bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer’s Disease Based on Major Depressive Disorder Risk Variants
Authors: Upadhya Suraj , Liu Hongliang , Luo Sheng , Lutz Michael W. , Chiba-Falek Ornit 
Published: March 2022

IntroductionDepression is a common, though heterogenous, comorbidity in late-onset Alzheimer’s Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, these previous studies suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD, and the various genetic etiologies predisposing depression in LOAD, are largely unknown.MethodsMajor Depressive Disorder (MDD) genome-wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP, n = 1,708) and National Alzheimer’s Coordinating Center (NACC, n = 10,256) datasets served as discovery and validation cohorts, respectively, to assess the PRS performance in predicting depression onset in LOAD patients.ResultsThe PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC = 0.540) and NACC (AUC = 0.527). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.581). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P = 0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P &lt; 0.001 for all).ConclusionThis study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.
Moderate Sun Exposure Is the Complementor in Insufficient Vitamin D Consumers
Authors: Wu Shou-En , Chen Wei-Liang 
Published: March 2022

Background and AimsVitamin (Vit) D plays a vital role in human health, and the prevalence of Vit D deficiency worldwide has been a rising concern. This study investigates the serum 25-hydroxy-Vit D [25(OH)D] status in healthy US civilians and identifies how the two main sources, sun exposure and dietary Vit D intake, determine the final 25(OH)D levels in individuals.MethodsA total of 2,360 of participants from The National Health and Nutrition Examination Survey (NHANES) 2009–2014 were analyzed. We divided the levels of sun exposure and dietary Vit D intake of all subjects into 10 strata and gave a score ranging from 1 to 10 points, respectively. Scores 1–5 in sun exposure and dietary intake were considered as relatively low exposure groups, whereas scores 6–10 were considered as relatively high exposure groups. Serum Vit D inadequacy was defined as &lt;50 nmol/L. Linear and logistic regression analyses were used to examine the associations between sources of Vit D and serum 25(OH)D levels.ResultsIn relatively low Vit D intake groups (Vit D intake score 1–5), relatively high sun exposure (sun exposure score &gt;5) resulted in higher serum 25(OH)D levels (average 57 nmol/L) compared with relatively low sun exposure (sun exposure score &lt;5) (average 50 nmol/L), whereas this difference became negligible in high intake groups (Vit D intake score 6–10). Moreover, the greatest slope occurred in the low Vit D intake curve (decile 3 of Vit D intake), which shows increased sun exposure time causing the greatest degree of change in serum 25(OH)D level in this group.ConclusionSun exposure can significantly make up for deficiencies in subjects who consume insufficient dietary Vit D. Compared with the extra cost and time for building habits of Vit D supplementation, moderate sun exposure appears to be a simple and costless means for the public to start in daily practice.
Paradoxical Association Between Relative Cerebral Blood Volume Dynamics Following Chemoradiation and Increased Progression-Free Survival in Newly Diagnosed IDH Wild-Type MGMT Promoter Methylated Glioblastoma With Measurable Disease
Authors: Goldman Jodi , Hagiwara Akifumi , Yao Jingwen , Raymond Catalina , Ong Christian , Bakhti Rojin , Kwon Elizabeth , Farhat Maguy , Torres Carlo , Erickson Lily G. , Curl Brandon J. , Lee Maggie , Pope Whitney B. , Salamon Noriko , Nghiemphu Phioanh L. , Ji Matthew , Eldred Blaine S. , Liau Linda M. , Lai Albert , Cloughesy Timothy F. , Chung Caroline , Ellingson Benjamin M. 
Published: March 2022

Background and PurposeWhile relative cerebral blood volume (rCBV) may be diagnostic and prognostic for survival in glioblastoma (GBM), changes in rCBV during chemoradiation in the subset of newly diagnosed GBM with subtotal resection and the impact of MGMT promoter methylation status on survival have not been explored. This study aimed to investigate the association between rCBV response, MGMT methylation status, and progression-free (PFS) and overall survival (OS) in newly diagnosed GBM with measurable enhancing lesions.Methods1,153 newly diagnosed IDH wild-type GBM patients were screened and 53 patients (4.6%) had measurable post-surgical tumor (&gt;1mL). rCBV was measured before and after patients underwent chemoradiation. Patients with a decrease in rCBV &gt;10% were considered rCBV Responders, while patients with an increase or a decrease in rCBV &lt;10% were considered rCBV Non-Responders. The association between change in enhancing tumor volume, change in rCBV, MGMT promotor methylation status, and PFS or OS were explored.ResultsA decrease in tumor volume following chemoradiation trended towards longer OS (p=0.12; median OS=26.8 vs. 16.3 months). Paradoxically, rCBV Non-Responders had a significantly improved PFS compared to Responders (p=0.047; median PFS=9.6 vs. 7.2 months). MGMT methylated rCBV Non-Responders exhibited a significantly longer PFS compared to MGMT unmethylated rCBV Non-Responders (p&lt;0.001; median PFS=0.5 vs. 7.1 months), and MGMT methylated rCBV Non-Responders trended towards longer PFS compared to methylated rCBV Responders (p=0.089; median PFS=20.5 vs. 13.8 months).ConclusionsThis preliminary report demonstrates that in newly diagnosed IDH wild-type GBM with measurable enhancing disease after surgery (5% of patients), an enigmatic non-response in rCBV was associated with longer PFS, particularly in MGMT methylated patients.
Clinical Outcomes and Complications of Preoperative Embolization for Intracranial Giant Meningioma Tumorectomy: A Retrospective, Observational, Matched Cohort Study
Authors: Yin Yi , Li Yuhong , Jiang Zhouyang , Zhang Chao , Ge Hongfei , Chen Zhi , Hu Rong , Chen Yujie , Li Xuegang , Li Fei , Feng Hua 
Published: March 2022

ObjectiveThe potential benefits of preoperative embolization for intracranial meningiomas are still under debate. We aimed to investigate whether preoperative embolization can improve surgical and functional outcomes, based on controlling patient- and tumor-related confounding factors.MethodsWe reviewed all meningioma cases in our department from January 2016 to May 2021. Cases in the nonembolization cohort were matched to the embolization cohort by 1:1 ratio propensity score matching, through controlling patient- and tumor-related confounds. Surgical outcomes, complications, and functional outcomes were retrospectively compared between these two groups.ResultsSixty-six cases in each group were included in our study after being matched. We did not find any significant differences of estimated blood loss (600.00 (400) vs. 500.00 (500.00) ml, p = 0.31), decrease of HGB level (30.81 ± 15.82 vs. 26.59 ± 12.90 g/L, p = 0.09), gross total resection rate (74.24% vs. 77.27%, p = 0.68), surgical time (302.50 (136) vs. 300.00 (72) min, p = 0.48), blood transfusion rates (53.03% vs. 42.42%, p = 0.35), blood transfusion volume [650.00 (657.50) vs. 535.00 (875.00) ml, p = 0.63] between the embolization group and nonembolization group. The number of patients who experience postsurgery complications were significantly higher in the nonembolization group (39.39% vs. 21.21%, p = 0.02). Patients in the nonembolization group were more likely to have a higher rate of mRS decline postsurgery (31.82% vs. 15.15%, p = 0.04).ConclusionOur study showed significant lower rates of surgical complications and long-term disabilities of meningioma patients treated with preoperative embolization. There were no significant differences in estimated blood loss, surgical time, and blood transfusion volume between embolization and nonembolization groups.
Conversion Surgery in Gastric Cancer Carcinomatosis
Authors: Morgagni Paolo , Solaini Leonardo , Saragoni Luca , Monti Manlio , Valgiusti Martina , Vittimberga Giovanni , Frassineti Giovanni Luca , Framarini Massimo , Ercolani Giorgio 
Published: March 2022

BackgroundAfter the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.MethodsAll patients with stage IV gastric cancer with peritoneal metastases as a single metastatic site operated at a single centre between 2005 and 2020 were included. Cases were grouped according to the treatment received.ResultsA total of 118 patients were considered, 46 were submitted to palliative gastrectomy (11 were considered M1 because of an unsuspected positive peritoneal cytology), and 20 were submitted to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) because of a &lt;6 Peritoneal Cancer Index (PCI). The median overall survival (OS) after surgery plus HIPEC was 46.7 (95% CI 15.8–64.0). Surgery (without HIPEC) after CHT presented a median OS 14.4 (8.2–26.8) and after upfront surgery 14.7 (10.9–21.1). Patients treated with upfront surgery and considered M1 only because of a positive cytology, had a median OS of 29.2 (25.2–29.2). The OS of patients treated with surgery plus HIPEC were 60.4 months (9.2–60.4) in completely regressed cancer after chemotherapy and 31.2 (15.8–64.0) in those partially regressed (p = 0.742).ConclusionsConversion surgery for peritoneal carcinomatosis from gastric cancer was associated with long survival and it should always be taken into consideration in this group of patients.
A Deep-Learning Aided Diagnostic System in Assessing Developmental Dysplasia of the Hip on Pediatric Pelvic Radiographs
Authors: Xu Weize , Shu Liqi , Gong Ping , Huang Chencui , Xu Jingxu , Zhao Jingjiao , Shu Qiang , Zhu Ming , Qi Guoqiang , Zhao Guoqiang , Yu Gang 
Published: March 2022

BackgroundDevelopmental dysplasia of the hip (DDH) is a common orthopedic disease in children. In clinical surgery, it is essential to quickly and accurately locate the exact position of the lesion, and there are still some controversies relating to DDH status. We adopt artificial intelligence (AI) to solve the above problems.MethodsIn this paper, automatic DDH measurements and classifications were achieved using a three-stage pipeline. In the first stage, we used Mask-RCNN to detect the local features of the image and segment the bony pelvis, including the ilium, pubis, ischium, and femoral heads. For the second stage, local image patches focused on semantically related areas for DDH landmarks were extracted by high-resolution network (HRNet). In the third stage, some radiographic results are obtained. In the above process, we used 1,265 patient x-ray samples as the training set and 133 samples from two other medical institutions as the verification set. The results of AI were compared with three orthopedic surgeons for reliability and time consumption.ResultsAI-aided diagnostic system's Tönnis and International Hip Dysplasia Institute (IHDI) classification accuracies for both hips ranged from 0.86 to 0.95. The measurements of numerical indices showed that there was no statistically significant difference between surgeons and AI. Tönnis and IHDI indicators were similar across the AI system, intermediate surgeon, and junior surgeon. Among some objective interpretation indicators, such as acetabular index and CE angle, there were good stability and consistency among the four observers. Intraclass consistency of acetabular index and CE angle among surgeons was 0.79–0.98, while AI was 1.00. The measurement time required by AI was significantly less than that of the doctors.ConclusionThe AI-aided diagnosis system can quickly and automatically measure important parameters and improve the quality of clinical diagnosis and screening referral process with a convenient and efficient way.
Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study
Authors: Shi Lu , Zhuang Zhiwei , Duan Lufen , Zhu Chenqi , Xue Hongzhi , Wang Xiao , Xu Xiaowen , Yuan Yunlong , Shi Ling , Li Jiahui , Sun Jiantong , Liu Xin , Zhou Qin , Lu Jian , Tang Lian 
Published: March 2022

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI.Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI.Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10–30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th–8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th–8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p &lt; 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = −0.06204; r = −0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = −0.6305, p = 0.0013).Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.
Cajaninstilbene Acid Ameliorates Acetaminophen-Induced Liver Injury Through Enhancing Sestrin2/AMPK-Mediated Mitochondrial Quality Control
Authors: Yan Mingzhu , Jin Suwei , Liu Yongguang , Wang Lisha , Wang Zhi , Xia Tianji , Chang Qi 
Published: March 2022

Acetaminophen (APAP)-induced liver injury (AILI) is the main cause of acute liver failure in the developed countries. The present study aimed to evaluate the therapeutic efficacy of cajaninstilbene acid (CSA), a major stilbene compound derived from the leaves of pigeon pea [Cajanus cajan (L.) Millsp.], against AILI. CSA (50, 75 mg/kg, p. o.) was administered to male C57BL/6 N mice 0.5 h after a toxic dose of APAP (300 mg/kg, i. p.). The direct effect of CSA on hepatocytes was tested on primary mouse hepatocytes. Serum transaminases, hematoxylin and eosin staining, TUNEL and propidium iodide staining were used to assess hepatic damage and cell death. The results demonstrated that APAP-induced liver injury was ameliorated by CSA, as evidenced by decreased alanine aminotransferase and aspartate aminotransferase levels in the serum, and fewer necrotic and apoptotic hepatocytes in vitro and in vivo. Consequently, the inflammation in response to APAP overdose was inhibited by CSA. Without affecting APAP metabolic activation, CSA interrupted the sustained JNK-Sab-ROS activation loop and alleviated oxidative stress. Additionally, CSA promoted mitochondrial quality control, including mitochondrial biogenesis and mitophagy, as revealed by increased PGC-1α, TFAM, LC3-Ⅱ, PINK1 and mitochondrial Parkin expression and decreased p62 expression. Further mechanistic investigations showed that independent of CAMKK2, LKB1-mediated AMPK activation, which was promoted by Sestrin2, might be responsible for the protective effect of CSA. Our study demonstrates that CSA alleviates APAP-induced oxidative stress and enhanced mitochondrial quality control through Sestrin2/AMPK activation, thereby protecting against AILI,.
The Resistance of Cancer Cells to Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, is Mediated by the ABCB1 Transporter
Authors: Fu Han , Wu Zhuo-Xun , Lei Zi-Ning , Teng Qiu-Xu , Yang Yuqi , Ashby Charles R. , Lei Yixiong , Lian Yuyin , Chen Zhe-Sheng 
Published: March 2022

Palbociclib was approved by the United States Food and Drug Administration for use, in combination with letrozole, as a first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) postmenopausal metastatic breast cancer. However, recent studies show that palbociclib may be an inhibitor of the ABCB1 transporter, although this remains to be elucidated. Therefore, we conducted experiments to determine the interaction of palbociclib with the ABCB1 transporter. Our in vitro results indicated that the efficacy of palbociclib was significantly decreased in the ABCB1-overexpressing cell lines. Furthermore, the resistance of ABCB1-overexpressing cells to palbociclib was reversed by 3 μM of the ABCB1 inhibitor, verapamil. Moreover, the incubation of ABCB1-overexpressing KB-C2 and SW620/Ad300 cells with up to 5 μM of palbociclib for 72 h, significantly upregulated the protein expression of ABCB1. The incubation with 3 µM of palbociclib for 2h significantly increased the intracellular accumulation of [3H]-paclitaxel, a substrate of ABCB1, in ABCB1 overexpressing KB-C2 cells but not in the corresponding non-resistant parental KB-3-1 cell line. However, the incubation of KB-C2 cells with 3 μM of palbociclib for 72 h decreased the intracellular accumulation of [3H]-paclitaxel due to an increase in the expression of the ABCB1 protein. Palbociclib produced a concentration-dependent increase in the basal ATPase activity of the ABCB1 transporter (EC50 = 4.73 μM). Molecular docking data indicated that palbociclib had a high binding affinity for the ABCB1 transporter at the substrate binding site, suggesting that palbociclib may compete with other ABCB1 substrates for the substrate binding site of the ABCB1. Overall, our results indicate that palbociclib is a substrate for the ABCB1 transporter and that its in vitro anticancer efficacy is significantly decreased in cancer cells overexpressing the ABCB1.
Postexercise Hypotension Is Delayed in Men With Obesity and Hypertension
Authors: Jarrett Catherine L. , Tucker Wesley J. , Angadi Siddhartha S. , Gaesser Glenn A. 
Published: March 2022

BackgroundPostexercise hypotension (PEH) can play a major role in the daily blood pressure management among individuals with hypertension. However, there are limited data on PEH in persons with obesity and hypertension, and no PEH data in this population beyond 90 min postexercise.PurposeThe purpose of this study was to determine if PEH could be elicited in men with obesity and hypertension during a 4-h postexercise measurement period.MethodsSeven men [age = 28 ± 4 years; body mass index = 34.6 ± 4.8 kg/m2; brachial systolic blood pressure (SBP): 138 ± 4 mmHg; brachial diastolic BP (DBP): 80 ± 5 mmHg; central SBP: 125 ± 4 mmHg; central DBP: 81 ± 8 mmHg] performed two exercise sessions on a cycle ergometer, each on a separate day, for 45 min at ∼65% VO2max. One exercise session was performed at a cadence of 45 RPM and one at 90 RPM. Blood pressure was monitored with a SunTech Oscar2 ambulatory blood pressure monitor for 4 h after both exercise sessions, and during a time-matched control condition.ResultsBoth brachial and central SBP were not changed during the first h postexercise but were reduced by ∼5–11 mmHg between 2 and 4 h postexercise (p &lt; 0.05) after both exercise sessions. Brachial and central DBP were elevated by ∼5 mmHg at 1 h postexercise (p &lt; 0.05) but were ∼2–3 mmHg lower compared to control at 4 h postexercise, and ∼2–4 mmHg lower at 3 h postexercise compared to baseline. Mean arterial pressure (MAP) was elevated compared to control at 1 h postexercise after both exercise sessions, but was ∼2–3 mmHg lower compared to control at 2, 3, and 4 h postexercise, and ∼4–7 mmHg lower at 3 h postexercise compared to baseline.ConclusionDespite the small sample size and preliminary nature of our results, we conclude that PEH is delayed in men with obesity and hypertension, but the magnitude and duration of PEH up to 4 h postexercise is similar to that reported in the literature for men without obesity and hypertension. The PEH is most pronounced for brachial and central SBP and MAP. The virtually identical pattern of PEH after both exercise trials indicates that the delayed PEH is a reproducible finding in men with obesity and hypertension.