bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide-Preconditioned Mesenchymal Stem Cell Transplantation Attenuates Critical Persistent Inflammation Immune Suppression and Catabolism Syndrome in Mice
Authors: Chen Xiancheng , Chen Ming , Yang Yang , Xu Can , Lu Huimin , Xu Yali , Li Xiaojing , Wei Yu , Zhu Zhanghua , Ding Yitao , Yu Wenkui 
Published: September 2022

Abstract

Background
Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is associated with high mortality and high health care costs, and there is currently no effective target treatment. Mesenchymal stem cells (MSCs) possess multipotent immunomodulatory properties. Lipopolysaccharide (LPS)-preconditioned type 1 MSCs (MSC1s) are potentially beneficial for PIICS treatment because of their pro-inflammatory, anti-infective, and healing properties. Here, we investigated the therapeutic efficacy and mechanisms of action of MSC1s in PIICS.

Methods
We previously optimized a reaggravated PIICS mouse model, which was employed in this study. PIICS mice were subjected to cecal ligation and puncture (CLP) on day 1 and LPS injection on day 11. Subsequently, the mice were treated with or without MSC1s. Animal survival and phenotypes, along with the levels of catabolism, inflammation, and immunosuppression, were evaluated. MSC1s were co-cultured with CD8+ T cells in vitro, and inflammatory cytokine levels and CD8+ T cell function were assessed.

Results
MSC1 transplantation alleviated weight loss and muscle wasting, inhibited catabolism and inflammation, and considerably improved the proportion and function of CD8+ T cells in the PIICS mice. After co-culture with MSC1s, the expression levels of CD107a and interferon gamma increased, whereas the expression level of programmed death 1 (PD-1) decreased significantly in CD8+ T cells. MSC1s also promoted pro-inflammatory cytokine secretion and reduced the concentration of soluble PD-L1 in vitro.

Conclusions
MSC1s can protect mice against critical PIICS, partly by enhancing CD8+ T cell function. Therefore, MSC1 transplantation is a novel therapeutic candidate for PIICS.
Infrared thermography-based body-surface thermal inhomogeneity monitoring to assess the severity of hypoperfusion in critically ill patients
Authors: Luo Jing-chao , Zhang Jia-dong , Zhao Qin-yu , Wang Huan , Tu Guo-wei , Luo Ming-hao , Huang Dan-lei , Zhang Ji-yang , Lu Wei , Gao Fei , Luo Zhe 
Published: September 2022

Abstract

Background
Uneven body-surface thermal distribution is a manifestation of hypoperfusion and can be quantified by infrared thermography. Our aim was to investigate whether body-surface thermal inhomogeneity could accurately evaluate the severity of patients at risk of hypoperfusion.

Methods
This was a prospective cohort study in which infrared thermography images were taken from unilateral legs of critically ill patients at high-risk of hypoperfusion in a cardiac surgical intensive care unit. For each patient, five body-surface thermal inhomogeneity parameters, including standard deviation (SD), kurtosis, skewness, entropy and low temperature area rate (LTAR), were calculated. Demographic, clinical, and thermal characteristics of deceased and living patients were compared. The risk of mortality and capillary refill time (CRT) were chosen as the primary outcome and benchmarking parameter for hypoperfusion, respectively. The area under the receiver operating characteristic curve (AUROC) was used to evaluate predictive accuracy.

Results
373 patients were included and 55 (14.7%) died during hospital stay. Of inhomogeneity parameters, SD (0.738) and LTAR (0.768), had similar AUROC to CRT (0.757) for assessing mortality risk. Besides, there was a tendency for LTAR (1 to 3 to 7%) and SD (0.81 to 0.88 to 0.94 °C) to increase in normotensive, hypotensive, and shock patients. These thermal parameters are associated with CRT, lactate, and blood pressure. The AUROC of a combined prediction incorporating three thermal inhomogeneity parameters (SD, kurtosis and entropy) was considerably higher at 0.866.

Conclusions
Body-surface thermal inhomogeneity provided a non-invasive and accurate assessment of the severity of critically ill patients at high-risk of hypoperfusion.
BACTERIAL PATHOGEN–ASSOCIATED MOLECULAR PATTERNS UPREGULATE HUMAN GLUCOCORTICOID RECEPTOR EXPRESSION IN PERIPHERAL BLOOD MONONUCLEAR CELLS
Authors: Greenhalgh David G. , Green Tajia L. , Lim Debora , Cho Kiho 
Published: September 2022

ABSTRACT
It is well known that bacterial components (pathogen-associated molecular patterns [PAMPs]) induce a proinflammatory response through pattern recognition receptor signaling. What is not known, however, is how the inflammatory response is downregulated. We hypothesize that bacterial products initiate compensatory anti-inflammatory responses by inducing expression of the human glucocorticoid receptor (hGR). Peripheral blood mononuclear cells (PBMCs) were isolated from leukocytes concentrated from single human donors (Leukopaks). PBMCs were treated with a gram-negative bacterial component, LPS, or gram-positive bacterial components, lipoteichoic acid (LTA) or peptidoglycan (PGN), for 1, 3, or 13 h. Protein expression of hGR was evaluated by Western blot analysis. RNA was extracted from similarly treated cells for reverse transcription-polymerase chain reaction analysis of hGR and cytokine expression. At 13 h after LPS treatment, there was an increase in the reference hGR protein (hGRα) expressed within some but not all PBMCs isolated from Leukopaks. There was also a dose-dependent increase in hGRα expression with increasing concentrations of PGN (10 and 50 μg/mL). LTA, however, did not affect hGRα expression. PGN also increased the mRNA expression of an hGR splice variant, hGR-B(54). The mRNA expression changes for the inflammatory cytokines were Leukopak specific. We found that cell wall components of both gram-positive and gram-negative bacteria can increase the expression of hGRα. Although these PAMPs augment the inflammatory response, it seems that there is a simultaneous upregulation of hGRα expression. Because binding of cortisol to hGRα typically induces anti-inflammatory proteins, the same PAMPs that induce an inflammatory response seem to also initiate a negative feedback system by inducing hGRα expression in PBMCs.
The Association Between Extravascular Lung Water and Critical Care Outcomes Following Bilateral Lung Transplantation
Authors: Munshi Laveena , Cypel Marcelo , Mohamed Alaa , Elhazmi Alyaa , Fan Eddy , Scales Damon , Tikkanen Jussi , Del Sorbo Lorenzo , Ferguson Niall D. , Keshavjee Shaf , Granton John 
Published: September 2022

Background.
Primary graft dysfunction (PGD) is a form of acute respiratory failure that complicates 30% of bilateral lung transplants. Higher grades of PGD correlate with higher severity of respiratory failure and unfavorable outcomes. Immediate PGD determination posttransplant‚ however, is not always predictive of PGD over subsequent days or intensive care unit outcomes. We aimed to evaluate whether extravascular lung water index (ELWI) measured immediately post bilateral lung transplant was associated with higher severity of PGD at 72 h and duration of mechanical ventilation.

Methods.
We conducted a prospective, observational study of bilateral lung transplant patients admitted to the intensive care unit. ELWI measurements were performed at admission, 6, 12, 24, 36, 48, 60, and 72 h following transplant or until extubation. We evaluated the association between admission ELWI and 72-h PGD grade and duration of mechanical ventilation.

Results.
Across 56 patients enrolled, 268 transpulmonary thermodilution measurements were conducted. At admission, median ELWI increased with PGD grade (grade 1: 9 mL/kg [interquartile range (IQR), 8–11 mL/kg]‚ grade 2 [10 mL/kg (IQR, 8–12 mL/kg)]‚ and grade 3 [17 mL/kg (IQR, 14–19 mL/kg); P < 0.001]). Using multivariable Poisson regression analysis adjusting for confounders, admission ELWI elevation was associated with higher severity of PGD at 72 h (incidence rate ratio [IRR], 1.06; 95% confidence interval, 1.01-1.12) and duration of mechanical ventilation (IRR, 1.62; 95% confidence interval, 1.23-2.14). The combination of an ELWI of ≥13 mL/kg and partial pressure of oxygen/fraction of inspired oxygen ≤ 100 within 6 h of admission had high sensitivity (75%) and specificity (100%) for grade 3 PGD at 72 h (area under the curve, 0.95) and performed better than ELWI or partial pressure of oxygen/fraction of inspired oxygen alone.

Conclusions.
Our exploratory study demonstrates an association between admission ELWI and high grades of PGD at 72 h and longer duration of ventilation. These results provide the impetus to study whether goal-directed ELWI algorithms can improve transplant outcomes.
3D-printed capillaric ELISA-on-a-chip with aliquoting
Authors: Parandakh Azim , Ymbern Oriol , Jogia Will , Renault Johan , Ng Andy , Juncker David 
Published: September 2022

AbstractSandwich immunoassays such as the enzyme-linked immunosorbent assay (ELISA) have been miniaturized and performed in a lab-on-a-chip format, but the execution of the multiple assay steps typically requires a computer or complex peripherals. Recently, an ELISA for detecting antibodies was encoded structurally in a chip thanks to the microfluidic chain reaction but the need for precise pipetting and intolerance to commonly used surfactant concentrations limited the potential for broader adoption. Here, we introduce the ELISA-on-a-chip with aliquoting functionality that obviates the need for precise pipetting, accommodates higher surfactant concentrations, includes barrier channels that delay the contact between solutions and prevent undesired mixing, and that executed a quantitative, high sensitivity assay for the SARS-CoV-2 nucleocapsid protein in 4×-diluted saliva. Upon loading the chip using disposable pipettes, capillary flow draws each reagent and the sample into a separate volumetric measuring reservoir for detection antibody (70 µL), enzyme conjugate (50 µL), substrate (80 µL), and sample (210 µL), and splits washing buffer into 4 different reservoirs of 40, 40, 60, and 20 µL. The excess volume is autonomously drained via a structurally encoded capillaric aliquoting circuit, creating aliquots with an accuracy of >93%. Next, the user click-connects the assay module, comprising a nitrocellulose membrane with immobilized capture antibodies and a capillary pump, to the chip which triggers the step-by-step, timed flow of all aliquoted solutions. A colored precipitate forming a line on a nitrocellulose strip serves as an assay readout, and upon digitization, yielded a binding curve with a limit of detection of 54 and 91 pg/mL for buffer and diluted saliva respectively, vastly outperforming rapid tests. The ELISA chip is 3D-printed, modular, adaptable to other targets and assays, and could be used to automate ELISA in the lab; or as a diagnostic test at the point of care with the convenience and form factor of rapid tests while preserving the protocol and performance of central laboratory ELISA.
Engineering non-cytotoxic delivery of proteins by T cells via fusion to NPC2
Authors: Saeedi Arash , Bandey Irfan N. , Leekha Ankita , Fathi Mohsen , Rezvan Ali , Montalvo Melisa J. , Wu Kwan-Ling , Bohat Ritu , Peng Weiyi , Varadarajan Navin 
Published: September 2022

AbstractEngineering cellular therapeutics by programming T cells has great potential in immunology. The primary mechanism employed by T cells for the specific transfer of proteins at the immunological synapse is via the lysosomal perforin pathway that facilitates the transfer of cytotoxic granzymes leading to apoptosis in target cells. Facilitating the delivery of non-cytotoxic proteins through perforin oligomers will dramatically expand the range of protein cargos that T cells can traffic to the target cells. Here, we have identified the intralysosomal protein, NPC2, as a chaperone that can facilitate the delivery of T-cell derived reporter proteins through perforin pores at the immunological synapse. Structural and biophysical considerations suggested that NPC2 could traverse through perforin pores and in vitro experiments confirmed the transport of purified NPC2 through perforin pores on cell membranes. To characterize the ability of NPC2 to facilitate the transfer of payloads in T cells, we constructed NPC2-mCherry fusion proteins in T cells. Using confocal microscopy and flow cytometry, we confirmed the colocalization of the NPC2 fused protein with lytic granules and the transfer of the fluorescent protein payload from T cells to target cells in co-culture experiments. The NPC2 fusion enabled the localization of mCherry to secretory lysosomes in mouse TCR CD8+ T cells and human CD4+ and CD8+ chimeric antigen receptor (CAR) T cells. These results illustrate that by using NPC2 as a molecular chaperone, the NPC2-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.
Small-molecule ketone esters treat brain network abnormalities in an Alzheimer’s disease mouse model
Authors: Newman John C. , Ma Keran , Kroll François , Higgins Erin , Ulrich Scott , Palop Jorge J. , Verdin Eric 
Published: September 2022

SummaryAltered brain network activity and the resulting hypersynchrony are important for the pathogenesis of cognitive decline in Alzheimer’s disease (AD) mouse models. Treatments that reduce epileptiform discharges (EDs) or network hyperactivity improve cognition in AD models and humans. We first show that ketogenic diet, but not fasting, rapidly and persistently reduced EDs in the hAPPJ20 Alzheimer’s mouse model over timescales of hours to months. Then, to identify the specific mechanism of the pleiotropic ketogenic diet, we developed small molecule ketone esters to deliver ketone bodies pharmacologically. Two ketone esters recapitulate ED suppression without other dietary manipulation, over time scales of minutes to one week. This small molecule rescue was associated with reduced low-frequency oscillatory activity similar to the recently reported mechanism of an NMDA receptor modulator molecule in this model. Long-term KD resulted in cognitive improvement and in a sex-stratified analysis also improved survival in the more severely affected hAPPJ20 males. Agents that deliver ketone bodies via small molecules or act on downstream targets may hold therapeutic promise in AD through the mechanism of improved network function and reduced epileptiform activity.
The interplay of gendered identities and employees perception of organizational citizenship behavior
Authors: Kaur Navneet , Kang Lakhwinder Singh 
Published: September 2022

PurposeDrawing from the gender schema theory and social role theory, the purpose of this study is to assess the gender-congruent nature of organizational citizenship behaviors (OCBs) through the mediating role of gender role orientation (femininity and masculinity) in the relationship between individuals sex and OCB dimensions. It also explores the moderating effect of gender ideology on the influence of sex on the exhibition of gender-congruent OCBs.Design/methodology/approachData were collected in two waves with a time lag of three weeks from frontline employees and their peers working in the Indian private banking sector. PROCESS macro was used to assess the hypothesized relationships.FindingsThe results indicated that femininity mediated the influence of sex on OCBs directed toward co-workers (OCBI). However, the mediating role of femininity was not confirmed in the association between sex and OCBs targeted toward customers (OCBC). Further, masculinity mediated the influence of sex on OCBs directed toward the organization (OCBO). Gender ideology also moderated the relationship between sex and OCBs, such that traditional women displayed more OCBI as compared to egalitarian women, while egalitarian women displayed more OCBC than traditional women. Additionally, traditional men were found to display more OCBO than egalitarian men.Originality/valueThe paper contributes to the existing literature by suggesting that the performance of OCBs depends upon various gender identities, with each gender identity having its own and significant effect on the performance of OCB.
Are firms with women executives better at surviving a crisis? Evidence from South Korea during the COVID-19 pandemic
Authors: Shin Hyejeong , Park Sorah 
Published: September 2022

Purpose
This study aims to examine whether investors react differently to the crisis during the COVID-19 pandemic based on chief executive officer (CEO) gender.

Design/methodology/approach
This study is based on a sample of publicly listed companies in Korea. The study uses the ordinary least squares regression and propensity score matching approach to address the research question. The dependent variable used in the regressions is the cumulative abnormal returns over 30, 60 and 90 days after the first COVID-19 case was confirmed in Korea.

Findings
The results show that cumulative abnormal returns over 30, 60 and 90 days after the first COVID-19 case are less negative for firms led by women CEOs compared to firms led by men CEOs. This is consistent with the prediction that investors favor firms with women CEOs in times of high uncertainty.

Originality/value
This study adds to the growing literature on the stock market during the COVID-19 pandemic. It provides empirical evidence that the effect of the pandemic on stock market performance differs by management characteristics such as CEO gender.
A qualitative analysis of stressors affecting 999 ambulance call handlers' mental health and well-being
Authors: Powell Catherine , Fylan Beth , Lord Kathryn , Bell Fiona , Breen Liz 
Published: September 2022

PurposeThe 999 ambulance call handler is critical in responding to emergency patient treatment; however, the call handlers are often a hidden component of the healthcare workforce and an under-researched group. The objective of this study is to understand stress triggers experienced by 999 ambulance call handlers that could lead to burnout and examine personal and organisational mechanisms and strategies which reduced the risk of burnout.Design/methodology/approachA single interview case study approach applying qualitative methods was undertaken. Participants were identified through a purposive sample of 999 ambulance call handlers with the Yorkshire Ambulance Service National Health Service Trust (UK). Participants were interviewed via telephone between July 2019 and September 2019.FindingsIn total, 18 staff participated in this study. Societal factors including public incivility and media representation and organisational factors, such as a demanding environment, lack of appreciation and career progression, training issues and protocols were key stressors. Organisational well-being services were helpful for some, but for others lacked accessibility and appropriateness. Positive public feedback and speaking with peers bolstered well-being. 999 ambulance call handlers suggested that sufficient breaks, co-design or feeding back on training and protocols and creating more informal opportunities to discuss ongoing everyday stressors as methods to reduce stress and burnout.Originality/valueThis paper explores a previously under researched area on stressors and potential burnout in 999 call handlers. This paper highlights the need for improved organisational support services and appropriate public and sector peer recognition of the role of ambulance 999 ambulance call handlers.
Technical condition of houses: a framework for the Czech market
Authors: Jandásková Tereza , Hrdlicka Tomas , Cupal Martin , Kleparnik Petr , Komosná Milada , Kervitcer Marek 
Published: September 2022

Purpose
This study aims to provide a framework for assessing the technical condition of a house to determine its market value, including the identification of other price-setting factors and their statistical significance. Time on market (TOM) in relation to the technical condition of a house is also addressed.

Design/methodology/approach
The primary database contains 631 houses, and the initial asking price and selling price are examined. All the houses are located in the Brno–venkov district in the Czech Republic. Regression analysis was used to test the influence of price-setting factors. The standard ordinary least squares estimator and the maximum likelihood estimator were used in the frame of generalized linear models.

Findings
Using envelope components of houses separately, such as the façade condition, windows, roof, condition of interior and year of construction, brings better results than using a single factor for the technical condition. TOM was found to be 67 days lower for houses intended for demolition – as compared to new houses – and 18 days lower for houses to refurbishment.

Originality/value
To the best of the authors’ knowledge, this paper is original in the substitution of specific price-setting factors for factors relating to the technical condition of houses as well as in proposing the framework for professionals in the Czech Republic.
Trait resilience and work–family conflict: a two-study test into the role of employees' interpersonal vs. intrapersonal resilient traits
Authors: Nelson Noa , Fuchs Raphaele , Kurtz-Cohen Mayan 
Published: September 2022

PurposeWork–family conflict (WFC) is a chronic source of stress, threatening contemporary organizations. Employees' own characteristics, which have received limited scientific attention, can help mitigate WFC. The current two studies tested, for the first time, the links of higher-order trait resilience models to WFC, while exploring possible mediators and differentiating the contributions of interpersonal vs. intrapersonal resilient traits.Design/methodology/approachIn study 1, the authors tested a mediation model in which trait negotiation resilience (TNR), which is oriented toward challenges that involve balancing conflicting needs with others, predicted multidimensional (time, strain and behavior based) WFC, through three mediators: emotion regulation (intrapersonal), self-monitoring and work–family balance negotiation (both interpersonally oriented). In study 2, both TNR and the more intrapersonal Connor–Davidson Resilience Scale (CD-RISC) were associated with a global, more parsimonious measurement of WFC. Additionally, TNR's factors were separately correlated with the latter.FindingsTNR associated with lower multidimensional WFC through emotion regulation, which partly mediated TNR's effect; and through self-monitoring, which suppressed TNR's effect because it related to higher WFC (balance negotiation had no effect). In study 2, CD-RISC, but not TNR, related to lower global WFC. Additionally, two intrapersonal TNR factors tended to relate to lower WFC, while one interpersonal factor related to higher WFC.Originality/valueThe studies demonstrate the role of higher-order trait resilience in WFC, while fine-tuning understanding of the contributions of intrapersonal vs. interpersonal resilience. The findings may be relevant to other organizational challenges, beyond WFC, and inform employee recruitment and training.