bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevant mediators involved in and therapies targeting the inflammatory response induced by activation of the NLRP3 inflammasome in ischemic stroke
Authors: Xu Qingxue , Zhao Bo , Ye Yingze , Li Yina , Zhang Yonggang , Xiong Xiaoxing , Gu Lijuan 
Published: May 2021

AbstractThe nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome is a member of the NLR family of inherent immune cell sensors. The NLRP3 inflammasome can detect tissue damage and pathogen invasion through innate immune cell sensor components commonly known as pattern recognition receptors (PRRs). PRRs promote activation of nuclear factor kappa B (NF-κB) pathways and the mitogen-activated protein kinase (MAPK) pathway, thus increasing the transcription of genes encoding proteins related to the NLRP3 inflammasome. The NLRP3 inflammasome is a complex with multiple components, including an NAIP, CIITA, HET-E, and TP1 (NACHT) domain; apoptosis-associated speck-like protein containing a CARD (ASC); and a leucine-rich repeat (LRR) domain. After ischemic stroke, the NLRP3 inflammasome can produce numerous proinflammatory cytokines, mediating nerve cell dysfunction and brain edema and ultimately leading to nerve cell death once activated. Ischemic stroke is a disease with high rates of mortality and disability worldwide and is being observed in increasingly younger populations. To date, there are no clearly effective therapeutic strategies for the clinical treatment of ischemic stroke. Understanding the NLRP3 inflammasome may provide novel ideas and approaches because targeting of upstream and downstream molecules in the NLRP3 pathway shows promise for ischemic stroke therapy. In this manuscript, we summarize the existing evidence regarding the composition and activation of the NLRP3 inflammasome, the molecules involved in inflammatory pathways, and corresponding drugs or molecules that exert effects after cerebral ischemia. This evidence may provide possible targets or new strategies for ischemic stroke therapy.
Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study
Authors: Seo Kyoung-Ho , Jang Joonyoung , Jang Eun Gyeong , Park Yulhyun , Lee So Young , Kim Bo Ryun , Park Donghwi , Park Sungwon , Hwang Hyeoncheol , Kim Nam Hun , Oh Byung-Mo , Seo Han Gil , Lee Jun Chang , Ryu Ju Seok 
Published: May 2021

Abstract
Background
To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles.

Objective
To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES.

Methods
In this prospective randomized case–control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2–3 weeks (minimal session: 7 times, treatment duration: 300–800 min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale.

Results
The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores.

Conclusions
The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia.
Trial registration: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1.
Existence results for coupled nonlinear fractional differential equations of different orders with nonlocal coupled boundary conditions
Authors: Alsaedi Ahmed , Hamdan Soha , Ahmad Bashir , Ntouyas Sotiris K. 
Published: May 2021

AbstractThis paper is concerned with the solvability of coupled nonlinear fractional differential equations of different orders supplemented with nonlocal coupled boundary conditions on an arbitrary domain. The tools of the fixed point theory are applied to obtain the criteria ensuring the existence and uniqueness of solutions of the problem at hand. Examples illustrating the main results are presented.
Disruption of orbitofrontal-hypothalamic projections in a murine ALS model and in human patients
Authors: Bayer David , Antonucci Stefano , Müller Hans-Peter , Saad Rami , Dupuis Luc , Rasche Volker , Böckers Tobias M. , Ludolph Albert C. , Kassubek Jan , Roselli Francesco 
Published: May 2021

Abstract
Background
Increased catabolism has recently been recognized as a clinical manifestation of amyotrophic lateral sclerosis (ALS). The hypothalamic systems have been shown to be involved in the metabolic dysfunction in ALS, but the exact extent of hypothalamic circuit alterations in ALS is yet to be determined. Here we explored the integrity of large-scale cortico-hypothalamic circuits involved in energy homeostasis in murine models and in ALS patients.

Methods
The rAAV2-based large-scale projection mapping and image analysis pipeline based on Wholebrain and Ilastik software suites were used to identify and quantify projections from the forebrain to the lateral hypothalamus in the SOD1(G93A) ALS mouse model (hypermetabolic) and the FusΔNLS ALS mouse model (normo-metabolic). 3 T diffusion tensor imaging (DTI)-magnetic resonance imaging (MRI) was performed on 83 ALS and 65 control cases to investigate cortical projections to the lateral hypothalamus (LHA) in ALS.

Results
Symptomatic SOD1(G93A) mice displayed an expansion of projections from agranular insula, ventrolateral orbitofrontal and secondary motor cortex to the LHA. These findings were reproduced in an independent cohort by using a different analytic approach. In contrast, in the FusΔNLS ALS mouse model hypothalamic inputs from insula and orbitofrontal cortex were maintained while the projections from motor cortex were lost. The DTI-MRI data confirmed the disruption of the orbitofrontal-hypothalamic tract in ALS patients.

Conclusion
This study provides converging murine and human data demonstrating the selective structural disruption of hypothalamic inputs in ALS as a promising factor contributing to the origin of the hypermetabolic phenotype.
Platelet-driven coagulopathy in COVID-19 patients: in comparison to seasonal influenza cases
Authors: Zhang Jianguo , Huang Xing , Ding Daoyin , Tao Zhimin 
Published: May 2021

Abstract
Background
One year into the coronavirus diseases 2019 (COVID-19) pandemic we analyzed the blood coagulopathy in severe and non-severe COVID-19 patients and linked to those of influenza patients for a comparative study.

Methods
We reported 461 COVID-19 patients and 409 seasonal influenza patients admitted at separated medical centers. With their demographic data and medical history, hematological profiles with coagulation characters were emphasized, and compared between two cohorts before and after treatment.

Results
For 870 patients included in this study, their median age was (64.0, 51.0–76.0), and among them 511 (58.7%) were male. Hypertension, diabetes, cardiovascular diseases, and bronchitis constituted the leading comorbidities. Upon hospital admission blood test results differentiated COVID-19 patients from influenza cases, and for COVID-19 patients, leukocytosis, neutrophilia, lymphocytopenia, and thrombocytopenia were associated with disease severity and mortality. In addition, COVID-19 cohort demonstrated a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), increased INR, shortened thrombin time and decreased fibrinogen, compared to those in influenza cohort, leaving D-dimer levels indistinguishably high between both cohorts. Platelet hyperreactivity in COVID-19 is more evident, associated with worse hyper-inflammatory response and more refractory coagulopathy. For severe COVID-19 patients administered with anticoagulants, bleeding incidence was substantially higher than others with no anticoagulant medications.

Conclusions
Comparison of coagulation characteristics between COVID-19 and influenza infections provides an insightful view on SARS-CoV-2 pathogenesis and its coagulopathic mechanism, proposing for therapeutic improvement.
Dynamics of the terrestrial radiation belts: a review of recent results during the VarSITI (Variability of the Sun and Its Terrestrial Impact) era, 2014–2018
Authors: Kanekal Shrikanth , Miyoshi Yoshizumi 
Published: May 2021

AbstractThe Earth’s magnetosphere is region that is carved out by the solar wind as it flows past and interacts with the terrestrial magnetic field. The inner magnetosphere is the region that contains the plasmasphere, ring current, and the radiation belts all co-located within about 6.6 Re, nominally taken to be bounding this region. This region is highly dynamic and is home to a variety of plasma waves and particle populations ranging in energy from a few eV to relativistic and ultra-relativistic electrons and ions. The interplanetary magnetic field (IMF) embedded in the solar wind via the process of magnetic reconnection at the sub-solar point sets up plasma convection and creates the magnetotail. Magnetic reconnection also occurs in the tail and is responsible for explosive phenomena known as substorms. Substorms inject low-energy particles into the inner magnetosphere and help generate and sustain plasma waves. Transients in the solar wind such as coronal mass ejections (CMEs), co-rotating interaction regions (CIRs), and interplanetary shocks compress the magnetosphere resulting in geomagnetic storms, energization, and loss of energetic electrons in the outer radiation belt nad enhance the ring current, thereby driving the geomagnetic dynamics. The Specification and Prediction of the Coupled Inner-Magnetospheric Environment (SPeCIMEN) is one of the four elements of VarSITI (Variability of the Sun and Its Terrestrial Impact) program which seeks to quantitatively predict and specify the inner magnetospheric environment based on Sun/solar wind driving inputs. During the past 4 years, the SPeCIMEN project has brought together scientists and researchers from across the world and facilitated their efforts to achieve the project goal. This review provides an overview of some of the significant scientific advances in understanding the dynamical processes and their interconnectedness during the VarSITI era. Major space missions, with instrument suites providing in situ measurements, ground-based programs, progress in theory, and modeling are briefly discussed. Open outstanding questions and future directions of inner magnetospheric research are explored.
Drug-related problems and its determinant among hospitalized neonates with sepsis at Jimma University Medical Center, Ethiopia: a prospective observational study
Authors: Awoke Mengist , Melaku Tsegaye , Beshir Mohammed 
Published: May 2021

Abstract
Background
Neonatal populations are quite susceptible to drug-related problems (DRPs) because of clinical heterogeneity and clinical practice trends. However, studies reporting DRPs in the neonatal population are quite limited.

Objective
This study aimed to assess the magnitude and types of DRPs and determinant factors among neonates admitted with neonatal sepsis at the Neonatal Intensive Care Unit (NICU) of the Jimma University Medical Center (JUMC), Ethiopia.

Methods
A hospital-based prospective observational study was conducted involving 201 neonates with sepsis admitted to the NICU from May to August 30, 2018. DRPs were classified using Cipolle’s classification method. Statistical Package for Social Science Version 22 was employed for data analysis. Logistical regression was carried out to determine the determinants of DRPs. A p-value < 0.05 was considered to be statistically significant.

Results
Of 201 neonates with sepsis included in this study, 125 (62.2%) were males and the median age of the neonate was 5 days. The mean (±standard deviation) number of medications taking during their hospital stay was 2.6 ± 0.7. DRPs were identified in 98 neonates, at a rate of 48.8% (95% CI, 41.7–55.9). Dose too high (42, 35.8%) and need additional drug therapy (40, 34.1%) were the commonly identified DRPs. Taking antibiotics plus other medications (Adjusted Odds Ratio (AOR) =5.2, 95%CI [1.2–22.0], p = 0.02) was a determinant factor for the occurrence of DRPs.

Conclusion
The burdens of DRPs occurrence were high in hospitalized neonates with sepsis. The most common DRPs identified were dose too high and need additional drug therapy. Combined use of other medicines with antibiotics was a predictor of DRP occurrence. The innovative way to tackle the occurrence of DRPs, such as the incorporation of clinical pharmacy service provider into the neonatal care team, which will prevent, detect and/or minimize the occurrence of DRPs, is highly recommended.
Enhancement and evaluation of a prescription audit system for direct oral anticoagulants using a check sheet
Authors: Ishikawa Naoto , Oshikiri Hanae , Takasaki Shinya , Kikuchi Masafumi , Obara Taku , Akasaka Kazutoshi , Matsuura Masaki , Yamaguchi Hiroaki , Mano Nariyasu 
Published: May 2021

Abstract
Background
Renal function and use of concomitant medications should be carefully monitored in patients subjected to treatment with direct oral anticoagulants (DOACs); the dose should be individually designed for each patient. Owing to the complex therapeutic indications and dose reduction criteria, pharmacists exercise caution when determining the optimal dose for each patient. A DOAC check sheet has been developed that is automatically printed in the dispensing room at the same time as the prescription and can be used by pharmacists to dispense DOACs promptly and correctly. The purpose of this study was to evaluate the system for dispensing DOACs using a check sheet.

Methods
The study was conducted at Tohoku University Hospital in Japan; prescriptions containing DOACs dispensed by the hospital pharmacists were evaluated. The DOAC check sheet described indications, dosage regimens, dose reduction criteria, and contraindications for each drug and included the patient’s information. The check sheet was set to print automatically in the dispensing room at the same time as the prescription when an inpatient was prescribed DOACs. This check sheet was evaluated using a prescription survey and a questionnaire for pharmacists.

Results
The usefulness of this check sheet for the correct use of DOACs was evaluated. There were four inquiries out of 642 (0.6%) prescriptions from pharmacists to physicians regarding DOAC prescriptions, such as the dose introduced before DOAC check sheet utilization, and there were 21 out of 905 (2.3%) prescriptions when the DOAC check sheet was used it, showing a significant increase (p = 0.0089). After the introduction of this sheet, overdoses of DOACs were identified at the time of dispensing. Of the 52 pharmacists who responded to the questionnaire, 51 (98%) stated that the check sheet was useful.

Conclusion
The use of the DOAC check sheet is likely to render safety to DOAC drug therapy for individual patients.
Contraceptive prevalence rate and associated factors among reproductive age women in four emerging regions of Ethiopia: a mixed method study
Authors: Bekele Delayehu , Surur Feiruz , Nigatu Balkachew , Teklu Alula , Getinet Tewodros , Kassa Munir , Gebremedhin Merhawi , Gebremichael Berhe , Abesha Yonas 
Published: May 2021

Abstract
Background
Ethiopia is the second most populous country in Africa, known for its high fertility and low contraceptive use. The magnitude of contraceptive use in the emerging regions of the country is below the national average. However, there is a paucity of evidence regarding the reasons for low contraceptive use in these regions. Therefore, this study aimed to assess contraceptive use and associated factors in the emerging regions of Ethiopia.

Methods
For the quantitative part, a community based cross-sectional study was conducted among 2891 reproductive age women who were selected by multistage sampling technique. Data were collected face to face using an open data kit software, and STATA version 14 was used for data analysis. Frequencies, percentages, summary measures and tables were used to summarize and present the data. Bivariable and multivariable logistic regression analyses were performed to identify factors associated with contraceptive use, by computing odds ratio with 95% confidence interval. Level of significance was considered at p-value < 0.05. For the qualitative part, phenomenological study was conducted among 252 health care workers and community members who were selected purposely. The data were collected by focused group discussions, in-depth interviews and key informant interviews. The data were audio-recorded in the local languages, and then translated to English verbatim. NVivo version 11 was used to analyze the data through a thematic analysis method.

Results
The overall contraceptive prevalence rate was 22.2%; with 11.7, 38.6, 25.5 and 8.8% for Afar, Benshangul Gumuz, Gambela and Somali Regions, respectively. Age, religion, education, marital status, family size, ideal children, knowledge and attitude were significantly associated with contraceptive use. Additionally, the qualitative study identified three themes as barriers to contraceptive use: individual, health care system and sociocultural factors.

Conclusions
Contraceptive prevalence rate was low in this study compared to the national average. Age, religion, education, marital status, family size, ideal children, knowledge and attitude were significantly associated with contraceptive use. From the qualitative aspect, individual, health care system and sociocultural factors were identified as barriers to contraceptive use. Therefore, the emerging regions of Ethiopia need special focus in increasing contraceptive use through behavioral influence/change.
Development and double cross-validation of new spot urine sodium equation to predict 24-h urine sodium in the Malaysian population
Authors: Othman Fatimah , Ambak Rashidah , Omar Mohd Azahadi , Shahar Suzana , Nor Noor Safiza Mohd , Ahmad Mohamad Hasnan , Yusoff Muhammad Fadhli Mohd , Haron Hasnah , Noh Mohd Fairulnizal Md , Aris Tahir 
Published: May 2021

Abstract
Background
Monitoring sodium intake through 24-h urine collection sample is recommended, but the implementation of this method can be difficult. The objective of this study was to develop and validate an equation using spot urine concentration to predict 24-h sodium excretion in the Malaysian population.

Methods
This was a Malaysian Community Salt Study (MyCoSS) sub-study, which was conducted from October 2017 to March 2018. Out of 798 participants in the MyCoSS study who completed 24-h urine collection, 768 of them have collected one-time spot urine the following morning. They were randomly assigned into two groups to form separate spot urine equations. The final spot urine equation was derived from the entire data set after confirming the stability of the equation by double cross-validation in both study groups. Newly derived spot urine equation was developed using the coefficients from the multiple linear regression test. A Bland-Altman plot was used to measure the mean bias and limits of agreement between estimated and measured 24-h urine sodium. The estimation of sodium intake using the new equation was compared with other established equations, namely Tanaka and INTERSALT.

Results
The new equation showed the least mean bias between measured and predicted sodium, − 0.35 (− 72.26, 71.56) mg/day compared to Tanaka, 629.83 (532.19, 727.47) mg/day and INTERSALT, and 360.82 (284.34, 437.29) mg/day. Predicted sodium measured from the new equation showed greater correlation with measured sodium (r = 0.50) compared to Tanaka (r =0.24) and INTERSALT (r = 0.44), P < 0.05.

Conclusion
Our newly developed equation from spot urine can predict least mean bias of sodium intake among the Malaysian population when 24-h urine sodium collection is not feasible.
Sodium intake assessed by 24-h urine excretion and its relationship with anthropometric measurements in Malaysian adults
Authors: Sallehuddin Syafinaz Mohd , Ambak Rashidah , Othman Fatimah , Aziz Nur Shahida Abd , Palaniveloo Lalitha , Nor Noor Safiza Mohd , Jamaluddin Rasidah , Baharudin Azli , Zaki Nor Azian Mohd , Ahmad Mohamad Hasnan 
Published: May 2021

Abstract
Background
Sodium intake is associated with anthropometric measurement including weight, waist circumference (WC), and body mass index (BMI). Higher intake of sodium is usually linked to higher risk of obesity among adults globally, especially in developing countries. This study aims to explore the probable relationship between sodium intake by 24-h urine excretion assessment and anthropometric measurement of adults in Malaysia.

Methods
A cross-sectional study was conducted from October 2017 to March 2018 using a multi-stage stratified sampling method among Malaysian adults aged 18 years old and above. Sodium intake was determined by 24-h urinary sodium excretion, estimated from the respondents’ 24-h urinary sample. Height was obtained based on standard protocol. Weight and WC were measured twice using validated anthropometric equipment and BMI was calculated according to World Health Organization (WHO) 1998 classification. Descriptive analysis was done to describe socio-demographic characteristics. A simple linear regression and multiple linear regression tests were done to assess the relationship of 24-h urinary excretion and anthropometric measurement. All statistical analysis was done using SPSS version 22.0.

Results
Of 1047 interviewed respondents, 798 respondents had done the 24-h urine collection (76.0% response rate). Majority was between 40 and 59 years old (43.5%) and married (77.7%). Simple linear regression showed a significant positive linear association between 24-h urinary excretion and household income, WC, and obese group. In the multivariate analysis, it was indicated that, an increase of 1 unit of BMI will significantly increase the sodium intake by 129.20 mg/dl and an increase of 1 cm of WC will significantly increase the sodium intake by 376.45 mg/dl.

Conclusion
Our study showed a positive significant relationship between sodium intake estimated by 24-h urinary sodium excretion and BMI of Malaysian adults. More research is suggested on how sodium control can potentially contribute to obesity prevention.