bluuebunny/crossref_metadata_2025_split huggingface dataset:
ECT-induced cognitive side effects are associated with hippocampal enlargement
Authors: Argyelan Miklos , Lencz Todd , Kang Simran , Ali Sana , Masi Paul J. , Moyett Emily , Joanlanne Andrea , Watson Philip , Sanghani Sohag , Petrides Georgios , Malhotra Anil K. 
Published: October 2021

AbstractElectroconvulsive therapy (ECT) is of the most effective treatments available for treatment-resistant depression, yet it is underutilized in part due to its reputation of causing cognitive side effects in a significant number of patients. Despite intensive neuroimaging research on ECT in the past two decades, the underlying neurobiological correlates of cognitive side effects remain elusive. Because the primary ECT-related cognitive deficit is memory impairment, it has been suggested that the hippocampus may play a crucial role. In the current study, we investigated 29 subjects with longitudinal MRI and detailed neuropsychological testing in two independent cohorts (N = 15/14) to test if volume changes were associated with cognitive side effects. The two cohorts underwent somewhat different ECT study protocols reflected in electrode placements and the number of treatments. We used longitudinal freesurfer algorithms (6.0) to obtain a bias-free estimate of volume changes in the hippocampus and tested its relationship with neurocognitive score changes. As an exploratory analysis and to evaluate how specific the effects were to the hippocampus, we also calculated this relationship in 41 other areas. In addition, we also analyzed cognitive data from a group of healthy volunteers (N = 29) to assess practice effects. Our results supported the hypothesis that hippocampus enlargement was associated with worse cognitive outcomes, and this result was generalizable across two independent cohorts with different diagnoses, different electrode placements, and a different number of ECT sessions. We found, in both cohorts, that treatment robustly increased the volume size of the hippocampus (Cohort 1: t = 5.07, Cohort 2: t = 4.82; p < 0.001), and the volume increase correlated with the neurocognitive T-score change. (Cohort 1: r = −0.68, p = 0.005; Cohort 2: r = −0.58; p = 0.04). Overall, our research indicates that novel treatment methods serving to avoid hippocampal volume increase may result in a better side effect profile.
Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma
Authors: Talluri Srikanth , Samur Mehmet K. , Buon Leutz , Kumar Subodh , Potluri Lakshmi B. , Shi Jialan , Prabhala Rao H. , Shammas Masood A. , Munshi Nikhil C. 
Published: October 2021

AbstractMultiple myeloma (MM) is a heterogeneous disease characterized by significant genomic instability. Recently, a causal role for the AID/APOBEC deaminases in inducing somatic mutations in myeloma has been reported. We have identified APOBEC/AID as a prominent mutational signature at diagnosis with further increase at relapse in MM. In this study, we identified upregulation of several members of APOBEC3 family (A3A, A3B, A3C, and A3G) with A3G, as one of the most expressed APOBECs. We investigated the role of APOBEC3G in MM and observed that A3G expression and APOBEC deaminase activity is elevated in myeloma cell lines and patient samples. Loss-of and gain-of function studies demonstrated that APOBEC3G significantly contributes to increase in DNA damage (abasic sites and DNA breaks) in MM cells. Evaluation of the impact on genome stability, using SNP arrays and whole genome sequencing, indicated that elevated APOBEC3G contributes to ongoing acquisition of both the copy number and mutational changes in MM cells over time. Elevated APOBEC3G also contributed to increased homologous recombination activity, a mechanism that can utilize increased DNA breaks to mediate genomic rearrangements in cancer cells. These data identify APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.
Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment
Authors: Wang Yimin , Zhao Xiaohuan , Gao Min , Wan Xiaoling , Guo Yinong , Qu Yingying , Chen Yuhong , Li Tong , Liu Haiyun , Jiang Mei , Wang Feng , Sun Xiaodong 
Published: October 2021

AbstractPhotoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.
AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice
Authors: Han Ya-chun , Tang Shi-qi , Liu Yu-ting , Li Ai-mei , Zhan Ming , Yang Ming , Song Na , Zhang Wei , Wu Xue-qin , Peng Can-hui , Zhang Hao , Yang Shikun 
Published: October 2021

AbstractRenal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
TDAG51 induces renal interstitial fibrosis through modulation of TGF-β receptor 1 in chronic kidney disease
Authors: Carlisle Rachel E. , Mohammed-Ali Zahraa , Lu Chao , Yousof Tamana , Tat Victor , Nademi Samera , MacDonald Melissa E. , Austin Richard C. , Dickhout Jeffrey G. 
Published: October 2021

AbstractChronic kidney disease (CKD) is characterized by the gradual loss of renal function and is a major public health concern. Risk factors for CKD include hypertension and proteinuria, both of which are associated with endoplasmic reticulum (ER) stress. ER stress-induced TDAG51 protein expression is increased at an early time point in mice with CKD. Based on these findings, wild-type and TDAG51 knock-out (TDKO) mice were used in an angiotensin II/deoxycorticosterone acetate/salt model of CKD. Both wild-type and TDKO mice developed hypertension, increased proteinuria and albuminuria, glomerular injury, and tubular damage. However, TDKO mice were protected from apoptosis and renal interstitial fibrosis. Human proximal tubular cells were used to demonstrate that TDAG51 expression induces apoptosis through a CHOP-dependent mechanism. Further, a mouse model of intrinsic acute kidney injury demonstrated that CHOP is required for ER stress-mediated apoptosis. Renal fibroblasts were used to demonstrate that TGF-β induces collagen production through an IRE1-dependent mechanism; cells treated with a TGF-β receptor 1 inhibitor prevented XBP1 splicing, a downstream consequence of IRE1 activation. Interestingly, TDKO mice express significantly less TGF-β receptor 1, thus, preventing TGF-β-mediated XBP1 splicing. In conclusion, TDAG51 induces apoptosis in the kidney through a CHOP-dependent mechanism, while contributing to renal interstitial fibrosis through a TGF-β-IRE1-XBP1 pathway.
Requirement of transcription factor NME2 for the maintenance of the stemness of gastric cancer stem-like cells
Authors: Qi Yaxin , Wei Jun , Zhang Xiaobo 
Published: October 2021

AbstractCancer stem cells (CSCs), which can self-renew and produce heterogeneous cancer cells, are the key factors during tumorigenesis. Transcription factors take essential effects on CSCs. However, the role of transcription factors in regulating the stemness of gastric cancer stem-like cells has not been well explored. In this investigation, it was found that transcription factor NME2 (NME/NM23 nucleoside diphosphate kinase 2) was upregulated in gastric cancer stem-like cells that sorted from the solid tumors of patients with gastric cancer and gastric cancer cell lines. NME2 could preserve the stemness of gastric cancer stem-like cells via suppressing their apoptosis. In vitro and in vivo data revealed that NME2 was crucial for maintaining the stemness of gastric cancer stem cells by enhancing the expression of anti-apoptosis genes. Consequently, our data contributed a new perspective to the relationship between transcription factor and the stemness maintenance of gastric cancer stem cells.
Estrogen receptors and the aging brain
Authors: Maioli Silvia , Leander Karin , Nilsson Per , Nalvarte Ivan 
Published: October 2021

AbstractThe female sex hormone estrogen has been ascribed potent neuroprotective properties. It signals by binding and activating estrogen receptors that, depending on receptor subtype and upstream or downstream effectors, can mediate gene transcription and rapid non-genomic actions. In this way, estrogen receptors in the brain participate in modulating neural differentiation, proliferation, neuroinflammation, cholesterol metabolism, synaptic plasticity, and behavior. Circulating sex hormones decrease in the course of aging, more rapidly at menopause in women, and slower in men. This review will discuss what this drop entails in terms of modulating neuroprotection and resilience in the aging brain downstream of spatiotemporal estrogen receptor alpha (ERα) and beta (ERβ) signaling, as well as in terms of the sex differences observed in Alzheimer’s disease (AD) and Parkinson’s disease (PD). In addition, controversies related to ER expression in the brain will be discussed. Understanding the spatiotemporal signaling of sex hormones in the brain can lead to more personalized prevention strategies or therapies combating neurodegenerative diseases.
Membrane lipid raft homeostasis is directly linked to neurodegeneration
Authors: Moll Tobias , Marshall Jack N.G. , Soni Nikita , Zhang Sai , Cooper-Knock Johnathan , Shaw Pamela J. 
Published: October 2021

Abstract
Age-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are an unmet health need, with significant economic and societal implications, and an ever-increasing prevalence. Membrane lipid rafts (MLRs) are specialised plasma membrane microdomains that provide a platform for intracellular trafficking and signal transduction, particularly within neurons. Dysregulation of MLRs leads to disruption of neurotrophic signalling and excessive apoptosis which mirrors the final common pathway for neuronal death in ALS, PD and AD. Sphingomyelinase (SMase) and phospholipase (PL) enzymes process components of MLRs and therefore play central roles in MLR homeostasis and in neurotrophic signalling. We review the literature linking SMase and PL enzymes to ALS, AD and PD with particular attention to attractive therapeutic targets, where functional manipulation has been successful in preclinical studies. We propose that dysfunction of these enzymes is upstream in the pathogenesis of neurodegenerative diseases and to support this we provide new evidence that ALS risk genes are enriched with genes involved in ceramide metabolism (P=0.019, OR = 2.54, Fisher exact test). Ceramide is a product of SMase action upon sphingomyelin within MLRs, and it also has a role as a second messenger in intracellular signalling pathways important for neuronal survival. Genetic risk is necessarily upstream in a late age of onset disease such as ALS. We propose that manipulation of MLR structure and function should be a focus of future translational research seeking to ameliorate neurodegenerative disorders.
Modified Halbach design for torque profile improvement in a permanent magnet synchronous motor dedicated to an electric city bus
Authors: Nobahari Amin , Vahedi Abolfazl 
Published: October 2021

AbstractIn this work, a permanent magnet synchronous motor is designed for an electric city bus. The unit winding factor is considered for torque capability enhancement and completely open slots are adopted for low‐cost rectangular wire winding implementation. Accordingly, extremely large pulsating torques that are predictable should be mitigated through the rotor design possibilities. In this regard, a modified Halbach pole configuration, named axially segmented Halbach, that is capable of producing considerably smooth torque as well as retaining the large mean torque is proposed. First, an optimised conventional Halbach array is calculated as the initial design. Then, following a detailed introduction to the new design concept, the modified Halbach pole parameters are obtained through the proposed 2D model‐based optimisation algorithm. A rotor step skewing scheme is also evaluated to make the final comparisons, which are carried out via 3D FE models. The results demonstrate the admirable performance of the proposed Halbach configuration as an effective solution for torque profile improvement.
A multi‐objective optimization for planning of networked microgrid using a game theory for peer‐to‐peer energy trading scheme
Authors: Ali Liaqat , Muyeen S. M. , Bizhani Hamed , Ghosh Arindam 
Published: October 2021

AbstractIn this paper, a multi‐objective optimization technique is proposed for the planning of a networked microgrid based on peer‐to‐grid (P2G) and peer‐to‐peer (P2P) energy trading schemes. Two different criteria's including annual profit and energy index of reliability are taken into consideration to form a multi‐objective function. The networked microgrid consists of three individual microgrids containing their own combinations of generation resources, batteries and residential loads. All microgrids are connected together and also to the main grid to meet the energy exchange requirements of P2P energy trading. A cooperative game theory technique based on a particle swarm optimization algorithm is used to model the networked microgrid, and to find the suitable sizes of the players that simultaneously maximize the payoff values of both objective functions. Besides, a comparative analysis is carried out for both P2G and P2P energy trading schemes. The results show that the outcomes are maximum when both criteria are considered in the optimization and P2P energy trading is carried out. The sensitivity analysis is performed on the selected parameters and verified the right change 0.003% and 4.5% in discount rate and electricity prices, respectively.
Asymmetric Aldol Reaction of Alkenyl Esters with α-Keto Esters Catalyzed by Chiral Tin Alkoxides
Authors: Yanagisawa Akira , Uchiyama Chika , Takagi Kotaro 
Published: October 2021

AbstractA catalytic enantioselective aldol reaction of alkenyl esters with α-keto esters was achieved by using an (R)-BINOL-derived chiral tin dibromide possessing 4-t-butylphenyl groups at the 3- and 3′-positions as a chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon were diastereoselectively obtained with up to 92% ee and moderate to high yields, not only from cyclic alkenyl esters, but also from acyclic ones under the influence of the chiral tin methoxide generated in situ.
Venous Thromboembolism Risk and Thromboprophylaxis in Pediatric Neurosurgery and Spinal Injury: Current Trends and Literature Review
Authors: Panagopoulos Dimitrios , Karydakis Ploutarchos , Noutsos Georgios , Themistocleous Marios 
Published: October 2021

AbstractAlthough the entities of venous thromboembolism (VTE), deep venous thrombosis, pulmonary embolus, and thromboprophylaxis in adult patients undergoing brain tumor and spine surgery, traumatic brain injury and elective neurosurgical procedures are widely elucidated, the same is not valid when pediatric patients are under consideration. An attempt to review the peculiarities of these patients through a comprehensive bibliographic review is undertaken. We performed a narrative summary of the relevant literature dedicated to pediatric patients, centered on traumatic brain injury, the general incidence of thromboembolic disease in this patient population, the role of low molecular weight heparin (LMWH) in the treatment and prophylaxis of VTE, and its role in elective neurosurgical procedures, including spinal operations. Additionally, the risk of deep venous thrombosis in elective neurosurgical procedures is reviewed. Due to inherent limitations of the current studies, particularly a restricted number of patients, our data are underpowered to give a definitive protocol and guidelines for all the affected patients. Our current conclusions, based only on pediatric patients, argue that there is limited risk of VTE in pediatric patients suffering from brain tumors and that the possibility of VTE is very low in children undergoing elective neurosurgical procedures. There is no consensus regarding the exact incidence of VTE in traumatic brain injury patients. LMWH seems to be a safe and effective choice for the “at risk” pediatric patient population defined as being older than 15 years, venous catheterization, nonaccidental trauma, increased length of hospital stays, orthopaedic (including spinal) surgery, and cranial surgery.
Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients
Authors: Hollander Seth A. , Chung Sukyung , Reddy Sushma , Zook Nina , Yang Jeffrey , Vella Tristan , Navaratnam Manchula , Price Elizabeth , Sutherland Scott M. , Algaze Claudia A. 
Published: October 2021

AbstractAcute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index (p = 0.001), higher hematocrit (p < 0.001), lower body temperature (p < 0.001), lower renal near-infrared spectroscopy (p = 0.001), lower postoperative mean arterial blood pressure (MAP: p = 0.001), and higher central venous pressure (CVP; p < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48–12.3, p = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07–22.5, p = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival (p = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.
Active disease-related compound identification based on capsule network
Authors: Yang Bin , Bao Wenzheng , Wang Jinglong 
Published: October 2021

Abstract
Pneumonia, especially corona virus disease 2019 (COVID-19), can lead to serious acute lung injury, acute respiratory distress syndrome, multiple organ failure and even death. Thus it is an urgent task for developing high-efficiency, low-toxicity and targeted drugs according to pathogenesis of coronavirus. In this paper, a novel disease-related compound identification model–based capsule network (CapsNet) is proposed. According to pneumonia-related keywords, the prescriptions and active components related to the pharmacological mechanism of disease are collected and extracted in order to construct training set. The features of each component are extracted as the input layer of capsule network. CapsNet is trained and utilized to identify the pneumonia-related compounds in Qingre Jiedu injection. The experiment results show that CapsNet can identify disease-related compounds more accurately than SVM, RF, gcForest and forgeNet.