bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy
Authors: Wu Chan , Zhou Xiao-Xia , Li Jing-Zhou , Qiang Hai-Feng , Wang Yan , Li Gang 
Published: August 2021

Abstract
Background
Previous studies have demonstrated that human cardiac c-Kit+ progenitor cells (hCPCs) can effectively improve ischemic heart disease. However, the major challenge in applying hCPCs to clinical therapy is the low survival rate of graft hCPCs in the host heart, which limited the benefit of transplanted hCPCs. Bradykinin (BK) is a principal active agent of the tissue kinin-kallikrein system. Our previous studies have highlighted that BK mediated the growth and migration of CPCs by regulating Ca2+ influx. However, the protective effect of BK on CPCs, improvement in the survival rate of BK-pretreated hCPCs in the infarcted heart, and the related mechanism remain elusive.

Methods
HCPCs were treated with H2O2 to induce cell apoptosis and autophagy, and different concentration of BK was applied to rescue the H2O2-induced injury detected by MTT assay, TUNEL staining, flow cytometry, western blotting, and mitoSOX assays. The role of autophagy in the anti-apoptotic effect of BK was chemically activated or inhibited using the autophagy inducer, rapamycin, or the inhibitor, 3-methyladenine (3-MA). To explore the protective effect of BK on hCPCs, 3-MA or BK-pretreated hCPCs were transplanted into the myocardial infarcted rats. An echocardiogram was used to determine cardiac function, H&E and Masson staining were employed to assess pathological characteristics, HLA gene expression was quantified by qRT-PCR, and immunostaining was applied to examine neovascularization using confocal microscopy.

Results
The in vitro results showed that BK suppressed H2O2-induced hCPCs apoptosis and ROS production in a concentration-dependent manner by promoting pAkt and Bcl-2 expression and reducing cleaved caspase 3 and Bax expression. Moreover, BK restrained the H2O2-induced cell autophagy by decreasing LC3II/I, Beclin1, and ATG5 expression and increasing P62 expression. In the in vivo experiment, the transplanted BK- or 3-MA-treated hCPCs were found to be more effectively improved cardiac function by decreasing cardiomyocyte apoptosis, inflammatory infiltration, and myocardial fibrosis, and promoting neovascularization in the infarcted heart, compared to untreated-hCPCs or c-kit- cardiomyocytes (CPC- cells).

Conclusions
Our present study established a new method to rescue transplanted hCPCs in the infarcted cardiac area via regulating cell apoptosis and autophagy of hCPCs by pretreatment with BK, providing a new therapeutic option for heart failure.
Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study
Authors: Iida Megan A. , Farrell Kurt , Walker Jamie M. , Richardson Timothy E. , Marx Gabriel A. , Bryce Clare H. , Purohit Dushyant , Ayalon Gai , Beach Thomas G. , Bigio Eileen H. , Cortes Etty P. , Gearing Marla , Haroutunian Vahram , McMillan Corey T. , Lee Edward B. , Dickson Dennis W. , McKee Ann C. , Stein Thor D. , Trojanowski John Q. , Woltjer Randall L. , Kovacs Gabor G. , Kofler Julia K. , Kaye Jeffrey , White Charles L. , Crary John F. 
Published: August 2021

AbstractPrimary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.
A scoping review of registry captured indicators for evaluating quality of critical care in ICU
Authors: Jawad Issrah , Rashan Sumayyah , Sigera Chathurani , Salluh Jorge , Dondorp Arjen M. , Haniffa Rashan , Beane Abi 
Published: August 2021

Abstract
Background
Excess morbidity and mortality following critical illness is increasingly attributed to potentially avoidable complications occurring as a result of complex ICU management (Berenholtz et al., J Crit Care 17:1-2, 2002; De Vos et al., J Crit Care 22:267-74, 2007; Zimmerman J Crit Care 1:12-5, 2002). Routine measurement of quality indicators (QIs) through an Electronic Health Record (EHR) or registries are increasingly used to benchmark care and evaluate improvement interventions. However, existing indicators of quality for intensive care are derived almost exclusively from relatively narrow subsets of ICU patients from high-income healthcare systems. The aim of this scoping review is to systematically review the literature on QIs for evaluating critical care, identify QIs, map their definitions, evidence base, and describe the variances in measurement, and both the reported advantages and challenges of implementation.

Method
We searched MEDLINE, EMBASE, CINAHL, and the Cochrane libraries from the earliest available date through to January 2019. To increase the sensitivity of the search, grey literature and reference lists were reviewed. Minimum inclusion criteria were a description of one or more QIs designed to evaluate care for patients in ICU captured through a registry platform or EHR adapted for quality of care surveillance.

Results
The search identified 4780 citations. Review of abstracts led to retrieval of 276 full-text articles, of which 123 articles were accepted. Fifty-one unique QIs in ICU were classified using the three components of health care quality proposed by the High Quality Health Systems (HQSS) framework. Adverse events including hospital acquired infections (13.7%), hospital processes (54.9%), and outcomes (31.4%) were the most common QIs identified. Patient reported outcome QIs accounted for less than 6%. Barriers to the implementation of QIs were described in 35.7% of articles and divided into operational barriers (51%) and acceptability barriers (49%).

Conclusions
Despite the complexity and risk associated with ICU care, there are only a small number of operational indicators used. Future selection of QIs would benefit from a stakeholder-driven approach, whereby the values of patients and communities and the priorities for actionable improvement as perceived by healthcare providers are prioritized and include greater focus on measuring discriminable processes of care.
PSTEP: project for solar–terrestrial environment prediction
Authors: Kusano Kanya , Ichimoto Kiyoshi , Ishii Mamoru , Miyoshi Yoshizumi , Yoden Shigeo , Akiyoshi Hideharu , Asai Ayumi , Ebihara Yusuke , Fujiwara Hitoshi , Goto Tada-Nori , Hanaoka Yoichiro , Hayakawa Hisashi , Hosokawa Keisuke , Hotta Hideyuki , Hozumi Kornyanat , Imada Shinsuke , Iwai Kazumasa , Iyemori Toshihiko , Jin Hidekatsu , Kataoka Ryuho , Katoh Yuto , Kikuchi Takashi , Kubo Yûki , Kurita Satoshi , Matsumoto Haruhisa , Mitani Takefumi , Miyahara Hiroko , Miyoshi Yasunobu , Nagatsuma Tsutomu , Nakamizo Aoi , Nakamura Satoko , Nakata Hiroyuki , Nishizuka Naoto , Otsuka Yuichi , Saito Shinji , Saito Susumu , Sakurai Takashi , Sato Tatsuhiko , Shimizu Toshifumi , Shinagawa Hiroyuki , Shiokawa Kazuo , Shiota Daikou , Takashima Takeshi , Tao Chihiro , Toriumi Shin , Ueno Satoru , Watanabe Kyoko , Watari Shinichi , Yashiro Seiji , Yoshida Kohei , Yoshikawa Akimasa 
Published: August 2021

AbstractAlthough solar activity may significantly impact the global environment and socioeconomic systems, the mechanisms for solar eruptions and the subsequent processes have not yet been fully understood. Thus, modern society supported by advanced information systems is at risk from severe space weather disturbances. Project for solar–terrestrial environment prediction (PSTEP) was launched to improve this situation through synergy between basic science research and operational forecast. The PSTEP is a nationwide research collaboration in Japan and was conducted from April 2015 to March 2020, supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan. By this project, we sought to answer the fundamental questions concerning the solar–terrestrial environment and aimed to build a next-generation space weather forecast system to prepare for severe space weather disasters. The PSTEP consists of four research groups and proposal-based research units. It has made a significant progress in space weather research and operational forecasts, publishing over 500 refereed journal papers and organizing four international symposiums, various workshops and seminars, and summer school for graduate students at Rikubetsu in 2017. This paper is a summary report of the PSTEP and describes the major research achievements it produced.
PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40
Authors: Moriwaki Takahito , Yoshimura Akari , Tamari Yuki , Sasanuma Hiroyuki , Takeda Shunichi , Seki Masayuki , Tano Keizo 
Published: August 2021

Abstract
Background
Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study.

Results
The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS.

Conclusions
PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.
A new multi-level algorithm for balanced partition problem on large scale directed graphs
Authors: Li Xianyue , Pang Yufei , Zhao Chenxia , Liu Yang , Dong Qingzhen 
Published: August 2021

AbstractGraph partition is a classical combinatorial optimization and graph theory problem, and it has a lot of applications, such as scientific computing, VLSI design and clustering etc. In this paper, we study the partition problem on large scale directed graphs under a new objective function, a new instance of graph partition problem. We firstly propose the modeling of this problem, then design an algorithm based on multi-level strategy and recursive partition method, and finally do a lot of simulation experiments. The experimental results verify the stability of our algorithm and show that our algorithm has the same good performance as METIS. In addition, our algorithm is better than METIS on unbalanced ratio.
Emerging Use of Public-Private Partnerships in Public Radiotherapy Facilities in Nigeria
Authors: Anakwenze Akinfenwa Chidinma P. , Ibraheem Abiola , Nwankwo Kenneth , Lasebikan Nwamaka , Ali-Gombe Musa , Aliyu Usman Malami , Ikhile Emmanuel , Adegboyega Omobolanle , Abdullahi Adamu , Klopp Ann H. , Schmeler Kathleen , Lin Lilie L. , Jhingran Anuja , Page Brandi R. , Leng Jim , Grover Surbhi , Ntekim Atara 
Published: August 2021

PURPOSE Radiotherapy (RT) treatment at public hospitals in Nigeria is often interrupted by prolonged periods of machine breakdown because of insufficient funds for maintenance and repair. These delays have prompted the uptake of public-private partnerships (PPPs) to acquire and maintain RT equipment. This study aimed to understand Nigeria's current RT capacity and the impact of PPPs on RT availability and cost. METHODS Eleven radiation oncologists, each representing one of the 11 RT centers in Nigeria (eight public and three private), were invited to complete a survey on the type, status, acquisition, and maintenance plan of existing RT equipment, cost incurred by patients for external-beam radiation (EBRT) and brachytherapy treatment, and number of patients treated per year on each machine. Type and status of equipment at nonresponding facilities were obtained through literature review and confirmed with the facility. RESULTS A total of eight (81%) respondents completed the survey, all representing public centers, three of which reported PPP use. They reported 11 megavoltage units in total (seven linear accelerators [LINACs] and four Cobalt-60s) and 10 brachytherapy afterloaders. Of those, 57% (4/7) of the LINACs, 100% (4/4) of the Cobalt-60s, and 63% (7/11) of the afterloaders were in clinical use. All commissioned equipment supported by PPPs (three LINACs and one afterloader) were in operation. The public EBRT equipment were nonfunctional 35% of the year (resulting in 60% fewer patients treated per year). The PPP EBRT and afterloaders did not experience any periods of breakdown, but PPP costs were 338% higher than public equipment. CONCLUSION This study characterizes the use of PPP as a more reliable method of RT delivery in Nigeria, albeit at higher costs.
Impact of Performance Status on Response and Survival Among Patients Receiving Checkpoint Inhibitors for Advanced Solid Tumors
Authors: Krishnan Mridula , Kasinath Pooja , High Robin , Yu Fang , Teply Benjamin A. 
Published: August 2021

PURPOSE: Clinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance status (ECOG PS of 0-1). However, ICI remains an attractive option for patients with advanced tumors and poor PS. We hypothesized that patients with ECOG PS ≥ 2 would have worse outcomes with ICI. METHODS: We retrospectively identified patients with advanced solid tumors who were treated with ICI at our institution. The log-rank test compared the survival among patients with different ECOG PS. We used a proportional hazards model to assess association between ECOG PS and overall survival (OS) with adjustment for covariates including age, sex, malignancy type, time from advance disease diagnosis, and line of therapy. We compared overall response rates between groups with Pearson chi-square exact test. We also analyzed in-hospital mortality and hospice referral rates. RESULTS: We identified 257 patients treated with ICI. One hundred eighty-two patients had ECOG PS 0-1, and 75 had ECOG PS ≥ 2. The median overall survival was 12.6 months for the ECOG PS 0-1 group compared with 3.1 months for the ECOG PS ≥ 2 group ( P < .001). The overall response rate for patients with ECOG PS 0-1 was 23% compared with 8% for those with poor PS ( P = .005). Patients with poor PS treated with ICI had similar hospice referral rates (67% for ECOG PS ≥ 2 v 61.9% for ECOG PS 0-1, P = .50) but were more likely to have in-hospital death as compared with the good PS group (28.6% v 15.1%, P = .035). CONCLUSION: Despite the appeal of ICI in patients with advanced malignancy and poor PS, outcomes in this cohort were poor. Prospective trials defining the activity and role of ICI in poor PS are urgently needed.
Gender, Generation, and Multiracial Identification in the United States
Authors: Xu Janet , Saperstein Aliya , Morning Ann , Iverson Sarah 
Published: August 2021

AbstractMultiracial self-identification is frequently portrayed as a disproportionately female tendency, but previous research has not probed the conditions under which this relationship might occur. Using the 2015 Pew Survey of Multiracial Adults, we offer a more comprehensive analysis that considers gender differences at two distinct stages: reporting multiple races in one's ancestry and selecting multiple races to describe oneself. We also examine self-identification patterns by the generational locus of multiracial ancestry. We find that females are more likely to be aware of multiracial ancestry overall, but only first-generation females are more likely than their male counterparts to self-identify as multiracial. Finally, we explore the role of racial ancestry combination, finding that multiracial awareness and self-identification are likely gendered differently for different segments of the mixed-race population. This offers a more nuanced picture of how gender interacts with other social processes to shape racial identification in the United States.
Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease
Authors: McCarthy Gizelle M. , Blasio Angelo , Donovan Olivia G. , Schaller Lena B. , Bock-Hughes Althea , Magraner Jose M. , Suh Jung Hee , Tattersfield Calum F. , Stillman Isaac E. , Shah Shrijal S. , Zsengeller Zsuzsanna K. , Subramanian Balajikarthick , Friedman David J. , Pollak Martin R. 
Published: August 2021

ABSTRACT
People of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction of this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting two copies of these APOL1 risk variants, known as G1 and G2, causes high rates of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy and hypertension-associated end-stage kidney disease. Disease risk follows a recessive mode of inheritance, which is puzzling given the considerable data that G1 and G2 are toxic gain-of-function variants. We developed coisogenic bacterial artificial chromosome (BAC) transgenic mice harboring either the wild-type (G0), G1 or G2 forms of human APOL1. Expression of interferon gamma (IFN-γ) via plasmid tail vein injection results in upregulation of APOL1 protein levels together with robust induction of heavy proteinuria and glomerulosclerosis in G1/G1 and G2/G2 but not G0/G0 mice. The disease phenotype was greater in G2/G2 mice. Neither heterozygous (G1/G0 or G2/G0) risk variant mice nor hemizygous (G1/−, G2/−) mice had significant kidney injury in response to IFN-γ, although the heterozygous mice had a greater proteinuric response than the hemizygous mice, suggesting that the lack of significant disease in humans heterozygous for G1 or G2 is not due to G0 rescue of G1 or G2 toxicity. Studies using additional mice (multicopy G2 and a non-isogenic G0 mouse) supported the notion that disease is largely a function of the level of risk variant APOL1 expression. Together, these findings shed light on the recessive nature of APOL1-nephropathy and present an important model for future studies.
S-palmitoylation determines TMEM55B-dependent positioning of lysosomes
Authors: Rudnik Sönke , Heybrock Saskia , Saftig Paul , Damme Markus 
Published: August 2021

ABSTRACT
The spatiotemporal cellular distribution of lysosomes depends on active transport mainly driven by microtubule motors such as kinesins and dynein. Different protein complexes attach these molecular motors to their vesicular cargo. TMEM55B (also known as PIP4P1), as an integral lysosomal membrane protein, is a component of such a complex that mediates the retrograde transport of lysosomes by establishing interactions with the cytosolic scaffold protein JIP4 (also known as SPAG9) and dynein–dynactin. Here, we show that TMEM55B and its paralog TMEM55A (PIP4P2) are S-palmitoylated proteins that are lipidated at multiple cysteine residues. Mutation of all cysteines in TMEM55B prevents S-palmitoylation and causes retention of the mutated protein in the Golgi. Consequently, non-palmitoylated TMEM55B is no longer able to modulate lysosomal positioning and the perinuclear clustering of lysosomes. Additional mutagenesis of the dileucine-based lysosomal sorting motif in non-palmitoylated TMEM55B leads to partial missorting to the plasma membrane instead of retention in the Golgi, implicating a direct effect of S-palmitoylation on the adaptor protein-dependent sorting of TMEM55B. Our data suggest a critical role for S-palmitoylation in the trafficking of TMEM55B and TMEM55B-dependent lysosomal positioning.
Activation of IRE1, PERK and salt-inducible kinases leads to Sec body formation inDrosophilaS2 cells
Authors: Zhang Chujun , van Leeuwen Wessel , Blotenburg Marloes , Aguilera-Gomez Angelica , Brussee Sem , Grond Rianne , Kampinga Harm H. , Rabouille Catherine 
Published: August 2021

ABSTRACTThe phase separation of the non-membrane bound Sec bodies occurs in Drosophila S2 cells by coalescence of components of the endoplasmic reticulum (ER) exit sites under the stress of amino acid starvation. Here, we address which signaling pathways cause Sec body formation and find that two pathways are critical. The first is the activation of the salt-inducible kinases (SIKs; SIK2 and SIK3) by Na+ stress, which, when it is strong, is sufficient. The second is activation of IRE1 and PERK (also known as PEK in flies) downstream of ER stress induced by the absence of amino acids, which needs to be combined with moderate salt stress to induce Sec body formation. SIK, and IRE1 and PERK activation appear to potentiate each other through the stimulation of the unfolded protein response, a key parameter in Sec body formation. This work shows the role of SIKs in phase transition and re-enforces the role of IRE1 and PERK as a metabolic sensor for the level of circulating amino acids and salt.This article has an associated First Person interview with the first author of the paper.
Inventar der Basler Stadtbefestigungen - Planvorlage und Katalog
Authors: Helmig Guido , Matt Christoph Ph. 
Published: August 2021

Beim vorliegenden Inventar der Basler Stadtbefestigungen handelt es sich um den ersten Teil, der die landseitige Äussere Grossbasler Stadtmauer thematisiert. Der zweite Teil behandelt die rheinseitigen Grossbasler Stadtbefestigungen.
Ziel war es, den genauen Verlauf der Stadtmauer zu illustrieren sowie den Kenntnisstand zu den verschiedenen archäologischen Aufschlüssen zusammenzustellen. Es war uns ein Anliegen, die Ergebnisse der Untersuchungen nicht nur in einem Plan festzuhalten und ein Inventar der mittelalterlichen Stadtmauern herzustellen, vielmehr wollten wir die Stadtbefestigungen als kulturgeschichtliches Denkmal begreifen und Informationen über die ganze Zeit ihres rund 500jährigen Bestehens sammeln.