bluuebunny/crossref_metadata_2025 huggingface dataset:
Is more better? Do statewide increases in trauma centers reduce injury-related mortality?
Authors: Truong Evelyn I. , Ho Vanessa P. , Tseng Esther S. , Ngana Colette , Curtis Jacqueline , Curfman Eric T. , Claridge Jeffrey A.
Published: April 2021

OBJECTIVES

Trauma centers are inconsistently distributed throughout the United States. It is unclear if new trauma centers improve care and decrease mortality. We tested the hypothesis that increases in trauma centers are associated with decreases in injury-related mortality (IRM) at the state level.

METHODS

We used data from the American Trauma Society to geolocate every state-designated or American College of Surgeons–verified trauma center in all 50 states and the District of Columbia from 2014 to 2018. These data were merged with publicly available IRM data from the Centers for Disease Control and Prevention. We used geographic information systems methods to map and study the relationships between trauma center locations and state-level IRM over time. Regression analysis, accounting for state-level fixed effects, was used to calculate the effect of total statewide number of trauma center on IRM and year-to-year changes in statewide trauma center with the IRM (shown as deaths per additional trauma center per 100,000 population, p value).

RESULTS

Nationwide between 2014 and 2018, the number of trauma center increased from 2,039 to 2,153. Injury-related mortality also increased over time. There was notable interstate variation, from 1 to 284 trauma centers. Four patterns in statewide trauma center changes emerged: static (12), increased (29), decreased (5), or variable (4). Of states with trauma center increases, 26 (90%) had increased IRM between 2014 and 2017, while the remaining 3 saw a decline. Regression analysis demonstrated that having more trauma centers in a state was associated with a significantly higher IRM rate (0.38, p = 0.03); adding new trauma centers was not associated with changes in IRM (0.02, p = 0.8).

CONCLUSION

Having more trauma centers and increasing the number of trauma center within a state are not associated with decreases in state-level IRM. In this case, more is not better. However, more work is needed to identify the optimal number and location of trauma centers to improve IRM.

LEVEL OF EVIDENCE

Epidemiologic, level III; Care management, level III.
Four-factor prothrombin complex concentrate in adjunct to whole blood in trauma-related hemorrhage: Does whole blood replace the need for factors?
Authors: Khurrum Muhammad , Ditillo Michael , Obaid Omar , Anand Tanya , Nelson Adam , Chehab Mohamad , Kitts Daniel James , Douglas Molly , Bible Letitia , Joseph Bellal
Published: April 2021

BACKGROUND

The use of whole blood (WB) for the treatment of hemorrhagic shock and coagulopathy is increasing in civilian trauma patients. Four-factor prothrombin complex concentrate (4-PCC) in adjunct to component therapy showed improved outcomes in trauma patients. Our study aims to evaluate the outcomes of trauma patients who received 4-PCC and WB (4-PCC–WB) compared with WB alone.

METHODS

We performed a 3-year (2015–2017) analysis of the American College of Surgeons—Trauma Quality Improvement Program database. All adult (age, ≥18 years) trauma patients who received WB were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups, 4-PCC–WB versus WB alone, and matched in a 1:2 ratio using propensity score matching. Outcome measures were packed red blood cells, plasma, platelets, and cryoprecipitate transfused, in-hospital complications, hospital and intensive care unit (ICU) length of stay (LOS) among survivors, and mortality.

RESULTS

A total of 252 patients (4-PCC–WB, 84; WB alone, 168) were matched. The mean ± SD age was 47 ± 21 years, 63% were males, median Injury Severity Score was 30 (21–40), and 87% had blunt injuries. Patients who received 4-PCC–WB had decreased requirement for packed red blood cell (8 U vs. 10 U, p = 0.04) and fresh frozen plasma (6 U vs. 8 U, p = 0.01) transfusion, lower rates of acute kidney injury (p = 0.03), and ICU LOS (5 days vs. 8 days, p = 0.01) compared with WB alone. There was no difference in the platelet transfusion (p = 0.19), cryoprecipitate transfusion (p = 0.37), hospital LOS (p = 0.72), and in-hospital mortality (p = 0.72) between the two groups.

CONCLUSION

Our study demonstrates that the use of 4-PCC as an adjunct to WB is associated with a reduction in transfusion requirements and ICU LOS compared with WB alone in the resuscitation of trauma patients. Further studies are required to evaluate the role of PCC with WB in the resuscitation of trauma patients.

LEVEL OF EVIDENCE

Therapeutic, level III.
Milestone Development in Genetic Conditions from SFARI Registries
Authors: Wickstrom Jordan , Farmer Cristan , Snyder LeeAnne Green , Mitz Andrew R. , Sanders Stephan J. , Bishop Somer , Thurm Audrey
Published: April 2021

Background

Several recent initiatives have sought to better understand characteristic behaviors of rare genetic conditions associated with autism spectrum disorder (ASD). The onset of developmentally expected skills, such as walking and talking, serve as readily quantifiable aspects of the behavioral phenotype. The goals of this study were to describe attainment of major motor and language milestones in genetic conditions implicated in the etiology of ASD and other neurodevelopmental disorders and to compare those phenotypes to idiopathic ASD.

Methods

Participants ages 3 years and older were drawn from two Simons Foundation Autism Research Initiative-funded registries with consistent phenotyping protocols. Inclusion criteria consisted of a confirmed genetic diagnosis for one of 16 specific genetic conditions (Simons Searchlight), and absence of pathogenic genetic findings in idiopathic ASD controls (SPARK). Parent-reported age of acquisition of three motor and two language milestones was described and quantified as on-time or delayed relative to normative expectations.

Results

Delay was more common among participants with rare genetic conditions than idiopathic ASD for all milestones. Compared to the idiopathic ASD group, the median odds of delay among the genetic groups were 8.3 times (IQR 5.8-16.3) higher for sitting, 12.4 times (IQR 5.3-19.5) higher for crawling, 26.8 times (IQR 7.7-41.1) higher for walking, 2.7 times (IQR 1.7-5.5) higher for single words, and 5.7 times (IQR 2.8-18.3) higher for combined words.

Conclusion

Delays in major developmental milestones, particularly in motor skills, may be among the earliest clues that developmental processes may be differentially affected in specific genetically defined conditions versus a behaviorally defined disorder such as idiopathic ASD.
Cardiac Surgery during the Covid-19 Pandemic: Evidence from the first wave
Authors: Vandoros Sotiris , Schizas Nikolaos , Apostolopoulos Alkis , Patris Vasilios , Argiriou Mihalis
Published: April 2021

Background

The Covid-19 pandemic has affected human behaviour and burdened health systems and has thus had an impact on other health outcomes.

Objective

This paper studies whether there was a decrease in cardiac surgery operations in Greece during the first wave of the Covid-19 pandemic.

Data and Methods

We used data from 7 major hospitals that geographically cover about half the country and more than half the population, including a mix of public, private, military and children’s hospitals. We used a difference-in-differences econometric approach to compare trends in cardiac surgery before and after the pandemic in 2020, to the same months in 2019, controlling for seasonality and unemployment, and using hospital fixed effects.

Results

We found that during the first wave of the pandemic and the associated lockdown, there were 35-56% fewer cardiac surgery operations compared to what we would have expected in the absence of the pandemic.

Conclusions

There was a steep decline in Cardiac surgery operations in Greece during the first wave of the Covid-19 pandemic. Possible reasons may include people not seeking medical attention to avoid the risk of catching Covid-19; fewer referrals; and working from home, thus not being exposed to a stressful work environment or commute.
Hematopoietic stem cell requirement for macrophage regeneration is tissue-specific
Authors: Eddins Devon J. , Kosters Astrid , Waters Jeffrey , Sosa Jasmine , Phillips Megan , Yadava Koshika , Herzenberg Leonore A. , Kuipers Hedwich F. , Ghosn Eliver Eid Bou
Published: April 2021

Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny where now most TRMΦ are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (Large and Small Peritoneal Macrophages; LPM and SPM, respectively) whose origins and relationship to both fetal and adult long-term (LT)-HSCs have not been fully investigated. Here we employ highly purified LT-HSC transplantation and in vivo lineage tracing to show a dual ontogeny for LPM and SPM, where the initial wave of peritoneal macrophages is seeded from yolk sac-derived precursors, which later require LT-HSCs for regeneration. In contrast, transplanted fetal and adult LT-HSCs are not able to regenerate brain-resident microglia. Thus, we demonstrate that LT-HSCs retain the potential to develop into TRMΦ, but their requirement is tissue-specific.
Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina
Authors: Chen Si , Lathrop Kira L. , Kuwajima Takaaki , Gross Jeffrey M.
Published: April 2021

Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, our results support a model in which pro-survival signals in RGCs, mediated by JAK/STAT signaling, counteract the activity of innate immune responses to modulate RGC vulnerability and resilience in the zebrafish retina after severe optic nerve damage.
Differential Interaction between RAC/ROP-GTPases and RIC-Effectors: A Network Hub for Broader Signal Transduction in Pollen Tubes
Authors: Stephan Octavian O. H.
Published: April 2021

To date knowledge about plant RAC/ROP-GTPase effectors and downstream targets is still limited. This work aims on elucidation of related signal transduction networks involved in pollen tube growth. Yeast two-hybrid and Pull Down methodology were used to identify and characterize hitherto unknown components of RAC-related protein complexes fromNicotiana tabacum. Nt-RIC11pt specifically interacts with diverse active tobacco RAC-GTPases, and it is particularly significant, that their binding affinity is differential, thus implicating a multifaceted role in an interconnected RIC-RAC network. Moreover, Y2H-screening for Nt-RIC11pt targets identified Nt-CAR4, which is phylogenetically assigned to a multifaceted family of novel unusualGTPaseactivatingproteins (GAP). It is argued that scaffold Nt-RIC11pt connects active Nt-RAC3 with membrane-bound Nt-CAR4, thus relaying GAP-activity. Quantitative RT-PCR demonstrates Nt-RIC11pt is primarily expressed in pollen and YFP-fusion proteins show homogeneous cytoplasmic localization in growing tubes, what builds the prerequisite for a proposed role in broader signal transduction. By synoptically integrating experimental data, bioinformatic sequence comparison, phylogenetic analyses, and detailed literature review, this study hypothesizes a concept in which RIC-effectors collectively constitute a multifaceted network hub linking diverse GTPase-dependent processes.
Nasal delivery of single-domain antibodies improves symptoms of SARS-CoV-2 infection in an animal model
Authors: Haga Kei , Takai-Todaka Reiko , Matsumura Yuta , Takano Tomomi , Tojo Takuto , Nagami Atsushi , Ishida Yuki , Masaki Hidekazu , Tsuchiya Masayuki , Ebisudani Toshiki , Sugimoto Shinya , Sato Toshiro , Yasuda Hiroyuki , Fukunaga Koichi , Sawada Akihito , Nemoto Naoto , Song Chihong , Murata Kazuyoshi , Morimoto Takuya , Katayama Kazuhiko
Published: April 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the disease COVID-19 can lead to serious symptoms, such as severe pneumonia, in the elderly and those with underlying medical conditions. While vaccines are now available, they do not work for everyone and therapeutic drugs are still needed particularly for treating life-threatening conditions. Here, we showed nasal delivery of a new, unmodified camelid single-domain antibody (VHH), termed K-874A, effectively inhibited SARS-CoV-2 titers in infected lungs of Syrian hamsters without causing weight loss and cytokine induction.In vitrostudies demonstrated that K-874A neutralized SARS-CoV-2 in both VeroE6/TMPRSS2 and human lung-derived alveolar organoid cells. Unlike other drug candidates, K-874A blocks viral membrane fusion rather than viral attachment. Cryo-electron microscopy revealed K-874A bound between the receptor binding domain and N-terminal domain of the virus S protein. Further, infected cells treated with K-874A produced fewer virus progeny that were less infective. We propose that direct administration of K-874A to the lung via a nebulizer could be a new treatment for preventing the reinfection of amplified virus in COVID-19 patients.

Author summary

Vaccines for COVID-19 are now available but therapeutic drugs are still needed to treat life-threatening cases and those who cannot be vaccinated. We discovered a new heavy-chain single-domain antibody that can effectively neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. Unlike other drug candidates, which prevent the virus from attaching to the receptor on the host cell, this new antibody acts by blocking the virus membrane from fusing with the host cell membrane. We studied the behavior of the new antibodyin vitrousing VeroE6/TMPRSS2 cells and human lung organoids. When delivered through the nose to infected Syrian hamsters, we found that this antibody could prevent the typical symptoms caused by SARS-CoV-2. Our results are significant because delivering simple drugs directly to infected lungs using a nebulizer could increase the potency of the drugs while reducing the risk of immune reaction that could occur if the drugs escape or are delivered through the blood stream.
Regulation of the Dimerization and Activity of SARS-CoV-2 Main Protease through Reversible Glutathionylation of Cysteine 300
Authors: Davis David A. , Bulut Haydar , Shrestha Prabha , Yaparla Amulya , Jaeger Hannah K. , Hattori Shin-ichiro , Wingfield Paul T. , Mitsuya Hiroaki , Yarchoan Robert
Published: April 2021

SARS-CoV-2 encodes main protease (Mpro), an attractive target for therapeutic interventions. We show Mprois susceptible to glutathionylation leading to inhibition of dimerization and activity. Activity of glutathionylated Mprocould be restored with reducing agents or glutaredoxin. Analytical studies demonstrated that glutathionylated Mproprimarily exists as a monomer and that a single modification with glutathione is sufficient to block dimerization and loss of activity. Proteolytic digestions of Mprorevealed Cys300 as a primary target of glutathionylation, and experiments using a C300S Mpromutant revealed that Cys300 is required for inhibition of activity upon Mproglutathionylation. These findings indicate that Mprodimerization and activity can be regulated through reversible glutathionylation of Cys300 and provides a novel target for the development of agents to block Mpro dimerization and activity. This feature of Mpromay have relevance to human disease and the pathophysiology of SARS-CoV-2 in bats, which develop oxidative stress during flight.
Rad53 checkpoint kinase regulation of DNA replication fork rate via Mrc1 phosphorylation
Authors: McClure Allison W. , Diffley John F.X.
Published: April 2021

The Rad53 DNA checkpoint protein kinase plays multiple roles in the budding yeast cell response to DNA replication stress. Key amongst these is its enigmatic role in safeguarding DNA replication forks. Using DNA replication reactions reconstituted with purified proteins, we show Rad53 phosphorylation of Sld3/7 or Dbf4-dependent kinase blocks replication initiation whilst phosphorylation of Mrc1 or Mcm10 slows elongation. Mrc1 phosphorylation is necessary and sufficient to slow replication forks in complete reactions; Mcm10 phosphorylation can also slow replication forks, but only in the absence of unphosphorylated Mrc1. Mrc1 stimulates the unwinding rate of the replicative helicase, CMG, and Rad53 phosphorylation of Mrc1 prevents this. We show that a phosphorylation-mimicking Mrc1 mutant cannot stimulate replicationin vitroand partially rescues the sensitivity of arad53null mutant to genotoxic stressin vivo. Our results show that Rad53 protects replication forks in part by antagonising Mrc1 stimulation of CMG unwinding.
A sensory intervention to improve sleep behaviours and sensory processing behaviours of children with sensory processing disorders
Authors: Spira Geela
Published: April 2021

Purpose

This paper aims to investigate if a sensory intervention of moderate pressure touch of children with sensory processing disorder (SPD) affects sleep behaviours and sensory processing behaviours.

Design/methodology/approach

A total of 50 children, aged 5–11 years with both SPD and sleep difficulties in Israel, were randomly divided into an experimental and a control group, nonblinded. Participants in the experimental group received three weeks of nightly massage by their parents, with a baseline week on both ends. Parents filled out questionnaires reporting on sensory and sleep behaviours and filled out a nightly sleep log. Parents determined outcome goals using goal attainment scoring. The assessment tools used were the short sensory profile and the child sleep habits questionnaire (Dunn, 1999; Owens et al., 2000).

Findings

Significant improvement was found in the total and subgroup scores of sleep participation measures including sleep onset, sleep anxiety, parasomnias, sleep duration, daytime sleepiness, as well as the total sleep score (F (1,48) = 24.71, p < 0.001).

Originality/value

Results of this study suggest that consistent application of moderate pressure touch as advised or trained by an occupational therapist may be used in clinical practice to improve sleep participation in children with SPD.
Novel fractional hybrid impedance control of series elastic muscle-tendon actuator
Authors: Fotuhi Mohammad Javad , Bingul Zafer
Published: April 2021

Purpose

This paper aims to develope a novel fractional hybrid impedance control (FHIC) approach for high-sensitive contact stress force tracking control of the series elastic muscle-tendon actuator (SEM-TA) in uncertain environments.

Design/methodology/approach

In three different cases, the fractional parameters of the FHIC were optimized with the particle swarm optimization algorithm. Its adaptability to the pressure of the sole of the foot on real environments such as grass (soft), carpet (medium) and solid floors (hard) is far superior to traditional impedance control. The main aim of this paper is to derive the dynamic simulation models of the SEM-TA, to develop a control architecture allowing for high-sensitive contact stress force control in three cases and to verify the simulation models and the proposed controller with experimental results. The performance of the optimized controllers was evaluated according to these parameters, namely, maximum overshoot, steady-state error, settling time and root mean squared errors of the positions. Moreover, the frequency robustness analysis of the controllers was made in three cases.

Findings

Different simulations and experimental results were conducted to verify the control performance of the controllers. According to the comparative results of the performance, the responses of the proposed controller in simulation and experimental works are very similar.

Originality/value

Origin approach and origin experiment.
Reputation and financial reporting in Finnish public organizations
Authors: Rautiainen Antti , Luoma-aho Vilma
Published: April 2021

Purpose

This article analyzes the links between financial reports and reputation in the context of Finnish public sector organizations. In general, the paper discusses the accounting treatment of intangible and tangible assets and the quality and relevance of public sector financial reporting.

Design/methodology/approach

For data, we combine three data sets: financial statement information of eight anonymous Finnish public organizations, the results of a reputation survey among their key stakeholders (N = 914) and a sample of the social media sentiment around the organizations.

Findings

Our findings suggest that a decrease in spending and, surprisingly in the nonprofit sector, an increase in the surplus, indicate better perceived financial performance. An increase in surplus is positively linked with the reputational factors, for example, trust. However, disclosing excessive amounts of information, for example, in financial reporting seems to contribute to negative discussions on social media.

Practical implications

We highlight the importance of managing intangibles, including those not recognized in the balance sheet, such as reputation. We present three propositions with potential managerial relevance.

Originality/value

Despite the considerable amount of financial information disclosed by public sector organizations, few studies have analyzed its relevance or connection to reputation. This first-of-a-kind paper combines intangible and tangible assets by analyzing how financial data and intangible reputation are linked in the public sector accounting context. Six reputational factors were discovered, and financial performance was found to correlate with trust in the public sector.
“Can I go or should I stay?” A theoretical framework of social lock-in during unsatisfactory service encounters
Authors: Volkers Maarten
Published: April 2021

Purpose

This article demonstrates that the type of service setting and the first interaction with an employee influences the customers' intention to stay or leave during an unsatisfactory service encounter, and that these effects are mediated by social lock-in, which describes the perception of a customer that exiting a service encounter early violates social norms.

Design/methodology/approach

The hypotheses are tested with two scenario-based experiments using a collective (theater) and high-contact service (restaurant) (N = 1143; 1485).

Findings

The results suggest that social lock-in and the intention to stay are higher in a closed as opposed to an open setting and that the type of setting is, in fact, more important for the decision to stay than sunk costs. Moreover, customers are more likely to stay after an interaction with an employee.

Research limitations/implications

This article contributes to the research aimed at explaining customers' decisions to stay or leave during an unsatisfactory service encounter. In doing so, the study highlights the constraining power of social norms in service encounters, which contributes to the research on the relationship between the social context and customers' behavior.

Practical implications

This study suggests that service providers can manage servicescape cues and employee behavior to influence customers' social lock-in perceptions and their decision to stay on or to leave early.

Originality/value

This is the first study to provide quantitative evidence for social lock-in and its determinants in service encounters.
How over-the-top (OTT) platforms engage young consumers over traditional pay television service? An analysis of changing consumer preferences and gamification
Authors: Sadana Mayank , Sharma Dipasha
Published: April 2021

Purpose

This paper aims to analyse how the top over-the-top (OTT) platform is becoming a preferred source of entertainment amongst young consumers over traditional Pay TV service (Cable TV/DTH) in India and what factors play a vital role in such preferences along with gamification of content. The study follows the theoretical framework of use and gratifications theory and Niche analysis.

Design/methodology/approach

The study establishes a conceptual framework of understanding the preference of consumers, which triggers the shift from old media to new. This research develops an approach to understanding the relevant implications in responses of consumers through a structured online survey conducted amongst different age groups by applying exploratory and confirmatory factor analysis. To further comprehend the relations between measured variables and constructs, the statistical technique is incorporated, i.e. logistic regression.

Findings

Empirical results and discussion insinuated the five factors which affect consumers’ choices concerning entertainment i.e. content and viewing behaviour, expenses incurred on services, shifts influenced by offerings/incentives, convenience and telecom. Logistic regression validated the strength of these factors which made content and viewing behaviour, expenses incurred on services and convenience the three most important factors.

Research limitations/implications

This study analyses the driving factors that are revolutionising the entertainment industry and can be applied in designing a comfortable and engaging experience for a consumer in the future.

Originality/value

This research is original in nature and the findings of this study are valuable for online streaming services, video-on-demand services, Cable TV operators and entertainment content producers.
Pathophysiological roles of cell surface and extracellular protein disulfide isomerase and their molecular mechanisms
Authors: Xu Xulin , Chiu Joyce , Chen Shuai , Fang Chao
Published: April 2021

Protein disulfide isomerase (PDI) is the prototypic member of the thiol isomerase family that catalyses disulfide bond rearrangement. Initially identified in the endoplasmic reticulum as folding catalysts, PDI and other members in its family have also been widely reported to reside on the cell surface and in the extracellular matrix. Although how PDI is exported and retained on the cell surface remains a subject of debate, this unique pool of PDI is developing into an important mechanism underlying the redox regulation of protein sulfhydryls that are critical for the cellular activities under various disease conditions. This review aims to provide an overview of the pathophysiological roles of surface and extracellular PDI and their underlying molecular mechanisms. Understanding the involvement of extracellular PDI in these diseases will advance our knowledge in the molecular aetiology to facilitate the development of novel pharmacological strategies by specifically targeting PDI in extracellular compartments.
CCCP‐induced mitochondrial dysfunction – characterization and analysis of integrated stress response to cellular signaling and homeostasis
Authors: Koncha Ramagopal Reddy , Ramachandran Gayatri , Sepuri Naresh Babu V. , Ramaiah Kolluru V. A.
Published: April 2021

Mitochondrial dysfunction mediated by CCCP (carbonyl cyanide m‐chlorophenyl hydrazone), an inhibitor of mitochondrial oxidative phosphorylation, evokes the integrated stress response (ISR), which is analyzed here by eIF2α phosphorylation and expression profiles of ATF4 and CHOP proteins. Our findings suggest that the CCCP‐induced ISR pathway is mediated by activation of HRI kinase, but not by GCN2, PERK, or PKR. Also, CCCP activates AMPK, a cellular energy sensor, and AKT, a regulator implicated in cell survival, and suppresses phosphorylation of mTORC1 substrates eIF4E‐BP1 and S6K. CCCP also downregulates translation and promotes autophagy, leading to noncaspase‐mediated cell death in HepG2 cells. All these events are neutralized by NAC, an anti‐ROS, suggesting that CCCP‐induced mitochondrial dysfunction promotes oxidative stress. ISRIB, an inhibitor of the ISR pathway, mitigates CCCP‐induced expression of ATF4 and CHOP, activation of AKT, and autophagy, similar to NAC. However, it fails to reverse CCCP‐induced AMPK activation, suggesting that CCCP‐induced autophagy is dependent on ISR and independent of AMPK activation. ISRIB restores partly, inhibition in eIF4E‐BP1 phosphorylation, promotes eIF2α phosphorylation, albeit slowly, and mitigates suppression of translation accordingly, in CCCP‐treated cells. These findings are consistent with the idea that CCCP‐induced oxidative stress leading to eIF2α phosphorylation and ATF4 expression, which is known to stimulate genes involved in autophagy, play a pro‐survival role together with AKT activation and regulate mTOR‐mediated eIF4E‐BP1 phosphorylation.
Comparing the clinicopathological characteristics of combined hepatocellular–cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification
Authors: Yen Chih‐Chieh , Yen Chia‐Jui , Shan Yan‐Shen , Lin Yih‐Jyh , Liu I‐Ting , Huang Hsuan‐Yi , Yeh Matthew M , Chan Shih‐Huang , Tsai Hung‐Wen
Published: April 2021

Aims

Combined hepatocellular–cholangiocarcinoma (cHCC‐CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC‐CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC‐CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification.

Methods and results

We retrospectively analysed 64 cHCC‐CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event‐free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow‐up of 55.9 months, cHCC‐CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour‐infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC‐CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC‐CCA patients. After being pooled with other primary liver cancers, cHCC‐CCA and iCCA resulted in the worse survival.

Conclusions

cHCC‐CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.
FABP5 enhances malignancies of lower‐grade gliomas via canonical activation of NF‐κB signaling
Authors: Wang Yichang , Wahafu Alafate , Wu Wei , Xiang Jianyang , Huo Longwei , Ma Xudong , Wang Ning , Liu Hao , Bai Xiaobin , Xu Dongze , Xie Wanfu , Wang Maode , Wang Jia
Published: April 2021

Low‐grade gliomas (LGGs) are grade III gliomas based on the WHO classification with significant genetic heterogeneity and clinical properties. Traditional histological classification of gliomas has been challenged by the improvement of molecular stratification; however, the reproducibility and diagnostic accuracy of LGGs classification still remain poor. Herein, we identified fatty acid binding protein 5 (FABP5) as one of the most enriched genes in malignant LGGs and elevated FABP5 revealed severe outcomes in LGGs. Functionally, lentiviral suppression of FABP5 reduced malignant characters including proliferation, cloning formation, immigration, invasion and TMZ resistance, contrarily, the malignancies of LGGs were enhanced by exogenous overexpression of FABP5. Mechanistically, epithelial‐mesenchymal transition (EMT) was correlated to FABP5 expression in LGGs and tumour necrosis factor α (TNFα)‐dependent NF‐κB signalling was involved in this process. Furthermore, FABP5 induced phosphorylation of inhibitor of nuclear factor kappa‐B kinase α (IKKα) thus activated nuclear factor kappa‐B (NF‐κB) signalling. Taken together, our study indicated that FABP5 enhances malignancies of LGGs through canonical activation of NF‐κB signalling, which could be used as individualized prognostic biomarker and potential therapeutic target of LGGs.
Comparison of patients’ and staff’s perspectives on the causes of violence and aggression in psychiatric inpatient settings: An integrative review
Authors: Fletcher Alice , Crowe Marie , Manuel Jenni , Foulds James
Published: April 2021

Accessible summary

What is known on the subject?

Aggression and violence are persistent problems in psychiatric inpatient units.

Violence preventive factors have been identified from both staff's and patients’ perspectives.

Violent and aggressive inpatient incidents have not been adequately explained in research and reviews to date.

What this paper adds to existing knowledge?

This review is novel in that it provides a comparison of patients’ and staff's perspectives and identified that these differ and were influenced by factors attributable to the inpatient culture.

The one contributory factor both agreed upon was the role of staff's interpersonal skills in either exacerbating or de‐escalating aggression and violence.

The inpatient culture was found to engender differing perceptions of most contributory factors to violence and aggression.

What are the implications for practice?

While staff's interpersonal skills were identified as a primary influence on whether their interaction with patients contributed to aggression and violence, this was shaped by the inpatient environment's culture.

Patient‐centred interactional skills need to focus on the patients’ needs for respect and active participation rather than engendering feelings of disrespect or coercion.

Patient‐centred communication skills that demonstrate an understanding of the patient's experience in the inpatient environment need to be core skills for mental health nurses.

Introduction

High rates of aggression and violence are a persistent problem in inpatient mental health environments. A comparison of staff's and patients’ perceptions of the causes may provide novel insights.

Aim

This review aimed to compare patients’ and staff's perspectives on the causes of aggression and violence in inpatient environments.

Method

An integrative review of the literature was conducted with a search of Ovid (Medline, Embase, PsycINFO) databases and manual searching.

Results

Thirty articles met criteria for inclusion. Interactions prior to aggressive or violent incidents were characterized by patients as disrespectful and coercive, and by staff as indicative of the patient's mental state or personality. Both groups identified the importance of patient‐centred communication skills.

Discussion

The review identified that patients and staff have differing perspectives on the causes of violence and aggression. There was an interactional dynamic between staff and patients that was shaped by the culture of the inpatient setting.

Implications for Practice

Understanding how the inpatient culture plays a role in shaping a dynamic between patients and staff and developing communication skills that acknowledge this may help reduce violence and aggression in inpatient settings.
SLI1 confers broad‐spectrum resistance to phloem‐feeding insects
Authors: Kloth Karen J. , Shah Parth , Broekgaarden Colette , Ström Cecilia , Albrectsen Benedicte R. , Dicke Marcel
Published: April 2021

Resistance (R) genes usually compete in a coevolutionary arms race with reciprocal effectors to confer strain‐specific resistance to pathogens or herbivorous insects. Here, we investigate the specificity of SLI1, a recently identified R gene in Arabidopsis that encodes a small heat shock‐like protein involved in resistance to Myzus persicae aphids. In a panel with several aphid and whitefly species, SLI1 compromised reproductive rates of three species: the tobacco aphid M. persicae nicotianae, the cabbage aphid Brevicoryne brassicae and the cabbage whitefly Aleyrodes proletella. Electrical penetration graph recording of aphid behaviour, revealed shorter salivations and a 3‐to‐5‐fold increase in phloem feeding on sli1 loss‐of‐function plants. The mustard aphid Lipaphis erysimi and Bemisia tabaci whitefly were not affected by SLI1. Unlike the other two aphid species, L. erysimi exhibited repetitive salivations preceding successful phloem feeding, indicating a role of salivary effectors in overcoming SLI1‐mediated resistance. Microscopic characterization showed that SLI1 proteins localize in the sieve tubes of virtually all above‐ and below‐ground tissues and co‐localize with the aphid stylet tip after penetration of the sieve element plasma membrane. These observations reveal an unconventional R gene that escapes the paradigm of strain specificity and confers broad‐spectrum quantitative resistance to phloem‐feeding insects.
Salesforce Compensation and Two‐Sided Ambiguity: Robust Moral Hazard with Moment Information
Authors: Li Zhaolin , Kirshner Samuel N.
Published: April 2021

We analyze a salesforce principal‐agent model where both the firm and sales agent have limited information on the effort‐dependent demand distribution, creating two‐sided ambiguity. Under the max–min decision criteria, the firm offers a contract to the agent who exerts unobservable effort to influence the demand distribution. We formulate the problem as a semi‐infinite program and use the agent's shadow prices to construct the least expensive contract. Next, we use the least expensive contract to create a non‐linear optimization model, which provides the firm's optimal robust contract. Due to the problem's complexity, we focus our attention on the class of distribution‐free contracts. We show that using a distribution‐free contract is a necessary condition for achieving the first‐best outcome. Our analysis reveals that the index of dispersion determines whether the optimal distribution‐free contract is linear or quadratic. Finally, we extend our model to incorporate quota‐bonus contracts and inventory considerations. Overall, our results demonstrate that variance information plays a critical role in designing contracts under distributional ambiguity and provides justification for the application of quadratic contracts in practice.
The Effects of Instrument-Assisted Soft Tissue Mobilization, Tissue Flossing, and Kinesiology Taping on Shoulder Functional Capacities in Amateur Athletes
Authors: Angelopoulos Pavlos , Mylonas Konstantinos , Tsepis Elias , Billis Evdokia , Vaitsis Nikolaos , Fousekis Konstantinos
Published: April 2021

Context: Instrument-assisted soft tissue mobilization (IASTM), tissue flossing, and kinesiology taping are increasingly popular treatments among athletes for improving functional performance, despite limited evidence for their efficacy. Objective: Previous research regarding the efficacy of soft tissues and neuromuscular techniques on improving functional capacity of shoulder joints in athletes has yielded conflicting results. We examined the immediate and short-term effects of IASTM, flossing, and kinesiology taping on the functional capacities of amateur athletes’ shoulders. Design: Randomized controlled study. Setting: Clinical assessment laboratory. Participants: Eighty amateur overhead athletes (mean [SD]: age = 23.03 [1.89]; weight = 78.36 [5.32]; height = 1.77 [.11]). Interventions: We randomly assigned participants to 4 research sub-groups in which they received the following treatments on their dominant shoulders: IASTM (n = 20), flossing (n = 20), both IASTM and flossing (n = 20), and kinesiology tape (n = 20). Nondominant shoulders served as controls. Main Outcome Measure: We evaluated participants—before, immediately after, and 45 minutes after the therapeutic interventions—with the following tests: internal and external shoulder rotation range of motion, isokinetic strength and total work, the functional throwing performance index, and the one-arm seated shot put throw performance. Results: All therapeutic interventions significantly improved the strength and functional performance of the dominant shoulder in comparison with the control (P < .005) immediately after and 45 minutes after the treatment. The IASTM led to significantly greater improvement in shoulder internal rotation than kinesiology taping immediately after (P = .049) and 45 minutes after the treatment (P = .049). We observed no significant differences between the other treatment interventions (P > .05). Conclusion: Findings from the current study support the use of novel soft tissue and neuromuscular techniques for the immediate and short-term improvement of the shoulder functional capacities in amateur overhead athletes.
Mimetic-metric-torsion with induced axial mode and phantom barrier crossing
Authors: Sur Sourav , Dutta Ashim , Chothe Hiyang Ramo
Published: April 2021

We extend the basic formalism of mimetic-metric-torsion gravity theory, in a way that the mimetic scalar field can manifest itself geometrically as the source of not just the trace mode of torsion, but its axial (or, pseudo-trace) mode as well. Specifically, we consider the mimetic field to be (i) coupled explicitly to the well-known Holst extension of the Riemann–Cartan action, and (ii) identified with the square of the associated Barbero–Immirzi field, presumably a pseudo-scalar. The conformal symmetry originally prevaling in the theory would still hold, as the associated Cartan transformations do not affect the torsion pseudo-trace, and hence the Holst term. Demanding the theory to preserve the spatial parity symmetry as well, we show a geometric unification of the cosmological dark sector, and the feasibility of a super-accelerating regime in the course of evolution of the universe. From the observational perspective, assuming the cosmological evolution profile to be very close to that for $$\varLambda $$
Λ
CDM, we further illustrate a smooth crossing of the so-called phantom barrier at a low red-shift, albeit with a restricted parametric domain. Subsequently, we determine the extent of the super-acceleration by examining the evolution of the relevant torsion parameters.
Designing of a Simulation Tool for the Performance Analysis of Hybrid Data Center Networks (DCNs)
Authors: Ahmad Muhib , Zeeshan Khan Farrukh , Iqbal Zeshan , Ahmad Muneer , Ali Ihsan , Alshamrani Sultan S. , Talha Muhammad , Raza Muhammad Ahsan
Published: April 2021

Data center (DC) technology changes the mode of computing. Traditional DCs consist of a single layer and only have Ethernet connections among switches. Those old‐fashioned DCs cannot fulfill the high resource demand compared with today’s DCs. The architectural design of the DCs is getting substantial importance and acting as the backbone of the network because of its essential feature of supporting and maintaining the rapidly increasing Internet‐based applications which include search engines (e.g., Google and Yandex) and social networking applications (e.g., YouTube, Twitter, and Facebook). Every application has its parameters, like latency and blocking in the DC network. Every data center network (DCN) has its specialized architecture. It has a specific arrangement of layers and switches, which increase or decrease the DC network’s efficiency. We develop a simulation tool that comprises two different DC architectures: basic tree architecture and c‐Through architecture. Using this simulation, we analyze the traffic behavior and the performance of the simulated DCN. Our main purpose is to focus on mean waiting time, load, and blocking with respect to the traffic within the DCN.
Application and Evolution for Neural Network and Signal Processing in Large‐Scale Systems
Authors: Jia Dongbao , Li Cunhua , Liu Qun , Yu Qin , Meng Xiangsheng , Zhong Zhaoman , Ban Xinxin , Wang Nizhuan
Published: April 2021

Low frequency oscillation is an important attribute of human brain activity, and the amplitude of low frequency fluctuation (ALFF) is an effective method to reflect the characteristics of low frequency oscillation, which has been widely used in the treatment of brain diseases and other fields. However, due to the low accuracy of the current analysis methods for low frequency signal extraction of ALFF, we propose the Fourier‐based synchrosqueezing transform (FSST), which is often used in the field of signal processing to extract the ALFF of the low frequency power spectrum of the whole‐time dimension. The low frequency characteristics of the extracted signal are compared with those of FSST and fast Fourier transform (FFT) through the resting‐state data. It is clear that the signal extracted by FSST has more low frequency characteristics, which is significantly different from FFT.
Assessing and Improving the Knowledge of Sexually Transmitted Infections among High School Adolescents
Authors: Jefferson Itisha S. , Robinson S. Kayo , Tung-Hahn Eleanor , Schumann Roan , Marrero-Conti Synthia , Walton Jasmine M. , Golden Eileen , Poon Emily , Alam Murad , Tung Rebecca
Published: April 2021

Background. According to the Center for Disease Control and Prevention (CDC), half of the 20 million new sexually transmitted infections (STIs) occur annually in youth aged 15 to 24. It is critical for dermatologists to be able to provide young patients with accessible education about how to identify, prevent, and treat these conditions. Our pilot study sought to assess the impact of a live presentation about STIs in high school students and to evaluate students’ baseline and acquired knowledge about common STIs using a before and after survey. Methods. This survey study was conducted as part of the health education curriculum at a suburban high school. An interactive scenario-based presentation about STIs was given to participants. Identical, deidentified preintervention and postintervention surveys were completed by subjects to assess their baseline and acquired knowledge of STIs. Each question was worth 1 point, for a total of 8 points. Results. 74 high school students were surveyed. Overall, there was a mean improvement of 1.85 points in the posttest score in comparison to pretest score with a standard deviation of 1.58 (

p
<
0.0001

). Among all participants, the mean pretest score was 1.07 (SD = 0.75) and the mean posttest score was 2.92 (SD = 1.59). Conclusions. This study demonstrated that many young adults are unaware of the common types of STIs, symptoms, and potential complications. While our scenario-based presentation was effective at providing understandable content to help improve students’ knowledge regarding STIs, additional educational resources in varied formats could likely further these gains.