bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to use new antibiotics in the therapy of ventilator-associated pneumonia
Authors: Miwa Toshiki , Lizza Bryan , Burnham Jason , Honda Hitoshi , Kollef Marin 
Published: December 2021

Purpose of review
Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critically ill patients requiring endotracheal intubation and mechanical ventilation. Recently, the emergence of multidrug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales, multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species, has complicated the selection of appropriate antimicrobials and contributed to treatment failure. Although novel antimicrobials are crucial to treating VAP caused by these multidrug-resistant organisms, knowledge of how to optimize their efficacy while minimizing the development of resistance should be a requirement for their use.

Recent findings
Several studies have assessed the efficacy of novel antimicrobials against multidrug-resistant organisms, but high-quality studies focusing on optimal dosing, infusion time and duration of therapy in patients with VAP are still lacking. Antimicrobial and diagnostic stewardship should be combined to optimize the use of these novel agents.

Summary
Improvements in diagnostic tests, stewardship practices and a better understanding of dosing, infusion time, duration of treatment and the effects of combining various antimicrobials should help optimize the use of novel antimicrobials for VAP and maximize clinical outcomes while minimizing the development of resistance.
Geriatric assessment-informed treatment decision making and downstream outcomes: what are the research priorities?
Authors: Hsu Tina , Leung Bonnie , Mariano Caroline 
Published: December 2021

Purpose of review
Geriatric assessment (GA) can predict outcomes relevant to patients and clinicians but is not widely used. The objective of this review is to summarize the evidence supporting use of GA to facilitate decision making and improve outcomes and identify gaps that need to be addressed to further bolster the rationale for the use of GA.

Recent findings
Recently several randomized controlled studies exploring the impact of GA-directed care have been reported. Although GA-directed care has not been shown to improve survival, it can decrease moderate to severe toxicity from chemotherapy, increase the likelihood of completing planned chemotherapy and improve quality of life without adversely affecting survival. In the surgical setting, GA-directed care may decrease duration of hospitalization, but does not affect rates of re-hospitalization.

Summary
GA-directed care can improve patient-important outcomes compared to usual care. However, more research on whether these findings apply to other contexts and whether GA-directed care can improve other outcomes important to patients, such as function and cognition, is needed. Also more clarity about how oncologic treatments should be modified based on results of a GA are needed if oncologists are to utilize this information effectively to obtain the reported results.
Correlation Between Microvascular Inflammation in Endomyocardial Biopsies and Rejection Transcripts, Donor-specific Antibodies, and Graft Dysfunction in Antibody-mediated Rejection
Authors: Coutance Guillaume , Zouhry Ilyass , Racapé Maud , Drieux Fanny , Viailly Pierre-Julien , Rouvier Philippe , François Arnaud , Chenard Marie-Pierre , Toquet Claire , Rabant Marion , Berry Gerald J. , Angelini Annalisa , Bruneval Patrick , Duong Van Huyen Jean-Paul 
Published: December 2021

Background.
The pathology-based diagnosis of cardiac antibody-mediated rejection (AMR) relies on the 2013 International Society for Heart and Lung Transplantation Working Formulation, in which microvascular inflammation (MVI) is considered as present or absent regardless of its extent. This work assessed the biological and clinical value of a semiquantitative evaluation of the extent of MVI in endomyocardial biopsies (EMBs).

Methods.
We retrospectively graded the extent of MVI in 291 EMB from 291 patients according to a 4-point scale in which MVI scores of 0, 1, 2, and 3 represented 0%, 1%–10%, 11%–50%, and >50% of the myocardial area, respectively. We analyzed the association between the MVI score and tissue rejection molecular activity assessed by microarrays or reverse transcriptase multiplex ligation-dependent probe amplification, current pathology classification (pathologic AMR [pAMR]), anti-HLA donor-specific antibodies, and graft dysfunction.

Results.
Overall, 172 (59.1%), 33 (11.4%), 42 (14.4%), and 44 (15.1%) EMB were given MVI scores of 0, 1, 2, and 3, respectively. pAMR1(H+) and pAMR2/3 categories were found to be heterogeneous in terms of MVI score. Acute cellular rejection grades did not influence the MVI score. In both molecular approaches, we observed a stepwise increase in the expression of AMR-related transcripts with increasing MVI scores, independent of the C4d or CD68 status (P < 0.001). Both the frequency and mean fluorescence intensity of donor-specific antibodies gradually increased with the MVI score (P < 0.001). Acute graft dysfunction was more frequent in MVI score 3 (P < 0.001).

Conclusions.
The intensity of MVI in EMB, based on a semiquantitative evaluation of its extent, has biological and clinical importance.
DAMPs Released From Injured Renal Tubular Epithelial Cells Activate Innate Immune Signals in Healthy Renal Tubular Epithelial Cells
Authors: DeWolf Sean E. , Kasimsetty Sashi G. , Hawkes Alana A. , Stocks Lisa M. , Kurian Sunil M. , McKay Dianne B. 
Published: December 2021

Background.
Renal ischemia-reperfusion injury (IRI) predictably causes acute kidney injury after shock and major cardiovascular procedures in all kidneys procured for transplantation. The earliest events of IRI are triggered by molecules released from injured cells, damage-associated molecular patterns (DAMPs), that bind pattern recognition receptors (PRRs) constitutively expressed on many cells within the kidney. Activation of PRR signaling leads to production of proinflammatory molecules, which incite a cascade of inflammatory events leading to acute kidney injury. Renal tubular epithelial cells (RTECs) are particularly susceptible to ischemic injury, and proximal RTEC injury is pathognomonic of renal IRI. To better understand how injured RTECs contribute to the cycle of deleterious inflammation in the setting of renal IRI, this study asked whether DAMPs released from injured RTECs induced PRR signals in healthy RTECs.

Methods.
Human RTECs were necrosed ex vivo to release intracellular DAMPs and resulting necrotic supernatant used to stimulate healthy RTECs, T lymphocytes, and monocytes.

Results.
DAMPs released from necrosed RTECs upregulated PRRs known to be associated with renal IRI and activated mitogen-activated protein kinase signaling pathways. Proinflammatory cytokines were upregulated in response to necrotic supernatant, and this upregulation was abrogated by MEK-1 inhibition. The RTEC-derived DAMPs were also potent inducers of T-cell activation/proliferation and monocyte migration.

Conclusions.
This is the first study to our knowledge to show that endogenous DAMPs released from injured RTECs directly activate PRR signaling in healthy RTECs. These findings provide new insights directed to therapeutics for renal IRI.
The mental health of children and young people living in big cities in a revolving postpandemic world
Authors: Marchionatti Laura Estivalete , Caye Arthur , Kieling Christian 
Published: December 2021

Purpose of review
The world's population is increasingly urban, with most children and young people growing up and living in cities. Evidence suggests that urbanicity is linked to an increased risk for the development of mental health disorders. Rather than an accumulation of risk factors, urbanization is a complex process that profoundly structures living conditions. In this sense, it is timely to discuss what are the social and structural determinants of mental health of children and young people in such settings.

Recent findings
Three domains of determinants of mental health were selected for discussion: economics and living conditions, crime and violence, and urban layouts. For each, we debated realities faced by urban children and young people, providing an overview of recent evidence on implications for mental disorders and well being. We also discuss the potential impacts of the covid-19 pandemic on each domain, as well as recommendations for future action.

Summary
Structural factors are of major relevance for the mental health of children and young people living in cities. The agenda of mental health promotion and prevention must include whole-of-society interventions aimed at improving living conditions, including economic and social capital, violence prevention and urbanistic planning.
Air pollution and mental health: associations, mechanisms and methods
Authors: King Jacob D. , Zhang Shuo , Cohen Alex 
Published: December 2021

Purpose of review
There is increasing interest in the links between exposure to air pollution and a range of health outcomes. The association with mental health however is much less established. This article reviews developments in the field over the past 12 months, highlighting the evidence for causation, associations between multiple air pollutants and mental health outcomes, and assesses the challenges of researching this topic.

Recent findings
Increasingly rigorous methods are being applied to the investigation of a broader range of mental health outcomes. These methods include basic science, neuroimaging, and observational studies representing diverse geographical locations. Cohort studies with linked high-resolution air pollutant exposure data are common, facilitating advanced analytic methods. To date, meta-analyses have demonstrated small and significant positive associations between long-term exposure to fine particulate matter and depressive symptoms and cognitive decline. Methodological complexities in measuring exposure and outcome pose ongoing difficulties for the field.

Summary
Literature on this topic has recently seen an appreciable expansion. Work that better estimates daily exposure, controls for complex confounders, and is driven by hypotheses founded in candidate causal mechanisms would help clarify associations, and inform targeted interventions and policymakers.
Neuropsychological and neuropsychiatric recovery from mild traumatic brain injury
Authors: Ritchie Kathryn A. , Slomine Beth S. 
Published: December 2021

Purpose of review
Mild traumatic brain injury (mTBI) is a significant public health concern for children. This review summarizes recent literature on early symptoms and neuropsychiatric and neuropsychological outcomes following pediatric mTBI and highlights factors that predict prolonged recovery. Evidence-based recommendations for assessment and treatment are also discussed.

Recent findings
Whereas most children recover within 1 month after mTBI, 10–30% of children experience lingering neuropsychiatric or neuropsychological symptoms 3 months or more after injury. For the subset who experience prolonged recovery, new or worsening emotional and behavioral symptoms are the most frequent concerns. Recent research has suggested that specific factors, including preinjury mental health concerns, female sex, and family characteristics, are associated with increased risk of experiencing prolonged recovery. Early management includes reassurance, brief rest (1–3 days), and gradual return to typical activities. When symptoms linger for more than 4 weeks, evaluation in a specialty clinic is recommended and multimodal therapies are considered. Active recovery models, which include gradual return to aerobic exercise and cognitive behavioral approaches, are promising for the management of prolonged symptoms.

Summary
A minority of children with mTBI experience prolonged neuropsychiatric or neuropsychological concerns. While our understanding of pediatric mTBI is growing, and recommendations for assessment and management have been developed, many gaps remain.
Social health, social reserve and dementia
Authors: Sachdev Perminder S. 
Published: December 2021

Purpose of review
There is increasing recognition of social health being protective against disease, including age-related cognitive decline and dementia. Many concepts around social health, reserve and connectedness are imprecise and without agreed definitions. The mechanisms by which social health is protective are not well understood.

Recent findings

Several observational studies suggest that social participation and connectedness are protective against cognitive decline whereas loneliness is a risk factor for dementia. The possible mechanisms include effects on inflammatory process and immune function, reduced vascular disease risk, improved health behaviours, lower risk of depression, and increased cognitive reserve through cognitive stimulation and physical activity. Social networks have been shown to modify the relationship between Alzheimer's disease and cognitive impairment. The relationship of social networks is, however, reciprocal, with dementia leading to social loss, which in turn worsens cognitive decline. Social reserve is conceptualized as both brain processes underlying the ability and predisposition to form meaningful social ties, and their instantiation as an environmental resource in high-quality social networks.

Summary
Consistent definitions of social health-related terms will lead to better understanding of their determinants so that tailored interventions can be developed to increase social reserve and improve social health of an individual.
Dying From COVID-19 or With COVID-19: A Definitive Answer Through a Retrospective Analysis of Mortality in Italy
Authors: Rovetta Alessandro , Bhagavathula Akshaya Srikanth 
Published: December 2021

AbstractBackgroundCOVID-19 mortality was associated with several reasons, including conspiracy theories and infodemic phenomena. However, little is known about the potential endogenous reasons for the increase in COVID-19 associated mortality in Italy.ObjectiveThis study aimed to search the potential endogenous reasons for the increase in COVID-19 mortality recorded in Italy during the year 2020 and evaluate the statistical significance of the latter.MethodsWe analyzed all the trends in the timelapse 2011-2019 related to deaths by age, sex, region, and cause of death in Italy and compared them with those of 2020. Ordinary least squares (OLS) linear regressions and ARIMA (p, d, q) models were applied to investigate the predictions of death in 2020 as compared to death reported in the same year. Grubbs and Iglewicz-Hoaglin tests were used to identify the statistical differences between the predicted and observed deaths. The relationship between mortality and predictive variables was assessed using OLS multiple regression models.ResultsBoth ARIMA and OLS linear regression models predicted the number of deaths in Italy during 2020 to be between 640,000 and 660,000 (95% confidence intervals range: 620,000 – 695,000) and these values were far from the observed deaths reported (above 750,000). Significant difference in deaths at national level (P = 0.003), and higher male mortality than women (+18% versus +14%, P < 0.001 versus P = 0.01) was observed. Finally, higher mortality was strongly and positively correlated with latitude (R = 0.82, P < 0.001).ConclusionsOur findings support the absence of historical endogenous reasons capable of justifying the increase in deaths and mortality observed in Italy in 2020. Together with the current knowledge on the novel coronavirus 2019, these findings provide decisive evidence on the devastating impact of COVID-19 in Italy. We suggest that this research be leveraged by government, health, and information authorities to furnish proof against conspiracy hypotheses. Moreover, given the marked concordance between the predictions of the ARIMA and OLS regression models, we suggest that these models be exploited to predict mortality trends.
IL4I1 binds to TMPRSS13 and competes with SARS-Cov2 Spike
Authors: Gatineau Jérôme , Nidercorne Charlotte , Dupont Aurélie , Puiffe Marie-Line , Cohen José L , Molinier-Frenkel Valérie , Niedergang Florence , Castellano Flavia 
Published: December 2021

AbstractThe secreted enzyme interleukin four-induced gene 1 (IL4I1) is involved in the negative control of the adaptive immune response. IL4I1 expression in human cancer is frequent and correlates with poor survival and resistance to immunotherapy. Nevertheless, its mechanism of action remains partially unknown. Here, we identified transmembrane serine protease 13 (TMPRSS13) as an immune cell-expressed surface protein that binds IL4I1. TMPRSS13 is a paralog of TMPRSS2, whose protease activity participates in the cleavage of SARS-Cov2 Spike protein and facilitates virus induced-membrane fusion. We show that TMPRSS13 is expressed by human lymphocytes, monocytes and monocyte-derived macrophages, can cleave the Spike protein and allow Sars-Cov2 Spike pseudotyped virus entry into cells. We identify regions of homology between IL4I1 and Spike and demonstrate competition between the two proteins for TMPRSS13 binding. These findings may be relevant for both interfering with SARS-Cov2 infection and limiting IL4I1-dependent immunosuppressive activity in cancer.One-Sentence SummaryThrough binding to its newly identified receptor TMPRSS13, the enzyme IL4I1 interferes with SARS-Cov2 Spike cleavage thereby blocking viral entry into host cells.
Scholar Metrics Scraper (SMS): automated retrieval of citation and author data
Authors: Cheung Nicole A. , Giustini Dean , LeDue Jeffrey , Murphy Tim H. 
Published: December 2021

AbstractAcademic departments, research clusters and evaluators analyze author and citation data to measure research impact and to support strategic planning. We created a tool, Scholar Metrics Scraper (SMS), to automate the retrieval of this bibliometric data for our research team. The project contains Jupyter notebooks (publicly-shared here) that take a list of researchers as an input to export a CSV file of citation metrics from Google Scholar and figures to visualize the group’s impact. SMS is a scalable, open and publicly-accessible solution for automating the retrieval of citation data over time for a group of researchers.
Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19
Authors: Li Jing , Zaslavsky Maxim , Su Yapeng , Sikora Michael J. , van Unen Vincent , Christophersen Asbjørn , Chiou Shin-Heng , Chen Liang , Li Jiefu , Ji Xuhuai , Wilhelmy Julie , McSween Alana M. , Palanski Brad A. , Aditya Mallajosyula Venkata Vamsee , Dhondalay Gopal Krishna R. , Bhamidipati Kartik , Pai Joy , Kipp Lucas B. , Dunn Jeffrey E. , Hauser Stephen L. , Oksenberg Jorge R. , Satpathy Ansuman T. , Robinson William H. , Steinmetz Lars M. , Khosla Chaitan , Utz Paul J. , Sollid Ludvig M. , Heath James R. , Fernandez-Becker Nielsen Q. , Nadeau Kari C. , Saligrama Naresha , Davis Mark M. 
Published: December 2021

AbstractPrevious reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients’ leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells.One-Sentence SummaryHere we identified KIR+CD8+ T cells as a regulatory CD8+ T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4+ T cells.
Reward priming differentially modulates enhancement and inhibition in auditory decision-making
Authors: Nagamura Hidekazu , Onishi Hiroshi , Hishitani Momoko , Murai Shota , Osako Yuma , Kobayasi Kohta I. 
Published: December 2021

AbstractIn cognitive sciences, rewards, such as money and food, play a fundamental role in individuals’ daily lives and well-being. Moreover, rewards that are irrelevant to the task alter individuals’ behavior. However, it is unclear whether explicit knowledge of reward irrelevancy has an impact on reward priming enhancements and inhibition. In this study, an auditory change-detection task with task-irrelevant rewards was introduced. The participants were informed explicitly in advance that the rewards would be given randomly. The results revealed that while inhibition related to reward priming only occurred when the participants were explicitly informed about rewards, implicit instruction thereof resulted in enhancement and inhibition associated with reward priming. These findings highlight the contribution of explicit information about rewards associated with auditory decisions.
Designing multi-epitope based peptide vaccine targeting spike protein SARS-CoV-2 B1.1.529 (Omicron) variant using computational approaches
Authors: Parmar Meet , Thumar Ritik , Sheth Jigar , Patel Dhaval 
Published: December 2021

AbstractSince the SARS-CoV-2 outbreak in 2019, millions of people have been infected with the virus, and due to its high human-to-human transmission rate, there is a need for a vaccine to protect people. Although some vaccines are in use, due to the high mutation rate in the SARS-CoV-2 multiple variants, the current vaccines may not be sufficient to immunize people against new variant threats. One of the emerging variants of concern is B1.1.529 (Omicron), which carries∼30 mutations in the Spike protein of SARS-CoV-2 is predicted to evade antibodies recognition even from vaccinated people. We used a structure-based approach along with an epitope prediction server to develop a Multi-Epitope based Subunit Vaccine (MESV) involving SARS-CoV-2 B1.1.529 variant spike glycoprotein. The predicted epitope with better antigenicity and non-toxicity were used for designing and predicting vaccine construct features and structure models. The MESV construct In-silico cloning in pET28a expression vector predicted the construct to be highly translational. The proposed MESV vaccine construct was also subjected to immune simulation prediction and was found to be highly antigenic and elicit a cell-mediated immune response. The proposed MESV in the present study has the potential to be evaluated further for vaccine production against the newly identified B1.1.529 (Omicron) variant of concern.