bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
Authors: Zhang Yufang , Wu Yuanyuan , Wang Wei , Liu Feng , Zhang Yiwen , Yang Cheng , Liu Aifen , Wu Jing , Zhu Tongyu , Nicholson Michael L. , Fan Yaping , Yang Bin 
Published: July 2021

Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.
Liver Failure of Wilson's Disease With Manifestations Similar to Porphyria and Uncommon ATP7B Gene Mutation: A Case Report and Literature Review
Authors: Zou Ju , Wang Ying-Hao , Wang Ling , Chen Ruo-Chan 
Published: July 2021

Background: Wilson's disease (WD) is a rare condition; its diagnosis is challenging owing to a wide spectrum of ATP7B genotypes and variable clinical phenotypes, along with environmental factors. Few cases of WD with presentation of skin lesions and acute neurovisceral symptoms have been reported in the literature. To our knowledge, this is the first reported case of WD with an uncommon ATP7B gene mutation and rare symptoms of photosensitivity, sensation abnormality, and skin eruption occurring in a 19-year-old woman.Case presentation: We report the case of a 19-year-old woman with WD presenting with liver failure, skin manifestations, and acute neurovisceral symptoms.The rare mutation in intron 1 of ATP7B (c.51+2T &gt; G) was further confirmed by gene sequencing. The patients' symptoms improved after administration of penicillamine and zinc therapy combined with plasma exchange. She received long-term penicillamine treatment, and her liver function was within the normal range at 1 year after discharge. However, she underwent liver transplantation at 1.5 years after discharge.Conclusions: We present a case of WD with a novel ATP7B gene mutation that may serve as a reference to generalists and specialists in hepatology or neurology of the rare clinical characteristics of WD, to prevent misdiagnosis and aid in the early diagnosis and treatment of the condition.
Age-Related Olfactory Decline Is Associated With Levels of Exercise and Non-exercise Physical Activities
Authors: Sollai Giorgia , Crnjar Roberto 
Published: July 2021

Objective: This cross-sectional study evaluates the impact of active or non-active lifestyle in terms of physical, cognitive and social activity on the olfactory function in Elderly Subjects (ES) and aims at looking for a correlation between the time devoted to life activities and the score obtained during the olfactory tests by each individual.Methods: One hundred and twenty-two elderly volunteers were recruited in Sardinia (Italy) and divided into active ES (n = 60; 17 men, 43 women; age 67.8 ± 1.12 years) and inactive ES (n = 62; 21 men, 41 women, age 71.1 ± 1.14 years) based on their daily physical activities. The olfactory function was evaluated using the “Sniffin’s Sticks” battery test, while the assessment of daily activities was made by means of personal interviews.Results: A significant effect of active or inactive lifestyle was found on the olfactory function of ES (F(1,120) &gt; 10.16; p &lt; 0.005). A positive correlation was found between the olfactory scores and the number of hours per week dedicated to physical activities (Pearson’s r &gt; 0.32, p ≤ 0.014) in both active and inactive ES.Conclusions: High levels of exercise and non-exercise physical activity are strongly associated with the olfactory function and, consequently, with the quality of life of the elderly. Given the limited physical exercise of elderly people, they can benefit from a more active lifestyle by increasing non-exercise physical activities.
Gait Speed Trajectory During the Six-Minute Walk Test in Multiple Sclerosis: A Measure of Walking Endurance
Authors: Chen Shanshan , Sierra Salvador , Shin Yongyun , Goldman Myla D. 
Published: July 2021

Background: The six-minute walk (6MW) test is a validated assessment method in Multiple Sclerosis (MS) research. While the total distance covered during six minutes (6MWTD) is often used as the standard measurement of gait capacity (i.e., the maximum distance one can achieve), we hypothesize that endurance (i.e., ability to maintain speed over a prolonged time) can be inferred by the gait speed trajectory (GST) during the 6MW test (6MWGST).Objective: To characterize group differences in 6MWGST between MS patients and healthy controls (HCs), and to assess information added by 6MWGST for discerning between MS patients and HCs.Methods: We performed a secondary data analysis on a cross-sectional cohort of 40 MS and 20 HC subjects with three repeated 6MW tests. We modeled 6MWGST using a linear mixed-effects model with time in minutes and replicated walks nested within individuals. We compared the discernibility of 6MWGST with that of conventional metrics using likelihood ratio tests and receiver operating characteristic (ROC) analysis on logistic regression models.Results: MS subjects showed a concave, quadratic GST during 6MW tests, slowing down more than the HC subjects, especially at the beginning of 6MW tests. Despite accelerating at the end of the 6MW, MS subjects were unable to attain or surpass their initial 6MW gait speeds. 6MWGST added useful information (p = 0.002) to the conventional metrics (e.g., 6MWTD) for discerning between MS and HC subjects, and increased the area under the ROC curve from 0.83 to 0.93 (p = 0.037).Conclusions: The distinctive 6MWGST pattern of MS patients provided increased discernibility compared with currently used gait metrics. Both gait capacity measured by the 6MWTD, and gait endurance measured by parameters of 6MWGST, are significant functional indicators for the MS population.
Prognostic Value of Tumor Regression Grading in Patients Treated With Neoadjuvant Chemotherapy Plus Surgery for Gastric Cancer
Authors: Xie Jian-Wei , Lu Jun , Xu Bin-bin , Zheng Chao-Hui , Li Ping , Wang Jia-Bin , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Truty Mark J. , Huang Chang-Ming 
Published: July 2021

ObjectiveTo validate the prognostic value of tumor regression grading (TRG) and to explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery.MethodsTwo hundred forty-nine AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting tumor regression grading.ResultsFor patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively (p&lt;0.001). TRGs were independent risk factors for OS. Similar findings were observed in RFS. Multivariable analysis revealed that an oxaliplatin-based regimen (p=0.017) was an independent predictor of TRG. The oxaliplatin-based regimen was superior to the nonoxaliplatin-based regimen for OS (38.4 months vs 19.5 months, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in nonsignet ring cell carcinoma compared to the nonoxaliplatin-based regimen (53.7 months vs 19.5 months, respectively; p=0.011). However, similar findings were not observed in RFS.ConclusionTRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with nonsignet ring cell carcinoma.
The Impact of Foundation Medicine Testing on Cancer Patients: A Single Academic Centre Experience
Authors: Karol Dalia , McKinnon Mathieu , Mukhtar Lenah , Awan Arif , Lo Bryan , Wheatley-Price Paul 
Published: July 2021

BackgroundThe use of Next-Generation Sequencing (NGS) has recently allowed significant improvements in cancer treatment. Foundation Medicine® (FM) provides a genomic profiling test based on NGS for a variety of cancers. However, it is unclear if the Foundation Medicine test would result in a better outcome than the standard on-site molecular testing. In this retrospective chart review, we identified the FM cases from an academic Canadian hospital and determined whether these test results improved treatment options for those patients.Materials and MethodsA retrospective analysis was performed on patients with solid tumors who had FM testing between May 1, 2014 and May 1, 2018. Clinical factors and outcomes were measured using descriptive statistics using Microsoft Excel® Software.ResultsOut of 66 FM tests, eight patients (= 12%) had a direct change in therapy based on the FM tests. Identified were 285 oncogenic mutations (median 1, range 0–31); where TP53 (n = 31, 10.9%), CDKN2A (n = 19, 6.7%), KRAS (n = 16, 5.6%) and APC (n = 9, 3.2%) were the most common FM mutations identified.ConclusionA small proportion of FM reports identified actionable mutations and led to direct treatment change. FM testing is expensive and a few of the identified mutations are now part of routine on-site testing. NGS testing is likely to become more widespread, but this research suggests that its true clinical impact may be restricted to a minority of patients.
Assessment of Systemic Inflammation and Nutritional Indicators in Predicting Recurrence-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors
Authors: Lu Zhenhua , Li Rui , Cao Xianglong , Liu Chengyu , Sun Zhen , Shi Xiaolei , Shao Weiwei , Zheng Yangyang , Song Jinghai 
Published: July 2021

BackgroundRecent studies have shown that the systemic inflammation and nutritional indicators are prognostic for a variety of malignancies. However, only limited data have so far demonstrated their usefulness in gastrointestinal mesenchymal tumors (GIST).MethodsWe retrospectively analyzed the data of GIST patients who underwent radical surgery in Beijing hospital from October 2004 to July 2018. The area under the receiver operating characteristic curve (AUC) was used to compare several commonly used inflammatory and nutritional indicators. The indicators with largest AUC were further analysis. Optimal cut-off values of those indicators in predicting recurrence-free survival (RFS) were determined. Kaplan-Meier curve and the time-dependent receiver operating characteristic (ROC) curve were used to assess the prognostic values. We then used univariate and multivariate Cox regression analyses to identify prognostic factors that were associated with RFS.ResultsIn total, 160 patients who underwent surgery for GIST were included in the study. The median survival time was 34.5 months, with 1-, 3-, and 5-year RFS rates of 96.1%, 84.7%, and 80.8%, respectively. The inflammatory and nutritional indicators with largest AUC were Systemic immunoinflammatory Index (SII) and Geriatric Nutrition Risk Index (GNRI), reached 0.650 and 0.713, respectively. The optimal cutoff of GNRI and SII were 98.3, and 820.0, respectively. Univariate analysis showed that GNRI, SII, KI67, surgery method, tumor location, tumor size, and mitotic index were all significant prognostic indicators of RFS. After multivariate Cox analysis, independent prognostic factors for RFS in GIST included tumor location, mitotic index, tumor size, and GNRI (HR=2.802,95% CI: 1.045 to 7.515, p = 0.041). Besides, SII also tended to be associated with RFS (HR = 2.970, 95% CI: 0.946 to 9.326, p = 0.062).ConclusionsHigh GNRI is an independent prognostic factor for RFS in GIST, while SII can be considered as a prognostic factor. GNRI and SII can be used as tools to evaluate the prognosis of patients before surgery, helping doctors to better treat high-risk patients.
CaMKII Inhibition is a Novel Therapeutic Strategy to Prevent Diabetic Cardiomyopathy
Authors: Veitch Christopher R. , Power Amelia S. , Erickson Jeffrey R. 
Published: July 2021

Increasing prevalence of diabetes mellitus worldwide has pushed the complex disease state to the foreground of biomedical research, especially concerning its multifaceted impacts on the cardiovascular system. Current therapies for diabetic cardiomyopathy have had a positive impact, but with diabetic patients still suffering from a significantly greater burden of cardiac pathology compared to the general population, the need for novel therapeutic approaches is great. A new therapeutic target, calcium/calmodulin-dependent kinase II (CaMKII), has emerged as a potential treatment option for preventing cardiac dysfunction in the setting of diabetes. Within the last 10 years, new evidence has emerged describing the pathophysiological consequences of CaMKII activation in the diabetic heart, the mechanisms that underlie persistent CaMKII activation, and the protective effects of CaMKII inhibition to prevent diabetic cardiomyopathy. This review will examine recent evidence tying cardiac dysfunction in diabetes to CaMKII activation. It will then discuss the current understanding of the mechanisms by which CaMKII activity is enhanced during diabetes. Finally, it will examine the benefits of CaMKII inhibition to treat diabetic cardiomyopathy, including contractile dysfunction, heart failure with preserved ejection fraction, and arrhythmogenesis. We intend this review to serve as a critical examination of CaMKII inhibition as a therapeutic strategy, including potential drawbacks of this approach.
Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D3 Supplementation in High Iodide Intake–Induced Hypothyroid Offspring Rats
Authors: Liu Qing , Zhang Yue , Zhao Hailing , Yao Xiaomei 
Published: July 2021

Aim: This study aimed to investigate the potential role of fatty acids in high iodide intake–induced hypothyroidism and its complications and also in the intervention of iodide intake adjustment and 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] supplementation.Methods: Pregnant rats were allocated to two groups, namely, normal iodide (NI, 7.5 μg/day) intake and 100 times higher-than-normal iodide (100 HI, 750 μg/day) intake. The offspring were continuously administered potassium iodide from weaning [i.e., postnatal day 21 (PN21)] to PN90. After PN90, the offspring were either administered iodide intake adjustment (7.5 μg/day) or 1,25(OH)2D3 supplementation (5 μg·kg−1·day−1), or both, for 4 weeks. Thyroid function tests (free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibody, and thyroglobulin antibody), blood lipids (triglyceride, total cholesterol, free fatty acid, and low-density lipoprotein cholesterol), and vitamin D3 (VD3) levels were detected by ELISA. Cardiac function was measured by echocardiography. Blood pressure was measured using a non-invasive tail-cuff system. The serum fatty acids profile was analyzed by liquid chromatography–mass spectrometry.Results: In the offspring rats with continued 100 HI administration, the levels of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET) and thromboxane B2 (TXB2) were decreased, while those of prostaglandin J2 (PGJ2), prostaglandin B2 (PGB2), 4-hydroxydocosahexaenoic acid (4-HDoHE), 7-HDoHE, 8-HDoHE, and 20-HDoHE were increased. Significant correlations were found between PGB2, 8,9-DHET, 7-HDoHE levels and thyroid dysfunction, between PGJ2, 20-HDoHE, PGB2, 8,9-DHET levels and cardiac dysfunction, between PGJ2, 20-HDoHE levels and hypertension, between 4-HDoHE, 8-HDoHE, TXB2 levels and dyslipidemia, and between PGB2 and decreased VD3 level. After the treatment of iodide intake adjustment and 1,25(OH)2D3 supplementation, the levels of 16-hydroxyeicosatetraenoic acids (16-HETE), 18-HETE, 5,6-epoxyeicosatrienoic acid (5,6-EET), 8,9-EET, 11,12-EET, 14,15-EET, PGE2, 5-oxo-ETE, and 15-oxo-ETE were increased. The significant associations between PGE2, 16-HETE, 18-HETE and improved thyroid function and also between 5,6-EET, 11,12-EET, 14,15-EET, 16-HETE, 15-oxo-ETE and attenuated dyslipidemia were detected.Conclusion: Increased levels of prostaglandins (PGs) and HDoHEs and decreased levels of 8,9-DHET and TXB2 might occur in the progression of cardiac dysfunction, hypertension, and dyslipidemia in high iodide intake–induced hypothyroidism. The increased levels of EETs and HETEs might help to ameliorate these complications after iodide intake adjustment and 1,25(OH)2D3 supplementation.
Maternal Alexithymic Traits Are Related to Lower Maternal Sensitivity and Higher Hostility in Maternal Caregiving Behavior—The FinnBrain Birth Cohort Study
Authors: Ahrnberg Hanna , Korja Riikka , Scheinin Noora M. , Nolvi Saara , Kataja Eeva-Leena , Kajanoja Jani , Hakanen Hetti , Karlsson Linnea , Karlsson Hasse , Karukivi Max 
Published: July 2021

Background: The quality of parental caregiving behavior with their child plays a key role in optimal mother–infant interaction and in supporting child adaptive development. Sensitive caregiving behavior, in turn, requires the ability to identify and understand emotions. Maternal alexithymia, with difficulties in identifying and describing feelings or emotions, as well as a concrete way of thinking, could potentially complicate the quality of caregiving. In this study, we aim to explore the possible association between maternal alexithymic traits and the quality of maternal caregiving behavior.Methods: The study sample consisted of 158 mother–infant dyads within the FinnBrain Birth Cohort Study population with an available report of maternal alexithymic traits at 6 months postpartum and observational data on maternal caregiving behavior at 8 months postpartum. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) including three alexithymia dimensions—Difficulty Identifying Feelings, Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Maternal caregiving behavior was assessed using the Emotional Availability Scale and in this study, all four parent dimensions (Sensitivity, Structuring, Non-intrusiveness and Non-hostility) were included. Maternal depressive and anxiety symptoms at 6 months postpartum were controlled for as potential confounders. In addition, background factors of mother's age and gestational weeks at the time of child birth, maternal educational level, monthly income and parity, as well as relationship status and the gender of the baby were assessed.Results: Maternal TAS-20 total score correlated negatively with Sensitivity (r = −0.169, p = 0.034) and with non-intrusiveness (r = −0.182, p = 0.022). In addition, maternal DDF correlated negatively with Sensitivity (r = −0.168, p = 0.035) and EOT with Non-hostility (r = −0.159, p = 0.047). Furthermore, in regression analyses with controlling for the associated background factors, maternal total score of alexithymic traits (p = 0.034, η2p = 0.029) and higher DDF (p = 0.044, η2p = 0.026) remained significantly associated with lower Sensitivity and higher EOT remained significantly associated with lower Non-hostility (p = 0.030, η2p = 0.030).Conclusions: In this explorative study we found preliminary evidence for the hypothesis that higher maternal alexithymic traits associate with lower maternal sensitivity and more hostile maternal caregiving behavior. Further studies are needed to explore these hypotheses and to investigate their possible implications for child development.
The Impact of Negative Symptoms and Neurocognition on Functioning in MDD and Schizophrenia
Authors: Quek Yue Feng , Yang Zixu , Dauwels Justin , Lee Jimmy 
Published: July 2021

Introduction: Negative symptoms, neurocognitive deficits and functional impairment are prevalent in individuals with major depressive disorder (MDD) and schizophrenia (SCZ). However, unlike neurocognitive deficits, little is known about the role of negative symptoms toward functioning in individuals with MDD. On the other hand, both factors are well-studied in individuals with SCZ. Thus, this study aimed to examine the contributions of negative symptoms and neurocognitive impairments in functioning in individuals with MDD, compared to individuals with SCZ.Methods: Participants included 50 individuals with MDD, 49 individuals with SCZ and 49 healthy controls. The following measures were administered—Negative Symptom Assessment (NSA-16), Brief Assessment of Cognition in Schizophrenia (BACS), Patient Health Questionnaire (PHQ-9), and MIRECC-Global Assessment of Functioning (MIRECC-GAF) to evaluate negative symptoms, neurocognition, depressive symptoms, and functioning respectively.Results: Both MDD and SCZ groups had significantly more severe negative symptoms, depressive symptoms, and poorer functioning than healthy controls. Individuals with SCZ performed significantly poorer on the BACS than the other two groups. Both negative symptoms and neurocognition were significantly correlated with social and occupational functioning in SCZ. Motivation subdomain of the negative symptoms was significantly correlated with occupational functioning, while depressive symptoms correlated with functioning in MDD.Conclusion: Both negative symptoms and neurocognitive deficits appear to play differential roles on individual domains of functioning between MDD and SCZ. Future longitudinal studies with larger sample sizes should be done for a better understanding about the associations between the factors and functioning.