bluuebunny/crossref_metadata_2025_split huggingface dataset:
α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline
Authors: Kawashita Eri , Ishihara Keiichi , Miyaji Haruko , Tanishima Yu , Kiriyama Akiko , Matsuo Osamu , Akiba Satoshi 
Published: October 2020

Abstractα2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal development of the neural network for spatial memory. However, it is still unclear whether α2AP plays a role in the memory process. The present study demonstrated that adult hippocampal neurogenesis and remote spatial memory were enhanced by the injection of an anti-α2AP neutralizing antibody in WT mice, while the injection of α2AP reduced hippocampal neurogenesis and impaired remote spatial memory, suggesting that α2AP is a negative regulator in memory processing. The present study also found that the levels of α2AP in the brains of old mice were higher than those in young mice, and a negative correlation between the α2AP level and spatial working memory. In addition, aging-dependent brain oxidative stress and hippocampal inflammation were attenuated by α2AP deficiency. Thus, an age-related increase in α2AP might cause cognitive decline accompanied by brain oxidative stress and neuroinflammation. Taken together, our findings suggest that α2AP is a key regulator of the spatial memory process, and that it may represent a promising target to effectively regulate healthy brain aging.
Implementing a nurse-enabled, integrated, shared-care model involving specialists and general practitioners in breast cancer post-treatment follow-up: a study protocol for a phase II randomised controlled trial (the EMINENT trial)
Authors: Chan Raymond Javan , Emery Jon , Cuff Katharine , Teleni Laisa , Simonsen Camilla , Turner Jane , Janda Monika , Mckavanagh Daniel , Jones Lee , McKinnell Emma , Gosper Melissa , Ryan Juanita , Joseph Ria , Crowe Bethany , Harvey Jennifer , Ryan Marissa , Carrington Christine , Nund Rebecca , Crichton Megan , McPhail Steven 
Published: October 2020

Abstract
Background
Due to advances in early detection and cancer treatment, 5-year relative survival rates for early breast cancer surpass 90% in developed nations. There is increasing focus on promotion of wellness in survivorship and active approaches to reducing morbidity related to treatment; however, current models of follow-up care are heavily reliant on hospital-based specialist-led care. This study aims to test the feasibility of the EMINENT intervention for implementing an integrated, shared-care model involving both cancer centre specialists and community-based general practitioners for early breast cancer post-treatment follow-up.

Methods
We describe a protocol for a phase II, randomised controlled trial with two parallel arms and 1:1 allocation. A total of 60 patients with early-stage breast cancer will be randomised to usual, specialist-led, follow-up care (as determined by the treating surgeons, medical oncologists, and radiation oncologists) or shared follow-up care intervention (i.e. EMINENT). EMINENT is a nurse-enabled, pre-specified shared-care pathway with follow-up responsibilities divided between cancer centre specialists (i.e. surgeons and oncologists) and general practitioners. The primary outcome is health-related quality of life as measured by the Functional Assessment of Cancer Therapy—Breast Cancer. Secondary outcomes include patient experience, acceptance, and satisfaction of care; dietary, physical activity, and sedentary behaviours; financial toxicity; adherence; health resource utilisation; and adverse events.

Discussion
The trial is designed to identify the barriers to implementing a shared-care model for breast cancer survivors following treatment. Results of this study will inform a definitive trial testing the effects of shared-care model on health-related quality of life of breast cancer survivors, as well as its ability to alleviate the growing demands on the healthcare system.

Trial registration
Australia and New Zealand Clinical Trials Registry ACTRN12619001594112. Registered on 19 November 2019
Tailored, psychological intervention for anxiety and/or depression in people with chronic obstructive pulmonary disease (COPD), TANDEM (Tailored intervention for ANxiety and DEpression Management in COPD): statistical analysis plan for a randomised controlled trial
Authors: Chan Claire L. , Smuk Melanie , Sohanpal Ratna , Pinnock Hilary , Taylor Stephanie J. C. ,   On behalf of the TANDEM Investigators
Published: October 2020

Abstract
Background
The aim of the TANDEM trial is to evaluate whether a tailored, psychological cognitive behavioural approach intervention, which links into, and optimises the effects of routine pulmonary rehabilitation (PR), leads to a reduction in mild/moderate anxiety and/or depression in people with moderate, severe or very severe chronic obstructive pulmonary disease.

Methods and design
TANDEM is a multi-centre, two-arm, parallel group, pragmatic, individually randomised controlled, superiority trial including an internal pilot. Participants are randomised to receive either the intervention (a tailored psychological intervention plus usual care including referral to PR) or the control (usual care including referral to PR). The designed randomisation ratio is 1.25:1 in favour of the intervention. The multiple-primary outcomes are participant depression and anxiety at 6 months, measured using the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales.

Results
This article describes the statistical analysis plan (SAP) for the TANDEM trial. In particular, we describe the general analysis principles, how we will handle missing data, the primary and secondary outcomes and how these will be analysed, sensitivity analyses for the multiple-primary outcomes, and any other analyses and data summaries. The SAP was developed and published prior to completion of follow-up of the last participant.

Trial registration
ISRCTN registry ISRCTN59537391. Registered on 20 March 2017.
Multiple myeloma presenting as an intramedullary spinal cord tumor: a case report and review of the literature
Authors: Di Long , Huang Kevin , Kesayan Tigran , Kroll Derek , Baz Rachid C. , Macaulay Robert J. , Tran Nam D. 
Published: October 2020

Abstract
Background
Extramedullary disease in multiple myeloma often portends a worse diagnosis. In approximately 1% of cases, multiple myeloma may metastasize to the central nervous system as either leptomeningeal involvement or an intracranial, intraparenchymal lesion. Spinal cord metastases, however, are exceedingly rare. We present a case of spinal cord multiple myeloma as well as a literature review of reported cases.

Case presentation
A 66-year-old African American man with multiple myeloma presented with acute midthoracic pain and lower extremity paresis and paresthesia. Magnetic resonance imaging of the spine revealed two contrast-enhancing intramedullary enhancing lesions in the T1–T2 and T6–T7 cord. Resection with biopsy yielded a diagnosis of metastatic multiple myeloma.

Conclusion
To date, only six cases of extramedullary disease to the spinal cord in patients with multiple myeloma have been reported, including our patient’s case. In all cases, neurologic deficit was observed at presentation, and magnetic resonance imaging of the spine revealed an intramedullary, homogeneously enhancing lesion. Current evidence suggests worse prognosis in patients with extramedullary disease to the central nervous system, and treatment paradigms remain debatable.
Melatonin suppresses ER stress-dependent proapoptotic effects via AMPK in bone mesenchymal stem cells during mitochondrial oxidative damage
Authors: Fan Chongxi , Feng Jianyu , Tang Chi , Zhang Zhengbin , Feng Yingtong , Duan Weixun , Zhai Mingming , Yan Zedong , Zhu Liwen , Feng Lele , Zhu Hanzhao , Luo Erping 
Published: October 2020

Abstract
Background
Bone marrow mesenchymal stem cells (BMSCs) have been used as important cell-based tools for clinical applications. Oxidative stress-induced apoptosis causes a low survival rate after transplantation, and the underlying mechanisms remain unknown. The endoplasmic reticulum (ER) and mitochondria are vital organelles regulated by adenosine monophosphate (AMP)-activated protein kinase (AMPK), especially during oxidative stress injury. Melatonin exerts an antioxidant effect by scavenging free radicals. Here, we aimed to explore whether cytoprotective melatonin relieves ER stress-mediated mitochondrial dysfunction through AMPK in BMSCs after oxidative stress injury.

Methods
Mouse BMSCs were isolated and exposed to H2O2 in the absence or presence of melatonin. Thereafter, cell damage, oxidative stress levels, mitochondrial function, AMPK activity, ER stress-related proteins, and apoptotic markers were measured. Additionally, the involvement of AMPK and ER stress in the melatonin-mediated protection of BMSCs against H2O2-induced injury was investigated using pharmacologic agonists and inhibitors.

Results
Melatonin improved cell survival and restored mitochondrial function. Moreover, melatonin intimately regulated the phosphorylation of AMPK and molecules associated with ER stress pathways. AMPK activation and ER stress inhibition following melatonin administration improved the mitochondrial membrane potential (MMP), reduced mitochondria-initiated oxidative damage, and ultimately suppressed apoptotic signaling pathways in BMSCs. Cotreatment with N-acetyl-l-cysteine (NAC) significantly enhanced the antioxidant effect of melatonin. Importantly, pharmacological AMPK activation/ER stress inhibition promoted melatonin-induced cytoprotection, while pharmacological AMPK inactivation/ER stress induction conferred resistance to the effect of melatonin against H2O2 insult.

Conclusions
Our data also reveal a new, potentially therapeutic mechanism by which melatonin protects BMSCs from oxidative stress-mediated mitochondrial apoptosis, possibly by regulating the AMPK-ER stress pathway.
Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients
Authors: Al-Khawaga Sara , Abdelalim Essam M. 
Published: October 2020

AbstractThe COVID-19 pandemic has negatively impacted the global public health and the international economy; therefore, there is an urgent need for an effective therapy to treat COVID-19 patients. Mesenchymal stem cells (MSCs) have been proposed as an emerging therapeutic option for the SARS-CoV-2 infection. Recently, numerous clinical trials have been registered to examine the safety and efficacy of different types of MSCs and their exosomes for treating COVID-19 patients, with less published data on the mechanism of action. Although there is no approved effective therapy for COVID-19 as of yet, MSC therapies showed an improvement in the treatment of some COVID-19 patients. MSC’s therapeutic effect is displayed in their ability to reduce the cytokine storm, enhance alveolar fluid clearance, and promote epithelial and endothelial recovery; however, the safest and most effective route of MSC delivery remains unclear. The use of poorly characterized MSC products remains one of the most significant drawbacks of MSC-based therapy, which could theoretically promote the risk for thromboembolism. Optimizing the clinical-grade production of MSCs and establishing a consensus on registered clinical trials based on cell-product characterization and mode of delivery would aid in laying the foundation for a safe and effective therapy in COVID-19. In this review, we shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. We further highlight the challenges and opportunities in the use of MSC-based therapy.
Predicting target profiles with confidence as a service using docking scores
Authors: Ahmed Laeeq , Alogheli Hiba , McShane Staffan Arvidsson , Alvarsson Jonathan , Berg Arvid , Larsson Anders , Schaal Wesley , Laure Erwin , Spjuth Ola 
Published: October 2020

AbstractBackgroundIdentifying and assessing ligand-target binding is a core component in early drug discovery as one or more unwanted interactions may be associated with safety issues.ContributionsWe present an open-source, extendable web service for predicting target profiles with confidence using machine learning for a panel of 7 targets, where models are trained on molecular docking scores from a large virtual library. The method uses conformal prediction to produce valid measures of prediction efficiency for a particular confidence level. The service also offers the possibility to dock chemical structures to the panel of targets with QuickVina on individual compound basis.ResultsThe docking procedure and resulting models were validated by docking well-known inhibitors for each of the 7 targets using QuickVina. The model predictions showed comparable performance to molecular docking scores against an external validation set. The implementation as publicly available microservices on Kubernetes ensures resilience, scalability, and extensibility.
Biased and unbiased estimation of the average length of stay in intensive care units in the Covid-19 pandemic
Authors: Lapidus Nathanael , Zhou Xianlong , Carrat Fabrice , Riou Bruno , Zhao Yan , Hejblum Gilles 
Published: October 2020

Abstract
Background
The average length of stay (LOS) in the intensive care unit (ICU_ALOS) is a helpful parameter summarizing critical bed occupancy. During the outbreak of a novel virus, estimating early a reliable ICU_ALOS estimate of infected patients is critical to accurately parameterize models examining mitigation and preparedness scenarios.

Methods
Two estimation methods of ICU_ALOS were compared: the average LOS of already discharged patients at the date of estimation (DPE), and a standard parametric method used for analyzing time-to-event data which fits a given distribution to observed data and includes the censored stays of patients still treated in the ICU at the date of estimation (CPE). Methods were compared on a series of all COVID-19 consecutive cases (n = 59) admitted in an ICU devoted to such patients. At the last follow-up date, 99 days after the first admission, all patients but one had been discharged. A simulation study investigated the generalizability of the methods' patterns. CPE and DPE estimates were also compared to COVID-19 estimates reported to date.

Results
LOS ≥ 30 days concerned 14 out of the 59 patients (24%), including 8 of the 21 deaths observed. Two months after the first admission, 38 (64%) patients had been discharged, with corresponding DPE and CPE estimates of ICU_ALOS (95% CI) at 13.0 days (10.4–15.6) and 23.1 days (18.1–29.7), respectively. Series' true ICU_ALOS was greater than 21 days, well above reported estimates to date.

Conclusions
Discharges of short stays are more likely observed earlier during the course of an outbreak. Cautious unbiased ICU_ALOS estimates suggest parameterizing a higher burden of ICU bed occupancy than that adopted to date in COVID-19 forecasting models.

Funding
Support by the National Natural Science Foundation of China (81900097 to Dr. Zhou) and the Emergency Response Project of Hubei Science and Technology Department (2020FCA023 to Pr. Zhao).
Undernutrition and associated factors among adult HIV/AIDS patients receiving antiretroviral therapy in eastern zone of Tigray, Northern Ethiopia: a cross-sectional study
Authors: Gebru Tsegu Hailu , Mekonen Haftea Hagos , Kiros Kbrom Gemechu 
Published: October 2020

Abstract
Background
Undernutrition and HIV/AIDS are highly prevalent in sub-Saharan Africa, Ethiopia inclusive as linked in a vicious cycle. Thus, several studies have documented that undernutrition among HIV/AIDS patients increases the risk of mortality, decrease survival rates, affect the overall clinical outcome and quality of life.
Despite this fact, information about the burden of undernutrition and associated factors among adults receiving antiretroviral therapy is lacking in the particular study area. Hence, this study aimed to examine the prevalence of undernutrition and associated factors among adult HIV/AIADS patients receiving antiretroviral therapy patients in Eastern Zone of Tigray, Northern Ethiopia.

Methods
A cross-sectional research design was adopted in data collection while systematic sampling technique was employed to sample and select the study subjects. A structured questionnaire was used to collect information from 394 study subjects through face to face method.
Also, data on demographics, laboratory and anthropometric variables were collected from each selected patients sampled.
The data collected were entered and analyzed using SPSS version 22.. Bivariate and multivariable logistic regression analysis with 95% confidence interval were used to find factors associated with undernutrition. The adjusted odds ratio was calculated to show the strength of the association. Variables with p-value of < 0.05 were considered statically significant.

Results
The mean age of the respondents was 41 (± 10). Out of 394 study respondents, about 42.9% of them were undernourished (95% CI: 37.8–47.7).
Respondents who had CD4+ count less than 200 cells/μl (AOR = 1.84; 95% CI: 1–3.36), being advanced clinical staging (AOR = 3.6; 95% CI: 2.11–6.18), and not taking co-trimoxazole preventive therapy (AOR = 2.38; 95% CI: 1.21–4.6) were independently associated with undernutrition.

Conclusion
The result of this study indicated that the prevalence of undernutrition was high.
Respondents with advanced clinical stage of CD4+ count less than 200 cells/ul and those that were not taking co-trimoxazole preventive therapy was found to be positively associated with undernutrition.
Therefore, the implementation of nutritional programs is very crucial to improve the nutritional status of HIV/AIDS patients in the particular study.
The social, economic, political, and genetic value of race and ethnicity in 2020
Authors: Mersha Tesfaye B. , Beck Andrew F. 
Published: October 2020

AbstractDisparities across racial and ethnic groups are present for a range of health outcomes. In this opinion piece, we consider the origin of racial and ethnic groupings, a history that highlights the sociopolitical nature of these terms. Indeed, the terms race and ethnicity exist purely as social constructs and must not be used interchangeably with genetic ancestry. There is no scientific evidence that the groups we traditionally call “races/ethnicities” have distinct, unifying biological or genetic basis. Such a focus runs the risk of compounding equity gaps and perpetuating erroneous conclusions. That said, we suggest that the terms race and ethnicity continue to have purpose as lenses through which to quantify and then close racial and ethnic disparities. Understanding the root cause of such health disparities—namely, longstanding racism and ethnocentrism—could promote interventions and policies poised to equitably improve population health.
Dietary intake and cardiometabolic risk factors among Venezuelan adults: a nationally representative analysis
Authors: Goodman Dina , González-Rivas Juan P. , Jaacks Lindsay M. , Duran Maritza , Marulanda María Inés , Ugel Eunice , Mattei Josiemer , Chavarro Jorge E. , Nieto-Martinez Ramfis 
Published: October 2020

Abstract
Background
Increasing trends in global obesity have been attributed to a nutrition transition where healthy foods are replaced by ultra-processed foods. It remains unknown if this nutrition transition has occurred in Venezuela, a country undergoing a socio-political crisis with widespread food shortages.

Methods
We described dietary intake of Venezuelans from a nationally representative study conducted between 2014 and 2017. We conducted a cross-sectional analysis of dietary, sociodemographic, and clinical data from Venezuelans ≥20 years of age (n = 3420). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. Standardized clinical and anthropometric measurements estimated obesity, type 2 diabetes, and hypertension. A Dietary Diversity Score (DDS) was calculated using an amended Minimum Dietary Diversity for Women score where the range was 0 to 8 food groups, with 8 being the most diverse. Analyses accounted for complex survey design by estimating weighted frequencies of dietary intake and DDS across sociodemographic and cardiometabolic risk-based subgroups.

Results
The prevalence of obesity was 24.6% (95% CI: 21.6–27.7), type 2 diabetes was 13.3% (11.2–15.7), and hypertension was 30.8% (27.7–34.0). Western foods were consumed infrequently. Most frequently consumed foods included coffee, arepas (a salted corn flour cake), and cheese. Mean DDS was 2.3 food groups (Range: 0–8, Standard Error: 0.07) and this score did not vary among subgroups. Men, younger individuals, and those with higher socioeconomic status were more likely to consume red meat and soft drinks once or more weekly. Women and those with higher socioeconomic status were more likely to consume vegetables and cheese once or more daily. Participants with obesity, type 2 diabetes, and hypertension had lower daily intake of red meat and arepas compared to participants without these risk factors.

Conclusions
Despite high prevalence of cardiometabolic risk factors, adults in Venezuela have not gone through a nutrition transition similar to that observed elsewhere in Latin America. Dietary diversity is low and widely consumed food groups that are considered unhealthy are part of the traditional diet. Future studies are needed in Venezuela using more comprehensive measurements of dietary intake to understand the effect of the socio-political crisis on dietary patterns and cardiometabolic risk factors.
Comparative histological and histochemical studies between ranitidine and nizatidine in treatment of peptic ulcer with evaluation of their adverse effects on male sex hormones
Authors: Alazzouni Ahmed S. , Abdel Aziz Elsayed A. , Elnabtity Sameh , Salem Areej I. 
Published: October 2020

Abstract
Background
Peptic ulcer is an excoriated area of stomach or intestinal mucosa. Two experimental designs were proceeded: the first aimed. on twenty adult male albino rats, used to study the protective effect of both ranitidine and nizatidine; on the second, including sixty adult male albino rats, was used to study the therapeutic effect of ranitidine and nizatidine after induction of ulcer and also to evaluate the adverse effects of therapeutic doses of H2-receptor antagonists on male hormonal profile. The study aims to assess the gastroprotective effects of nizatidine and ranitidine and on treating of non-steroidal anti-inflammatory drugs (NSAIDs) induced peptic ulcer and to evaluate its adverse effect on male sex hormones.

Result
The result revealed that ranitidine and nizatidine reduced incidence of ulceration. Histopathological findings showed a significant recovery of the alteration, and disturbance in male sex hormones.

Conclusion
Nizatidine is better than ranitidine in the management of NSAIDs induced peptic ulcer in rats.