bluuebunny/crossref_metadata_2025 huggingface dataset:
Training and testing practices of strength and conditioning coaches in Argentinian Rugby Union
Authors: Zabaloy Santiago , Tondelli Eduardo , Pereira Lucas A , Freitas Tomás T , Loturco Irineu
Published: July 2022

The Argentine Rugby Union is a top-tier rugby nation (ranked 8th according to World Rugby), with the Buenos Aires Rugby Union being the largest competitive league. To date, the training practices of Argentinian rugby strength and conditioning coaches have not yet been documented and analyzed. We used an online survey to characterize the training and testing strategies commonly implemented by Argentinian rugby strength and conditioning coaches, which could serve as a guideline for coaching education programs. Thirty-five rugby strength and conditioning coaches (age: 42.0 ± 8.9 years; professional experience: 16.8 ± 8.3 years) working across 35 clubs (from a total of 40 clubs) participated in the study. The survey consisted of eight sections: 1) background information; 2) strength-power development; 3) speed training; 4) plyometrics; 5) flexibility training; 6) physical testing; 7) technology use; and 8) programming. Overall, Argentinian strength and conditioning coaches did not frequently use periodization strategies to structure programs, reported a progressive reduction in training loads across the season, and prescribed primarily Olympic weightlifting and squat as resistance exercises during different training periods. The analyses of speed training revealed high utilization of form-running, plyometrics, and sport-specific movements. Our results also indicated that physical testing and technology may be affected by the economic difficulties of Argentinian clubs. This study presents new information regarding the training methods adopted by Argentinian rugby strength and conditioning coaches, while providing them with new insights to improve their professional practices. Practitioners from different countries working in competitive rugby leagues can use the information provided here to examine their own practices and implement evidence-based programs for elite rugby players.
Risk factors in distal interphalangeal joint arthrodesis in the hand: a retrospective study of 173 cases
Authors: Runkel Alexander , Bonaventura Bastian , Sundermann Britta , Zajonc Horst , Eisenhardt Steffen , Leibig Nico
Published: July 2022

In this retrospective study we aimed to analyse the risk factors for complications after different methods of distal interphalangeal arthrodesis in the hand. Forty-four per cent were treated with K-wire/cerclage fixation, 46% with X-fuse® implants (Stryker GmbH, Selzach, Switzerland) and 10% with headless compression screws (HBS®-screw, KLS Martin Group, Tuttlingen, Germany). The median follow-up was 16 weeks (range 6–224). The overall complication incidence was 44% (minor complications 29% and major 15%). The logistic regression showed that osteoarthritis, revisional arthrodesis and smoking had a negative impact on the total complication incidence. A Cox-regression analysis showed that HBS®-screw arthrodesis was associated with a significantly lower incidence of major complications compared with K-wire/cerclage and X-Fuse®-arthrodesis. Revisional arthrodesis was five times more frequently connected with major complications than primary surgery. Smokers were three times more likely to experience major complications than non-smokers. We conclude that arthrodesis of the distal interphalangeal joint often leads to complications. Risk factors must be kept in mind.

Level of evidence: III
Potential use of the medicine ball throw test to reveal the upper-body maximal capacities to produce force, velocity, and power
Authors: Marovic Ivan , Janicijevic Danica , Knežević Olivera M. , Garcia-Ramos Amador , Prebeg Goran , Mirkov Dragan M.
Published: July 2022

The aims of this study were (1) to evaluate the shape of the load-velocity (L-V) and force-velocity (F-V) relationships obtained during the medicine ball throw (MBT) test, (2) to explore the reliability of their parameters (L-V parameters: maximal load ( L0), maximal velocity ( V0(L-V)), slope of the L-V relationship ( a(L-V)), and area under the L-V relationship line (Aline); F-V parameters: maximal force ( F0), maximal velocity ( V0(F-V)), slope of the F-V relationship ( a(F-V)), and maximal power ( Pmax)), (3) to explore the concurrent validity of the two-point with respect to the multiple-point method, and (4) to evaluate the external validity of L0 and F0 with respect to the maximal strength. Twelve males performed MBTs against four loads, a bench press 1-repetition maximum (1 RM), and maximal isometric medicine ball push. The L-V and F-V relationships were strongly linear (individual r ≥ 0.886). V0 was the only variable that always showed an acceptable reliability (CV ≤ 3.4%). L0 and F0 presented trivial to moderate correlations with the bench press 1RM and maximal isometric medicine ball push performance. Therefore, the MBT test can be implemented to reveal the maximal velocity capacity of upper-body muscles, but not maximal force or power capacities due to their low reliability and external validity.
The role of automated computed topography perfusion in prediction of hemorrhagic transformation after acute ischemic stroke
Authors: Elsaid Nada , Bigliardi Guido , Dell’Acqua Maria Luisa , Vandelli Laura , Ciolli Ludovico , Picchetto Livio , Borzì Giuseppe , Ricceri Riccardo , Pentore Roberta , Vallone Stefano , Meletti Stefano , Saied Ahmed
Published: July 2022

Introduction

The role of computed tomography perfusion (CTP) in prediction of hemorrhagic transformation (HT) has been evolving. We aimed to study the role of automated perfusion post-processing software in prediction of HT using the commercially available RAPID software.

Methods

Two hundred eighty-two patients with anterior circulation ischemic stroke, who underwent CTP with RAPID automated post-processing, were retrospectively enrolled and divided into HT ( n = 91) and non-HT groups ( n = 191). The automated RAPID-generated perfusion maps were reviewed. Mismatch volume and ratio, time to maximum (Tmax) > 4‐10s volumes, hypoperfusion index, cerebral blood flow (CBF) < 20–38% volumes, cerebral blood volume (CBV) < 34%–42% volumes, and CBV index were recorded and analyzed.

Results

The volumes of brain tissues suffering from reduction of cerebral blood flow (CBF < 20%–38%), reduction in cerebral blood volumes (CBV < 34–42%), and delayed contrast arrival times (Tmax > 4–10s) were significantly higher in the HT group. The mismatch volumes were also higher in the HT group ( p = .001). Among these parameters, the Tmax > 6s volume was the most reliable and sensitive predictor of HT ( p = .001, AUC = 0.667). However, the combination of the perfusion parameters can slightly improve the diagnostic efficiency (AUC = 0.703). There was no statistically significant difference between the non-HT group and either the parenchymal or the symptomatic subtypes.

Conclusion

The RAPID automated CTP parameters can provide a reliable predictor of HT overall but not the parenchymal or the symptomatic subtypes. The infarct area involving the penumbra and core represented by the Tmax > 6s threshold is the most sensitive predictor; however, the combination of the perfusion parameters can slightly improve the diagnostic efficiency.
Increased IL-31 expression in serum and tissue protein in prurigo nodularis
Authors: Chaowattanapanit Suteeraporn , Wongjirattikarn Rachot , Chaisuriya Nipon , Ungarreevittaya Piti , Poosekeaw Pirawan , Winaikosol Kengkart , Choonhakarn Charoen , Julanon Narachai , Salao Kanin
Published: July 2022

Background:

Prurigo nodularis (PN) is a chronic pruritic skin disease which can greatly impact patients’ quality of life. Moreover, the pathogenesis remains unclear, making it a difficult-to-treat condition.

Aims:

To investigate the expression of interleukin-31 (IL-31) in serum and skin biopsy specimens of PN patients and healthy subjects and identify its possible correlation to disease severity and itch intensity.

Methods:

Patients with PN and healthy volunteers were recruited for the study. Expression levels of IL-31 were measured by enzyme-linked immunosorbent assay and immunohistochemistry. Baseline characteristics, disease activity, itch intensity, and related laboratory results were collected.

Results:

Forty-three PN patients and 31 healthy subjects participated in our study. The PN patients had significantly higher mean serum IL-31 levels than the healthy subjects (52.9 ± 18.2 versus 36.3 ± 10.7 pg/ml, p < 0.001). Epidermal and dermal PN lesions also exhibited significantly higher IL-31 expression compared with the healthy skin ( p < 0.001 and p = 0.01, respectively). However, there was no significant difference in serum or lesional expression of IL-31 by disease severity or itch intensity.

Conclusion:

Increased IL-31 expression in serum and PN lesions suggests that IL-31 has a potential role in the pathogenesis of PN.
Rethinking the impact of interactive technologies on the retailing experience: Synthesis, conceptual approach, and research agenda
Authors: Yang Xingming , Garnier Marion
Published: July 2022

Implementing in-store technologies (ISTs) has become a common strategy to enhance the retail experience. As ISTs become increasingly interactive, sophisticated, and present in stores, research would benefit from an updated approach to interactive technologies in the physical retail context and an integrated perspective on their impact on the consumer in-store experience. A systematic review of 125 articles is conducted, leading to a renewed and integrative approach to in-store interactive technologies, structured along with a Person-Object-Situation perspective, based on technology responsiveness and consumer participation, and adapted to physical retail. Three complementary research models are proposed, addressing key issues: the understanding of interactivity and the impact of ISTs on the consumer experience in physical stores, the impact of highly interactive technologies, and the question of forced use of ISTs. Priority research perspectives are discussed and a research agenda is proposed.
Taking a critical look at the critical turn in data science: From “data feminism” to transnational feminist data science
Authors: Tacheva Zhasmina
Published: July 2022

Through a critical analysis of recent developments in the theory and practice of data science, including nascent feminist approaches to data collection and analysis, this commentary aims to signal the need for a transnational feminist orientation towards data science. I argue that while much needed in the context of persistent algorithmic oppression, a Western feminist lens limits the scope of problems, and thus—solutions, critical data scholars, and scientists can consider. A resolutely transnational feminist approach on the other hand, can provide data theorists and practitioners with the hermeneutic tools necessary to identify and disrupt instances of injustice in a more inclusive and comprehensive manner. A transnational feminist orientation to data science can pay particular attention to the communities rendered most vulnerable by algorithmic oppression, such as women of color and populations in non-Western countries. I present five ways in which transnational feminism can be leveraged as an intervention into the current data science canon.
E-solutions in Estonian community pharmacies: A literature review
Authors: Tuula Anita , Sepp Kristiina , Volmer Daisy
Published: July 2022

Objective

Estonian innovative electronic solutions have long been leading the way in the healthcare sector. This article aims to give an overview of all e-solutions and their usability in community pharmacies in Estonia and how they compare and operate with the wider e-health system.

Methods

A comprehensive literature review was conducted on publicly accessible information regarding Estonian e-health and electronic community pharmacy solutions.

Findings

While Estonian e-health system, including the e-prescription system is developed and maintained by the nationally funded Health and Wellbeing Infosystem Center, community pharmacy owners have established many noteworthy systems such as the e-pharmacist decision-support system, commodities info systems, online pharmacies, a telehealth prescription reminder service, and an automated dosage dispense system. Some pharmacies are collaborating with private healthcare service providers to allow quick and easy prescription renewal through an electronic channel.

Conclusion

Different electronic systems have overall greatly improved Estonian pharmacy services, accuracy and flow of consultations, and accessibility of medicines. In some cases, more support and active involvement is still needed from government agencies for full implementation.
Politicization and Radicalization of Discourses in the Alt-Tech Ecosystem: A Case Study on Gab Social
Authors: Dehghan Ehsan , Nagappa Ashwin
Published: July 2022

With the increasing popularity of some alternative social media platforms, the flow of information has to some extent shifted from the periphery to the core, where problematic discourses are produced, reproduced, and amplified in the alternative ecosystem, to later find their way into mainstream platforms. The non- or less-moderated nature of some alternative platforms provides a suitable space for politicization and radicalization of discourses. In this article, we use a case study of conversations about vaccination on Gab Social—an alternative platform often conceptualized as a far-right platform—to examine this radicalization process through a mixed-methods analysis of over 68,000 vaccination-related posts from before the COVID-19 pandemic until August 2021. The article shows that while antagonistic and conspiratorial thinking was an element of vaccination discourses on Gab even before the pandemic, such conversations became gradually politicized, and expanded far beyond the medical discourse and entered the domain of organizational politics.
Complexity of the Contexts: Features of Private Tutoring and Units for Comparison in the GCC Countries of the Middle East
Authors: Bray Mark , Hajar (أنس حجّار) Anas
Published: July 2022

Purpose

Private supplementary tutoring—widely known as shadow education because of the ways in which it mimics regular schooling—is increasingly visible across the globe. The Middle East is no exception, though the phenomenon has received relatively little attention in the English-language literature. This article maps some key features of shadow education, identifying ways in which contextual forces have shaped it.

Design/Approach/Methods

The article focuses on patterns across and within the six members of the Gulf Cooperation Council (GCC), namely Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. It draws on literature in both Arabic and English and shows the value of multiple units of comparison.

Findings

Private tutoring has a long history as a significant phenomenon in some GCC countries, but in others developed more recently. Some governments have had active policies to dampen the phenomenon, but with little success. Factors in the complex dynamics include social, economic and cultural forces.

Originality/Value

The article assembles literature from around the region, noting both commonalities and diversities among GCC members. It contributes to the global literature by providing the regional mapping from this specific part of the world and by showing comparisons with other world regions.
Prevalence of Social Determinants of Health Among Health System Employees
Authors: Seeholzer Eileen L. , Santiago Marielee , Thomas Charles , DeAngelis Monica , Scarl Francesca , Webb Anastasia , Woods Tangela , Sehgal Ashwini R.
Published: July 2022

Introduction/Objectives:

Many health systems screen patients for social determinants of health and refer patients with social needs to community service organizations for assistance. However, little is known about social determinants of health among health system employees. We sought to examine the prevalence of social determinants among employees of The MetroHealth System, a large safety-net health system in Cleveland, Ohio.

Methods:

We invited participants in an employee wellness program to answer the same screening questions that patients answer about 9 social determinants of health, including food insecurity, financial strain, transportation difficulty, inability to pay for housing or utilities, intimate partner violence, social isolation, infrequent physical activity, daily stress, and lack of internet access. We then determined the percentage of employees who met pre-defined criteria for being at risk for each social determinant. We also examined how these percentages varied across employee job categories.

Results:

Of 4191 full-time employees, 1932 (46%) completed the survey. The percentage of employees at risk for each social determinant were: food insecurity (11%), financial strain (12%), transportation difficulty (4%), inability to pay for housing or utilities (10%), intimate partner violence (4%), social isolation (48%), infrequent physical activity (10%), daily stress (58%), and lack of internet access (3%). Being at risk for specific social determinants was more common among support staff compared to staff physicians and nurses. For example, the survey participants included 436 administrative support staff, a job category that includes secretaries and patient service representatives. Among this group, 20% reported food insecurity, 20% financial strain, and 17% inability to pay for housing or utilities.

Conclusions:

Social determinants of health are common among health system employees, especially among workers in lower paid job categories. Health systems should routinely screen employees for social determinants and adjust salaries, benefits, and assistance programs to address their social needs.
Book review: Sukhpal Singh (2018). Institutional Innovations in the Delivery of Farm Services in India: A Small Holder Perspective
Authors: Jha Praveen
Published: July 2022

Sukhpal Singh (2018). Institutional Innovations in the Delivery of Farm Services in India: A Small Holder Perspective. New Delhi and IIM Ahmedabad: Springer India. CMA Publication No. 251 (Hardback), xxiv + 246 pp., Bibliography, Index, $149.99.
A Multilevel Framework of Racism as a Barrier to Teachers’ Implementation of Culturally Relevant Pedagogy
Authors: Pagán Olga
Published: July 2022

Culturally relevant pedagogy (CRP; e.g., Ladson-Billings, 1995) is a set of beliefs and practices that aim to serve culturally and linguistically diverse student learners. Although a large body of work describes its tenets and permutations, and its implications for students, less work has been done to outline the myriad barriers that teachers face when trying to implement CRP. This paper addresses this gap by proposing a race-conscious, multilevel, ecological framework to illuminate the societal, institutional, and individual obstacles that teachers must navigate in the pursuit of CRP. Implications for teacher training and development are discussed.
Diabetic Kidney Disease Is Associated With Increased Complications Following Operative Management of Ankle Fractures
Authors: Polachek William S. , Baker Hayden P. , Dahm James S. , Strelzow Jason A. , Hynes Kelly K.
Published: July 2022

Background:

Diabetes mellitus and peripheral neuropathy are established risk factors for complications in operatively treated ankle fractures. Generally, the presence of peripheral neuropathy and diabetic nephropathy have been used as independent variables in studies of diabetic ankle fracture cohorts but are typically treated as binary risk factors. Our purpose was to quantify the effects of risk factors on complication rate specific to diabetic patients undergoing ankle fracture fixation.

Methods:

We identified 617 rotational ankle fractures treated operatively at a single academic medical center from 2010 to 2019, of which 160 were identified as diabetic. Of these, 91 ankle fractures in 90 diabetic patients met criteria for retrospective review of clinical and radiographic data. Criteria included perioperative laboratory studies, including glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR), as well as follow-up radiographs in the electronic record. We defined complications in this surgical cohort as deep surgical site infection, unplanned return to the operating room, and failure of fixation. Logistic regression was performed and odds ratios (ORs) calculated.

Results:

The overall complication rate was 28.6% (26/91) in this cohort. Median follow-up was 29 weeks (range: 5-520 weeks). Mean perioperative HbA1c in patients who experienced postoperative complications was 7.6% (range: 5.1%-14.2%) compared with 7.8% (range: 5.6%-13.5%) who did not ( P = .69). Diabetic patients with chronic kidney disease (eGFR <60 mL/min per body surface area) (OR 5.29, P = .006) and peripheral neuropathy (OR 4.61, P = .003) were at significantly higher risk of all complications compared with diabetic patients without these comorbidities. Of note, we did not find an association between perioperative HbA1c or body mass index and complication rate.

Conclusion:

Patients with diabetes complicated by chronic kidney disease are at significantly higher risk of complications following operative management of ankle fractures. Our study also corroborated previous reports that within this high-risk cohort, the presence of peripheral neuropathy is a significant risk factor for complications. These sequalae of diabetic disease are manifestations of microvascular disease, glycosylation of soft tissues, and impaired metabolic pathways. Identifying these risk factors in diabetic patients allows for patient-specific risk stratification, education, and management decisions of ankle fractures.

Level of Evidence:

Level III, retrospective cohort study.
Easy Arthroscopic Transseptal Approach of the Knee
Authors: Gousopoulos Lampros , Hopper Graeme , Levy Yoann , Grob Charles , Vieira Thais Dutra , Sonnery-Cottet Bertrand
Published: July 2022

Background:

The arthroscopic approach to the posterior compartment of the knee is always challenging. This easy arthroscopic transseptal approach allows safe access to the posterior compartment of the knee, avoiding any potential neurovascular injury.

Indications:

Indications include arthroscopic posterior cruciate ligament (PCL) reconstruction, fixation of avulsion fractures of the tibial attachment of the PCL, arthroscopic posterolateral corner reconstruction, removal of loose bodies from the posterior compartment, PCL cyst removal, ramp repair, and arthroscopic arthrolysis of the posterior compartment.

Technique Description:

Using a posteromedial portal, a shaver is introduced with the tip in direct contact with the medial side of the septum facing anteriorly, away from the popliteal neurovascular bundle. The scope is then inserted into the posterolateral compartment to visualize the lateral side of the septum while the shaver remains in the posteromedial compartment. The septum is then released until the tip of the shaver is visible. The shaver is then removed and the scope can now be inserted from the posteromedial portal to the posterolateral compartment through the released septum.

Results:

The transseptal approach can be performed without any additional risk if the shaver remains centrally on the inferior aspect of the septum. Therefore, the risk of iatrogenic injury of the middle genicular artery is minimized. Likewise, with the knee flexed to 90°, there is no risk of damaging the popliteal neurovascular bundle. Having a precise knowledge of the anatomy of the posterior compartment of the knee minimizes any risks of the transseptal approach, avoiding any additional surgical time whilst facilitating the indicated operation.

Conclusion:

This easy arthroscopic transseptal approach allows safe access to the posterior compartment of the knee, avoiding any potential neurovascular injury.
China’s extended urbanization driven by the “consumption city” in the context of financialized ecological civilization
Authors: Theurillat Thierry , Graezer Bideau Florence
Published: July 2022

This article seeks to address current debates on ongoing China’s urban development and makes a theoretical proposal that links financialization and ecological civilization through the perspective of the increasing role of consumption in today’s transition to an upgraded domestic economy. While both financialized land value capture and the role of quality are now fundamental to the construction of the built environment in Chinese cities, we argue that the “consumption city” refers to an economic and urban production process as well as to a societal transformation. First, the economic upgrading has gone along with a greater mobility of people travelling ever longer distances who spend their income or invest in the places they travel to rather than necessarily their places of residence or of work. To attract these consumers, whether they are residents, tourist or property investors, the quality of the living and consumption environments play a dominant role in the complex urban production and in governance, beyond the classic model of development based on the city as a production place. Simultaneously, the rising role of financialization by external households as investors raises the issue of how and to what extent the construction of consumption places has been a way for the state to further enhance the land value capture in (new or not) cities. Second, as the latest government strategy, ecological civilization is part of a social engineering process aiming to shape people’s lifestyles in terms of both their everyday consumption practices and their mindsets. The current transition aims to “civilize” citizens by enlarging the scope of urban consumers beyond the upper and middle classes to people from rural areas who are encouraged to become urban. Ecological civilization promotes a better quality of life for all, together with new outdoor and experiential activities, although this comes with a high ecological footprint.
Beyond abstract space: Architectural experiments for dwelling and concrete utopia in urban China
Authors: Qian Junxi , Lu Yanheng
Published: July 2022

Urban transformation in China is witnessing a diversification of architectural designs and the more prominent roles played by architects. Notably, recent architectural practices in urban and regional China have increasingly emphasised the social functions and uses of architecture – architecture is mobilised by many architects and their clients to promote public goods, social improvement and extra-economic purposes. The dialectic between material and social transformations constitutes the focus of this paper. To reconceptualise architecture as an active social intervention, this paper first delineates a theoretical outline that starts from Henri Lefebvre’s thesis on the alienation of everyday life and proliferation of abstract space in modern cities. We then engage with the notion of concrete utopia that highlights alternative urban spaces produced by architectural works, which do not radically transcend the dominant capitalist system but intervene into the current conditions by enriching and improving them incrementally. To illustrate this perspective, this paper develops a preliminary reading of two empirical cases based on second-hand materials collected from public media and social media, namely the Aranya project in Changli County, Hebei Province and the renovation project of a traditional house in central Shanghai.
The Role of Clinical Pharmacist in Pediatrics’ Adherence to Antiepileptic Drugs
Authors: Jarad Suha , Akour Amal , Khreisat Wael H. , Elshammari Afrah K. , Madae’en Saba
Published: July 2022

Background:

Rate of nonadherence to antiepileptic drugs (AEDs) in children is about 33%. Engaging clinical pharmacists in the management of patients has proved to increase adherence to medications which will improve the outcomes of treatment.

Objectives:

To investigate the effect of a clinical pharmacist-led education on the adherence to AEDs in pediatric patients with epilepsy. Secondary outcomes include effectiveness and safety of AEDs, satisfaction with information about AEDs provided to the caregivers, and patients quality of life (QoL).

Methods:

This was an interventional study where pediatric patients were randomly assigned to the intervention (n = 41) or the control (n = 40) group. A 30-minute clinical pharmacist-led educational interview to the parent/caregiver was provided to the first group as add-on to standard medical care received by latter. Outcomes were measured at baseline and after 8-week follow-up.

Results:

The intervention group had an increase in mean adherence score from 6 ± 1.09 at baseline to 7.6 ± 0.9 at follow-up ( P value < 0.001), while the control group had no significant change ( P value > 0.05), the difference between the 2 groups at follow-up was significant ( P value < 0.0001). No significant difference was observed between groups at follow-up with regard to effectiveness ( P value > 0.05), and safety ( P value = 0.08). While higher satisfaction with information ( P value < 0.0001), and higher QoL ( P value < 0.05) was observed in the intervention group.

Conclusion and relevance:

Clinical pharmacist-led education had a positive outcome on pediatric patients with epilepsy with regard to adherence, effectiveness, safety, satisfaction with information about AEDs, and QoL.
Targeting MDM2 enhances antileukemia immunity after allogeneic transplantation via MHC-II and TRAIL-R1/2 upregulation
Authors: Ho Jenny N. H. G. , Schmidt Dominik , Lowinus Theresa , Ryoo Jeongmin , Dopfer Elaine-Pashupati , Gonzalo Núñez Nicolás , Costa-Pereira Sara , Toffalori Cristina , Punta Marco , Fetsch Viktor , Wertheimer Tobias , Rittmann Marie-Claire , Braun Lukas M. , Follo Marie , Briere Christelle , Vinnakota Janaki Manoja , Langenbach Marlene , Koppers Felicitas , Shoumariyeh Khalid , Engel Helena , Rückert Tamina , Märklin Melanie , Holzmayer Samuel , Illert Anna L. , Magon Federica , Andrieux Geoffroy , Duquesne Sandra , Pfeifer Dietmar , Staniek Julian , Rizzi Marta , Miething Cornelius , Köhler Natalie , Duyster Justus , Menssen Hans D. , Boerries Melanie , Buescher Joerg M. , Cabezas-Wallscheid Nina , Blazar Bruce R. , Apostolova Petya , Vago Luca , Pearce Erika L. , Becher Burkhard , Zeiser Robert
Published: July 2022

Patients with acute myeloid leukemia (AML) often achieve remission after allogeneic hematopoietic cell transplantation (allo-HCT) but subsequently die of relapse driven by leukemia cells resistant to elimination by allogeneic T cells based on decreased major histocompatibility complex II (MHC-II) expression and apoptosis resistance. Here we demonstrate that mouse-double-minute-2 (MDM2) inhibition can counteract immune evasion of AML. MDM2 inhibition induced MHC class I and II expression in murine and human AML cells. Using xenografts of human AML and syngeneic mouse models of leukemia, we show that MDM2 inhibition enhanced cytotoxicity against leukemia cells and improved survival. MDM2 inhibition also led to increases in tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and -2 (TRAIL-R1/2) on leukemia cells and higher frequencies of CD8+CD27lowPD-1lowTIM-3low T cells, with features of cytotoxicity (perforin+CD107a+TRAIL+) and longevity (bcl-2+IL-7R+). CD8+ T cells isolated from leukemia-bearing MDM2 inhibitor-treated allo-HCT recipients exhibited higher glycolytic activity and enrichment for nucleotides and their precursors compared with vehicle control subjects. T cells isolated from MDM2 inhibitor-treated AML-bearing mice eradicated leukemia in secondary AML-bearing recipients. Mechanistically, the MDM2 inhibitor-mediated effects were p53-dependent because p53 knockdown abolished TRAIL-R1/2 and MHC-II upregulation, whereas p53 binding to TRAILR1/2 promotors increased upon MDM2 inhibition. The observations in the mouse models were complemented by data from human individuals. Patient-derived AML cells exhibited increased TRAIL-R1/2 and MHC-II expression on MDM2 inhibition. In summary, we identified a targetable vulnerability of AML cells to allogeneic T-cell–mediated cytotoxicity through the restoration of p53-dependent TRAIL-R1/2 and MHC-II production via MDM2 inhibition.
Sputter-Deposited Binder-Free Nanopyramidal Cr/γ-Mo2N TFEs for High-Performance Supercapacitors
Authors: Govindarajan Durai , Palaniyandy Nithyadharseni , Chinnakutti Karthik Kumar , Nguyen Mai Thanh , Yonezawa Tetsu , Qin Jiaqian , Kheawhom Soorathep
Published: July 2022

Due to their outstanding power density, long cycle life and low cost, supercapacitors have gained much interest. As for supercapacitor electrodes, molybdenum nitrides show promising potential. Molybdenum nitrides, however, are mainly prepared as nanopowders via a chemical route and require binders for the manufacture of electrodes. Such electrodes can impair the performance of supercapacitors. Herein, binder-free chromium (Cr)-doped molybdenum nitride (Mo2N) TFEs having different Cr concentrations are prepared via a reactive co-sputtering technique. The Cr-doped Mo2N films prepared have a cubic phase structure of γ-Mo2N with a minor shift in the (111) plane. While un-doped Mo2N films exhibit a spherical morphology, Cr-doped Mo2N films demonstrate a clear pyramid-like surface morphology. The developed Cr-doped Mo2N films contain 0–7.9 at.% of Cr in Mo2N lattice. A supercapacitor using a Cr-doped Mo2N electrode having the highest concentration of Cr reveals maximum areal capacity of 2780 mC/cm2, which is much higher than that of an un-doped Mo2N electrode (110 mC/cm2). Furthermore, the Cr-doped Mo2N electrode demonstrates excellent cycling stability, achieving ~ 94.6% capacity retention for about 2000 cycles. The reactive co-sputtering proves to be a suitable technique for fabrication of binder-free TFEs for high-performance energy storage device applications.

Graphical Abstract
Multi-head attention-based U-Nets for predicting protein domain boundaries using 1D sequence features and 2D distance maps
Authors: Mahmud Sajid , Guo Zhiye , Quadir Farhan , Liu Jian , Cheng Jianlin
Published: July 2022

The information about the domain architecture of proteins is useful for studying protein structure and function. However, accurate prediction of protein domain boundaries (i.e., sequence regions separating two domains) from sequence remains a significant challenge. In this work, we develop a deep learning method based on multi-head U-Nets (called DistDom) to predict protein domain boundaries utilizing 1D sequence features and predicted 2D inter-residue distance map as input. The 1D features contain the evolutionary and physicochemical information of protein sequences, whereas the 2D distance map includes the structural information of proteins that was rarely used in domain boundary prediction before. The 1D and 2D features are processed by the 1D and 2D U-Nets respectively to generate hidden features. The hidden features are then used by the multi-head attention to predict the probability of each residue of a protein being in a domain boundary, leveraging both local and global information in the features. The residue-level domain boundary predictions can be used to classify proteins as single-domain or multi-domain proteins. It classifies the CASP14 single-domain and multi-domain targets at the accuracy of 75.9%, 13.28% more accurate than the state-of-the-art method. Tested on the CASP14 multi-domain protein targets with expert annotated domain boundaries, the average per-target F1 measure score of the domain boundary prediction by DistDom is 0.263, 29.56% higher than the state-of-the-art method.
DecodeME: community recruitment for a large genetics study of myalgic encephalomyelitis / chronic fatigue syndrome
Authors: Devereux-Cooke Andy , Leary Sian , McGrath Simon J. , Northwood Emma , Redshaw Anna , Shepherd Charles , Stacey Pippa , Tripp Claire , Wilson Jim , Mar Margaret , Boobyer Danielle , Bromiley Sam , Chowdhury Sonya , Dransfield Claire , Almas Mohammed , Almelid Øyvind , Buchanan David , Garcia Diana , Ireland John , Kerr Shona M. , Lewis Isabel , McDowall Ewan , Migdal Malgorzata , Murray Phil , Perry David , Ponting Chris P. , Vitart Veronique , Wolfe Jareth C.
Published: July 2022

Background

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy.

Methods

Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants’ saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants’ genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology.

Discussion

The DecodeME study has been reviewed and given a favourable opinion by the North West – Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online (www.decodeme.org.uk). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.
Exercise training and NR supplementation to improve muscle mass and fitness in adolescent and young adult hematopoietic cell transplant survivors: a randomized controlled trial {1}
Authors: Song Minkeun , Armenian Saro H. , Bhandari Rusha , Lee Kyuwan , Ness Kirsten , Putt Mary , Lindenfeld Lanie , Manoukian Saro , Wade Kristin , Dedio Anna , Guzman Tati , Hampton Isabella , Lin Kimberly , Baur Joseph , McCormack Shana , Mostoufi-Moab Sogol
Published: July 2022

Background

Advances in hematopoietic cell transplantation (HCT) have led to marked improvements in survival. However, adolescents and young adults (AYAs) who undergo HCT are at high risk of developing sarcopenia (loss of skeletal muscle mass) due to the impact of HCT-related exposures on the developing musculoskeletal system. HCT survivors who have sarcopenia also have excess lifetime risk of non-relapse mortality. Therefore, interventions that increase skeletal muscle mass, metabolism, strength, and function are needed to improve health in AYA HCT survivors. Skeletal muscle is highly reliant on mitochondrial energy production, as reflected by oxidative phosphorylation (OXPHOS) capacity. Exercise is one approach to target skeletal muscle mitochondrial OXPHOS, and in turn improve muscle function and strength. Another approach is to use “exercise enhancers”, such as nicotinamide riboside (NR), a safe and well-tolerated precursor of nicotinamide adenine dinucleotide (NAD+), a cofactor that in turn impacts muscle energy production. Interventions combining exercise with exercise enhancers like NR hold promise, but have not yet been rigorously tested in AYA HCT survivors.

Methods/design

We will perform a randomized controlled trial testing 16 weeks of in-home aerobic and resistance exercise and NR in AYA HCT survivors, with a primary outcome of muscle strength via dynamometry and a key secondary outcome of cardiovascular fitness via cardiopulmonary exercise testing. We will also test the effects of these interventions on i) muscle mass via dual energy x-ray absorptiometry; ii) muscle mitochondrial OXPHOS via an innovative non-invasive MRI-based technique, and iii) circulating correlates of NAD+metabolism via metabolomics. Eighty AYAs (ages 15-30y) will be recruited 6–24 months post-HCT and randomized to 1 of 4 arms: exercise + NR, exercise alone, NR alone, or control. Outcomes will be collected at baseline and after the 16-week intervention.

Discussion

We expect that exercise with NR will produce larger changes than exercise alone in key outcomes, and that changes will be mediated by increases in muscle OXPHOS. We will apply the insights gained from this trial to develop individualized, evidence-supported precision initiatives that will reduce chronic disease burden in high-risk cancer survivors.

Trial registration

ClinicalTrials.gov, NCT05194397. Registered January 18, 2022,https://clinicaltrials.gov/ct2/show/NCT05194397{2a}.
An M0 macrophage-related prognostic model for hepatocellular carcinoma
Authors: Zhang Yiya , Zou Ju , Chen Ruochan
Published: July 2022

Background

The role of M0 macrophages and their related genes in the prognosis of hepatocellular carcinoma (HCC) remains poorly characterized.

Methods

Multidimensional bioinformatic methods were used to construct a risk score model using M0 macrophage-related genes (M0RGs).

Results

Infiltration of M0 macrophages was significantly higher in HCC tissues than in normal liver tissues (P = 2.299e-07). Further analysis revealed 35 M0RGs that were associated with HCC prognosis; two M0RGs (OLA1 and ATIC) were constructed and validated as a prognostic signature for overall survival of patients with HCC. Survival analysis revealed the positive relationship between the M0RG signature and unfavorable prognosis. Correlation analysis showed that this risk model had positive associations with clinicopathological characteristics, somatic gene mutations, immune cell infiltration, immune checkpoint inhibitor targets, and efficacy of common drugs.

Conclusions

The constructed M0RG-based risk model may be promising for the clinical prediction of prognoses and therapeutic responses in patients with HCC.
Health literacy and recovery following a non-catastrophic road traffic injury
Authors: Gopinath Bamini , Jagnoor Jagnoor , Kifley Annette , Pozzato Ilaria , Craig Ashley , Cameron Ian D.
Published: July 2022

Background

Health literacy (HL) is rarely addressed in rehabilitation research and practice but can play a substantial role in the recovery process after an injury. We aimed to identify factors associated with low HL and its relationship with 6-month health outcomes in individuals recovering from a non-catastrophic road traffic injury.

Methods

Four hundred ninety-three participants aged ≥17 years who had sustained a non-catastrophic injury in a land-transport crash, underwent a telephone-administered questionnaire. Information was obtained on socio-economic, pre-injury health and crash-related characteristics, and health outcomes (quality of life, pain related measures and psychological indices). Low HL was defined as scoring < 4 on either of the two scales of the Health Literacy Questionnaire that covered: ability to actively engage with healthcare providers (‘Engagement’ scale); and/or understanding health information well enough to know what to do (‘Understanding’ scale).

Results

Of the 493, 16.9 and 18.7% scored < 4 on the ‘Understanding’ and ‘Engagement’ scale (i.e. had low HL), respectively. Factors that were associated with low HL as assessed by both scales were: having pre-injury disability and psychological conditions; lodging a third-party insurance claim; experiencing overwhelming/great perceived sense of danger/death during the crash; type of road user; low levels of social satisfaction; higher pain severity; pain catastrophizing; and psychological- and trauma-related distress. Low HL (assessed by both scales) was associated with poorer recovery outcomes over 6 months. In these longitudinal analyses, the strongest association was with disability (p < 0.0001), and other significant associations were higher levels of catastrophizing (p = 0.01), pain severity (p = 0.04), psychological- (p ≤ 0.02) and trauma-related distress (p = 0.003), lower quality of life (p ≤ 0.03) and physical functioning (p ≤ 0.01).

Conclusions

A wide spectrum of factors including claim status, pre-injury and psychological measures were associated with low HL in injured individuals. Our findings suggest that targeting low HL could help improve recovery outcomes after non-catastrophic injury.
Supporting community overdose response planning in Ontario, Canada: Findings from a situational assessment
Authors: Khorasheh Triti , AbuAyyash Caroline Bennett , Mallakin Maryam , Sellen Kate , Corace Kim , Pauly Bernadette , Buchman Daniel , Hamilton Michael , Boyce Nick , Ng Karen , Strike Carol , Taha Sheena , Manson Heather , Leece Pamela
Published: July 2022

Background

Many communities across North America are coming together to develop comprehensive plans to address and respond to the escalating overdose crisis, largely driven by an increasingly toxic unregulated drug supply. As there is a need to build capacity for successful implementation, the objective of our mixed methods study was to identify the current planning and implementation practices, needs, and priority areas of support for community overdose response plans in Ontario, Canada.

Methods

We used a situational assessment methodology to collect data on current planning and implementation practices, needs, and challenges related to community overdose response plans in Ontario, consisting of three components. Between November 2019 to February 2020, we conducted ten semi-structured key informant interviews, three focus groups with 25 participants, and administered an online survey (N = 66). Purposeful sampling was used to identify professionals involved in coordinating, supporting, or partnering on community overdose response plans in jurisdictions with relevant information for Ontario including other Canadian provinces and American states. Key informants included evaluators, representatives involved in centralised supports, as well as coordinators and partners on community overdose response plans. Focus group participants were coordinators or leads of community overdose response plans in Ontario.

Results

Sixty-six professionals participated in the study. The current planning and implementation practices of community overdose response plans varied in Ontario. Our analysis generated four overarching areas for needs and support for the planning and implementation of community overdose response plans: 1) data and information; 2) evidence and practice; 3) implementation/operational factors; and 4) partnership, engagement, and collaboration. Addressing stigma and equity within planning and implementation of community overdose response plans was a cross-cutting theme that included meaningful engagement of people with living and lived expertise and meeting the service needs of different populations and communities.

Conclusions

Through exploring the needs and related supports for community overdose response plans in Ontario, we have identified key priority areas for building local capacity building to address overdose-related harms. Ongoing development and refinement, community partnership, and evaluation of our project will highlight the influence of our supports to advance the capacity, motivation, and opportunities of community overdose response plans.