bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Cell Transcriptome Sequencing Reveals the Potential Mechanism of Heterogeneity in Immunoregulatory Function Between Mesenchymal Stromal Cells
Authors: Cai Siyu , Fan Chuiqin , Xie Lichun , Zhong Huifeng , Li Aijia , Lv Siyu , Liao Maochuan , Yang Xixi , Su Xing , Wang Yue , Wang Hongwu , Wang Manna , Huang Peng , Liu Yulin , Wang Yu , Liu Yufeng , Wang Tianyou , Zhong Yong , Ma Lian 
Published: August 2021

Abstract
Background: Mesenchymal stromal cells (MSCs) could be applied for the treatment of immune-related diseases. However, some studies have found there is enormous heterogeneity in immunomodulatory function of MSCs isolated from different tissue. At present, the underlying mechanism of heterogeneity in immunoregulatory function is still unclear. Methods: In this study, the foreskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured to the 3rd passage. Cell types were confirmed according to the standard of International Association for Cell Therapy. Then, FSMSCs and HuMSCs were co-cultured with human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharides (LPS) in viro respectively. And the supernatant was sampled for enzyme-linked immunosorbent assay to investigate the secretion of IL-1β, IL-6, IL-10, TNF-α and TGF-β. Finally, single cell transcriptome sequencing was performed in order to elucidate the mechanism for the difference of immunomodulatory function.Results: FSMSCs and HuMSCs are successfully identified as MSCs. When co-cultured with LPS pre-treated PBMC, FSMSCs and HuMSCs could effectively reduce the secretion of IL-1β and TNF-α. But FSMSCs were able to stimulate the PBMC to secrete more IL-10, TGF-β and IL-6. Furthermore, 4 MSCs subsets in integrated data were identified, including Proliferative MSCs , Pericyte, Immune MSCs and Progenitor Proliferative MSCs. Among them, the proportions of Immune MSCs in FSMSCs and HUMSCs were 56% and 10% respectively. Varieties of immune-related genes, gene sets and regulons were enriched in Immune MSCs. And Immune MSCs with powful transcriptional activity were found to be near to Pericyte at the degree of differentiation and closed to other cell subsets. Finally, the foreskin tissue might be an ideal source of isolating Immune MSCs when comparing the subset composition of MSCs derived from adipose tissue and bone marrow from public database. Conclusions: Immune MSCs may play a key role in the heterogeneity of immunoregulatory function. It is a new insight that Immune MSCs could be isolated and better applied for the treatment of immune-related diseases without being limited by the heterogeneity of immunomodulatory function derived from different tissues.
Study of Ionized Magnesium and Calcium Levels in a Cohort of Patients with Septic Shock Treated with Standard Therapy and Antioxidants
Authors: Aisa-Álvarez Alfredo , Soto María Elena , Camarena-Alejo Gilberto , Franco-Granillo Juvenal , Soto Randall Cruz , Pérez-Torres Israel , Gómez Claudia Huesca , Torres-Paz Yazmín Estela , Fuentevilla-Álvarez Giovanny , Gamboa Ricardo 
Published: August 2021

Abstract
Background: Septic shock is the most serious form of sepsis and can be due to several factors, such as hypovolemia, vascular hyporesponsiveness, myocardial dysfunction, or dysfunction of the circulation. Likewise, electrolyte levels have been associated with septic shock in intensive care units, although it has been underdiagnosed. Based on this, the purpose of the present work was to evaluate plasma ionic levels in patients with septic shock before and after treatment with different antioxidants. Methods: Plasma ionic levels were measured (Na+, K+, Cl- and ionized Ca2+ and Mg2+) in 194 subjects, 129 healthy control patients, 14 patients with septic shock without treatment and 51 patients with septic shock under treatment with 4 different antioxidants (N-acetyl cysteine, melatonin, vitamin C and vitamin E). Results: We found important differences when comparing the plasma ionic levels of K+, Ca2+ and Mg2+ between the control group versus in both groups with sepsis at the time of hospital admission. In patients with septic shock, there is a decrease in the serum levels of ionized Na+, K+, Cl- and Ca2+ and Mg2+. Antioxidant treatment as an adjunct to the standard management of patients with septic shock increases the electrolyte deficit. The correction of the magnesium deficit also leads to an increase in serum calcium and potassium levels. Conclusion: The management of antioxidant therapy in patients with septic shock within the first hours of admission can help to improve their ionic levels of Ca2+ and Mg2+, mainly in patients with lung damage.Clinical Trial gov registration: NCT03557229. Registered june 14, 2018. https://clinicaltrials.gov/ct2/show/NTC03557229?term=aISA+ALFREDO&draw=2&rank=1
Non-Linear And Cross-Interaction Analyses of SOFA Subscores As Predictive Markers For Sepsis: A Nationwide Retrospective Study
Authors: Umemura Yutaka , Yamakawa Kazuma , Murao Shuhei , Mitsuyama Yumi , Ogura Hiroshi , Fujimi Satoshi 
Published: August 2021

Abstract
Background: The Sequential Organ Failure Assessment (SOFA) score is predominantly used to assess the severity of organ dysfunction in sepsis and is definitely proved to be associated with mortality. However, differences in prognostic value between SOFA subscores have not been sufficiently evaluated so far, and detailed evaluation of subscores is required to verify the clinical significance of the SOFA score. The present study aimed to evaluate the non-linear prognostic association of SOFA subscores and the cross-interaction effects on mortality when SOFA subscores were simultaneously increased.Methods: This retrospective observational study used a part of a large-scale database containing about 30 million patients. Among them, we included all adult patients requiring unplanned hospital admission and were diagnosed as having sepsis by Sepsis-3 criteria from February 2006 to December 2019. A proven/suspected infection was defined as having any of the ICD-10 codes for infection. Associations between the SOFA components and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated two-way interaction effects on mortality between an increase of one SOFA subscore and another.Results: The final study cohort included 38,869 patients with sepsis. Restricted cubic spline analyses showed that an increase in total SOFA score was sharply and linearly associated with increased mortality. However, the prognostic association of SOFA subscores was non-linear and varied widely by biomarker: platelet count showed a J-shaped association, creatinine showed an inverted J-shaped association, and bilirubin showed only a weak association with mortality. The mortality odds ratios of SOFA scores were synergistically increased when another SOFA subscore was higher than 2 points, and the effect modifications were statistically significant in almost all subgroups. Especially in patients with cardiovascular or hepatic subscores of ≥ 2 points, odds ratios of the other SOFA subscores were remarkably increased (double to triple) compared to those in the whole study population.Conclusion: Despite the widely varied prognostic associations of SOFA subscores, total SOFA score was sharply and almost linearly associated with increased mortality. Cross-interactions between subscores synergistically enhanced its prognostic associations and might be responsible for the high prognostic accuracy of the total SOFA score.
Identifying the critically ill cirrhotics who benefit the most from nutrition therapy: The mNUTRIC score study
Authors: Tripathi Harshita , Benjamin Jaya , Maiwall Rakhi , Puri Puneet , Kapoor Puja Bhatia , Shasthry Varsha , Saluja Vandana , Agrawal Prashant , Kumar Guresh , Joshi Yogendra Kumar , Sarin Shiv Kumar 
Published: August 2021

Abstract
Background

Malnutrition increases risk of mortality in critically ill cirrhotics. Modified Nutrition Risk in Critically ill (mNUTRIC) score is a validated tool to identify patients at nutrition risk that may benefit the most from goal directed nutrition therapy. We aimed to study the association between mNUTRIC score and 28-day mortality and its modulation by nutritional adequacy in critically ill cirrhotics.
Methods

A prospective study in critically ill adult cirrhotics was designed with collection of baseline and follow-up data pertaining to mNUTRIC score, clinical, hemodynamic, biochemical, nutritional parameters, use of mechanical ventilation (MV), length of ICU stay, and development of new onset infection (NOI). Daily nutritional adequacy was calculated as percentage of prescribed energy and protein received.
Results

150 cirrhotics [(males-83%, age-51 ± 12.1 years, BMI-24 ± 4.7kg/m2; median LOS 6 (2–24 days)] were enrolled. At ICU admission 116 (77%) had high NUTRIC Score (HNS) and 34 (23%) low NUTRIC score (LNS). Patients with HNS had significantly higher mortality [54% vs. 10%; p = 0.008; OR(95%CI) adjusted 3.0(1.39,6.9;p = 0.006)] for etiology and blood sugar ; longer MV days [5(2–24) vs. 3(1–24) ; p = 0.02]; and high incidence of NOI [32% vs. 2.6%; p = 0.002; OR(95% CI:7(2,24.5)] compared to LNS. A logistic regression analysis for interaction of nutritional adequacy and 28 day survival revealed that the probability of survival increases with increase in nutritional adequacy (p < 0.01) in patients with HNS.
Conclusion

mNUTRIC score is a useful tool in recognizing nutrition risk in critically ill cirrhotics and goal directed nutrition therapy; especially in patients with high mNUTRIC score can significantly improve survival.
Representing Uncertainty in Group Decision Making Through the Hesitant Information Set Approach
Authors: Agarwal Manish 
Published: August 2021

Abstract
In multi attribute group decision making (MAGDM), different types of un- certainties co-exist on account of hesitancy, vagueness, and incompleteness besides the diversity in evaluations. To cater to this problem of represent- ing such uncertain evaluations in their original form, new datastructures have been proposed. In this regard, the concept of hesitant information set (HIS) [Applied Soft Computing, 2018] is of great significance. To add to its usefulness in the representation of vague evaluations, it is extended to the continuous and interval-valued domains. A number of illustrative examples are included to show their worth in the real world group decision-making. The basic operations for them, along with their properties, are investigated. A real case-study is included.
Vitiligo-like Leukoderma as an Indicator of Clinical Response to Immune Checkpoint Inhibitors in Late-stage Melanoma Patients
Authors: Verkhovskaia Sofia , Pietro Francesca Romana Di , Mastroeni Simona , Carbone Maria Luigia , Abeni Damiano , Morese Roberto , Morelli Francesca Maria , D’Atri Stefania , Marchetti Paolo , De Galitiis Federica , Failla Cristina M. , Fortes Cristina 
Published: August 2021

Abstract
Purpose. Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.Methods. A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated. Results. Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR = 0.23; 95% CI = 0.11-0.44, p <0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N=153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR:0.17; 95% CI:0.06-0.44). Conclusion. Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.
Mutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airway.
Authors: Zhou Jie , Peacock Thomas , Brown Jonathan , Goldhill Daniel , Elrefaey Ahmed , Penrice-Randal Rebekah , Cowton Vanessa , De Lorenzo Giuditta , Furnon Wilhelm , Harvey William , Kugathasan Ruthiran , Frise Rebecca , Baillon Laury , Lassauniere Ria , Thakur Nazia , Gallo Giulia , Goldswain Hannah , Donovan-Banfield I'ah , Dong Xiaofeng , Randle Nadine , Sweeney Fiachra , Glynn Martha , Quantrill Jessica , McKay Paul , Patel Arvind , Palmarini Massimo , Hiscox Julian , Bailey Dalan , Barclay Wendy 
Published: August 2021

Abstract
SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs and farmed mink. Since the start of the 2019 pandemic several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all 3 mink-adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.
The Impact of Cancer Concealment on Postoperative Esophageal Cancer Patients in Stage T3: A Propensity Scores Matching Analysis
Authors: Yu Minhao , Long Zhiquan 
Published: August 2021

Abstract
Background
Esophageal cancer has a poor prognosis and high mortality rate, and the overall five-year survival rate is pretty low. In addition to medical factors, some psychological and sociological factors can also contribute to it.
Methods
We selected postoperative T3 esophageal cancer patients hospitalized from June 2015 to December 2016 as research subjects, and divided them into a cancer-awareness group and a cancer-concealment group. Several variables are allowed for evaluating 36-month progress-free survival of the two groups. Propensity Scores Matching analysis were used to adjust selection bias.
Results
There were 72 patients enrolled in the study. Sex and cancer concealment were significantly predicted poor survival while stage, pathological differentiation, education background and age were not (P = 0.017, 0.020, 0.302, 0.177, 0.068, 0.054, respectively). Cox multivariate regression analysis shows sex and cancer concealment were independent predictors of progress-free survival of esophageal cancer at postoperative T3 stage (harzard ratio = 0.264, 95% confidence interval: 0.099–0.703, P = 0.008; harzard ratio = 2.823, 95% confidence interval: 1.360–5.861, P = 0.005, respectively).
Conclusions
Cancer concealment is an important negative predictors of postoperative esophageal cancer patients' progress-free survival.
The contribution of galenics to patients’ sensory perception of nasal sprays after nasal surgery – data from a prospective randomized, controlled, double-blind, cross-over, multi-centre study
Authors: Bergmann Christoph , Lander Jennifer , Radtke Lea , England Laura , Singh Jaswinder , Moesges Ralph 
Published: August 2021

Abstract
Introduction:Postoperative care after nasal surgery is commonly achieved with nasal sprays. The current study compared two decongesting, wound healing nasal sprays in patients after nasal surgery in order to investigate their sensoric perception. One of the sprays presented a new galenic formulation (nasic® neo, Cassella-med GmbH & Co. KG).Methods:Using a cross-over design, patients who had undergone nasal surgery applied two different nasal sprays during two treatment periods of 4 days each, interrupted by 3 days wash out period. Sensoric perception of the nasal sprays was assessed with the nasal-spray-sensoric-scale. Throughout the study, nasal obstruction was evaluated by patients, and physical examinations, measurements of vital parameters and rhinoscopic examinations were carried out by investigators. Adverse events were documented during the entire study, and following treatment, patients judged the overall preference, efficacy and tolerability of both products.Results:Overall, no significant differences in sum scores of the assessments of the nasal-spray-sensoric-scale were observed between treatments. Significant periodic effect observed during the cross-over study limited the overall analysis. Nevertheless, it could be shown that significantly more patients preferred the new galenics nasal spray compared to the comparator spray (57.1% vs. 34.7%; p=0.031). Further, 10% more patients rated the efficacy of new galenics as ‘good’ to ‘very good’ compared to the comparator. Importantly, a subgroup population of patients with more pronounced signs of inflammation present at screening evaluated the sensoric perception of new galenics significantly better (p=0.033) compared to the comparator. Within this subgroup, no periodic effect was observed. The application of both nasal sprays was shown to be safe and well-tolerated.Conclusion:The current study showed that the overall sensoric perception of both nasal sprays was evaluated comparably well in patients after nasal surgery and that overall, the application of the new galenics nasal spray was preferred by significantly more patients compared to the comparator nasal spray. Patients with marked nasal abnormalities may have a greater benefit from the contribution of galenics as significant differences in the sensoric evaluation by the nasal-spray-sensoric-scale in favour of the new galenics product were shown for this subgroup.Trial registration: The current study was registered in the EU Clinical Trials Register with the EudraCT No: 2019-004936-52.
Heart Rate Variability Predicts Treatment Efficacy in Patients with Chronic Migraine: An Exploratory Study
Authors: Chuang Chun-Hsiang , Lai Kuan-Lin , Li Jhe-Yu , King Jung-Tai , Chen Wei-Ta , Chen Shih-Pin , Wang Yen-Feng , Liu Hung-Yu , Hsiao Fu-Jung , Pan Li-Ling Hope , Wang Shuu-Jiun 
Published: August 2021

Abstract
Background : Chronic migraine (CM) is a disabling headache disorder. Autonomic nervous system (ANS) disturbance, as evidenced from heart rate variability (HRV) studies, has been documented in patients with episodic migraine and other pain disorders but not specifically in patients with CM. This study aimed to explore whether the HRV in patients with CM was impaired and whether it could be used to predict treatment outcomes.Methods : Patients with CM were recruited, along with age- and gender-matched healthy controls (CTLs). The time-domain, frequency-domain, and nonlinear metrics of HRV were calculated to evaluate the sympathetic and parasympathetic aspects of ANS function in patients with CM before and after 3-month (12 weeks) treatment with flunarizine as well as in CTLs. The patients were asked to keep a headache diary throughout the study period to determine the treatment efficacy.Results : A total of 81 patients with CM and 58 CTLs completed the study. Most HRV values in patients with CM were significantly lower than those in CTLs, suggesting decreased overall autonomic modulation and parasympathetic hypofunction but not sympathetic dysfunction. By unsupervised clustering analysis, patients with CM were divided into two cluster groups with high and low HRV at baseline. Patients with high baseline HRV, which was comparable to that of CTLs, showed significantly higher absolute and relative reductions in averaged monthly headache days across a 3-month preventive treatment compared with patients with low baseline HRV (-9.1 days vs. -6.4 days or -43.2% vs. -30.1%, both p < 0.05). The HRV increased after preventive treatment in the low-HRV group but not in the high-HRV group.Conclusions : HRV could distinguish patients with CM from CTLs, indicating the involvement of ANS dysfunction. Moreover, patients with CM having a near-normal baseline HRV, indicating a preserved parasympathetic function and overall ANS modulation reservoir, predicted a better outcome to preventive treatment with flunarizine than those with low HRV.Trial registration: Neurologic Signatures of Chronic Pain Disorders, NCT02747940.Registered 22 April 2016, https://clinicaltrials.gov/ct2/show/NCT02747940
Penyesuaian Metode Penanganan Proyek dan Desain Arsitektur pada Masa Pandemi
Authors: Gunawan Gede Arista 
Published: August 2021

Title: Adjustments of Project Handling and Architecture Design Method at Pandemic Time:
Case Studies: Painter House and Villa Nabu Projects by Bale Design

Architects have methods in project handling and architecture design. Physical interaction is an important part of the method, between architect and his client or his design or construction team. The pandemic has changed the design and construction process, because of the limitation of physical interaction between parties on a project. Physical interaction has been replaced with online interaction. The writer doing case studies to project handling of ongoing works, Painter House in Bali and Villa Nabu in Lombok. The architect has adjusted the method of the design process and design approach. Architect feels benefits from online interactions, like some technical practicalities in communication to many parties on the project. But architect also feels the downside of online interaction like the decreasing of psychological quality in communication, especially in convincing people because of the decreasing persuasive personal approaches which usually built from analyzing facial and body gestures in the physical interaction. The architect profession is much related to services, which needs to convinced many parties on the project. Architect has tried to improve the lack of psychological quality in online communication by increasing the number of online interactions, while also limiting the content of the communication and allowing enough time lags for other parties to be able to absorb the given information properly before responding back to it. Other factors also have increased the complexity of communication, like the position of the clients in foreign countries, the location of the project on a different island from the architect, the location of the developer on a different island from the architect, and the early phase of the projects where architect need to work in collaboration with a foreign architect on another country.