bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracellular Responses of Glial Cells To Monomeric Tau Protein Are Closely Mediated By Heparan Sulfate Proteoglycans (HSPGs)
Authors: Song Liqing , Oseid Daniel E. , Wells Evan A. , Coaston Troy , Robinson Anne S 
Published: July 2021

Abstract
The conversion of soluble tau protein to insoluble, hyperphosphorylated neurofibrillary tangles is a major hallmark leading to neuronal death observed in neurodegenerative tauopathies. Recent work suggests that extracellular, soluble tau binds to negatively charged heparan sulfate proteoglycans (HSPGs) available on the cell surface. In addition, LRP1 has recently been recognized as a major tau receptor, mediating tau uptake and spread. We hypothesized based on this data that monomeric tau would be endocytosed in both an HSPG- and LRP-dependent manner, activating intracellular signaling pathways that would regulate cellular phenotypes. Using live-cell confocal microscopy and flow cytometry, we show that soluble 0N4R monomers were rapidly endocytosed by SH-SY5Y and C6 glioma cells, via actin-dependent macropinocytosis. We also demonstrated the crucial role of HSPGs and LRP1 in cellular endocytosis of monomeric tau by observing reduced tau uptake in C6 glial cells with genetic knockouts of xylosyltransferase-1 – a key enzyme in HSPG synthesis – and LRP1. An ERK1/2 inhibition experiment showed that inhibiting the MEK-ERK1/2 signaling pathway attenuated IL-6 and IL-1β gene expression but not TNF-α . An LRP1 knockdown experiment led to an attenuated propensity for tau uptake and further elevated IL-6 gene expression. Collectively, our data suggest that tau has multiple extracellular binding partners that mediate its internalization through distinct mechanisms. Additionally, this study demonstrates the important role of both HSPG and LRP1 in regulating cellular immune responses to tau protein monomer, which provides a novel target for alleviating the neuroinflammatory environment before the formation of neurofibrillary tangles.
Comparison of two end-to-end continuous sutures for intestinal anastomoses in dogs.
Authors: IGNA CORNEL , DASCALU ROXANA , SICOE BOGDAN , ZAHA CRISTIAN , BRUDIU ILEANA , SCHUSZLER LARISA 
Published: July 2021

Abstract
Background: Single-layer appositional closures are preferred to inverting or everting patterns, as submucosal apposition has been shown to promote primary healing of the intestinal wall, whereas inverted or everted closures require second-intention healing and can increase the risk of luminal stenosis or anastomosis site leakage. There are different suture patterns available, but relatively few studies comparing these aspects have been published.The aim of this study was to compare two suture techniques for end-to-end anastomosis of the canine intestine (jejunum and colon): handsewn intestinal anastomosis by appositional simple continuous suture and inverting Cushing suture. The objectives of this study were to investigate 1.) whether the type of suture influences the specific effort to which the anastomosis site is submitted to, 2.) whether the anastomosis technique influences the diameter of the intestinal lumen and 3.) survival and complication rates in canine clinical cases undergoing end-to-end anastomoses. Results: The equilibrium angle for implanting the sutures in an anastomosis is 35°, aspect completely fulfilled by the simple continuous suture. The efforts to which sutures are submitted to in anastomoses are minimal for the Cushing suture. The difference in size of the anastomoses’ lumen between simple continuous suture and the Cushing suture are minimal, without being statistically relevant. The differences between the lumen of the anastomoses performed using PDS and those performed using PGA are not statistically relevant. The retrospective analysis of the outcome for 676 dogs (clinical cases) that underwent intestinal resection and anastomosis reveals that the dehiscence rate was 1.48%, out of which 1.18% following simple continuous anastomoses, and 0.3% following Cushing anastomoses. Narrowing of the intestinal lumen due to anastomotic healing was not registered.Conclusions: Use of the Cushing suture should be considered for performing an end-to-end intestinal anastomosis, although more studies are required to determine if there are any clinically significant differences between the sutures investigated in this study.
A Molecular View of Amyotrophic Lateral Sclerosis Through the Lens of Interaction Network Modules
Authors: Jensen Klaus Højgaard , Stalder Anna Katharina , Wernersson Rasmus , Roloff-Handschin Tim-Christoph , Hansen Daniel Hvidberg , Groenen Peter MA 
Published: July 2021

Abstract
Background: Despite the discovery of familial cases with mutations in Cu/Zn-superoxide dismutase (SOD1), Guanine nucleotide exchange C9orf72, TAR DNA-binding protein 43 (TARDBP) and RNA-binding protein FUS as well as a number of other genes linked to Amyotrophic Lateral Sclerosis (ALS), the etiology and molecular pathogenesis of this devastating disease is still not understood. As proteins do not act alone but rather in networks, conducting an analysis of ALS at the system level may provide new insights into the molecular biology of ALS around these potential ALS-associated genes and put it into relationship to other neurological diseases.Methods: A set of ALS-associated genes/proteins were collected from publicly available databases and text mining of scientific literature. We used these as seed proteins to build protein-protein interaction (PPI) networks serving as a scaffold for further analyses. From the collection of networks, a set of core modules enriched in seed proteins were identified. The core modules were investigated for overrepresentation of Gene Ontology categories and association to other diseases. To assess the core modules’ ability to describe unknown or less well-studied ALS biology, they were queried for proteins more recently associated to ALS and not involved in the primary analysis.Results: We describe a set of 26 ALS core modules enriched in ALS-associated proteins. Our workflow is robust against individual highly connected proteins often dominating this type of analysis due to study bias or experimental artefacts. We show that these ALS core modules not only capture most of the current knowledge about ALS, but they also allow us to suggest biological interdependencies. In addition, new associations of ALS networks with other neurodegenerative diseases, e.g. Alzheimer’s, Huntington’s and Parkinson’s disease were found. A follow-up analysis of 140 ALS-associated proteins identified since 2014 reveals a significant overrepresentation of new ALS proteins in these 26 disease modules.Conclusions: Using protein-protein interaction networks offers a relevant approach for broadening the understanding of the biological context of known ALS-associated genes. Using a bottom-up approach for the analysis of protein-protein interaction networks is a useful method to avoid bias caused by over-connected proteins. Our ALS-enriched modules cover most known biological functions associated with ALS. The presence of recently identified ALS-associated proteins in the top network highlights the potential for using the ALS-associated networks as a scaffold for identification of novel ALS disease mechanisms, investigation of complex networks and hypothesis generation.
Drivers of the evolution and amplitude of African Humid Periods
Authors: Menviel Laurie , Govin Aline , Avenas Arthur , Meissner Katrin , Grant Katharine , Tzedakis Polychronis 
Published: July 2021

Abstract
During orbital precession minima, the Sahara was humid and hosted tropical plant species thus providing a corridor for Hominins migration. Uncertainties remain over the climatic processes controlling the initiation, demise and amplitude of these African Humid Periods (AHPs). Here we present transient simulations of the penultimate deglaciation and Last Interglacial period (LIG), and compare them to transient simulations of the last deglaciation and Holocene. We find that the strengthening of the Atlantic Meridional Overturning Circulation (AMOC) at the end of the deglacial millennial-scale events exerts a dominant control on the abrupt initiation of AHPs, as the AMOC modulates the position of the Intertropical Convergence Zone (ITCZ). In addition, residual Northern Hemispheric (NH) ice-sheets can delay the AHP peak.
Through its impact on NH ice-sheets disintegration and thus AMOC variations, the larger rate of insolation increase during the penultimate compared to the last deglaciation can explain the earlier and more abrupt LIG AHP onset.
Finally, we show that the background climate state modulates precipitation variability with higher variability under wetter background conditions.
WITHDRAWN: LP-cs Ameliorated CCl 4 -Induced Acute Liver Injury by Suppression of Cellular Stress
Authors: Xu Zeping , Li Xiaofeng , Li Yuying , Wang Ping , Wu Junnan , Yang Shizhuo , Zhang Xie , Ma Yanyan , Xie Longteng , Jiang Yongsheng , Chen Li , Liu Yanlong , Wang Fan , Li Hong 
Published: July 2021

Abstract
Background: Acute liver injury (ALI) involves excessive oxidative stress(OS) and inflammatory responses, leading to a high mortality rate due to lack of effective therapy. Carbon tetrachloride (CCl4) is widely used to induce ALI by induction of reactive oxygen species. Probiotics, including Lactobacillus plantarum ST-III, have been shown to produce antibacterial and antioxidant substances such as organic acids or bacteriocins that reduce liver damage. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (L-P-cs) on CCl4-induced liver injury remains unclear.Methods: Mice were pretreated with L-P-cs or medium for 14days before one dose of 0.2% CCl4 at 10ml/kg body weight delivered by intraperitoneal injection. CCl4-induced liver injury was examined by measuring serum levels of liver transaminases and high mobility-group box 1 protein (HMGB1) and liver histological staining. Inflammation and apoptosis in liver were evaluated by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and TUNEL staining. Apoptosis in NCTC 1469 cells was detected using CCK8 and western blotting (WB). In liver, OS and endoplasmic reticulum stress(ERS)-related proteins were measured using kits and WB.Results: L-P-cs significantly ameliorated CCl4-induced liver injury and reduced CCl4- induced inflammatory response and apoptosis, consistent with NCTC 1469 cells' results. L-P-cs also restored CCl4-induced increases in cell OS and ERS to normalize liver function. Specifically, L-P-cs pretreatment decreased CCl4-induced increases in nuclear factor (erythroid-2 related) factor 2, HO-1, superoxide dismutase, glucose regulatory protein, and activating transcription factor 6.Conclusion: L-P-cs synergistically improves liver lobule necrosis, hepatocyte inflammation, and apoptosis by reducing liver OS and ERS.
Antibiotic-Loaded Bone Cement Combined With Vacuum Sealing Drainage To Treat Deep Sternal Wound Infection Following Cardiac Surgery: The First Case Report
Authors: Jiang Xia , Bu Fanyu , Xu Yong , Jing Zhaohui , Jiao GUOqing , Li Mingqiu , Rong Xiaosong 
Published: July 2021

Abstract
Background: Deep sternal wound infection (DSWI) is a rare but serious complication after median sternotomy, and treatment success depends mainly on surgical experience. Here we first present a case of a patient successfully treated for antibiotic-loaded bone cement(ALBC) combined with vacuum sealing drainage(VSD) of DSWI.Case presentation: This case report presented a patient who underwent open heart surgery, and suffered postoperatively from a DSWI associated with enterococcus cloacae. Focus debridement combined with ALBC filling and VSD was conducted in stage I. Appropriate antibiotics were started according to sensitivity to be continued for two weeks until the inflammatory markers decreased to normal. One month after the surgery, patient’s wound was almost healed and was discharged from hospital with a drainage tube. Two months after the stage I surgery procedure, the major step was removing the previous ALBC, and extensive debridement in stage II. The patient fully recovered without further surgical treatment.Conclusions: The results of this case suggest that ALBC combined with VSD may be a viable and safe option for deep sternal wound reconstruction.
Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike
Authors: Wilson Patrick , Changrob Siriruk , Fu Yanbin , Guthmiller Jenna , Halfmann Peter , Li Lei , Stamper Christopher , Dugan Haley , Accola Molly , Rehrauer William , Zheng Nai-Ying , Huang Min , Wang Jiaolong , Erickson Steven , Utset Henry , Graves Hortencia , Amanat Fatima , Sather D. Noah , Krammer Florian , Kawaoka Yoshihiro 
Published: July 2021

Abstract
Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484 and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and the variants of concern, including B.1.1.7 (alpha), P.1 (gamma) and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to wildtype (WT) SARS-CoV-2 do possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.
Prognostic significance of mean platelet volume in lung cancer patients: A meta-analysis
Authors: Kharel Sanjeev , Shrestha Suraj , Shakya Prafulla , Rawat Rohit , Shilpakar Ramila 
Published: July 2021

Abstract
Background Lung cancer is the most prevalent cancer globally with a grim prognosis alongside a very high number of cancer-related deaths. Mean platelet volume (MPV) is the measure of platelet size and is considered a surrogate marker of platelet activation. Low MPV indicates exhausted platelets causing worse outcomes in cancer patients. As the correlation between platelet count/platelet size and lung cancer prognosis still remains a topic of debate, this meta-analysis was done to comprehensively evaluate the prognostic significance of MPV among lung cancer patients.Methods A systematic search of electronic databases PubMed, Embase, and Google scholar and additional sources for relevant studies were done with no language restrictions from inception to 7th May 2021. Overall Survival (OS) and Disease-Free Survival (DFS)/Progression-Free Survival (PFS) and hazard ratio (HR) with 95% Confidence Interval (CI) were pooled to evaluate the relation of MPV with OS/DFS. Subgroup analysis based on cancer type, clinical stage, sample size, median age, cut-off value, and study region was done to identify the cause of significant heterogeneity.Results Eleven studies with 2421 lung cancer patients were included in our analysis. Our analysis showed no significant association between MPV levels with OS (H.R.:1.07, 95%C.I.:0.84–1.35, p = 0.60) and DFS/PFS (HR:1.04, 95%C.I.:0.68–1.60, p = 0.84). Under subgroup analysis, studies conducted in countries other than China (HR:1.53, 95% C.I.=1.14–2.03, p < 0.001, I2 = 42.11%) and studies with advanced-stage lung cancer patients (HR: 1.84, 95% C.I.=1.19–2.82, p-value = 0.01, I2 = 0%) showed significant association between MPV levels and worse DFS/PFS.Conclusion Pretreatment MPV levels did not show prognostic significance except in advanced lung cancer cases. Large multicentric studies with large samples and long follow-up times are necessary.
Vaginal Bleeding As The Presenting Manifestation of Post-Hepatectomy/-Splenectomy Portal-Mesenteric Venous Thrombosis
Authors: Yeh Che-Ming , Sun Jen-Tang , Fan Chieh-Min , Tsai Kuang-Chau , Chang Chih-Jung 
Published: July 2021

Abstract
Background: Portal-mesenteric venous thrombosis is not uncommon after hepatectomy or splenectomy but is under-recognized because of non-specific symptoms and lack of awareness of the clinicians. However, misdiagnosis or delayed treatment may have fatal consequences. Case Presentation: A 57-year-old menopausal woman with the medical history of hepatocellular carcinoma, stage I, underwent laparoscopic partial hepatectomy (S4) and splenectomy 2 months before the presentation of progressive vaginal spotting and vague abdominal pain. Dysfunctional uterine bleeding was suspected initially, but subsequent contrast-enhanced computed tomography due to concern for post-procedure complications revealed thrombosis in the portal vein and superior mesenteric vein. The patient received anticoagulant therapy, and her symptoms gradually resolved. Conclusions: To the best of our knowledge, vaginal variceal bleeding secondary to portal-mesenteric venous thrombosis has never been reported, but it can be the presenting manifestation for this condition. It should be considered in the differential diagnosis of patients who present with vague abdominal symptoms after hepatectomy or splenectomy.
Pre-Operative Modified Glasgow Prognostic Score 2 For The Prediction of Poor Post-Operative Performance Status Following Palliative Surgery For Pathological Spinal Fracture: A Retrospective Cohort Study
Authors: Ushiku Chikara , Akiyama Shoshi , Ikegami Taku , Inoue Takeshi , Shinohara Akira , Kajiwara Takayoshi , Arimura Daigo , Katsumi Shunsuke , Obata Shintaro , Soshi Shigeru , Saito Mitsuru 
Published: July 2021

Abstract
Background: Skeletal-related events due to spinal metastasis in cancer significantly impair patients’ activities of daily living and quality of life. Most of these events occur suddenly. To reduce their impairment occurred suddenly, and to allow them to return to their normal life immediately, many patients undergo palliative surgery; however, some patients do not improve their performance status (PS) as expected. There is little evidence regarding the factors influencing a patient’s PS after palliative surgery. We aimed to investigate the pre-operative predictors of poor PS 1 month after surgery.Methods: The study included a consecutive series of 71 patients with pathological spinal fracture who underwent palliative surgery. Pre-operative predictors of poor post-operative PS were investigated. The participants were categorized into two groups according to PS; the Good group (PS 0, 1, or 2) and the Poor group (PS 3 or 4). We performed univariate and multivariable logistic regression analyses on demographic information, unidentified primary site, AIS grade, poor PS, spinal instability neoplastic score, revised Tokuhashi score, New Katagiri score, modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio(NLR), and prognostic nutrition index (PNI). Results: Post-operatively, the Poor group included 38.0% of the patients. Univariate analysis revealed that the following pre-operative factors were related to poor outcomes (p<0.05): BMI<18.5; AIS grade C; poor PS; revised Tokuhashi score 0−8; New Katagiri score 7−10; mGPS 2; and PNI. In the multivariate analysis, mGPS 2 (OR = 22.8, 95% CI = 2.59−202.00, p<0.01) was a significant pre-operative predictor of poor post-operative PS. Conclusion: mGPS 2 was a predictive clinical factor that influenced PS 1 month after surgery. Patients with mGPS 2 should be carefully evaluated to determine their treatment, especially whether they should undergo palliative surgery.
Recombinant Production of IL-1Ra in Fusion to Albumin Binding Domain for Its Extended Half-Life
Authors: Shafiee Fatemeh , Yazdani Ali 
Published: July 2021

Abstract
Background: Anakinra, a FDA approved biological drug for Rheumatoid Arthritis, must be injected daily due to its short Half-life, leads to the lower patient compliance. So, the aim of this study was to produce IL-1Ra in fusing to albumin binding domain to extend its half-life and evaluate its biological effects.Methods and Results: The expression of IL-1Ra-ABD was performed in E. coli in fusing to intein1 of pTWIN1 in soluble and purified. The affinity of IL-1Ra-ABD to HSA was determined on Native-PAGE and its release percent toward time was determined. Finally, MTT assay was used to determine the antagonizing properties of recombinant IL-1Ra-ABD against IL-1β, on A375 cells. the expression induction of intein1-IL-1Ra-ABD using 0.1mM of IPTG at 15°C, and its cleavage represented a band approximately in 50 and 23 kDa respectively. Native-PAGE results showed that about 78% of IL-1Ra-ABD attached to the HSA after 2 hours of incubation, and MTT assay results showed no significant differences between the effects of our recombinant protein and native IL-1Ra.Conclusion: the production of soluble IL-1Ra-ABD with similar antagonizing effects to IL-1Ra was successfully performed. IL-1Ra-ABD showed suitable interaction with HSA and release over the time. However, pharmacokinetics and furthur biological evaluations are required.
Treatment and Outcomes of Primary Urethral Cancer
Authors: yang shujun , Wang Shun , Zheng Duo , Ma Gui , Ying Yongsheng , Li Weiping , Shang Panfeng 
Published: July 2021

Abstract
Objective: To evaluate the clinical data, pathological types, treatment methods, and long-term outcome of 17 cases on Primary Urethral Cancer (PUC).Patients and Methods: We did a retrospective review of 17 patients diagnosed with PUC from January 2011 to December 2020 at four hospitals in Gansu Province.We stratified the patient concerning to their age, gender, histological type, stage, treatment modality and final follow-up, among which those at an early stage were defined as Tis-T2N0M0, while those at an advanced stage as T3-4. Then we analyzed the stratified samples based on clinical stage, treatment method, and outcome.Results: The majority of the 17 patients were female (F: M=13:4), And the number of cases at an early stage is roughly the same as those at an advanced stage (9:8). The most common histologic types were squamous cell carcinoma (35.3%) and urothelial carcinoma (35.3%), while adenocarcinoma (11.8%), malignant melanoma (11.8%), and small cell carcinoma (6.9%) accounted for a relatively small proportion. Surgery was a primary treatment modality for early cases, While for advanced cases, multimodal treatment was preferred.Conclusion: Survival rates are significantly lower in rare tumors than common tumors; besides, patients with early-stage PUC show better outcomes thanks to the single-mode therapy, whereas patients with advanced cancers need the most advanced multimode treatment to benefit patients as much as possible. However, due to the rarity of this malignancy, multi-agency experience provides the best evidence available.