bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Gaming-Related Symptoms and Musculoskeletal Pain Complaints in Individuals Who Participate in Electronic Gaming
Authors: Geer Roderick , Cheng Jennifer , Rothman Rachel , Abutalib Zafir , Davenport Kathleen
Published: May 2023

The number of people participating in electronic gaming has increased exponentially in recent years. Gamers are susceptible to injuries. However, there are limited studies on gaming-related symptoms and musculoskeletal pain complaints amongst casual gamers. This study aimed to characterize gaming-related symptoms in adults participating in electronic gaming. An online survey assessing gaming characteristics, addictive qualities, and gaming-related symptoms was completed by 250 self-reported adult gamers (median age: 37.5 years; 56.0% female). Prevalence rates of gaming-related symptoms and musculoskeletal pain complaints were 61% (n = 153) and 34% (n = 86), respectively. Gaming session durations were significantly longer in participants reporting gaming-related symptoms or musculoskeletal pain complaints ( P < .001). Addictive qualities were independently associated with greater odds of having gaming-related symptoms (OR[95%-CI]: 3.69[1.84-7.39]; P < .001). Suboptimal screen height, concurrent mood disturbances, and concurrent sleep changes were independently associated with greater odds of having musculoskeletal pain complaints ( P < .05). Further analyses revealed significantly increased prevalence of mid-back, low-back, or mid + low-back pain in participants reporting poor ergonomics ( P < .05), compared to good ergonomics. Overall, increased time spent gaming, poor ergonomics, addictive qualities, and mood/sleep complaints were associated with gaming-related health conditions. As gaming continues to expand, recognition of gaming-related health conditions and their predisposing factors is critical.
Of Newcomers and Supervisors: Ethical Issues in Supervising Newcomers in Qualitative Health Research
Authors: Burner-Fritsch Isabel , Schwertel Tamara
Published: May 2023

This contribution focuses on our experiences as lecturers and supervisors in qualitative healthcare research in medicine, public health research and sociology, and the role of research ethics in guiding students in their qualitative studies. We argue that students themselves are vulnerable during the transition of becoming a qualitative researcher and that reflection on research is essential. Therefore, the selection of a topic, potential role conflicts and questions of field contingencies management become crucial elements in both teaching and researching. We use qualitative case vignettes, as suggested by Langer, to offer a reflective account of our experience. Protecting students from harm and preventing them from inadvertently causing harm to others are of utmost importance to us. Through these vignettes, we aim to provide a nuanced and reflective view of our experiences in supervising qualitative research.
Designing for Hope: Biophilic Color Associations and Their Relevance to Clinical Settings
Authors: Edwards Thomas Mark
Published: May 2023

Aim:

To consider one common aspect of biophilic design (BD; i.e., color) and its relationship to an important element of well-being (i.e., hope).

Background:

BD is multifaceted making the identification of critical design elements difficult. Further complexity is introduced given that practice assumptions stemming from the biophilia hypothesis may be questioned. Consistent with the biophilia hypothesis, the author considers the study’s findings from the perspectives of evolutionary psychology and psychobiology.

Methods:

One hundred and fifty four adult participants engaged in one of the three experiments. Using colored test cards, Experiment #1 sought to determine which of four biophilic colors (i.e., red, yellow, green, or blue) evoked the strongest experience of hope. Considering this color alone, Experiment #2 sought to manipulate “color depth.” Participants were asked to identify what color depth evoked the strongest experience of hope. Experiment #3 sought to determine if the outcomes of Experiments #1 and #2 were due to a priming effect. All participants were asked about color associations they held.

Results:

Experiments #1 and #2 demonstrated that yellow at maximal color depth evoked the strongest experience of hope ( p < .001). Experiment #3 demonstrated that no priming effect was evident ( p < .05). No participant had a strong personal preference for/against yellow. Natural world color associations existed for yellow, green, and blue. Red held emotive associations.

Conclusions:

These findings clearly associate yellow with hope. From the perspectives of evolutionary psychology and psychobiology this suggests color cues can evoke time-dependent motive states. Implications for practitioners designing spaces of hope within healthcare facilities are considered.
Safety Profile of High-Dose Intravenous Push Lacosamide
Authors: Torian Sterling C. , Jones G. Morgan
Published: May 2023

Lacosamide (LCM) is an antiseizure medication used to manage status epilepticus (SE). Previous retrospective analyses have demonstrated safety and efficiency in intravenous push (IVP) administration at 80 mg per minute. Quick administration can be achieved in a high-acuity setting without the additional time required for compounding. However, previous literature only partially represents high doses of IVP LCM, which limits the understanding of the safety profile of these doses. Our study was a single-center, retrospective, single-arm analysis of patients who received IVP LCM 300 mg or 400 mg during admission. The primary outcome was the incidence of infusion site reactions, hypotension, and bradycardia within 2 hours of IVP administration. Secondary outcomes included the incidence of PR prolongation. A total of 113 patients were evaluated for infusion site reactions. Of these, 108 patients had vital signs assessed within 2 hours of IVP LCM and could be evaluated for hypotension and bradycardia. The sample primarily consisted of LCM 400 mg IVP (85.8%). The primary outcome consisted of 7 (6.2%) infusion reactions, 12 (11.1%) hypotensive events, and no reports of bradycardia. Each adverse event was assessed using the Naranjo Adverse Drug Probability Scale. All events scored less than two, suggesting the possibility was likely related to factors other than the medication. In conclusion, LCM 300 mg and 400 mg IVP administration have the potential to facilitate more rapid treatment of seizures without additional risk of infusion site reactions, hypotension, and bradycardia.
The public library and the futures of social infrastructure
Authors: Schloffel-Armstrong Salene
Published: May 2023

The current abundance of geographical research on social infrastructure has drawn renewed attention to the enduring importance of a range of public services, including the public library. However, these works have not engaged at length with the infrastructural futures of such services, neither in their ongoing vulnerability, nor with what they may illuminate, or already contain of possible and more radical urban futures. This commentary considers the future of social infrastructure: the viability of the physical spaces themselves, and the need for the theoretical concept to engage more explicitly with questions of temporality.
From Silicon to Himalayan Valley(s): Tales of Serendipitous Exposure and Interfaith Contact on Social Media
Authors: Masood Muhammad , Skoric Marko M.
Published: May 2023

This study compares two adjacent remote valleys in the Himalayas of Pakistan, which only differ in terms of the availability of internet access. Using a unique methodological approach, combining a natural experiment design and an interview method, we explore the role of serendipitous exposure and interfaith contact on social media in relation to the religious majority’s knowledge about religious minorities and willingness to engage with them. We find that those who have internet access and use social media show more knowledge about and engagement with religious minorities than those who do not. Serendipitous exposure largely explains the differences—social media users do not intentionally seek information about religious minorities but still serendipitously come across it while using social media for other activities. Moreover, social media users tend to have extensive networks of social ties (i.e., Facebook friends), which frequently cut across religious lines and likely act as the main facilitators of serendipity. We argue that mediated serendipity and increased interfaith contact promoted by social media platforms are essential contributors to democratic citizenship in present-day Pakistan, where religious minorities represent a small segment of the population and often face discrimination and persecution.
Strategically matching messaging to the platform: The case of “Biolabs” on Instagram, Facebook, and Reddit
Authors: Faltesek Daniel
Published: May 2023

An important Russian strategic disinformation campaign, early in the Ukrainian war, contended that the United States was involved in clandestine biological weapons development in Ukraine under the sign “biolabs.” Depending on the platform, the propaganda messaging appeared differently. This study uses a multi-modal approach, featuring Image Plotting, to study the waves of messaging related involved in the biolabs campaign including both the qualitative analysis of text and the analysis of the images. Each platform includes a clear visual and textual strategy which align with known Russian strategies and multi-modal campaign operations.
Specifics of Public Administration in Countries With a Developed Energy Sector: The Case Study
Authors: Bashina Olga E. , Simonova Marina D. , Matraeva Lilia V. , Mamiy Irina P. , Korolkova Nataliya A.
Published: May 2023

Countries with a large energy sector are faced with the issues of forming and developing a state energy policy that takes into account not only sectoral and intersectoral aspects, but also the components of managing significant amounts of rental income. In this regard, any of these economic systems, on the one hand, has great opportunities associated with the management of energy resources as a factor of development, on the other hand, it is constantly at risk of destabilization of the economic system as a whole. To date, the economic history allows us to speak about the accumulation of a sufficient number of observations for conducting a comprehensive study of the features of the development of public energy policies. The study is based on the formalization of historical descriptions of the experience of 24 countries (30 cases). The article describes in detail the experience of 13 of the most striking cases. This made it possible to identify 14 variables for evaluating the state energy policy, while outlining three areas (areas of attention) of public administration. The choice of variables used in the model was made on the basis of the relative frequencies of the mechanism application for the observed population, MNRW-TF recommendations within the improving extractive industry, the formation of the contribution of resource industries to the socio-economic development of the country and etc. Further cluster analysis led to the identification of both a pronounced polarity in the development of the state energy policy and options for combining its areas.

JEL Classifications: C82, Q43, Q48, P51, O57, O11.
Bone Cement Reperfusion Revision Surgery for Symptomatic Recurrence of Kümmell’s Disease After Percutaneous Kyphoplasty
Authors: Chen Tangyiheng , Lin Cheng , Wang Yujie , Yang Huilin , Li Xuefeng , Chu Genglei , Jiang Weimin , Liu Yijie
Published: May 2023

Study Design

Retrospective study.

Objectives

To demonstrate that repeat Percutaneous vertebroplasty (PVP) performed for the same cemented vertebrae in Kümmell’s disease can offer therapeutic benefit for patients with recurrent symptoms after initial percutaneous kyphoplasty (PKP) treatment.

Methods

From January 2019 to December 2021, we investigated 2932 patients with PKP. Among them, 191 patients were diagnosed Kümmell’s disease. 33 patients upon presentation of recurrent symptoms underwent repeat PVP procedure. Radiologic outcomes and clinic indices were investigated.

Results

Bone cement reperfusion surgery was successfully completed in 33 patients. The average age was 73.5 ± 8.2 years old. The kyphosis angle showed significant correction from pre-operation to the final follow-up, descending from pre-operation (20.6 ± 11.1°) to final follow-up (15.4 ± 7.9°). The vertebral heights at different follow-up appointments were significantly higher than the pre-operative appointments. The VAS and ODI scores at final follow-up were respectively 1.2 ± .8 and 27.3 ± 5.4%, which were both significantly lower than those before operation. No complications such as cement leakage into the spinal canal or cement displacement occurred during follow-up.

Conclusions

Bone cement reperfusion surgery can ameliorate kyphosis and restore vertebral height to some extent. Repeat PVP is a minimally invasive surgery that provides superior long-term results in clinical and radiological outcomes but is technically more difficult to perform.
Seed Houses and the “Master’s Land”: A Study of the Ecology of Practices and Autonomy in Brazil’s Semi-arid Region
Authors: Lopes Helena Rodrigues
Published: May 2023

Seed storage is part of peasant livelihoods in Brazil’s semi-arid region. This study is based on empirical research carried out in the semi-arid region of Sobral, in the north-eastern state of Ceará, with peasants who participate in Seed Houses. The study seeks to understand how peasants engaged in multiple struggles and produced what they identify as “autonomy from the master’s seeds,” even in a context where the so-called master maintains control over land. The main question can be presented as what comes into play in this autonomy constituted by Seed Houses? The investigation intends to contribute to related debates on the agrarian question and the dimensions of autonomy, analysing the ecology of practices associated with seeds exercised through the collective action of the Seed Houses, involving continuities between land and natural resources.
Corporate Social Responsibility and Sustainability of Corporate Performance
Authors: Dhingra Kanika
Published: May 2023

A firm has a prospect to surge its assistance for the social order in an interchange of improved repute and development in industry, which finally hints at sturdy fiscal functioning and high productivity. Corporate sustainability is resultant from the perception of sustainable development. It fundamentally mentions toward the part, which corporations can show in gathering the schema of sustainable expansion and necessitates a steady line to financial development, societal evolution, and ecological stewardship. Corporate Social Responsibility (CSR) in India emphasizes on anything that ended with returns after they are completed.

On the other side, sustainability concerns factoring the societal and ecological influences of directing industry, that is, how revenues are created. Henceforth, ample of the Indian exercise of CSR occurs as a significant constituent of sustainability or accountable industry, which is a greater clue, a statistic obvious from numerous sustainability contexts.

The readings on the relationship between CSR and Sustainability by means of monetary functioning include fundamentally two types. The first practices procedure of studying the events to measure the short-run monetary effect (abnormal returns) when organizations involve in their publicly accountable or negligent deeds. The second observes the association among the certain degree of corporate social functioning and variables of long-term financial functioning by using accounting or financial measures of profitability. The objectives of the report are to analyse the impression of CSR proposals of a company on its financial performance, its net profit, and total resources (assets).

The data study is done with Statistical Package for the Social Sciences (SPSS) software and statistical tools such as correlation and regression are used. The correlation coefficient (a value between −1 and +1) states how sturdily two variables are associated with each other. The regression analysis is a statistical procedure used to estimate the consequences of independent variables on a particular dependent variable. After the analysis, it can be concluded that the CSR is positively correlated with the firm’s PAT (profit after tax) and firm’s total resources (assets) and since the significance value is less than 5% in both the cases of regression (CSR with PAT; PAT and CSR with total assets), therefore it is concluded that CSR acts as a major factor and certain additional factors are also answerable for the transformations in the PAT: profit after tax and total assets of the company.
Examining Adoption Drivers of Payments Bank Using Fuzzy Analytic Hierarchy Process Approach
Authors: Gupta Sanjay , Singh Simarjeet , Garg Aashish , Goel Pooja
Published: May 2023

Payments bank are a new addition to the family of digital payment services and are largely unexplored by the consumers. Hence there is a need to comprehend the underlying critical success factors that play a crucial role in the mass adoption of Payments bank. Further, to make Payments bank a standard digital payment option, converting imprecise information acquired from the respondents into key business insights is required. Hence, the present study aims to explore and prioritize the key factors responsible for the adoption of Payments bank. The study used the Fuzzy Analytic Hierarchy Process on the sample obtained from the northern region of India to identify the structure of the pertinent concerns and determine the criteria and sub-criteria of Payments bank services. Results of the study postulated that ease of use and facilitating conditions are the most prioritized factors. At the same time, personalization is ranked as the least preferred factor among all the factors. The present study sample is limited to a few parts of India, so generalizations of results should be made with caution. However, the current study strengthens the literature on Payments bank as it is one of the early studies in this area. Further, the insights generated by the study will help marketers and policymakers to pay broader attention to key parameters responsible for the success of Payments bank.
Retrospective Cohort Study Comparing Antiretroviral Treatment Outcomes Among Adolescents in Teen Clubs and Standard Care Clinics: Blantyre, Malawi
Authors: Alibi Michael , Mwapasa Victor , Ngwalangwa Fatsani
Published: May 2023

Introduction

This study investigated if the Teen Club model improves virological suppression and reduces virological failure. Viral load monitoring is a golden ART programme performance indicator. HIV treatment outcomes are poor among adolescents compared to adults. Different service delivery models are being implemented to address this; among them is the Teen Club model. Currently, teen clubs improve treatment adherence (short-term impact), but there is a knowledge gap regarding the long-term impact. The study compared the rate of virological suppression and failure among adolescents in Teen Clubs and those on the standard of care (SoC) model.

Methods

This was a retrospective cohort study. A total of 110 adolescents in teen clubs and 123 adolescents in SOC from six health facilities were selected using stratified simple random sampling. The participants were followed for 24 months. STATA version 16.0 was used for data analysis. Univariate analyses were performed for both demographic and clinical variables. A Chi-squared test was used to assess the differences between proportions. Crude and adjusted relative risks were calculated using a binomial regression model.

Results

At 24 months, 56% of adolescents in the SoC arm had viral load suppression compared to 90% in the Teen Club arm. Of those who achieved viral load suppression at 24 months, about 22.7% (SoC) and 76.4% (Teen Club) achieved undetectable viral load suppression rates. Adolescents in the Teen Club arm had a lower viral load than those in the SoC arm (adjusted RR 0.23, 95% CI: 0.11-0.61; p  =  0.002 adjusted for age and gender). Teen Club and SoC adolescents had virological failure rates of 3.1% and 10.9%, respectively. The adjusted RR was 0.16, 95% CI: 0.03-0.78; p  =  0.023; those in Teen Clubs were less likely to have virological failure relative to those in SoC after adjusting for age, sex, and place of residence.

Conclusion

The study found that Teen Club models are more effective at achieving virological suppression among HIV positive adolescents.
Superior Capsular Reconstruction Versus Latissimus Dorsi Tendon Transfer for Irreparable Rotator Cuff Tears: Minimum 5-year Outcomes
Authors: Hanson Jared A. , Lee Simon , Horan Marilee P. , Rakowski Dylan R. , Millett Peter J.
Published: May 2023

Background:

Arthroscopic superior capsular reconstruction (SCR) has been introduced as a successful alternative to latissimus dorsi tendon transfer (LDTT) for irreparable posterosuperior rotator cuff tears.

Purpose:

To compare minimum 5-year clinical outcomes of SCR and LDTT for the treatment of irreparable posterosuperior rotator cuff tears in patients with minimal evidence of arthritis and intact or reparable subscapularis tears.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Patients who underwent SCR or LDTT and had undergone surgery ≥5 years earlier were included. The SCR technique used a dermal allograft customized to the defect. Surgical, demographic, and subjective data were collected prospectively and reviewed retrospectively. Patient-reported outcome (PRO) scores utilized were the American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), the short version of the Disabilities of the Arm, Shoulder and Hand score (QuickDASH), 12-Item Short Form Health Survey Physical Component Summary (SF-12 PCS), and patient satisfaction. Further surgical procedures were documented, and treatment that progressed to reverse total shoulder arthroplasty (RTSA) or revision rotator cuff surgery was considered a failure. Kaplan-Meier survivorship analysis was performed.

Results:

Thirty patients (n = 20 men; n = 10 women) with a mean follow-up of 6.3 years (range, 5-10.5 years) were included. A total of 13 patients underwent SCR and 17 patients underwent LDTT. The mean age of the SCR group was 56 years (range, 41.2-63.9 years), and the mean age of the LDTT group was 49 years (range, 34.7-57 years) ( P = .006). One patient in the SCR group and 2 patients in the LDTT group progressed to RTSA. Two additional (11.8%) patients in the LDTT group had further surgery—1 had arthroscopic cuff repair and 1 had hardware removal with biopsies. The SCR group demonstrated significantly better ASES (94.1 ± 6.3 vs 72.3 ± 16.4; P = .001), SANE (85.6 ± 8 vs 48.7 ± 19.4; P = .001), QuickDASH (8.8 ± 8.7 vs 24.3 ± 16.5; P = .012), and SF-12 PCS (56.1 ± 2.3 vs 46.5 ± 6; P = .001) PROs at the final follow-up. There was no significant difference between groups in median satisfaction (SCR, 9; LDTT, 8 [ P = .379]). At 5 years, survivorship rates were 91.7% and 81.3% for the SCR and LDTT groups, respectively ( P = .421).

Conclusion:

At the final follow-up, SCR yielded superior PROs compared with LDTT for the treatment of massive, irreparable posterosuperior rotator cuff tears despite similar patient satisfaction and survivorship between procedures.
Clinical Feasibility and Familiarization Effects of Device Delay Mismatch Compensation in Bimodal CI/HA Users
Authors: Angermeier Julian , Hemmert Werner , Zirn Stefan
Published: May 2023

Subjects utilizing a cochlear implant (CI) in one ear and a hearing aid (HA) on the contralateral ear suffer from mismatches in stimulation timing due to different processing latencies of both devices. This device delay mismatch leads to a temporal mismatch in auditory nerve stimulation. Compensating for this auditory nerve stimulation mismatch by compensating for the device delay mismatch can significantly improve sound source localization accuracy. One CI manufacturer has already implemented the possibility of mismatch compensation in its current fitting software. This study investigated if this fitting parameter can be readily used in clinical settings and determined the effects of familiarization to a compensated device delay mismatch over a period of 3–4 weeks. Sound localization accuracy and speech understanding in noise were measured in eleven bimodal CI/HA users, with and without a compensation of the device delay mismatch. The results showed that sound localization bias improved to 0°, implying that the localization bias towards the CI was eliminated when the device delay mismatch was compensated. The RMS error was improved by 18% with this improvement not reaching statistical significance. The effects were acute and did not further improve after 3 weeks of familiarization. For the speech tests, spatial release from masking did not improve with a compensated mismatch. The results show that this fitting parameter can be readily used by clinicians to improve sound localization ability in bimodal users. Further, our findings suggest that subjects with poor sound localization ability benefit the most from the device delay mismatch compensation.
Collaborative Value Co-creation from a Stakeholder Perspective: A Literature Review
Authors: Bal Anik Shekhar , Käpylä Jonna , Li Hongxiu , Helander Nina
Published: May 2023

Since the value co-creation (VCC) concept was introduced as an alternative to the traditional value creation model, VCC has been studied in various contexts. The literature has mostly focused on a specific research context or a specific type of stakeholder group, leaving a comprehensive view of the stakeholders’ value elements in VCC poorly understood. To address this research gap, we conducted a systematic literature review to provide an overview of the conceptualization of VCC as well as stakeholders’ expected and realized value through collaboration. In accordance with the literature review, six value dimensions (economic, experiential, functional, relational, personal growth and corporate sustainability) are identified. On the basis of the findings of our literature review, we identify gaps in the literature and suggest an agenda for future research.
Experiences of Parenting a Child Receiving Dexamethasone During Maintenance Chemotherapy for Acute Lymphoblastic Leukemia
Authors: David Annabel L. , Darlington Anne-Sophie , Griffiths Helen C.
Published: May 2023

Background: The purpose of this research was to understand the experience of parenting a child receiving dexamethasone during maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Previous research has shown that dexamethasone's high level of toxicity causes many physical, behavioral, and emotional side effects, which reduce the quality of life during ALL treatment. Less is known about the experience of parenting a child receiving dexamethasone and the impact on the parent–child relationship. Methods: In-depth semi-structured interviews were conducted with 12 parents and data was analyzed using Interpretative Phenomenological Analysis. Results: Four superordinate themes emerged: “a child on steroids is not your child”: the behavioral and emotional changes in the child and their relationships; “you have to do what you have to do”: adapting parenting to manage dexamethasone; “it breaks your heart … it's a horrible medicine”: the emotional impact of parenting a child on dexamethasone; and, “it's the worst week ever”: finding ways to cope with the challenges of dexamethasone. Discussion A preparatory intervention for parents beginning the dexamethasone journey focused on likely challenges, managing boundary setting and discipline, and their own emotional struggles, could be beneficial. Research into the impact on siblings could further understand the systemic influence of dexamethasone and help develop further interventions.
CAR NK-92 cell–mediated depletion of residual TCR+ cells for ultrapure allogeneic TCR-deleted CAR T-cell products
Authors: Kath Jonas , Du Weijie , Martini Stefania , Elsallab Magdi , Franke Clemens , Hartmann Laura , Drosdek Vanessa , Glaser Viktor , Stein Maik , Schmueck-Henneresse Michael , Reinke Petra , Volk Hans-Dieter , Abou-el-Enein Mohamed , Wagner Dimitrios L.
Published: May 2023

Graft-versus-host disease (GVHD) is a major risk of the administration of allogeneic chimeric antigen receptor (CAR)-redirected T cells to patients who are HLA unmatched. Gene editing can be used to disrupt potentially alloreactive T-cell receptors (TCRs) in CAR T cells and reduce the risk of GVHD. Despite the high knockout rates achieved with the optimized methods, a subsequent purification step is necessary to obtain a safe allogeneic product. To date, magnetic cell separation (MACS) has been the gold standard for purifying TCRα/β– CAR T cells, but product purity can still be insufficient to prevent GVHD. We developed a novel and highly efficient approach to eliminate residual TCR/CD3+ T cells after TCRα constant (TRAC) gene editing by adding a genetically modified CD3-specific CAR NK-92 cell line during ex vivo expansion. Two consecutive cocultures with irradiated, short-lived, CAR NK-92 cells allowed for the production of TCR– CAR T cells with <0.01% TCR+ T cells, marking a 45-fold reduction of TCR+ cells compared with MACS purification. Through an NK-92 cell–mediated feeder effect and circumventing MACS-associated cell loss, our approach increased the total TCR– CAR T-cell yield approximately threefold while retaining cytotoxic activity and a favorable T-cell phenotype. Scaling in a semiclosed G-Rex bioreactor device provides a proof-of-principle for large-batch manufacturing, allowing for an improved cost-per-dose ratio. Overall, this cell-mediated purification method has the potential to advance the production process of safe off-the-shelf CAR T cells for clinical applications.
Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?
Authors: Sarkar Amrita , Khandelwal Sanjay , Koma Gavin T. , Kim Hyunjun , Gruel Yves , Rollin Jerome , Passam Freda , Wool Geoffrey D. , Arepally Gowthami M. , Cines Douglas B. , Rauova Lubica , Poncz Mortimer
Published: May 2023

Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human platelet factor 4 (hPF4) complexed with various polyanions. Although nonheparin anticoagulants are the mainstay of care in HIT, subsequent bleeding may develop, and the risk of developing new thromboembolic events remain. We previously described a mouse immunoglobulin G2bκ (IgG2bκ) antibody KKO that mimics the sentinel features of pathogenic HIT antibodies, including binding to the same neoepitope on hPF4–polyanion complexes. KKO, like HIT IgGs, activates platelets through FcγRIIA and induces complement activation. We then questioned whether Fc-modified KKO could be used as a novel therapeutic to prevent or treat HIT. Using the endoglycosidase EndoS, we created deglycosylated KKO (DGKKO). Although DGKKO retained binding to PF4–polyanion complexes, it inhibited FcγRIIA-dependent activation of PF4-treated platelets triggered by unmodified KKO, 5B9 (another HIT-like monoclonal antibody), and IgGs isolated from patients with HIT. DGKKO also decreased complement activation and deposition of C3c on platelets. Unlike the anticoagulant fondaparinux, injection of DGKKO into HIT mice lacking mouse PF4, but transgenic for hPF4 and FcγRIIA, prevented and reversed thrombocytopenia when injected before or after unmodified KKO, 5B9, or HIT IgG. DGKKO also reversed antibody-induced thrombus growth in HIT mice. In contrast, DGKKO was ineffective in preventing thrombosis induced by IgG from patients with the HIT-related anti-PF4 prothrombotic disorder, vaccine-induced immune thrombotic thrombocytopenia. Thus, DGKKO may represent a new class of therapeutics for targeted treatment of patients with HIT.
Diffuse large B-cell lymphomas have spatially defined, tumor immune microenvironments revealed by high-parameter imaging
Authors: Wright Kyle T. , Weirather Jason L. , Jiang Sizun , Kao Katrina Z. , Sigal Yari , Giobbie-Hurder Anita , Shipp Margaret A. , Rodig Scott J.
Published: May 2023

Diffuse large B-cell lymphoma (DLBCL) not otherwise specified is the most common aggressive non-Hodgkin lymphoma and a biologically heterogeneous disease. Despite the development of effective immunotherapies, the organization of the DLBCL tumor-immune microenvironment (TIME) remains poorly understood.We interrogated the intact TIME of 51 de novo DLBCLs with triplicate sampling to characterize 337 995 tumor and immune cells using a 27-plex antibody panel that captured cell lineage, architectural, and functional markers. We spatially assigned individual cells, identified local cell neighborhoods, and established their topographical organization in situ. We found that the organization of local tumor and immune cells can be modeled by 6 composite cell neighborhood types (CNTs). Differential CNT representation divided cases into 3 aggregate TIME categories: immune-deficient, dendritic cell–enriched (DC-enriched), and macrophage-enriched (Mac-enriched). Cases with immune-deficient TIMEs have tumor cell–rich CNTs, in which the few infiltrating immune cells are enriched near CD31+ vessels, in keeping with limited immune activity. Cases with DC-enriched TIMEs selectively include tumor cell–poor/immune cell–rich CNTs with high numbers of CD11c+ DCs and antigen-experienced T cells also enriched near CD31+ vessels, in keeping with increased immune activity. Cases with Mac-enriched TIMEs selectively include tumor cell–poor/immune cell–rich CNTs with high numbers of CD163+ macrophages and CD8 T cells throughout the microenvironment, accompanied by increased IDO-1 and LAG-3 and decreased HLA-DR expression and genetic signatures in keeping with immune evasion. Our findings reveal that the heterogenous cellular components of DLBCL are not randomly distributed but organized into CNTs that define aggregate TIMEs with distinct cellular, spatial, and functional features.
Next-generation sequencing–based MRD in adults with ALL undergoing hematopoietic cell transplantation
Authors: Liang Emily C. , Dekker Simone E. , Sabile Jean M. G. , Torelli Stefan , Zhang Amy , Miller Katharine , Shiraz Parveen , Hayes-Lattin Brandon , Leonard Jessica T. , Muffly Lori
Published: May 2023

Measurable residual disease (MRD) is an adverse prognostic factor in adult patients with acute lymphoblastic leukemia (ALL) undergoing hematopoietic cell transplant (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10–6, but the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT, patients aged ≥18 years with ALL who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014 and April 2021 and were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed before HCT (MRDpre) and up to 1 year after HCT (MRDpost). Patients were followed up for leukemia relapse and survival for up to 2 years after HCT. In total, 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10–4 (hazard ratio [HR], 3.56; 95% confidence interval [95% CI], 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR, 4.60; 95% CI, 3.01-7.02). In exploratory analyses limited to patients with B-cell ALL, the detection of post-HCT immunoglobulin H (IgH) MRD clonotypes, rather than non-IgH MRD clonotypes, was associated with relapse. In this analysis across 2 large transplant centers, we found that the detection of MRD by NGS at a level of 10–6 offers significant prognostic value in adults with ALL undergoing HCT.
Profiling the impact of the promoters on CRISPR-Cas12a system in human cells
Authors: Li Jinhe , Liang Qinchun , Zhou HuaPing , Zhou Ming , Huang Hongxin
Published: May 2023

The plasmid vector platform is the most commonly used vector for the expression of the versatile CRISPR-Cas technique and the promoter is a crucial element for the expression vector, thus profiling the impact of the promoters on CRISPR editors provides the basic information for the gene-editing toolkits and can be a guideline for its design. Herein, we made a parallel comparison among four commonly used promoters (CAG, ~ 1700 bp; EF1a core, ~ 210 bp; CMV, ~ 500 bp; and PGK, ~ 500 bp) in CRISPR-Cas12a system in mammalian cells to explore the impact of promoters on this powerful tool. We found that without badly damaging targeting specificity, the CAG promoter-driving Cas12a editor exhibited the most active (efficiency takes as 100%, specificity index =  ~ 75%) in genomic cleavage, multiplex editing, transcriptional activation, and base editing, followed by promoter CMV (efficiency = 70 ~ 90% (vs CAG), specificity index =  ~ 78%), and then EF1a core and PGK (both efficiency = 40–60%, vs CAG) but with higher specificity (specificity index =  ~ 84% and ~ 82%, respectively). Therefore, CAG is recommended in the CRISPR-Cas12a system for the applications that need a robust editing activity but without size limitation, CMV mostly can be an alternative for CAG when requiring a smaller space, EF1a is similar to PGK with relatively high specificity, but has a smaller size, thus is more suitable for in vivo therapeutic applications. The data outlined the properties of the widely used promoters in the CRISPR-Cas12a system, which can be a guide for its applications and can be a useful resource for the gene-editing field.
Implantation of skin-derived precursor Schwann cells improves erectile function in a bilateral cavernous nerve injury rat model
Authors: Ma Xiaolei , Yang Wende , Nie Pan , Zhang Zhenbin , Chen Zehong , Wei Hongbo
Published: May 2023

Background

This study was conducted to investigate the therapeutic potential of the skin-derived precursor Schwann cells for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerve injury.

Results

The skin-derived precursor Schwann cells-treatment significantly restored erectile functions, accelerated the recovery of endothelial and smooth muscle tissues in the penis, and promoted nerve repair. The expression of p-Smad2/3 decreased after the treatment, which indicated significantly reduced fibrosis in the corpus cavernosum.

Conclusions

Implantation of skin-derived precursor Schwann cells is an effective therapeutic strategy for treating erectile dysfunction induced by bilateral cavernous nerve injury.
Short-term labour transitions and informality during the COVID-19 pandemic in Latin America
Authors: Maurizio Roxana , Monsalvo Ana Paula , Catania María Sol , Martinez Silvana
Published: May 2023

Latin America was one of the regions hardest hit by the COVID-19 pandemic. This paper analyses, from a dynamic and comparative perspective, labour transitions triggered by the pandemic in six Latin American countries: Argentina, Brazil, Costa Rica, Mexico, Paraguay, and Peru. Special attention is paid to transits around labour informality during this period. Unlike previous crises, the fall in informal occupations deepened the overall contraction in employment. This was explained by a significant increase in exit rates from these jobs and, to a lesser extent, by reductions in entry rates. Most of the informal workers who lost their jobs left the labour force. Contrary to this labour movement, transits from informal to formal jobs significantly dropped during the most critical phase in this crisis. Partial recovery in employment since mid-2020 has been led by an increase in informal jobs. The labour dynamic has been different between men and women. This study reveals the relevance of dynamic analysis to clearly identify labour transitions that occurred during a labour crisis of unprecedented intensity and characteristics in Latin America.
Availability of healthy foods, fruit and vegetable consumption, and cognition among urban older adults
Authors: Hyun Jinshil , Katz Mindy J. , Derby Carol A. , Roque Nelson , Muñoz Elizabeth , Sliwinski Martin J. , Lovasi Gina S. , Lipton Richard B.
Published: May 2023

Background

. Although prior studies have examined the associations between neighborhood characteristics and cognitive health, little is known about whether local food environments, which are critical for individuals’ daily living, are associated with late-life cognition. Further, little is known about how local environments may shape individuals’ health-related behaviors and impact cognitive health. The aim of this study is to examine whether objective and subjective measures of healthy food availability are associated with ambulatory cognitive performance and whether behavioral and cardiovascular factors mediate these associations among urban older adults.

Methods

. The sample consisted of systematically recruited, community-dwelling older adults (N = 315, mean age = 77.5, range = 70–91) from the Einstein Aging Study. Objective availability of healthy foods was defined as density of healthy food stores. Subjective availability of healthy foods and fruit/vegetable consumption were assessed using self-reported questionnaires. Cognitive performance was assessed using smartphone-administered cognitive tasks that measured processing speed, short-term memory binding, and spatial working memory performance 6 times a day for 14 days.

Results

. Results from multilevel models showed that subjective availability of healthy foods, but not objective food environments, was associated with better processing speed (estimate= -0.176, p = .003) and more accurate memory binding performance (estimate = 0.042, p = .012). Further, 14~16% of the effects of subjective availability of healthy foods on cognition were mediated through fruit and vegetable consumption.

Conclusions

. Local food environments seem to be important for individuals’ dietary behavior and cognitive health. Specifically, subjective measures of food environments may better reflect individuals’ experiences regarding their local food environments not captured by objective measures. Future policy and intervention strategies will need to include both objective and subjective food environment measures in identifying impactful target for intervention and evaluating effectiveness of policy changes.
Dysphagia is closely related to frailty in mild-to-moderate Alzheimer’s disease
Authors: Güner Merve , Baş Arzu Okyar , Ceylan Serdar , Kahyaoğlu Zeynep , Çöteli Süheyla , Ünsal Pelin , Çavuşoğlu Çağatay , Özsürekci Cemile , Doğu Burcu Balam , Cankurtaran Mustafa , Halil Meltem Gülhan
Published: May 2023

Introduction

Physical phenotype and the cumulative deficit model are two well-known concepts of frailty. One of the main components of frailty is loss of muscle mass and function, which may also include swallowing muscles, therefore is a risk factor for dysphagia. Since dysphagia is seen starting from the early stages of Alzheimer’s Disease (AD), in this study we aimed to reveal the relationship between frailty and dysphagia and dysphagia-related quality of life through Swallow Quality of Life (SwalQoL) tool in patients with AD and compare them with cognitively intact older adults.

Methods

Comprehensive geriatric assessment, dysphagia evaluation by Eating-Assessment Tool (EAT-10) and SwalQoL questionnaire, and frailty assessment via FRAIL and Clinical Frailty Scale (CFS) were performed on all 101 participants of the study. Thirty-five patients were cognitively intact, 36 patients were diagnosed with mild AD, and 30 patients were diagnosed with moderate AD.

Results

Sex distribution was similar between the groups, however, there was a statistically significant age difference. The prevalence of frailty increased according to both frailty indexes as the cognitive status deteriorated. All parameters of SwalQoL except fear and sleep parameters deteriorated as cognitive status impaired. In quantile regression of the total score of the SwalQoL questionnaire and multivariable logistic regression of EAT-10, frailty, as defined by CFS and FRAIL, was associated with dysphagia and poor quality of life regardless of age, presence of dementia, as well as nutritional status.

Conclusion

Swallowing difficulties in AD negatively affects the quality of life, and it is closely related to frailty in mild-to-moderate AD.
Time to development of surgical site infection and its predictors among general surgery patients admitted at specialized hospitals in Amhara region, northwest Ethiopia: a prospective follow-up study
Authors: Alemayehu Meron Asmamaw , Azene Abebaw Gedef , Mihretie Kebadnew Mulatu
Published: May 2023

Background

Surgical site infection is an infection occurring within 30 days after surgery. It is recently reported that evidence-based information on the specific time when the majority of surgical site infections would develop is a key to early detect the infection as well as to preventing and early intervene against their pressing and fatal complications. Therefore, the current study aimed to determine the incidence, predictors, and time to development of surgical site infection among general surgery patients at specialized hospitals in the Amhara region.

Method

An institution-based prospective follow-up study was conducted. The two-stage cluster sampling procedure was used. A systematic sampling technique with a K interval of 2 was applied to prospectively recruit 454 surgical patients. Patients were followed up for 30 days. Data were collected using Epicollect5 v 3.0.5 software. Post-discharge follow-up and diagnosis were done by telephone call follow-up. Data were analyzed using STATA™ version 14.0. Kaplan–Meier curve was used to estimate survival time. Cox proportional regression model was used to determine significant predictors. Variables with a P-value less than 0.05 in the multiple Cox regression models were independent predictors.

Result

The incidence density was 17.59 per 1000 person-day-observation. The incidence of post-discharge Surgical site infection was 70.3%. The majority of surgical site infections were discovered after discharge between postoperative days 9 to 16. Being male (AHR: 1.98, 95% CI: 1.201 – 3.277, diabetes Mellitus (AHR: 1.819, 95% CI: 1.097 – 3.016), surgical history (AHR: 2.078, 95% CI: 1.345, 3.211), early antimicrobial prophylaxis (AHR: 2.60, 95% CI: 1.676, 4.039), American Society of Anesthesiologists score ≥ III AHR: 6.710, 95% CI: 4.108, 10.960), duration of the surgery (AHR: 1.035 95% CI: 1.001, 1.070), Age (AHR: 1.022 95% CI: 1.000, 1.043), and the number of professionals in the Operation Room (AHR: 1.085 95% CI: 1.037, 1.134) were found to be the predictors of time to development of Surgical site infection.

Conclusion

The incidence of surgical site infection was higher than the acceptable international range. The majority of infections were detected after hospital discharge between 9 to 16 postoperative days. The main predictors of Surgical site infection were Age, Sex, Diabetes Mellitus, previous surgical history, the timing of Antimicrobial prophylaxis, American Society of Anesthesiologists score, pre-operative hospital stay, duration of surgery, and the number of professionals in the operation room. Hence, hospitals should give great emphasis on pre-operative preparation, post-discharge surveillance, modifiable predictors, and high-risk patients, as they found in this study.