bluuebunny/crossref_metadata_2025 huggingface dataset:
Between fear of and desire for the digitalization of retailing: An initial conceptualization to understand the ambivalent reactions of shoppers
Authors: Rogeon Fabien , Michaud-Trevinal Aurélia , Collin-Lachaud Isabelle
Published: July 2022

Digitalization has resulted in deep changes to the retail landscape, which have been the subject of extensive research. Most studies have only seen this growing phenomenon as a source of benefits for shoppers. However, this technological optimism runs into problems when the technologies offered by retailers are ignored or abandoned by shoppers. To address this gap, our research investigates how shoppers react to the digitalization of retailing through the prism of ambivalence. A systematic literature review identified a dataset of 108 papers in major journals published between 2005 and 2020. Our critical analysis revealed positive and negative reactions to digitalization among shoppers. Grouping these into pairs of two opposites, we propose an initial conceptualization of shopper ambivalence divided into eight distinct components. We also highlight the components of shopper ambivalence that merit further attention and offer a research agenda accordingly. Finally, our conceptualization may help managers to make sense of the heterogeneous reactions of shoppers to the technologies they offer.
Determining Factors Influencing RAS Inhibitors Re-Initiation in ICU: A Modified Delphi Method
Authors: Dahel Hadjer , Lafrance Jean-Philippe , Patenaude Mathilde , Kilpatrick Kelley , Beaubien-Souligny William , Moreau Mathieu , Wang Han Ting
Published: July 2022

Background:

Renin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure.

Objective:

To determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters.

Design:

Three-round modified online Delphi survey.

Setting:

The study was conducted in Quebec, Canada.

Participants:

Twenty clinicians from nephrology, intensive care medicine, and internal medicine.

Measurements:

The factors’ importance was rated on 4-point Likert-type scale, ranging from “not important” to “very important” by the panelists.

Methods:

We conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors.

Results:

We recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation.

Limitations:

Quebec clinicians’ agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians’ belief rather than their actual practice.

Conclusion:

Renin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.
Healthy Lifestyles Associated With Socioeconomic Determinants in the Older Adult Population
Authors: Roldán González Elizabeth , Lerma Castaño Piedad Rocio , Aranda Zemanate Adriana Yulieth , Caicedo Muñoz Ángela Giovana , Bonilla Santos Gisella
Published: July 2022

Introduction/Objective:

The evaluation of lifestyle in older adults and the study of socioeconomic determinants becomes an essential indicator of the health conditions of older adults. The purpose of this study was to establish the relationship between socioeconomic factors and healthy lifestyles in older adults.

Methods:

Study with a quantitative approach, descriptive type, non-experimental design, cross-sectional in a sample of 407 elderlies who have applied a self-designed instrument for socioeconomic characterization and the FANTASTIC test to assess lifestyle. For data analysis, a bivariate analysis was applied using chi2 and multivariate analysis using ordinal logistic regression.

Results:

53% of elderlies aged between 60 and 70 years reported their lifestyle as excellent and very good. Age, average household income, and perceived health status are associated with healthy lifestyles in older adults.

Conclusions:

This study found that in addition to socioeconomic determinants, self-perceived health is a factor that influences the lifestyles of this population.
Faculty Members’ Attitudes and Practices: How They Responded to Forced Adoption of Distance Education?
Authors: Alsubaie Merfat Ayesh , Alzarah Layla Nasser , Alhemly Fatmah Abdulrahman
Published: July 2022

In 2020, the world faced a sudden change and general disruption that included all aspects of life because of the corona virus (COVID-19) pandemic. It has made the whole world adopt general and comprehensive emergency measures that have affected every sector, including health, business, and especially education. In order to continue the education process, educators have responded by adopting distance education. This paper explored the attitudes, practices, and emotions of faculty members in a college of education toward the forced adoption and educational transformation to distance education during the corona pandemic. A coding approach was used to analyze 20 reflective articles, which revealed main themes related to difficulties and challenges. The findings highlight skills and experiences that were gained. Hence, the findings promote that faculty members understand professional practices and behaviors in using distance education as an emergency solution for supporting the education process.
Expanding on Threat and Deprivation: Empirical Examination of Adversity Dimensions and Psychiatric Outcomes Among Emerging Adults
Authors: Sosnowski David W. , Rojo-Wissar Darlynn M. , Smail Emily J. , Musci Rashelle J. , Wilcox Holly C. , Johnson Sara B.
Published: July 2022

Dimensional models of adversity, whereby experiences lie along dimensions of threat and deprivation, are increasingly popular; however, their empirical validation is limited. In a sample of emerging adults ( N = 1662; M age = 20.72; 53% female; 72% Black), we conducted exploratory factor analyses using adversities derived from items probing family relationships and a validated assessment of traumatic events. Resulting factors were used to test associations with odds of lifetime diagnosis of a substance use disorder, other mental health disorders, and suicide attempt. Results supported a four-factor solution: threat (non-betrayal), emotional deprivation, sexual assault, and threat (betrayal). Threat (betrayal) summary scores were most strongly associated with increased odds of substance use and other disorders, whereas sexual assault was most strongly associated increased odds of lifetime suicide attempt. Findings provide some empirical support for categorizing adversity along dimensions of threat and deprivation. However, it also suggests the possibility of further divisions within these dimensions.
Effect of Sleep-Related Symptoms on Recovery From a Sport-Related Concussion
Authors: DuPrey Kevin M. , Char Amber S. , Loose Sean R. , Suffredini Michael V. , Walpole Kevin , Cronholm Peter F.
Published: July 2022

Background:

Sleep issues are commonly reported in athletes after a sport-related concussion (SRC). Further studies are needed to evaluate screening methods for sleep disturbances and the risk of persisting symptoms after an SRC.

Purpose:

To evaluate the association between the Sport Concussion Assessment Tool 5 (SCAT5) symptoms of trouble falling asleep, fatigue (or low energy), and drowsiness and the risk of persisting symptoms (≥28 days to recovery) in adolescent athletes.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A total of 519 athletes aged 13 to 18 years reported any sleep-related symptoms with an SRC, scored as none (0), mild (1-2), moderate (3-4), or severe (5-6), at their initial office visit (median, 5.4 days after an SRC). Scores were correlated with the risk of persisting symptoms. A composite “sleep cluster” score (range, 0-18) was calculated by summing the SCAT5 component items for trouble falling asleep, fatigue, and drowsiness.

Results:

The results indicated that, compared with athletes who reported that they did not have each symptom, (1) athletes who reported mild, moderate, or severe trouble falling asleep were 3.0, 4.6, and 6.7 times more likely to have persisting symptoms, respectively; (2) athletes reporting mild, moderate, or severe fatigue (or low energy) were 2.6, 4.8, and 7.6 times more likely to have persisting symptoms, respectively; and (3) athletes reporting mild, moderate, or severe drowsiness were 1.9, 4.6, and 6.8 times more likely to have persisting symptoms, respectively ( P < .001 for all). For every 1-point increase in the sleep cluster score, there was a 1.2-fold increased risk of persisting symptoms and an additional 2.4 days of recovery required ( P < .001 for both).

Conclusion:

Athletes who reported mild, moderate, or severe sleep-related symptoms on the SCAT5 were at a proportionally increased risk of persisting symptoms at the initial office visit.
Client Experiences With a Short-Term Case Management Mental Health Service
Authors: Duncan Andrea , Stergiopoulos Vicky , Wodchis Walter P , Kirst Maritt , Dainty Katie N
Published: July 2022

Short Term Case Management (STCM) was introduced in 2016 in Toronto, Ontario, as a brief intervention to address long wait-lists for case management services. STCM provides individuals with mental illness, living in the community, case management services on a weekly basis over 3 months to identify personal goals and work toward an improved state of health and well-being. Despite the small but growing body of evidence on short-term case management, there is limited research on clients’ reported experiences of these services. This study used a phenomenological approach to answer the question “What are the experiences with services of individuals who received short-term case management services?” Eight qualitative semistructured interviews were conducted between November 2019 and January 2020 to collect the perspectives and experiences of clients who had received STCM. Most participants valued engaging in a brief therapeutic relationship. Additionally, participants described that the intervention helped them connect with other agencies for ongoing support and begin achieving their own long-term goals. Some participants voiced concerns about the brief duration of the intervention. Future research should explore the role of briefcase management in the continuum of services and the typology of clients who may benefit from longer therapeutic relationship to achieve their goals.
Patient Preferences for Preventive Healthcare During the COVID-19 Pandemic in a Large Integrated Health System
Authors: Stults Cheryl D , Yan Xiaowei , Deng Sien , Dillon Ellis C , Liang Su-Ying , Jones JB , Bhanushali Minal , Frosch Dominick L
Published: July 2022

The COVID-19 pandemic caused healthcare systems and patients to cancel or postpone healthcare services, particularly preventive care. Many patients still have not received these services raising concerns about the potential for preventable morbidity and mortality. At Sutter Health, a large integrated healthcare system in Northern California, we conducted a population-based email survey in August 2020 to evaluate perceptions and preferences about where, when, and how healthcare is delivered during the COVID-19 pandemic. In total, 3351 patients completed surveys, and 42.6% reported that they would “wait until they felt safe” before receiving a colonoscopy as compared to 22.4% for a mammogram. The doctor's office was the most common preferred location for receiving vaccines/shots (79.9%), though many also reported preferring an outdoor setting or in a car (63.7%). With over 40% of patients reporting that they would “wait until they feel safe” for a colonoscopy, healthcare systems could focus on promoting other evidence-based options such a fecal-occult blood test to ensure timely colon cancer screening.
Professional Quality of Life Among Nurses: Compassion Satisfaction, Burnout, and Secondary Traumatic Stress: A Multisite Study
Authors: Bahari Ghareeb , Asiri Khulud , Nouh Nariman , Alqahtani Naji
Published: July 2022

Introduction

Increased stressors and decreased job satisfaction are major challenges in nursing. Important factors of better professional quality of life include compassion satisfaction, burnout, and secondary traumatic stress. It is critical to assess these factors to help improve nurses’ clinical practices.

Objective

The purpose of this study was to determine the relationships between the three factors and associated factors.

Methods

A cross-sectional, multisite study was conducted on a convenience sample of 464 nurses working at three public hospitals in Saudi Arabia. The Professional Quality of Life Version 5 was used to collect data. Bivariate and multivariate analyses were run using SPSS.

Results

Scores were slightly moderate on the compassion satisfaction, burnout, and secondary traumatic stress levels. Compassion satisfaction was statistically significantly and negatively associated with burnout. A statistically significant relationship was reported between compassion satisfaction and secondary traumatic stress. Further, there was a statistically significant association between burnout and secondary traumatic stress. In regression, only the secondary traumatic stress model was statistically significant.

Conclusions

Nurse managers should use highly standard guidelines to reduce secondary traumatic stress levels. Further actions addressing potential issues for improving compassion satisfaction and reducing burnout levels among nurses are also recommended.
Vacuolar tubular injury after exposure to immune check-point inhibitor
Authors: Parvathareddy Vishnu P , Glass William , Workeneh Biruh T
Published: July 2022

Renal toxicities have been increasingly recognized as complications of immune checkpoint inhibitor therapy. These drugs are associated with a broad range of immune-related adverse events in the kidney, including interstitial nephritis, glomerulonephritis, and acute tubular necrosis. We describe a woman with a rare pattern of injury, osmotic tubulopathy, after exposure to pembrolizumab that has been described only once before in the medical literature. As a result of these observations, vacuolar tubular injury pattern that has the appearance of an osmotic lesion should be considered as a possible consequence of immune checkpoint inhibitor therapy.
Exploring the concept of town centre paradigms and how they impact on town centre retail landscapes
Authors: Hehir Alan , Warnaby Gary , Theodoridis Costas
Published: July 2022

The radical changes to the UK town centre retail landscape over the past 60 years are well documented. What are less well documented are accounts of how the internal processes of town centre governance impact on the retail landscape. From the 1990s UK government dictums, aimed at arresting decline, have advised local authorities to engage with local stakeholders and invite otherwise excluded stakeholders into the previously established rituals and routines of local governance. The aim of this paper is to analyse the influence of the ‘organisational culture(s)’ of town centre custodians (which we conceptualise as the ‘town centre paradigm’) on their actions to improve the retail vitality and viability of their locale. Through a comparative case study of four UK town centres manifesting contrasting governance ‘stereotypes’, we explore how different town centre ‘custodians’ interpret government policies and, perhaps more importantly, how their behaviour impacts on the retail development landscapes of their town centres.
‘Thank you for having me’: The experiences and meanings of release from prison in Norway and England & Wales
Authors: Doxat-Pratt Sarah , Schliehe Anna , Laursen Julie
Published: July 2022

The day of release from prison can be one of the most highly anticipated events for prisoners, and one which holds a place in the public imagination as a significant and transformative moment. Yet in scholarly literature, although there is much on prisoner resettlement and reintegration, the moment of release itself is seldom mentioned. Drawing on interviews ( N:455) from a comparative research project in Norway and England & Wales, this paper will zoom in on the micro-processes that shape exit, capturing how prisoners prepare for release, the procedures and practices of the release day, and their first encounter with the outside world. In both countries, there was a juxtaposition of personal significance and institutional banality around exit, which contrast sharply with the highly ritualistic processes of sentencing and entry and which frequently led prisoners to reflect on the nature of their punishment and the meaning of their time in prison. By highlighting the details of release, the paper will explore these ideas, probing the boundaries that exist between the inside and outside worlds and connecting the experiences of exit with conceptual ideas of how punishment is experienced and how prisoners create meaning.
Researcher entanglements and the problem of evil
Authors: Laws Ben
Published: July 2022

Researchers can learn much from engaging with the complexities of evil. This article details how I felt enmeshed in a process where I was both seeing, and in some ways contributing to, aspects of evil while researching in prison. The context for this study was a high-security prison establishment recently scarred by three high-profile incidents that merged terror with violence. By introducing examples from my fieldwork, I explore various ways in which ‘researcher entanglements’ emerged. I argue that the real danger of evil is that it leads to moral righteousness and toxic cycles that are hard to break.
Seismic repair and retrofit prioritization framework
Authors: Brown Charlotte , Seville Erica , Horsfall Sophie , Bugler Graham , Brunsdon Dave , Hare John
Published: July 2022

The 2010–2011 Canterbury earthquake sequence caused significant damage to the Canterbury District Health Board (CDHB) building stock. The extent of damage, post-earthquake changes to the seismic code, new legislation around earthquake-prone buildings, and ongoing changes to clinical service requirements created a challenging decision-making environment for capital works repair and retrofit. In this article, we present a framework designed to assess the seismic resilience of buildings from a holistic perspective and to determine appropriate levels of seismic retrofit. The framework design ensures that decisions are driven by building criticality in the context of a healthcare system. It helps users to balance life safety risk and the demands of delivering critical clinical services day to day: resulting in safe facilities that provide effective health services under a range of future conditions. Pilot application of the framework enabled the reprioritization of significant capital toward buildings that provide the most life safety and health service resilience benefits in the long term. The process and resulting framework from this project is applicable to a wider range of building owners navigating seismic retrofit decision-making and the emerging movement toward functional recovery–based building regulation.
Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma
Authors: Elsawy Mahmoud , Chavez Julio C. , Avivi Irit , Larouche Jean-François , Wannesson Luciano , Cwynarski Kate , Osman Keren , Davison Kelly , Rudzki Jakob D. , Dahiya Saurabh , Dorritie Kathleen , Jaglowski Samantha , Radford John , Morschhauser Franck , Cunningham David , Martin Garcia-Sancho Alejandro , Tzachanis Dimitrios , Ulrickson Matthew L. , Karmali Reem , Kekre Natasha , Thieblemont Catherine , Enblad Gunilla , Dreger Peter , Malladi Ram , Joshi Namita , Wang Wei-Jhih , Solem Caitlyn T. , Snider Julia Thornton , Cheng Paul , To Christina , Kersten Marie José
Published: July 2022

Here, we report the first comparative analysis of patient-reported outcomes (PROs) with chimeric antigen receptor T-cell therapy vs standard-of-care (SOC) therapy in second-line relapsed/refractory large B-cell lymphoma (R/R LBCL) from the pivotal randomized phase 3 ZUMA-7 study of axicabtagene ciloleucel (axi-cel) vs SOC. PRO instruments were administered at baseline, day 50, day 100, day 150, month 9, and every 3 months from randomization until 24 months or an event-free survival event. The quality of life (QoL) analysis set comprised patients with a baseline and ≥1 follow-up PRO completion. Prespecified hypotheses for Quality of Life Questionnaire-Core 30 (QLQ-C30) physical functioning, global health status/QoL, and EQ-5D-5L visual analog scale (VAS) were tested using mixed-effects models with repeated measures. Clinically meaningful changes were defined as 10 points for QLQ-C30 and 7 for EQ-5D-5L VAS. Among 359 patients, 296 (165 axi-cel, 131 SOC) met inclusion criteria for QoL analysis. At day 100, statistically significant and clinically meaningful differences in mean change of scores from baseline were observed favoring axi-cel over SOC for QLQ-C30 global health status/QoL (estimated difference 18.1 [95% confidence interval (CI), 12.3-23.9]), physical functioning (13.1 [95% CI, 8.0-18.2]), and EQ-5D-5L VAS (13.7 [95% CI, 8.5-18.8]; P < .0001 for all). At day 150, scores significantly favored axi-cel vs SOC for global health status/QoL (9.8 [95% CI, 2.6-17.0]; P = .0124) and EQ-5D-5L VAS (11.3 [95% CI, 5.4-17.1]; P = .0004). Axi-cel showed clinically meaningful improvements in QoL over SOC. Superior clinical outcomes and favorable patient experience with axi-cel should help inform treatment choices in second-line R/R LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03391466.
Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial
Authors: Kumar Riten , Dunn Amy L. , Schneiderman Jane E. , Gonzales Anne , Bouskill Vanessa , Widener Pamela , Stanek Joseph , Pluthero Fred G. , Waller Amanda , Tarango Cristina , Ahuja Sanjay , Kerlin Bryce A. , Kahr Walter H. A. , Rand Margaret L. , Lillicrap David , Carcao Manuel
Published: July 2022

Persons with mild hemophilia A (HA) may use intranasal desmopressin prior to sports participation. Desmopressin is expensive and can cause vomiting, headache, palpitation, and occasionally seizures. Our group has previously documented a 2.3-fold increase in factor VIII activity (FVIII:C) in adolescents with mild HA after moderate-intensity aerobic exercise. Herein, we report principal findings of a randomized trial of intranasal desmopressin vs a standardized, moderate-intensity aerobic exercise regimen in adolescents with mild HA. Our primary objective was to compare the change in FVIII:C associated with these 2 interventions. We also examined changes in hemostatic parameters arising from their sequential administration. The study was conducted simultaneously at the Hospital for Sick Children, Canada, and Nationwide Children’s Hospital, USA. Thirty-two eligible male adolescents (mean age ± standard deviation: 16.1 ± 2.6 years) with mild HA (mean baseline FVIII:C: 27.9% ± 18.4%) were randomized to 1 of 4 study arms (desmopressin followed by exercise, desmopressin alone, exercise followed by desmopressin, and exercise alone). Blood work was obtained at baseline and at 3 subsequent time-points. Participants randomized to exercise cycled on an ergometer for approximately 12 minutes, with the final 3 minutes at 85% of their predicted maximum heart rate. Standard weight-based dosing of desmopressin was used. Mean immediate increase in FVIII:C was 1.7-fold with exercise compared with 1.9-fold with desmopressin (noninferiority, P = .04). Exercise-induced improvement in hemostatic parameters including FVIII:C was brief compared with more sustained improvements seen with desmopressin. More than 60% of participants randomized to receive both exercise and desmopressin achieved normal (>50%) FVIII:C, 75 and 135 minutes into the study protocol.
Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR inRUNX1deficiency
Authors: Jalagadugula Gauthami , Mao Guangfen , Goldfinger Lawrence E. , Wurtzel Jeremy , Del Carpio-Cano Fabiola , Lambert Michele P. , Estevez Brian , French Deborah L. , Poncz Mortimer , Rao A. Koneti
Published: July 2022

Transcription factor RUNX1 is a master regulator of hematopoiesis and megakaryopoiesis. RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia and platelet granule deficiencies and dysfunction. Platelet profiling of our study patient with RHD showed decreased expression of RAB31, a small GTPase whose cell biology in megakaryocytes (MKs)/platelets is unknown. Platelet RAB31 messenger RNA was decreased in the index patient and in 2 additional patients with RHD. Promoter-reporter studies using phorbol 12-myristate 13-acetate–treated megakaryocytic human erythroleukemia cells revealed that RUNX1 regulates RAB31 via binding to its promoter. We investigated RUNX1 and RAB31 roles in endosomal dynamics using immunofluorescence staining for markers of early endosomes (EEs; early endosomal autoantigen 1) and late endosomes (CD63)/multivesicular bodies. Downregulation of RUNX1 or RAB31 (by small interfering RNA or CRISPR/Cas9) showed a striking enlargement of EEs, partially reversed by RAB31 reconstitution. This EE defect was observed in MKs differentiated from a patient-derived induced pluripotent stem cell line (RHD-iMKs). Studies using immunofluorescence staining showed that trafficking of 3 proteins with distinct roles (von Willebrand factor [VWF], a protein trafficked to α-granules; epidermal growth factor receptor; and mannose-6-phosphate) was impaired at the level of EE on downregulation of RAB31 or RUNX1. There was loss of plasma membrane VWF in RUNX1- and RAB31-deficient megakaryocytic human erythroleukemia cells and RHD-iMKs. These studies provide evidence that RAB31 is downregulated in RHD and regulates megakaryocytic vesicle trafficking of 3 major proteins with diverse biological roles. EE defect and impaired vesicle trafficking is a potential mechanism for the α-granule defects observed in RUNX1 deficiency.
Differences in wild-type– and R338L-tenase complex formation are at the root of R338L-factor IX assay discrepancies
Authors: Foley Jonathan H. , Shehu Erald , Riddell Anne , Gray Elaine , Goodale Andrew , Yu I-Mei , Verhoef Daniël , Little John , Shattock Diane , Kitchen Steve , Chowdary Pratima , Corbau Romuald , Nathwani Amit C.
Published: July 2022

Adeno-associated virus (AAV) gene therapy has the potential to functionally cure hemophilia B by restoring factor (F)IX concentrations into the normal range. Next-generation AAV therapies express a naturally occurring gain-of-function FIX variant, FIX-Padua (R338L-FIX), that increases FIX activity (FIX:C) by approximately eightfold compared with wild-type FIX (FIX-WT). Previous studies have shown that R338L-FIX activity varies dramatically across different clinical FIX:C assays, which complicates the monitoring and management of patients. To better understand mechanisms that contribute to R338L-FIX assay discrepancies, we characterized the performance of R338L-FIX in 13 1-stage clotting assays (OSAs) and 2 chromogenic substrate assays (CSAs) in a global field study. This study produced the largest R338L-FIX assay dataset to date and confirmed that clinical FIX:C assay results vary over threefold. Both phospholipid and activating reagents play a role in OSA discrepancies. CSA generated the most divergent FIX:C results. Manipulation of FIX:C CSA kits demonstrated that specific activity gains for R338L-FIX were most profound at lower FIX:C concentrations and that these effects were enhanced during the early phases of FXa generation. Supplementing FX into CSA had the effect of dampening FIX-WT activity relative to R338L-FIX activity, suggesting that FX impairs WT tenase formation to a greater extent than R338L-FIX tenase. Our data describe the scale of R338L-FIX assay discrepancies and provide insights into the causative mechanisms that will help establish best practices for the measurement of R338L-FIX activity in patients after gene therapy.
A comprehensive prognostic and immune analysis of enhancer RNA identifies IGFBP7-AS1 as a novel prognostic biomarker in Uterine Corpus Endometrial Carcinoma
Authors: Liu Jinhui , Yin Jian , Wang Yuanyuan , Cai Lixin , Geng Rui , Du Mulong , Zhong Zihang , Ni Senmiao , Huang Xiaohao , Yu Hao , Bai Jianling
Published: July 2022

Background

Long non-coding RNAs (lncRNA) have been implicated in a hand of studies that supported an involvement and co-operation in Uterine Corpus Endometrial Carcinoma (UCEC). Enhancer RNAs (eRNA), a functional subtype of lncRNA, have a key role throughout the genome to guide protein production, thus potentially associated with diseases.

Methods

In this study, we mainly applied the Cancer Genome Atlas (TCGA) dataset to systematically discover crucial eRNAs involving UCEC. For the key eRNAs in UCEC, we employed RT-qPCR to compare eRNA expression levels in tumor tissues and paired normal adjacent tissues from UCEC patients for validation. Furthermore, the relationships between the key eRNAs and immune activities were measured from several aspects, including the analysis for tumor microenvironment, immune infiltration cells, immune check point genes, tumor mutation burden, and microsatellite instability, as well as m6A related genes. Finally, the key eRNAs were verified by a comprehensive pan-cancer analysis.

Results

IGFBP7 Antisense RNA 1 (IGFBP7-AS1) was identified as the key eRNA for its expression patterns of low levels in tumor tissues and favorable prognostic value in UCEC correlated with its target gene IGFBP7. In RT-qPCR analysis, IGFBP7-AS1 and IGFBP7 had down-regulated expression in tumor tissues, which was consistent with previous analysis. Moreover, IGFBP7-AS1 was found closely related with immune response in relevant immune analyses. Besides, IGFBP7-AS1 and its target gene IGFBP7 correlated with a multi-omics pan-cancer analysis.

Conclusions

Finally, we suggested that IGFBP7-AS1 played a key role in impacting on clinical outcomes of UCEC patients for its possible influence on immune activity.
High D-glucose levels induce ACE2 expression via GLUT1 in human airway epithelial cell line Calu-3
Authors: Wakabayashi Yoshitaka , Nakayama Shin , Yamamoto Ai , Kitazawa Takatoshi
Published: July 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 is expressed on human airway epithelial cells. Increased ACE2 expression may be associated with potentially high risk of COVID-19. However, the factors responsible for the regulation of ACE2 expression in human airway epithelial cells are unknown. Furthermore, hyperglycemia is a risk factor for poor disease prognosis.

Results

In this study, we investigated the effects of D-glucose on ACE2 mRNA and protein expressions in Calu-3 bronchial submucosal cells. The cells were cultured in minimal essential medium containing different D-glucose concentrations. After 48 and 72 h of high D-glucose (1000 mg/dL) treatment, ACE2 mRNA expressions were significantly increased. ACE2 protein expressions were significantly increased after 24 h of high D-glucose treatment. ACE2 mRNA expression was enhanced by a D-glucose concentration of 550 mg/dL or more after 72 h of treatment. In addition, we investigated the role of glucose transporters (GLUTs) in Calu-3 cells. ACE2 mRNA and protein expressions were suppressed by the GLUT1 inhibitor BAY-876 in high D-glucose-treated Calu-3 cells. GLUT-1 siRNA was also used and ACE2 mRNA expressions were suppressed in high D-glucose-treated Calu-3 cells with GLUT-1 knockdown.

Conclusions

This is the first report indicating that high D-glucose levels induced ACE2 expression via GLUT1 in bronchial submucosal cells in vitro. As hyperglycemia can be treated appropriately, these findings could help reduce the risk of worsening of coronavirus disease 2019.
Absence of genetic isolation across highly fragmented landscape in the ant Temnothorax nigriceps
Authors: Cordonnier Marion , Felten Dominik , Trindl Andreas , Heinze Jürgen , Bernadou Abel
Published: July 2022

Background

Human activities, including changes in agricultural landscapes, often impact biodiversity through habitat fragmentation. This potentially reduces genetic exchange between previously connected populations. Using a combination of nuclear and mitochondrial markers, we investigated (i) genetic diversity and population structure at multiple spatial scales and (ii) colony genetic structure and queen mating frequency in the ant species Temnothorax nigriceps in a highly anthropized environment.

Results

Although the results highlighted genetic structure on a European spatial scale, they did not reveal an impact of fragmentation on a regional scale, and we did not observe any genetic population structure on a regional scale. Across all populations, regardless of their geographical location, colony structure suggested monogyny (a single queen per colony) and monandry (single mating). However, nestmates were more related than expected, indicating that large-scale dispersal does not fully prevent genetic isolation.

Conclusions

Despite living in fragmented patches of habitat, populations of Temnothorax nigriceps are apparently genetically not isolated at a regional scale. However, large-scale dispersal alone does not prevent genetic isolation. The ecological requirements of T. nigriceps may explain their resilience to habitat fragmentation by allowing them to survive in very small patches of suitable habitat. The deeper investigation of the diversity of functional habitats for this species should allow to appreciate better the mechanisms permitting this species to overcome the negative impacts of fragmentation.
Motor training is improved by concurrent application of slow oscillating transcranial alternating current stimulation to motor cortex
Authors: Sale Martin V. , Kuzovina Anastasiia
Published: July 2022

Physical exercise and neurorehabilitation involve repetitive training that can induce changes in motor performance arising from neuroplasticity. Retention of these motor changes occurs via an encoding process, during which rapid neuroplastic changes occur in response to training. Previous studies show that transcranial alternating current stimulation (tACS), a form of non-invasive brain stimulation, can enhance encoding of a cognitive learning task during wakefulness. However, the effect of tACS on motor processes in the awake brain is unknown. In this study, forty-two healthy 18–35 year old participants received either 0.75 Hz (active) tACS (or sham stimulation) for 30 min during a ballistic thumb abduction motor training task. Training-related behavioural effects were quantified by assessing changes in thumb abduction acceleration, and neuroplastic changes were quantified by measuring motor evoked potential (MEP) amplitude of the abductor pollicis brevis muscle. These measures were reassessed immediately after the motor training task to quantify short-term changes, and then 24 h later to assess longer-term changes. Thumb abduction acceleration in both active and sham stimulation conditions increased immediately after the motor learning, consistent with effective training. Critically, participants in the active group maintained significantly higher thumb acceleration 24 h later (t40 = 2.810, P = 0.044). There were no significant changes or inter-group differences in MEPs for both conditions. The results suggest that 0.75 Hz tACS applied during motor training enhances the effectiveness of motor training, which manifests as enhancement in longer-term task benefits.
Identification and validation of necroptosis-related prognostic gene signature and tumor immune microenvironment infiltration characterization in esophageal carcinoma
Authors: Sun Kai , Hong Juan-juan , Chen Dong-mei , Luo Zhan-xiong , Li Jing-zhang
Published: July 2022

Background

Esophageal carcinoma (ESCA) is a common malignancy with a poor prognosis. Previous research has suggested that necroptosis is involved in anti-tumor immunity and promotes oncogenesis and cancer metastasis, which in turn affects tumor prognosis. However, the role of necroptosis in ESCA is unclear. This study aimed to investigate the relationships between necroptosis-related genes (NRGs) and ESCA.

Methods and results

The clinical data and gene expression profiles of ESCA patients were extracted from The Cancer Genome Atlas (TCGA), and 159 NRGs were screened from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We then identified 52 differentially expressed NRGs associated with ESCA and used them for further analysis. Gene ontology (GO) and KEGG functional enrichment analyses showed that these NRGs were mostly associated with the regulation of necroptosis, Influenza A, apoptosis, NOD-like receptor, and NF-Kappa B signaling pathway. Next, univariate and multivariate Cox regression and LASSO analysis were used to identify the correlation between NRGs and the prognosis of ESCA. We constructed a prognostic model to predict the prognosis of ESCA based on SLC25A5, PPIA, and TNFRSF10B; the model classified patients into high- and low-risk subgroups based on the patient’s risk score. Furthermore, the receiver operating characteristic (ROC) curve was plotted, and the model was affirmed to perform moderately well for prognostic predictions. In addition, Gene Expression Omnibus (GEO) datasets were selected to validate the applicability and prognostic value of our predictive model. Based on different clinical variables, we compared the risk scores between the subgroups of different clinical features. We also analyzed the predictive value of this model for drug sensitivity. Moreover, Immunohistochemical (IHC) validation experiments explored that these three NRGs were expressed significantly higher in ESCA tissues than in adjacent non-tumor tissues. In addition, a significant correlation was observed between the three NRGs and immune-cell infiltration and immune checkpoints in ESCA.

Conclusions

In summary, we successfully constructed and validated a novel necroptosis-related signature containing three genes (SLC25A5, PPIA, and TNFRSF10B) for predicting prognosis in patients with ESCA; these three genes might also play a crucial role in the progression and immune microenvironment of ESCA.
Worsening functional status in nephrogeriatrics needs to be accounted for when clinically assessing CKD advancement in addition to GFR; supporting evidence based on the practical application of theoretical modelling
Authors: Wisniewska Magdalena , Niemczyk Stanislaw
Published: July 2022

The incidence of chronic kidney disease (CKD) has been found to increase with age. This has resulted in an increase in the number of elderly patients undergoing renal replacement therapy. There is a significant risk of error in making treatment decisions in patients with advanced CKD based solely on biochemical parameters of renal function, if the changes in the functional status of patients' health are not taken into account.

Aim

To determine the interrelated dependencies between chronic kidney disease with the functional status of patients aged over 65 years and to elucidate differences in functional status between CKD patients and controls.

Methods

Patient subjects were qualified according to their assessed outcomes from the study protocol, which were achieved by: geriatric interview, assessing functional status by the IADL, Barthel and Tinetti tests together with assessing kidney function by performing laboratory tests of glomerular filtration rate (GFR), creatinine and urea. Subjects were divided into two groups: method 1—according to GFR and method 2—according to GFR and functional test results. The data were statistically analysed by structural equation modelling and k-means.

Results

Positive relationships were found between the CKD stage and comorbidity (β = 0.55,p < 0.01), along with the number of medications taken and age (respectively β = 0.19,p = 0.001 and β = 0.30,p < 0.001). A highly negative relationship was observed between the CKD stage and the Tinetti test results (β = -0.71,p < 0.001), whilst more moderate ones were found with the IADL and Barthel scores (respectively β = -0.49,p < 0.001 and β = -0.40,p < 0.001). The patient groups demonstrated differences in health status when selected by method-2 for: age, comorbidity, number of medications taken, fitness test outcomes (Tinetti, Barthel and IADL tests atp < 0.005). Those groups divided according to GFR, however only showed differences in age, comorbidity and the number of medication taken (p < 0.005).

Conclusions

The functional status worsens in geriatric patients suffering from CKD. It may thus be important to also account for disruptions to functional status when assessing CKD advancement in the elderly in addition to the GFR. The biggest problems for the over 80 s suffering from CKD are gait and balance disorders, leading to a high risk of falls. Another common problem is polypharmacy, found in both the geriatric population and particularly in those suffering from CKD.
Comparison of clinical characteristics and outcomes of hospitalized patients with seasonal coronavirus infection and COVID-19: a retrospective cohort study
Authors: Rodriguez-Nava Guillermo , Egoryan Goar , Dong Tianyu , Zhang Qishuo , Hyser Elise , Poudel Bidhya , Yanez-Bello Maria Adriana , Trelles-Garcia Daniela Patricia , Chung Chul Won , Pyakuryal Bimatshu , Imani-Ramos Taraz , Trelles-Garcia Valeria Patricia , Bustamante-Soliz Daniel Sebastian , Stake Jonathan J.
Published: July 2022

Background

Unlike SARS-CoV and MERS-C0V, SARS-CoV-2 has the potential to become a recurrent seasonal infection; hence, it is essential to compare the clinical spectrum of COVID-19 to the existent endemic coronaviruses. We conducted a retrospective cohort study of hospitalized patients with seasonal coronavirus (sCoV) infection and COVID-19 to compare their clinical characteristics and outcomes.

Methods

A total of 190 patients hospitalized with any documented respiratory tract infection and a positive respiratory viral panel for sCoV from January 1, 2011, to March 31, 2020, were included. Those patients were compared with 190 hospitalized adult patients with molecularly confirmed symptomatic COVID-19 admitted from March 1, 2020, to May 25, 2020.

Results

Among 190 patients with sCoV infection, the Human Coronavirus-OC43 was the most common coronavirus with 47.4% of the cases. When comparing demographics and baseline characteristics, both groups were of similar age (sCoV: 74 years vs. COVID-19: 69 years) and presented similar proportions of two or more comorbidities (sCoV: 85.8% vs. COVID-19: 81.6%). More patients with COVID-19 presented with severe disease (78.4% vs. 67.9%), sepsis (36.3% vs. 20.5%), and developed ARDS (15.8% vs. 2.6%) compared to patients with sCoV infection. Patients with COVID-19 had an almost fourfold increased risk of in-hospital death than patients with sCoV infection (OR 3.86, CI 1.99–7.49; p < .001).

Conclusion

Hospitalized patients with COVID-19 had similar demographics and baseline characteristics to hospitalized patients with sCoV infection; however, patients with COVID-19 presented with higher disease severity, had a higher case-fatality rate, and increased risk of death than patients with sCoV. Clinical findings alone may not help confirm or exclude the diagnosis of COVID-19 during high acute respiratory illness seasons. The respiratory multiplex panel by PCR that includes SARS-CoV-2 in conjunction with local epidemiological data may be a valuable tool to assist clinicians with management decisions.
The value of HPV genotypes combined with clinical indicators in the classification of cervical squamous cell carcinoma and adenocarcinoma
Authors: He Zhimin , Chen Rongsheng , Hu Shangying , Zhang Yajiao , Liu Yang , Li Chengwei , Lv Fajin , Xiao Zhibo
Published: July 2022

Background

To investigate the differences in HPV genotypes and clinical indicators between cervical squamous cell carcinoma and adenocarcinoma and to identify independent predictors for differentiating cervical squamous cell carcinoma and adenocarcinoma.

Methods

A total of 319 patients with cervical cancer, including 238 patients with squamous cell carcinoma and 81 patients with adenocarcinoma, were retrospectively analysed. The clinical characteristics and laboratory indicators, including HPV genotypes, SCCAg, CA125, CA19-9, CYFRA 21–1 and parity, were analysed by univariate and multivariate analyses, and a classification model for cervical squamous cell carcinoma and adenocarcinoma was established. The model was validated in 96 patients with cervical cancer.

Results

There were significant differences in SCCAg, CA125, CA19-9, CYFRA 21–1, HPV genotypes and clinical symptoms between cervical squamous cell carcinoma and adenocarcinoma (P < 0.05). Logistic regression analysis showed that SCCAg and HPV genotypes (high risk) were independent predictors for differentiating cervical squamous cell carcinoma from adenocarcinoma. The AUC value of the established classification model was 0.854 (95% CI: 0.804–0.904). The accuracy, sensitivity and specificity of the model were 0.846, 0.691 and 0.899, respectively. The classification accuracy was 0.823 when the model was verified.

Conclusion

The histological type of cervical cancer patients with persistent infection of high-risk HPV subtypes and low serum SCCAg levels was more prone to being adenocarcinoma. When the above independent predictors occur, the occurrence and development of cervical adenocarcinoma should be anticipated, and early active intervention treatment should be used to improve the prognosis and survival of patients.
ASIC1α up-regulates MMP-2/9 expression to enhance mobility and proliferation of liver cancer cells via the PI3K/AKT/mTOR pathway
Authors: Zhang Yinci , Liang Jiaojiao , Cao Niandie , Gao Jiafeng , Xie Yinghai , Zhou Shuping , Tang Xiaolong
Published: July 2022

A major challenge in the treatment of liver cancer is that a large proportion of patients fail to achieve long-term disease control, with death from liver cancer cell migration and invasion. Acid-sensitive ion channel 1α (ASIC1α) is involved in the migration, invasion, and proliferation of liver cancer cells. Therefore, we explored the mechanism of ASIC1α-mediated liver cancer cell migration and invasion. We determined the levels of ASIC1α by western blotting and immunofluorescence in HepG2 and SK-Hep1 cells cultured in various acidic conditions. In addition, wound healing assay, transwell invasion assay, and MTT assay were conducted to assess the migration, invasion, and proliferation abilities of liver cancer cells. Western blotting was conducted to determine the levels of MMP2, MMP9, ASIC1α, p-PI3Kp85, t-PI3Kp85, p-AKT(Ser473), t-AKT, p-mTOR (Ser2448), t-mTOR. We first found that the levels of ASIC1α in the HepG2 and SK-Hep1 cells in acidic conditions (pH 6.5) were significantly increased. Inhibition and knockdown of ASIC1α down-regulated MMP-2/9 expression and inhibited the migration, invasion, and proliferation of HepG2 and SK-Hep1 cells; overexpression of ASIC1α had the opposite effect. We further demonstrated that ASIC1α up-regulates MMP-2/9 via activation of the PI3K/AKT/mTOR pathway, thereby promoting migration, invasion, and proliferation of liver cancer cells. Overexpression of MMP-2/9 and activation of AKT reversed these effects on liver cancer cells caused by inhibition of ASIC1α. We conclude that ASIC1α can regulate migration, invasion, and proliferation of liver cancer cells through the MMP-2/9/PI3K/AKT/mTOR pathway. These observations may provide a new reference for liver cancer chemotherapy.