bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Targeting of Non-nuclear Estrogen Receptors with PaPE-1 as a New Treatment Strategy for Alzheimer’s Disease
Authors: Wnuk Agnieszka , Przepiórska Karolina , Rzemieniec Joanna , Pietrzak Bernadeta , Kajta Małgorzata 
Published: October 2020

AbstractAlzheimer’s disease (AD) is a multifactorial and severe neurodegenerative disorder characterized by progressive memory decline, the presence of Aβ plaques and tau tangles, brain atrophy, and neuronal loss. Available therapies provide moderate symptomatic relief but do not alter disease progression. This study demonstrated that PaPE-1, which has been designed to selectively activate non-nuclear estrogen receptors (ERs), has anti-AD capacity, as evidenced in a cellular model of the disease. In this model, the treatment of mouse neocortical neurons with Aβ (5 and 10 μM) induced apoptosis (loss of mitochondrial membrane potential, activation of caspase-3, induction of apoptosis-related genes and proteins) accompanied by increases in levels of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) as well as reduced cell viability. Following 24 h of exposure, PaPE-1 inhibited Aβ-evoked effects, as shown by reduced parameters of neurotoxicity, oxidative stress, and apoptosis. Because PaPE-1 downregulated Aβ-induced Fas/FAS expression but upregulated that of Aβ-induced FasL, the role of PaPE-1 in controlling the external apoptotic pathway is controversial. However, PaPE-1 normalized Aβ-induced loss of mitochondrial membrane potential and restored the BAX/BCL2 ratio, suggesting that the anti-AD capacity of PaPE-1 particularly relies on inhibition of the mitochondrial apoptotic pathway. These data provide new evidence for an anti-AD strategy that utilizes the selective targeting of non-nuclear ERs with PaPE-1.
Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid
Authors: Viklund Felicia , Hallingström Maria , Kacerovsky Marian , Cobo Teresa , Skogstrand Kristin , Hougaard David M. , Sävman Karin , Carlsson Ylva , Tsiartas Panagiotis , Juodakis Julius , Nilsson Staffan , Jacobsson Bo 
Published: October 2020

AbstractThe development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.
The Production of theMuselmannand the Singularity of Auschwitz: A Critique of Adriana Cavarero's Account of the “Auschwitz Event”
Authors: Riep Leonhard 
Published: October 2020

AbstractFeminist philosopher Adriana Cavarero claims in her bookHorrorism: Naming Contemporary Violencethat the core of the horror of Auschwitz is constituted by the figure of theMuselmann. I argue that Cavarero's lack of an accurate historical engagement with this figure in particular and with Auschwitz in general leads her to a speculative turn, thereby universalizing the phenomenon of theMuselmannby making ittheexample of Auschwitz, and moreover, the key factor to explain its singularity. I show that the phenomenon of theMuselmann, although a particular horrible effect of Auschwitz, is not limited to this concentration and extermination camp system. Consequently, the characteristic that makes Auschwitz aunicumcannot be found in theMuselmann. Rather, as I elucidate, the singularity of Auschwitz and the Shoah in general must be understood in relation to the true goal of this camp: the final extermination of European Jewry.
Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019
Authors: Janssen Rob , Visser Margot P. J. , Dofferhoff Anton S. M. , Vermeer Cees , Janssens Wim , Walk Jona 
Published: October 2020

AbstractCoronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
FOREIGN INVESTORS’ RESPONSIBILITIES AND CONTRIBUTORY FAULT IN INVESTMENT ARBITRATION
Authors: Marcoux Jean-Michel , Bjorklund Andrea K. 
Published: October 2020

AbstractSome investment arbitration tribunals have relied upon the principle of contributory fault to conclude that claimants have contributed to their own loss and should accordingly receive less compensation. The principle has not, however, been coherently applied. After analysing the use of contributory fault by tribunals and identifying factors contributing to an incoherent approach, the authors conclude that carefully crafted treaty provisions can improve the consistency of international investment arbitration by fostering a more coherent approach to both contributory fault and foreign investors’ responsibilities.
Appropriate use of echocardiography for palpitations in paediatric cardiology clinics
Authors: Sheth Saloni , Fares Munes , Kikano Sandra , Snyder Christopher , Dodgen Andrew , Wilhelm Carolyn M. 
Published: October 2020

AbstractObjectives:Identify diagnostic yield and frequency of echocardiograms for palpitation-related indications at outpatient paediatric cardiology clinics in relation to the 2014 ACC/AAP/AHA/ASE/HRS/SCAI/SCCT/SCMR/SOPE appropriate use criteria for Initial Transthoracic Echocardiography in Outpatient Paediatric Cardiology.Study design:A single-centre, retrospective study of children presenting for evaluation of a chief complaint of palpitations to outpatient paediatric cardiology clinics from 2015 to 2017. Palpitations were defined as an unpleasant sensation of rapid, irregular, and/or forceful beating of the heart. Indications for echocardiogram in patients were retrospectively classified based on the appropriate use criteria as “appropriate,” “may be appropriate,” or “rarely appropriate.” The incidence of abnormal and incidental echocardiographic findings for each category was determined.Results:A total of 286 patients presented with palpitations, with 128 (52% female) meeting inclusion criteria. Exclusion criteria included patients with additional cardiac complaints, prior echocardiogram, or history of congenital heart disease. Echocardiograms were performed on 36 (28%) patients. The appropriate use criteria were retrospectively applied, and indications for their performance were classified as “appropriate” (n = 4), “may be appropriate” (n = 17), or “rarely appropriate” (n = 15). Minor echocardiographic abnormalities were present in 22% (n = 8) of echocardiograms obtained for all appropriate use criteria classifications. No moderate or severe echocardiographic abnormalities were found. Incidental findings were noted in eight echocardiograms.Conclusion:Echocardiography in the evaluation of “rarely appropriate” and “may be appropriate” palpitation-related indications is of low diagnostic yield.
An Important Dilemma: Fibrinolytic Treatment in Bleeding Diathesis
Authors: Canakci Mustafa Emin , Ercan Volkan , Acar Nurdan , Efe Serdar 
Published: October 2020

AbstractPulmonary embolism is a clinical condition with high mortality rates in all age groups. The treatment includes anticoagulation and fibrinolytic therapy, and clinical management is challenging in cases of bleeding diathesis. Sepsis-induced coagulopathy (SIC), which has been recently defined to cause disruption of coagulation cascade accompanied by organ dysfunctions, is regarded as a major cause of mortality. It is noteworthy that there is no decrease in fibrinogen levels, unlike disseminated intravascular coagulopathy (DIC). This study aimed to present the management of a 70-year-old female patient who was admitted to emergency department with atypical complaints and diagnosed with pulmonary embolism due to deep vein thrombosis and septic shock. The clinical success of fibrinolytic therapy following the administration of fresh frozen plasma (FFP), although the patient had elevated international normalized ratio (INR), is presented in this case report. Since elevated INR and thrombocytopenia, which are observed in SIC, are caused by the inhibition of fibrinolysis, fibrinolytic therapy can be a rational treatment choice considering the profit/loss rate.
B-vitamins and metabolic syndrome in Mesoamerican children and their adult parents
Authors: Villatoro-Santos Claudia R , Ramirez-Zea Manuel , Villamor Eduardo ,   for the Nine Mesoamerican Countries Metabolic Syndrome (NiMeCoMeS) Study Group
Published: October 2020

AbstractObjective:To examine the associations between vitamins of the methionine-homocysteine (Hcys) cycle (B6, B12 and folate) and Hcys with metabolic syndrome (MetS) among Mesoamerican children and their adult parents.Design:We conducted a cross-sectional study. Exposures were plasma vitamins B6 and B12 concentrations, erythrocyte folate and plasma Hcys. In children, the outcome was a continuous metabolic risk score calculated through sex- and age standardisation of waist circumference, the homoeostatic model assessment for insulin resistance, mean arterial pressure (MAP), serum HDL-cholesterol and serum TAG. In parents, the outcome was the prevalence of MetS according to the Adult Treatment Panel III Criteria. We estimated mean differences in the metabolic risk score and prevalence ratios of MetS between quartiles of the exposures using multivariable-adjusted linear and Poisson regression models, respectively.Setting:Capital cities of Belize, Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica and Chiapas State in Mexico.Participants:In total, 237 school-aged children and 524 parents.Results:Among children, vitamin B12 was inversely associated with the metabolic risk score (quartiles 4–1 adjusted difference = –0·13; 95 % CI: –0·21, –0·04; Ptrend = 0·008) through MAP, HDL-cholesterol and TAG. In contrast, folate was positively associated with the metabolic risk score (quartiles 4–1 adjusted difference = 0·11; 95 % CI: 0·01, 0·20; Ptrend = 0·02). In adults, vitamin B6 was inversely associated with MetS prevalence, whereas vitamin B12 and folate were positively related to this outcome.Conclusions:Vitamins of the methionine-Hcys cycle are associated with MetS in different directions. The associations differ between children and adults.
Evaluating the effect of the initiative ‘Caring for the Newborn and the Mother at Home’ in Mexico
Authors: Unar-Munguía Mishel , González de Cosío Teresita , Escalante-Izeta Ericka Ileana , Ferré-Eguiluz Isabel , Sachse-Aguilera Matthias , Herrera Carolina 
Published: October 2020

AbstractObjective:The WHO and UNICEF recommend home visits to improve health outcomes for mothers and newborns. We evaluated the effect of home visits by community volunteers during pregnancy and postpartum on breast-feeding practices, women’s knowledge about benefits, beliefs and myths of breast-feeding, obstetric and neonatal warning signs, preparation for childbirth and initial care for newborns, and diarrhoea and respiratory diseases in children.Design:Community quasi-experimental design. We estimated difference-in-difference models with fixed effects at the community level weighted by propensity score and investigated implementation barriers through focus groups and semi-structured interviews.Setting:Poor rural communities in Mexico; 48 intervention and 29 control.Participants:Baseline and follow-up information were reported from two independent cross-sectional samples of women with babies aged between 6 and 18 months (baseline: 292 control, 320 intervention; follow-up: 292 control, 294 intervention).Results:The intervention increased reports of exclusive breast-feeding in the first 6 months by 24·4 percentage points (pp) (95 % CI: 13·4, 35·4), mothers’ knowledge of obstetric warning signs by 23·4 pp (95 % CI: 9·2, 37·5) and neonatal warning signs by 26·2 pp (95 % CI: 15·2, 37·2) compared to the control group. A non-linear dose–response relation with the number of home visits was found. Diarrhoea and respiratory diseases among children decreased in the interventionv. control group but were not statistically significant.Conclusions:Home visits should be implemented as a complementary strategy to the provision of prenatal and postnatal care in rural communities due to their potential positive effects on the health of mothers and their children.
Just war theory after colonialism and the war on terror: reexamining non-combatant immunity
Authors: Mares Gabriel 
Published: October 2020

AbstractI challenge a recent trend in just war theory – that civilians might be complicit with terrorists and lose non-combatant immunity – by reversing the gun sights and asking whether colonizing populations complicit with empire might compromise their non-combatant status. Employing colonial settlers as a thought experiment, I demonstrate the logic of expanded civilian culpability that has been proposed in the wake of the War on Terror would be unacceptable in other scenarios, and that these revisionist proposals are in service of ends incompatible with just war. In the process, I identify an important ambiguity regarding the performativity of non-combatant status, and show how this is used to aggressively expand civilian culpability for violence.
The epigenetic role of breastfeeding in mammary differentiation
Authors: Santiano Flavia E. , Campo Verde Arboccó Fiorella , Bruna Flavia A. , Zyla Leila E. , Sasso Corina V. , Gómez Silvina , Pistone-Creydt Virginia , López-Fontana Constanza M. , Carón Rubén W. 
Published: October 2020

AbstractMaternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.
Projected Strengthening of the Extratropical Surface Impacts of the Stratospheric Quasi‐Biennial Oscillation
Authors: Rao Jian , Garfinkel Chaim I. , White Ian P. 
Published: October 2020

AbstractUsing state‐of‐the‐art models with a spontaneous quasi‐biennial oscillation (QBO) from the Coupled Model Intercomparison Project Phases 5 and 6 (CMIP5/6), this study explores projected changes in the Holton‐Tan (HT) relationship and the near‐surface response to the QBO. Most models project an enhanced surface response to the QBO via a strengthened HT relationship in the future. Specifically, the North Atlantic Oscillation‐like response is projected to double and shift eastward in the future in the high‐end emission scenarios compared with the historical simulation. This strengthening occurs even as the amplitude of the QBO in the tropical stratosphere weakens from the historical simulation to the future projections. The seemingly contradictory projections of future changes in the QBO and the HT relationship might imply that the HT relationship changes nonlinearly with the QBO intensity, and the coherent changes in the background circulation structure should also be highlighted.
Treatments after progression to first-line FOLFOXIRI and bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies by GONO
Authors: Rossini Daniele , Lonardi Sara , Antoniotti Carlotta , Santini Daniele , Tomasello Gianluca , Ermacora Paola , Germani Marco Maria , Bergamo Francesca , Ricci Vincenzo , Caponnetto Salvatore , Moretto Roberto , Zaniboni Alberto , Pietrantonio Filippo , Buonadonna Angela , Ritorto Giuliana , Masi Gianluca , Latiano Tiziana Pia , Rapisardi Stefania , Falcone Alfredo , Cremolini Chiara 
Published: October 2020

Abstract
Background
FOLFOXIRI/bevacizumab (bev) is a first-line regimen of proven activity and efficacy in metastatic colorectal cancer. The upfront exposure to three cytotoxics raises concerns about the efficacy of treatments after progression.

Methods
We performed a pooled analysis of treatments after progression to upfront FOLFOXIRI/bev in patients enrolled in two randomised Phase 3 studies (TRIBE and TRIBE2) that compared FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev. Response rate, progression-free survival (2nd PFS) and overall survival (2nd OS) during treatments after progression were assessed. The RECIST response in first line and the oxaliplatin and irinotecan-free interval (OIFI) were investigated as potential predictors of benefit from FOLFOXIRI ± bev reintroduction.

Results
Longer 2nd PFS was reported in patients receiving FOLFOXIRI ± bev reintroduction compared to doublets ± bev or other treatments (6.1 versus 4.4 and 3.9 months, respectively, P = 0.013), and seems limited to patients achieving a response during first line (6.9 versus 4.2 and 4.7 months, respectively, P = 0.005) and an OIFI ≥ 4 months (7.2 versus 6.5 and 4.6 months, respectively, P = 0.045).

Conclusions
First-line FOLFOXIRI/bev does not impair the administration of effective second-line therapies. First-line response and longer OIFI seem associated with improved response and 2nd PFS from FOLFOXIRI ± bev reintroduction, without impacting 2nd OS.
Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM
Authors: Li Ting , Liu Nanjing , Gao Yingying , Quan Zhen , Hao Yanni , Yu Chaowen , Li Luo , Yuan Mengjuan , Niu Lingfang , Luo Chunli , Wu Xiaohou 
Published: October 2020

Abstract
Background
The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear.

Methods
The relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro.

Results
The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells.

Conclusions
This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer.