianxue , He Zhixu , Zhao Xing 
Published: May 2021

Abstract
Background
Cetuximab has been approved for use for first-line treatment of patients with wild-type KRAS metastatic colorectal cancer (CRC). However, treatment with cetuximab has shown limited efficacy as a CRC monotherapy. In addition, natural killer (NK) cell function is known to be severely attenuated in cancer patients. The goal of this study was to develop a new strategy to enhance antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells, in combination with cetuximab against CRC cells.

Methods
Ex vivo expanded NK cells were stimulated with reovirus, and reovirus-activated NK cells mediated ADCC assay were performed on CRC cells in combination with cetuximab. The synergistic antitumor effects of reovirus-activated NK cells and cetuximab were tested on DLD-1 tumor-bearing mice. Finally, Toll-like receptor 3 (TLR3) knockdown in NK cells, along with chemical blockade of TLR3/dsRNA complex, and inhibition of the TLR3 downstream signaling pathway, were performed to explore the mechanisms by which reovirus enhances NK cell cytotoxicity.

Results
We first confirmed that exposure of NK cells to reovirus enhanced their cytotoxicity in a dose-dependent manner.We then investigated whether reovirus-activated NK cells exposed to cetuximab-bound CRC cells exhibited greater anti-tumor efficacy than either monotherapy. Co-culture of CRC cell lines with reovirus-activated NK cells indicated that NK cytotoxicity was significantly higher in combination with cetuximab, regardless of KRAS mutation status or EGFR expression level. We also found that reovirus activation of NK cells, in conjunction with cetuximab, resulted in significantly stronger anti-tumor efficacy.Finally, TLR3 knockdown, inhibition of TLR3/dsRNA complex or TBK1/IKKε demonstrated that activation of NK cells by reovirus was dependent on TLR3 and its downstream signaling pathway.

Conclusions
This study demonstrated that combination treatment of reovirus-activated NK cells with cetuximab synergistically enhances their anti-tumor cytotoxicity, suggesting a strong candidate strategy for clinical treatment of CRC.
A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells is associated with acute hepatic rejection: a case control study
Authors: Zhu Ji-Qiao , Wang Jing , Li Xian-Liang , Xu Wen-Li , Lv Shao-cheng , Zhao Xin , Lang Ren , He Qiang 
Published: May 2021

Abstract
Background
T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker.

Methods
Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort.

Results
Upon activation the expression of TGF-β and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885–0.964; p = 0.000).

Conclusions
A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.
Disseminated coccidioidomycosis in a patient with juvenile idiopathic arthritis receiving infliximab
Authors: Trainor Megan , Henkel Emily , Diaz Lucia Z. , Carrasco Ruy 
Published: May 2021

Abstract
Background
Coccidioides immitis is a dimorphic fungus endemic to the arid climates of the Southwest United States, Mexico and parts of Central and South America. Human infection occurs through inhalation of spores with less than half of exposures progressing to a symptomatic state that primarily consists of pulmonary manifestations. Disseminated coccidioidomycosis is exceedingly rare, occurring in fewer than 1 % of symptomatic infections. Through hematogenous spread, the fungus can infect most organ systems and may be fatal without systemic antifungal treatment. Individuals with impaired cell-mediated immunity either from primary immunodeficiency disorders or secondary to immunosuppression with medications such as tumor necrosis factor alpha (TNF-α) inhibitors have increased risk of disseminated coccidioidomycosis and previous cases of coccidioidomycosis have been reported with biologic therapy.

Case presentation
We present a case of disseminated coccidioidomycosis in a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) being treated with prednisone, methotrexate, and infliximab. The patient presented with symptoms of meningeal irritation, bilateral choroidal lesions, and necrotizing peripheral pneumonia. Her infection was thought to be a reactivation of coccidioidomycosis given her history of resolved pneumonia that occurred after traveling to Arizona, New Mexico, and El Paso one year prior to presentation. Following diagnosis, she improved with discontinuation of her immunosuppressive medications and two weeks of intravenous amphotericin B and fluconazole with plans for lifetime treatment with fluconazole while immunosuppressed. Due to worsening arthritis, she will begin tofacitinib and continue close monitoring of chest x-rays and coccidioides antibody.

Conclusions
Patients undergoing immunosuppressive therapy for rheumatological conditions are at increased risk of disseminated coccidioidomycosis and should be evaluated with high suspicion when presenting with atypical symptoms and history of travel to endemic regions.
Trajectories of disease courses in the inception cohort of newly diagnosed patients with JIA (ICON-JIA): the potential of serum biomarkers at baseline
Authors: Ganeva Margarita , Fuehner Sabrina , Kessel Christoph , Klotsche Jens , Niewerth Martina , Minden Kirsten , Foell Dirk , Hinze Claas H. , Wittkowski Helmut 
Published: May 2021

Abstract
Objective
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory joint disorders with a chronic-remitting disease course. Treat-to-target approaches have been proposed but monitoring disease activity and predicting the response to treatment remains challenging.

Methods
We analyzed biomarkers and their relationship to outcome within the first year after JIA diagnosis in the German Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA). CRP, CXCL9, CXCL10, CXCL11, erythrocyte sedimentation rate, G-CSF, IL-6, IL-17A, IL-18, MCP-1, MIP-1α, MMP-3, S100A8/A9, S100A12, TNFα, and TWEAK were measured at baseline and 3 months later.

Results
Two-hundred-sixty-six JIA patients with active disease at baseline were included, with oligoarthritis and rheumatoid factor-negative polyarthritis representing the most frequent categories (72.9%). Most biomarkers were elevated in JIA compared to healthy pediatric controls. Patients with systemic JIA had higher CRP, S100A8/A9 and S100A12 levels compared to other JIA categories. Baseline levels of TWEAK, G-CSF and IL-18 were lower in oligoarthritis patients with disease extension within 1 year. Increased baseline levels of CRP, S100A8/A9, S100A12 and ESR were associated with the subsequent addition of biologic disease-modifying antirheumatic drugs (DMARDs). Higher baseline ESR, G-CSF, IL-6, IL-17A and TNF levels indicated an increased risk for ongoing disease activity after 12 months.

Conclusion
Our data demonstrate that elevated baseline levels of CRP, S100A8/A9 and S100A12 as well as increased ESR are associated with the necessity to escalate therapy during the first 12 month of follow-up. Furthermore, biomarkers related to Th17 activation may inform on future disease course in previously treatment-naïve JIA patients.
Impact of feature selection methods and subgroup factors on prognostic analysis with CT-based radiomics in non-small cell lung cancer patients
Authors: Sugai Yuto , Kadoya Noriyuki , Tanaka Shohei , Tanabe Shunpei , Umeda Mariko , Yamamoto Takaya , Takeda Kazuya , Dobashi Suguru , Ohashi Haruna , Takeda Ken , Jingu Keiichi 
Published: April 2021

Abstract
Background
Radiomics is a new technology to noninvasively predict survival prognosis with quantitative features extracted from medical images. Most radiomics-based prognostic studies of non-small-cell lung cancer (NSCLC) patients have used mixed datasets of different subgroups. Therefore, we investigated the radiomics-based survival prediction of NSCLC patients by focusing on subgroups with identical characteristics.

Methods
A total of 304 NSCLC (Stages I–IV) patients treated with radiotherapy in our hospital were used. We extracted 107 radiomic features (i.e., 14 shape features, 18 first-order statistical features, and 75 texture features) from the gross tumor volume drawn on the free breathing planning computed tomography image. Three feature selection methods [i.e., test–retest and multiple segmentation (FS1), Pearson's correlation analysis (FS2), and a method that combined FS1 and FS2 (FS3)] were used to clarify how they affect survival prediction performance. Subgroup analysis for each histological subtype and each T stage applied the best selection method for the analysis of All data. We used a least absolute shrinkage and selection operator Cox regression model for all analyses and evaluated prognostic performance using the concordance-index (C-index) and the Kaplan–Meier method. For subgroup analysis, fivefold cross-validation was applied to ensure model reliability.

Results
In the analysis of All data, the C-index for the test dataset is 0.62 (FS1), 0.63 (FS2), and 0.62 (FS3). The subgroup analysis indicated that the prediction model based on specific histological subtypes and T stages had a higher C-index for the test dataset than that based on All data (All data, 0.64 vs. SCCall, 060; ADCall, 0.69; T1, 0.68; T2, 0.65; T3, 0.66; T4, 0.70). In addition, the prediction models unified for each T stage in histological subtype showed a different trend in the C-index for the test dataset between ADC-related and SCC-related models (ADCT1–ADCT4, 0.72–0.83; SCCT1–SCCT4, 0.58–0.71).

Conclusions
Our results showed that feature selection methods moderately affected the survival prediction performance. In addition, prediction models based on specific subgroups may improve the prediction performance. These results may prove useful for determining the optimal radiomics-based predication model.
Implementation of second-tier tests in newborn screening for the detection of vitamin B12 related acquired and genetic disorders: results on 258,637 newborns
Authors: Pajares Sonia , Arranz Jose Antonio , Ormazabal Aida , Del Toro Mireia , García-Cazorla Ángeles , Navarro-Sastre Aleix , López Rosa María , Meavilla Silvia María , de los Santos Mariela Mercedes , García-Volpe Camila , de Aledo-Castillo Jose Manuel González , Argudo Ana , Marín Jose Luís , Carnicer Clara , Artuch Rafael , Tort Frederic , Gort Laura , Fernández Rosa , García-Villoria Judit , Ribes Antonia 
Published: April 2021

Abstract
Background
Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions.

Methods
A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated.

Results
During the period 2015–2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia.

Conclusions
When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
Quality of life and its contributors among adults with late-onset Pompe disease in China
Authors: Chen Shanquan , Wang Jingxuan , Zhu Jianfeng , Chung Roger Yat-Nork , Dong Dong 
Published: May 2021

Abstract
Background
Pompe disease (PD) is a rare inherited disorder caused by the deficiency of acid-α glucosidase, which leads to the impairment of organ and tissue functions and causes disabilities. As the first national survey on patients with late-onset PD (LOPD) in China, this study investigated the quality of life (QOL) of adult patients with LOPD in China and explored its contributors.

Methods
Data were derived from a nation-based, cross-sectional, self-response survey on rare diseases (RDs) in early 2018. Answers from 68 adult Chinese patients with LOPD were used for data analysis. QOL was measured using the World Health Organization Quality of Life: Brief Version. Covariates included age, gender, education, employment, reliance on assistive devices, medication history, social support, and disease economic burden. Data were analyzed using linear regression in R.

Results
For adult patients with LOPD, the average scores and standard deviations (SD) of the four dimensions of QOL were physical health = 33.77 (SD = 18.28), psychological health = 43.81 (SD = 21.70), environmental health = 39.43 (SD = 16.93), and social relationship = 46.20 (SD = 19.76); the scoring for each dimension was evaluated on a scale of 0 to 100. At the significance level of p < 0.05, with increasing age, the patients experienced a significant decrease in physical health QOL (β = − 0.75) and environmental health QOL (β = − 0.79). Those who relied heavily on assistive devices had lower perceived physical health (β = − 17.8), psychological health (β = − 22.76), environmental health (β = − 17.8), and social relationships (β = − 22.12) than those who did not. A one-unit increase in the amount of social support, as a form of social interaction, led to a significant increase in physical health (β = 0.28), psychological health (β = 0.71), environmental health (β = 0.72), and social relationships (β = 0.70).

Conclusion
Adult Chinese patients with LOPD had a lower physical health and QOL compared to their counterparts with other RDs. Being employed was found to affect the QOL of adult Chinese patients with LOPD in almost all dimensions. Encouraging adult Chinese patients with LOPD to be socially active and help them become more involved in social life might improve their QOL.
Child maltreatment, cognitive functions and the mediating role of mental health problems among maltreated children and adolescents in Uganda
Authors: Ainamani Herbert E. , Rukundo Godfrey Z. , Nduhukire Timothy , Ndyareba Eunice , Hecker Tobias 
Published: May 2021

Abstract
Background
Child maltreatment poses high risks to the mental health and cognitive functioning of children not only in childhood but also in later life. However, it remains unclear whether child maltreatment is directly associated with impaired cognitive functioning or whether this link is mediated by mental health problems. Our study aimed at examining this research question among children and adolescents in Uganda.

Methods
A sample of 232 school-going children and adolescents with a mean age of 14.03 (SD = 3.25) was assessed on multiple forms of maltreatment using the Maltreatment and Abuse Chronology Exposure—Pediatric Version (pediMACE). Executive functions were assessed by the Tower of London task and working memory by the Corsi Block Tapping task, while mental health problems were assessed using the Child PTSD Symptom Scale for PTSD and the Center for Epidemiological Studies Depression Scale for Children (CES-DC).

Results
In total, 232 (100%) of the participant reported to have experienced at least one type of maltreatment in their lifetime including emotional, physical, and sexual violence as well as neglect. We found a negative association between child maltreatment and executive functions (β = − 0.487, p < 0.001) and working memory (β = − 0.242, p = 0.001). Mental health problems did not mediate this relationship.

Conclusions
Child maltreatment seems to be related to lower working memory and executive functioning of affected children and adolescents even after controlling for potential cofounders. Our study indicates that child maltreatment the affects children’s cognitive functionality beyond health and well-being.