bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome: a multicenter retrospective cohort study
Authors: Fanelli Vito , Giani Marco , Grasselli Giacomo , Mojoli Francesco , Martucci Gennaro , Grazioli Lorenzo , Alessandri Francesco , Mongodi Silvia , Sales Gabriele , Montrucchio Giorgia , Pizzi Costanza , Richiardi Lorenzo , Lorini Luca , Arcadipane Antonio , Pesenti Antonio , Foti Giuseppe , Patroniti Nicolò , Brazzi Luca , Ranieri VMarco 
Published: February 2022

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS.

Methods
This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients’ characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications.

Results
Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17–2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78–2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients.

Conclusion
In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference.
Trial registration number: NCT05080933, retrospectively registered.
Single-cell isoform analysis in human immune cells
Authors: Volden Roger , Vollmers Christopher 
Published: February 2022

AbstractHigh-throughput single-cell analysis today is facilitated by protocols like the 10X Genomics platform or Drop-Seq which generate cDNA pools in which the origin of a transcript is encoded at its 5′ or 3′ end. Here, we used R2C2 to sequence and demultiplex 12 million full-length cDNA molecules generated by the 10X Genomics platform from ~3000 peripheral blood mononuclear cells. We use these reads, independent from Illumina data, to identify B cell, T cell, and monocyte clusters and generate isoform-level transcriptomes for cells and cell types. Finally, we extract paired adaptive immune receptor sequences unique to each T and B cell.
The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study
Authors: Pereira Diana R. , Silva Eunice R. , Carvalho-Maia Carina , Monteiro-Reis Sara , Lourenço Catarina , Calisto Rita , Teixeira Ricardo João , Carlson Linda E. , Bart Genevieve , Vainio Seppo J. , Sales M. Goreti F. , Jerónimo Carmen , Henrique Rui 
Published: February 2022

Abstract
Background
Mindfulness-based interventions (MBIs) have been used in oncology contexts as a promising tool with numerous benefits for various health-related and psychosocial outcomes. Despite the increasing popularity of MBIs, few randomized controlled trials (RCTs) have examined their effects upon biological parameters. Specifically, no previous study has examined the effects of MBIs on extracellular vesicles (EVs), which are potentially important markers of health, disease, and stress. Moreover, the lack of RCTs is even more limited within the context of technology-mediated MBIs and long-term effects.

Methods
The current study protocol presents a two-arm, parallel, randomized controlled study investigating the effects of internet-supported mindfulness-based cognitive therapy (MBCT) compared with treatment as usual (TAU). Primary outcomes are psychological distress and EV cargo of distressed participants with previous breast, colorectal, or prostate cancer diagnoses. Secondary outcomes are self-reported psychosocial and health-related measures, and additional biological markers. Outcomes will be assessed at baseline, 4 weeks after baseline (mid-point of the intervention), 8 weeks after baseline (immediately post-intervention), 24 weeks after baseline (after booster sessions), and 52 weeks after baseline. Our goal is to recruit at least 111 participants who have been diagnosed with breast, prostate, or colorectal cancer (cancer stage I to III), are between 18 and 65 years old, and have had primary cancer treatments completed between 3 months and 5 years ago. Half of the participants will be randomized to the TAU group, and the other half will participate in an 8-week online MBCT intervention with weekly group sessions via videoconference. The intervention also includes asynchronous homework, an online retreat after the fifth week, and 4 monthly booster sessions after completion of the 8-week programme.

Discussion
This study will allow characterizing the effects of internet-based MBCT on psychosocial and biological indicators in the context of cancer. The effects on circulating EVs will also be investigated, as a possible neurobiological pathway underlying mind-body intervention effects.

Trial registration
ClinicalTrials.govNCT04727593 (date of registration: 27 January 2021; date of record verification: 6 October 2021).
CCR2-overexpressing mesenchymal stem cells targeting damaged liver enhance recovery of acute liver failure
Authors: Xu Ruixuan , Ni Beibei , Wang Li , Shan Jiarou , Pan Lijie , He Yizhan , Lv Guo , Lin Huizhu , Chen Wenjie , Zhang Qi 
Published: February 2022

AbstractBackgroundMesenchymal stem cell (MSC) transplantation is emerging as a promising cell therapeutic strategy in acute liver failure (ALF) clinical research. The potency of MSCs to migrate and engraft into targeted lesions could largely determine their clinical efficacy, in which chemokine/receptor axes play a crucial role. Unfortunately, the downregulation of chemokine receptors expression after in vitro expansion results in a poor homing capacity of MSCs.MethodsBy evaluating the chemokine expression profile in the liver of ALF patients and ALF mice, we found that CCL2 expression was highly upregulated in damaged livers, while the corresponding receptor, CCR2, was lacking in cultured MSCs. Thus, we genetically modified MSCs to overexpress CCR2 and investigated the targeted homing capacity and treatment efficacy of MSCCCR2compared to those of the MSCvectorcontrol.ResultsIn vivo and ex vivo near-infrared fluorescence imaging showed that MSCCCR2rapidly migrated and localized to injured livers in remarkably greater numbers following systemic infusion, and these cells were retained in liver lesions for a longer time than MSCvector. Furthermore, MSCCCR2exhibited significantly enhanced efficacy in the treatment of ALF in mice, which was indicated by a dramatically improved survival rate, the alleviation of liver injury with reduced inflammatory infiltration and hepatic apoptosis, and the promotion of liver regeneration.ConclusionsAltogether, these results indicate that CCR2 overexpression enhances the targeted migration of MSCs to damaged livers, improves their treatment effect, and may provide a novel strategy for improving the efficacy of cell therapy for ALF.
The effect of hypoxia on myogenic differentiation and multipotency of the skeletal muscle-derived stem cells in mice
Authors: Elashry Mohamed I. , Kinde Mebrie , Klymiuk Michele C. , Eldaey Asmaa , Wenisch Sabine , Arnhold Stefan 
Published: February 2022

Abstract
Background
Skeletal muscle-derived stem cells (SC) have become a promising approach for investigating myogenic differentiation and optimizing tissue regeneration. Muscle regeneration is performed by SC, a self-renewal cell population underlying the basal lamina of muscle fibers. Here, we examined the impact of hypoxia condition on the regenerative capacity of SC either in their native microenvironment or via isolation in a monolayer culture using ectopic differentiation inductions. Furthermore, the effect of low oxygen tension on myogenic differentiation protocols of the myoblasts cell line C2C12 was examined.

Methods
Hind limb muscles of wild type mice were processed for both SC/fiber isolation and myoblast extraction using magnetic beads. SC were induced for myogenic, adipogenic and osteogenic commitments under normoxic (21% O2) and hypoxic (3% O2) conditions. SC proliferation and differentiation were evaluated using histological staining, immunohistochemistry, morphometric analysis and RT-qPCR. The data were statistically analyzed using ANOVA.

Results
The data revealed enhanced SC proliferation and motility following differentiation induction after 48 h under hypoxia. Following myogenic induction, the number of undifferentiated cells positive for Pax7 were increased at 72 h under hypoxia. Hypoxia upregulated MyoD and downregulated Myogenin expression at day-7 post-myogenic induction. Hypoxia promoted both SC adipogenesis and osteogenesis under respective induction as shown by using Oil Red O and Alizarin Red S staining. The expression of adipogenic markers; peroxisome proliferator activated receptor gamma (PPARγ) and fatty acid-binding protein 4 (FABP4) were upregulated under hypoxia up to day 14 compared to normoxic condition. Enhanced osteogenic differentiation was detected under hypoxic condition via upregulation of osteocalcin and osteopontin expression up to day 14 as well as, increased calcium deposition at day 21. Hypoxia exposure increases the number of adipocytes and the size of fat vacuoles per adipocyte compared to normoxic culture. Combining the differentiation medium with dexamethasone under hypoxia improves the efficiency of the myogenic differentiation protocol of C2C12 by increasing the length of the myotubes.

Conclusions
Hypoxia exposure increases cell resources for clinical applications and promotes SC multipotency and thus beneficial for tissue regeneration.
Human menstrual blood-derived stem cell transplantation suppresses liver injury in DDC-induced chronic cholestasis
Authors: Yang Ya , Chen Yanfei , Zhao Yalei , Ji Feiyang , Zhang Lingjian , Tang Shima , Zhang Sainan , Hu Qingqing , Li Zuhong , Zhang Fen , Li Qian , Li Lanjuan 
Published: February 2022

AbstractBackgroundCholestatic liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestatic liver injury. Human menstrual blood-derived stem cells (MenSCs) are considered as an emerging treatment in various diseases. This study aimed to explore the treatment effect of MenSCs in cholestatic liver injury.MethodsThe treatment effect of MenSCs on chronic cholestatic liver injury was verified in 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC)-induced C57/BL6 mice. Pathological, fibrosis area in the liver tissue and serum liver enzymes were tested. Proteomics and western blot were used to explore the related targets and molecular mechanisms. Adeno-associated virus (AAV) 9-infected mice were applied for verification.ResultsMenSCs markedly improved the survival rate of the DDC-treated mice (60% vs. 100%), and decreased the mouse serum aspartate aminotransferase (AST) (169.4 vs. 108.0 U/L,p < 0.001), alanine aminotransferase (ALT) (279.0 vs. 228.9 U/L,p < 0.01), alkaline phosphatase (ALP) (45.6 vs. 10.6 U/L,p < 0.0001), direct bilirubin (DBIL) (108.3 vs. 14.0 μmol/L,p < 0.0001) and total bilirubin (TBIL) (179.2 vs. 43.3 μmol/L,p < 0.0001) levels as well as intrahepatic cholestasis, bile duct dilation and fibrotic areas (16.12 vs. 6.57%,p < 0.05). The results further indicated that MenSCs repaired the DDC-induced liver tight junction (TJ) pathway and bile transporter (OATP2, BSEP and NTCP1) injury, thereby inhibiting COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression.ConclusionsMenSC transplantation could be an effective treatment method for cholestatic liver injury in mice. MenSCs may exhibit therapeutic effects by regulating β-catenin expression.
Osteogenic differentiation of mesenchymal stem cells promotes c-Jun-dependent secretion of interleukin 8 and mediates the migration and differentiation of CD4+ T cells
Authors: Ye Feng , Li Jinteng , Xu Peitao , Xie Zhongyu , Zheng Guan , Liu Wenjie , Ye Guiwen , Yu Wenhui , Lin Jiajie , Su Zepeng , Che Yunshu , Zhang Zhaoqiang , Wang Peng , Wu Yanfeng , Shen Huiyong 
Published: February 2022

Abstract
Background
The immune system and the skeletal system have complex interactions in the bone marrow and even in the joints, which has promoted the development of the concept of osteoimmunology. Some evidence has indicated that T cells and B cells contribute to the balance between the resorption and formation of bone. However, there has been little discussion on the regulation of CD4+ T lymphocytes by cells involved in bone metabolism. Mesenchymal stem cells (MSCs), which exert core functions related to immunoregulation and osteogenic differentiation, are crucial cells linked to both bone metabolism and the immune system. Previous studies have shown that the immunoregulatory capacity of MSCs changes following differentiation. However, it is still unclear whether the osteogenic differentiation of MSCs affects the migration and differentiation of CD4+ T cells.

Methods
MSCs were cultured in growth medium or osteogenic medium for 10 days and then cocultured with CD4+ T cells. CD4+ T cell migration and differentiation were detected by flow cytometry. Further, gene expression levels of specific cytokines were analyzed by quantitative real-time PCR and enzyme-linked immunosorbent assays. A Proteome Profiler Human XL Cytokine Array Kit was used to analyze supernatants collected from MSCs. Alizarin red S staining and Alkaline phosphatase assay were used to detect the osteogenic differentiation of MSCs.

Results
Here, we found that the migration of CD4+ T cells was elevated, and the capacity to induce the differentiation of regulatory T (Treg) cells was weakened during MSC osteogenic differentiation, while the differentiation of T helper 1 (Th1), T helper 2 (Th2) and T helper 17 (Th17) cells was not affected. Further studies revealed that interleukin (IL)-8 was significantly upregulated during MSC osteogenic differentiation. Both a neutralizing antibody and IL-8-specific siRNA significantly inhibited the migration of CD4+ T cells and promoted the differentiation of Treg cells. Finally, we found that the transcription factor c-Jun was involved in regulating the expression of IL-8 and affected the osteogenic differentiation of MSCs, thereby mediating the migration and differentiation of CD4+ T cells.

Conclusion
This study demonstrated that MSC osteogenic differentiation promoted c-Jun-dependent secretion of IL-8 and mediated the migration and differentiation of CD4+ T cells. These results provide a further understanding of the crosstalk between bone and the immune system and reveal information about the relationship between osteogenesis and inflammation in the field of osteoimmunology.
Hospital unit costs in Jordan: insights from a country facing competing health demands and striving for universal health coverage
Authors: Hammad Eman A. , Alabbadi Ibrahim , Taissir Fardos , Hajjwi Malek , Obeidat Nathir M. , Alefan Qais , Mousa Rimal 
Published: February 2022

Abstract
Background
Public providers in Jordan are facing increasing health demands due to human crises. This study aimed to benchmark the unit costs of hospital services in public providers in Jordan to provide insights into the outlook for public health care costs.

Methods
The unit costs of hospital services per admission, inpatient days, outpatient visits, emergency visits and surgical operations were estimated using the standard average costing method (top-down) for the fiscal year 2018–2019. The unit costs per inpatient day were estimated for nine specialities and staff in Jordanian dinars (exchange rate JOD 1 = USD 1.41).

Results
The average unit cost per admission in Jordan was JOD 782.300 (USD 1101.80), the per inpatient day cost was JOD 236.600 (USD 333.20), the per bed day cost was JOD 172.900 (USD 244.90), the per outpatient visit cost was JOD 58.400 (USD 82.30), the per operation cost was JOD 449.600 (USD 633.20) and the per emergency room visit cost was JOD 31.800 (USD 44.80). The specialities of ICU/CCU and OB/GYN presented the highest unit costs per inpatient day across providers: JOD 377.800 (USD 532.90) and JOD 362.600 (USD 510.70), respectively. The average salaried unit cost of staff depended mainly on year of employment. Nonetheless, the unit costs varied depending on the service utilization, type of service and organizational outlet.

Conclusions
Knowledge of how unit costs vary across public providers in Jordan is essential to outline cost control strategies and inform future research. Institutionalization of the cost information system and high-level governmental support are necessary to generate a routine practice of collecting and sharing cost information.
Staphylococcus aureus mediates pyroptosis in bovine mammary epithelial cell via activation of NLRP3 inflammasome
Authors: Wang Xiaozhou , Liu Mingchao , Geng Na , Du Yongzhen , Li Zhaoming , Gao Xin , Han Bo , Liu Jianzhu , Liu Yongxia 
Published: February 2022

AbstractCell death and inflammation are intimately linked during mastitis due to Staphylococcus aureus (S. aureus). Pyroptosis, a programmed necrosis triggered by gasdermin protein family, often occurs after inflammatory caspase activation. Many pathogens invade host cells and activate cell-intrinsic death mechanisms, including pyroptosis, apoptosis, and necroptosis. We reported that bovine mammary epithelial cells (MAC-T) respond to S. aureus by NOD-like receptor protein 3 (NLRP3) inflammasome activation through K+ efflux, leading to the recruitment of apoptosis-associated speck-like protein (ASC) and the activation of caspase-1. The activated caspase-1 cleaves gasdermin D (GSDMD) and forms a N-terminal pore forming domain that drives swelling and membrane rupture. Membrane rupture results in the release of the pro-inflammatory cytokines IL-18 and IL-1β, which are activated by caspase-1. Can modulate GSDMD activation by NLRP3-dependent caspase-1 activation and then cause pyroptosis of bovine mammary epithelial cells.
On multiple solutions to a nonlocal fractional $p(\cdot )$-Laplacian problem with concave–convex nonlinearities
Authors: Lee Jongrak , Kim Jae-Myoung , Kim Yun-Ho , Scapellato Andrea 
Published: February 2022

AbstractThe aim of this paper is to examine the existence of at least two distinct nontrivial solutions to a Schrödinger-type problem involving the nonlocal fractional $p(\cdot )$
p
(
⋅
)
-Laplacian with concave–convex nonlinearities when, in general, the nonlinear term does not satisfy the Ambrosetti–Rabinowitz condition. The main tools for obtaining this result are the mountain pass theorem and a modified version of Ekeland’s variational principle for an energy functional with the compactness condition of the Palais–Smale type, namely the Cerami condition. Also we discuss several existence results of a sequence of infinitely many solutions to our problem. To achieve these results, we employ the fountain theorem and the dual fountain theorem as main tools.
Hydrological alteration and biodiversity change along the river network caused by anthropogenic activities and climate variability
Authors: Zolfagharpour Farshid , Saghafian Bahram , Delavar Majid 
Published: February 2022

Abstract
Background
Population growth and intensified human activities in conjunction with climate variability continue to affect the hydrologic cycle, aquatic and terrestrial flora and fauna. In this regard, understanding interactions among ecosystem functions, impacts of anthropogenic interventions and those of climate variability is vital for projecting future ecosystem responses to human activities and climate forcing. The objectives of this study are to determine the ecological flow state via eco-flow index based on discharge hydrograph, to model the ecological diversity through the Shannon diversity index, and to assess the degree of hydrologic alteration using indicators of hydrologic alteration and range of variability approach in six hydrometric stations along the Zayandeh-Rud River in central Iran. The river drains into Gavkhuni Marsh. Also, the streamflow-induced potential changes for Capoeta damascina (a cyprinid fish species of the genus Capoeta), Petroleuciscus esfahani (a small cyprinid fish) and Aphanius isfahanensis (a Cyprinodontid fish) are evaluated. The outcome is expected to assist managers with understanding the effects of anthropogenic activities and climate variability on Gavkhuni aquatic ecosystems so that management options that enhance species resilience and adaptability are outlined.

Results
Human activities, a primary factor influencing the natural flow regime, caused a significant increase in the minimum flow, July to March streamflow, low pulse number, and the number of reversals in most studied stations. On the contrary, some other hydrologic indices declined in value. Reservoir impoundment, the most prominent factor among human interventions, resulted in an overall alteration degree of 74.8% in streamflow. Climate variability impacted the natural flow regime in the range of low degree hydrologic alteration (27.3%). In addition, the biodiversity of the study basin, as modeled by the Shannon diversity index, had strong relevance to the annual eco-surplus and was more sensitive to summer floods and autumn hydrological droughts than other factors.

Conclusions
This study corroborates the effectiveness of scenario-based hydrological modeling framework in evaluating the impacts of climate variability and human activities imposed on natural flow metrics. Additionally, the recently introduced eco-flow metrics based on discharge hydrographs and the Shannon diversity index based on indicators of hydrological alteration may be adopted in basins lacking ecological data. These two indices can effectively identify the most prominent factors in hydrological alteration and biodiversity change through a river network and may provide scientific decision-making support for water resource management in the study area.