bluuebunny/crossref_metadata_2025 huggingface dataset:
Repurposing FDA-approved drugs for COVID-19: targeting the main protease through multi-phase in silico approach
Authors: Metwaly Ahmed M , Elkaeed Eslam B , Alsfouk Aisha A , Ibrahim Ibrahim M , Elkady Hazem , Eissa Ibrahim H
Published: December 2024

Background

The COVID-19 pandemic has created an urgent need for effective therapeutic agents. The SARS-CoV-2 Main Protease (Mpro) plays a crucial role in viral replication and immune evasion, making it a key target for drug development. While several studies have explored Mpro inhibition, identifying FDA-approved drugs with potential efficacy remains a critical research focus.

Purpose

This study aims to identify FDA-approved drugs that could inhibit SARS-CoV-2 Mpro. Using computational screening, we seek compounds that share structural similarities with a known co-crystallized ligand (PRD_002214) and exhibit strong binding affinity to the enzyme, providing viable candidates for COVID-19 treatment.

Research Design

A systematic in silico approach was used, screening 3009 FDA-approved drugs. The initial screening focused on structural similarity to PRD_002214 (PDB ID: 6LU7), followed by molecular docking studies to predict binding affinity. Promising compounds were further analyzed through molecular dynamics (MD) simulations to evaluate their stability and interactions with Mpro over 100 ns.

Study Sample

Of the 3009 FDA-approved drugs screened, 74 were selected for initial evaluation. After refinement, 28 compounds underwent docking analysis, with eight showing strong binding potential to Mpro.

Analysis

Molecular docking assessed the binding affinity and interaction of the selected compounds with Mpro. MD simulations were conducted on the top compound, Atazanavir, to study its dynamic interactions. MM-GBSA, PLIP, and PCAT analyses were used to validate binding affinity and interactions.

Results

Eight compounds, including Carfilzomib, Atazanavir, Darunavir, and others, exhibited promising binding affinities. Among them, Atazanavir showed the highest binding strength and was selected for further MD simulation studies. These simulations revealed that Atazanavir forms stable interactions with Mpro, demonstrating favorable binding and dynamic stability. The binding affinity was further confirmed through MM-GBSA, PLIP, and PCAT analyses, supporting Atazanavir's potential as an effective Mpro inhibitor.

Conclusions

In silico results suggest that Atazanavir is a promising candidate for targeting SARS-CoV-2 Mpro, with strong binding affinity and dynamic stability. These findings support its potential as a lead compound for further preclinical and clinical testing, though in vitro and in vivo validation are needed to confirm its therapeutic efficacy against COVID-19.
Subject to Quarantine: A Narrative Analysis of COVID-19 Reporting in the Australian News Media
Authors: Plage Stefanie , Kuskoff Ella , Stambe Rose-Marie
Published: December 2024

COVID-19 pandemic responses saw the large-scale return of quarantine, a once-common public health technology which, in modern society, had largely been replaced by infection control regimen combining immunisation, personal hygiene, and sanitation. While anchored in biomedicine, quarantine is a profoundly relational practice with immediate infringements upon personal liberties such as freedom of movement. The socio-cultural repercussions of targeting specific parts of the population for quarantine are likely long-lasting. Drawing on Alison Bashford’s understanding of quarantine as co-constituted by and co-constituting objects, people, and places, we conducted a narrative analysis of Australian online news published between January 2020 and December 2020. Comparing the reporting on maritime, residential and hotel quarantine in over 847 articles, we explore socio-cultural continuities and shifts in narrative plots as well as emergent subjectivities. We trace how some objects (i.e. cruise ships) become reimagined as ‘harbingers of death’; how in some places of quarantine (i.e. public housing estates) the approximation of class and race to danger is reiterated; and how a nuanced subject position is brought about in the ‘returned traveller’ quarantining in hotels. What objects, places, and people are associated with disease inflects whether and how far quarantine practices are deemed morally and socially viable.
TikTok ‘dogshows’ and the amplification of online incivility among Gen Z influencers in the Philippines
Authors: Cabbuag Samuel I. , Abidin Crystal
Published: December 2024

Studies on digital platforms and online incivility have established that uses of humour can lean towards cyberbullying and hate speech. Focusing on TikTok's affordances and cultures of online incivility, this paper studies how TikTok influencers and their audiences manoeuvre legal-but-harmful humour. Specifically, we study how online incivility has become an accepted and negotiated practice in the Filipino context through the phenomenon of ‘dogshows’, where users throw jabs at individuals using derogatory humour and provocative memes. Through online observation and textual analysis of TikTok posts and their corresponding comment sections, we demonstrate how online incivility is subtly amplified through humour and play, and how Gen Z and young children became both objects and producers of these dogshows. We argue that while there is already peer surveillance at work on TikTok, there needs to be more deliberation between TikTok's policies and at-risk groups to make the platform a more civil space.
Historicising Mauritian self-determination at the International Court of Justice
Authors: Nahaboo Zaki
Published: December 2024

Between 2018 and 2019, the International Court of Justice considered whether the formation and current existence of British Indian Ocean Territory violated international law. This article reveals how three temporalities – decolonial nation-state, colonial and indigenous – shaped, and were shaped by, differing conceptions of Mauritian self-determination within the Case. In doing so, this study provides an account of previously unrecognised notions of self-determination that were formative of the recent Chagos Archipelago dispute. I argue that the British delegation recasts the meaning of Mauritian self-determination as an expression of intra-colonial rights, past and present. Furthermore, I contend that Chagossian responses to the Case advanced a notion of indigeneity as having multiple moments and sites of emergence – with corresponding rights claims that extricate self-determination from a singular period and space of injustice. These colonial and indigenous conceptions of self-determination are shown to challenge, yet ultimately become subordinated to, the familiar nation-state debates on complete/incomplete Mauritian decolonisation. A focus upon representations of time does more than uncover aspects of the recent Chagos Archipelago dispute, which were structured by novel attempts to conceptualise self-determination. This article holds wider significance for post-colonial IR. The competing registers of shaped time strove to reinforce or revise what counts as post-1960 norms of self-determination.
Alzheimer's disease-like pathology induced by Porphyromonas gingivalis in middle-aged mice is mediated by NLRP3 inflammasome via the microbiota-gut-brain axis
Authors: Zhang Pei , Liu Yan , Jin Xin , Hu Zhaoliang , Yang Jucui , Lu Haotian , Hang Taijun , Song Min
Published: December 2024

Background

Porphyromonas gingivalis ( P. gingivalis) has been found to enter the brain and induce inflammation, contributing to Alzheimer's disease (AD). P. gingivalis is also closely linked to gut dysbiosis. However, does P. gingivalis induce AD-like pathology through the microbiota-gut-brain axis? There is limited literature on this topic.

Objective

To determine the precise causal link among P. gingivalis, intestinal inflammation, and AD-related pathology.

Methods

12- to 13-month-old female C57BL/6J mice were subjected to ligature placement and oral administration of P. gingivalis over a 24-week period. Then, cognitive performance was evaluated with behavioral tests, while AD neuropathological changes, neuroinflammation, and intestinal inflammation were assessed through qPCR, immunofluorescence, and western blot, and gut microbiota was analyzed by 16S rRNA.

Results

Mice exposed to P. gingivalis showed impaired behavior in open field test, novel object recognition, and Y-maze tests. The bacterium infiltrated their brains, increasing Aβ42, AβPP, and Aβ fragments, promoting tau phosphorylation and microglial activation, and reducing levels of ZO-1, PSD95, SYP, and NeuN proteins. Inflammatory factors like NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were elevated in both brains and intestine, while ZO-1 and occludin levels decreased in intestine. P. gingivalis also altered gut microbial compositions.

Conclusions

P. gingivalis induced gut dysbiosis and activated the NLRP3 inflammasome in the intestine and brains of mice. This led to impairment of both the intestinal and brain-blood barriers, triggering neuroinflammation and promoting the progression of AD. These findings highlight the critical role of NLRP3 inflammasome activation in the microbiota-gut-brain axis in the AD-like pathology induced by P. gingivalis.
Co-creating with teachers during participatory action research: Teachers’ perceptions, researchers’ dilemmas, and some possible strategies to enhance communication in the field
Authors: Nasi Nicola
Published: December 2024

The study explores teachers’ perception of the level of involvement of academic researchers in participatory action research and outlines some possible strategies to enhance communication during the process of co-creation. Data were collected within a pilot action that involved 159 pupils and 16 teachers in a preschool and a primary school in Italy. Throughout the research process, researchers tended to limit their direct interventions in the planning and implementation of the activities in order to avoid surreptitiously shaping the activities from their epistemically authoritative position. This choice was effective in promoting teachers’ and children’s ideas and resulted in a set of activities that positively impacted everyday school life. However, the analysis of the post-hoc interviews illustrates that several teachers evaluated this posture negatively. It is argued that these negative evaluations point to a dilemma that researchers inevitably face when adopting a methodological framework based on co-creation. On the basis of this critical appraisal of teachers’ perceptions, the article outlines some implications for researchers’ professional practice and some possible strategies to improve communication in the field.
Combined valorization of industrial and post-consumer plastic waste. An industrial symbiosis approach
Authors: Volpin Marcos , Vazquez Yamila V , Barbosa Silvia E
Published: December 2024

The aim of this work is to analyze two different strategies based on industrial symbiosis (IS) approaches, for the combined valorization of plastic waste from rubber polymerization process (WSBR) and plastic from Waste Electrical and Electronic Equipment (WEEE). The proposed strategies are: (a) WSBR as compatibilizer for HIPS/ABS mixtures from WEEE; and (b) WSBR as a component in mixtures with plastics from WEEE (HIPS or ABS). In the first strategy, two different proportions of HIPS/ABS mixtures are studied using three different concentrations of WSBR onto each one. In the second one, mixtures of each plastic WEEE, ABS and HIPS, with two different amounts of WSBR are analyzed. Tensile strength and ductility of ABS with 20 wt% of WSBR, increased around 8% and 40% respectively, with respect to the ABS. Regarding tensile behavior of HIPS and HIPS with 20 wt% of WSBR, both matches up to the break of the last one at a strain of 1.5 %, approximately. Obtained results indicate that the second strategy, is the best one for the combined valorization of both plastic wastes. This conclusion is based on the fact that properties are not deteriorated in successive melt-mixing. It is completely aligned with IS approaches, combining two plastic waste, an industrial one (WSBR) and a postconsumer one (WEEE), for the obtention of new materials with appropriate properties for their use.
The Role of MIEF2 in Cisplatin Sensitivity in KIRP Patients: Insights from Four-gene Mitochondrial Fusion RNA Markers
Authors: Hou Yusong , Jiang Longyang , Liu Jing , Wang Dan , Luo Hongli
Published: December 2024

Background

Mitochondrial fusion is vital for cellular function and has been increasingly linked to cancer development. Kidney renal papillary cell carcinoma (KIRP), the second most common renal cell carcinoma, presents diverse prognostic outcomes. Identifying novel biomarkers is critical for improving prognosis and treatment response in KIRP.

Objective

This study aims to explore the gene expression associated with mitochondrial fusion and establish a novel gene signature model to predict KIRP prognosis and cisplatin sensitivity.

Methods

We analyzed RNA sequencing data and clinical records of 285 KIRP patients from The Cancer Genome Atlas (TCGA). LASSO regression identified four key mitochondrial fusion-related genes (BNIP3, GDAP1, MIEF2, PRKN). Multivariate Cox regression evaluated their association with overall survival. Risk stratification was developed based on gene expression. We assessed immunotherapy responses using checkpoint inhibitor scores, tumor mutation burden, TIDE scores, and tumor microenvironment characteristics. Cisplatin sensitivity was evaluated via correlation analysis of gene expression levels and half-maximal inhibitory concentration (IC50). In vitro loss- and gain-of-function experiments in KIRP cell lines (Caki-2, ACHN) assessed MIEF2's role in cisplatin sensitivity.

Results

The gene signature successfully stratified patients into high- and low-risk groups, with significant survival differences. The area under the ROC curve (AUC) for the risk model was 0.782. MIEF2 was notably associated with cisplatin sensitivity, confirmed through functional experiments. Patients in the high-risk group exhibited lower MIEF2 expression and increased cisplatin sensitivity.
Integrating Hedonic and Eudaimonic Perspectives of Well-Being: A Conceptual Model for Sustaining Employee Well-Being in the Remote Work Context
Authors: Chingan Thottathil Shilpa , Nandakumar M. K.
Published: December 2024

As remote work gained popularity in the wake of the pandemic and is expected to continue to be a significant part of future workplaces, the issues of lower well-being and organizational commitment in employees have come to the forefront. Despite its benefits, these challenges hinder the long-term adoption of remote work. Research has yet to explore strategies for maintaining well-being and commitment in remote settings through dual aspects of well-being. In this study, following a conceptual approach, we integrate two distinct and complementary approaches to well-being, Hedonic and Eudaimonic, in the remote work context, using the overarching framework of the conservation of resources theory. It contributes to the literature by addressing dual aspects of well-being in remote work and expands understanding of employee engagement and workplace spirituality in remote work contexts. The study offers practical insights for organizations and employees to sustain well-being and commitment in remote work environments.
Cancer and Stress: Understanding the Connections and Interventions
Authors: D'Andre Stacy D. , Ellsworth Lisa L. , Kirsch Janae L. , Montane Heather N. , Kruger Margaret B. , Donovan Kristine A. , Bronars Carrie A. , Markovic Svetomir N. , Ehlers Shawna L.
Published: December 2024

Stress is ubiquitous in our modern society and contributes to many disease states. This narrative review describes the effect of stress/distress on cancer development and progression. Seminal randomized controlled trials, systematic reviews/meta-analyses, and distress management guidelines from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the Society for Integrative LinearOncology (SIO) are highlighted. We describe the physiological effects of distress, distress assessment, and management. Psychological treatments are summarized. Evidence-based lifestyle modifications and integrative therapies are reviewed in detail, including mindfulness-based techniques, yoga, guided imagery, breathing techniques, hypnosis, exercise, music therapy, qigong/Tai Chi, eye movement desensitization and reprocessing, and improving sleep and heart rate variability. Recognition and treatment of distress can improve quality of life. More research is needed to determine the effects of managing distress on cancer outcomes, as well as the best type and duration of intervention, noting that the benefits of interventions may be specific for patients with different cancer types.
How stable are taste-shape crossmodal correspondences over time?
Authors: Tabassum Farhana , Chuquichambi Erick G , Spence Charles , Munar Enric , Velasco Carlos
Published: December 2024

The present research investigates the stability of taste-shape crossmodal correspondences (i.e., how people non-randomly associate tastes and visual shapes, such as sweetness matched to roundness) over time, exploring the temporal dimension of crossmodal interactions. While previous research has established the existence of various taste-shape crossmodal correspondences, this study addresses their consistency over time through a test-retest paradigm. Drawing parallels with the concept of synesthesia, in which stability is used as a criterion, the research focuses on taste-shape associations, a domain not previously explored for temporal stability. Participants rated the perceived curvature and symmetry that they associated with taste words (sweet, umami, sour, salty, and bitter) and their liking of tastes and shapes. The same participants performed this task three times over a 2-week period. The results consistently replicated previous findings, revealing that sweet tastes were perceived as significantly more curved and symmetrical than other tastes, and umami was rated as more curved and symmetrical than sour, salty, and bitter tastes. Notably, the study found moderate-to-substantial test-retest reliability for the majority of the taste-shape correspondences, indicating robust stability over time. Analyses suggested that differences in assessments between test and retest sessions were primarily due to random error, with no systematic biases. However, a small subset of participants showed significant differences from other participants in their associations, particularly for umami-related correspondences. This research contributes to our understanding of taste-shape correspondences by demonstrating their temporal stability, offering insights into the dynamics of taste, curvature, symmetry, and liking. We posit that consistency might be used as a criterion supporting the existence of a given crossmodal correspondence. The findings have implications for product design and marketing, emphasising the importance of considering temporal aspects when capitalising on crossmodal correspondences in creating product expectations and experiences.
Accessing distant analogues over surface matches: How efficient is our retrieval system?
Authors: Trench Máximo , Tavernini Lucía M , Minervino Ricardo A
Published: December 2024

A crucial aspect of human memory concerns the ability to retrieve analogous situations whose individual objects do not resemble those of the cues (distant analogues). Recent studies using a cued-recall paradigm suggest that distant analogues are more frequently retrieved than disanalogous situations that maintain a small set of object similarities with the cues (objects-only (OO) matches). In the first experiment of the present study, one condition had a distant analogue compete in long-term memory with an OO match involving a higher number of object similarities than in prior research. In another condition, the distant analogue competed in memory with a situation whose individual objects and first-order relations resembled those of the target (R+O matches) but yielded partial structural similarities that were insufficient for projecting meaningful inferences. Experiment 2 replicated this procedure with distant analogues whose similarity with the target only became apparent at higher levels of abstraction. In both experiments, retrieval rates of distant analogues were similar to those of OO matches, lower than those of R+O matches, and lower when competing against R+O matches than against OO matches. These results bear important implications for the current debate about the adequacy of our memory systems for the prospects of analogical transfer.
Assessing the completeness of patient-reported outcomes reporting in congestive heart failure clinical trials
Authors: Rorah Drayton , Pollard Jonathan , Walters Corbin , Roberts Will , Hartwell Micah , Hemmerich Christian , Vassar Matt
Published: December 2024

Objective:

We aim to evaluate the quality of patient-reported outcomes included in randomized control trials for the treatment of congestive heart failure using the International Society for Quality of Life Research (ISOQOL) checklist, a validated tool for critically appraising the quality of patient-reported outcomes.

Design:

We performed a cross-sectional analysis of 65 randomized control trials with patient-reported outcomes for drug intervention trials for treating congestive heart failure.

Setting:

N/A.

Participants:

N/A.

Main outcome measures:

The primary outcome of this study was to evaluate the reporting completeness of patient-reported outcomes in congestive heart failure clinical trials with drug interventions according to the ISOQOL checklist.

Results:

Our search returned 1114 studies, of which, 65 are included in the analysis. The average completion of the ISOQOL reporting standards was 44.51%. Higher completion of the ISOQOL patient-reported outcome standards was observed in the clinical trials with patient-reported outcomes as primary endpoints compared to the clinical trials with patient-reported outcomes as a secondary endpoint. The multivariable regression model showed that clinical trials with patient-reported outcomes as a primary endpoint had a 21.46% better completion percentage ( t = 4.45, p ⩽ 0.001) when controlling for PRO recording duration and trial registration. Eight (8/65, 12.31%) of the clinical trials met the satisfaction criteria of completing two-thirds of the ISOQOL patient-reported outcomes reporting standards. All of these RCTs had a patient-reported outcome as a primary endpoint.

Conclusion:

Our analysis of the reporting of patient-reported outcomes in congestive heart failure clinical trials with drug interventions suggests that the quality of reporting is suboptimal. This evidence of substandard reporting of patient-reported outcomes is disconcerting as it reduces the transparency of randomized control trials, which are considered the foundation of evidenced-based medicine. Inadequate reporting may result in clinicians implementing misrepresented or incomplete evidence into clinical practice. Validated reporting tools, such as the ISOQOL, can be used by trialists and clinicians alike to improve and critically appraise the reporting of patient-reported outcomes in randomized control trials.

Trial registration:

N/A.
Altered orbitofrontal and pars opercularis cortical thickness in betel quid dependence chewers
Authors: Fu Li Li , Chen Hui Juan , Huang Wei Yuan , Guo Yi Hao , Liu Li Ting , Fu Qing Qing , Qin Hao Dong , Liu Tao , Chen Feng
Published: December 2024

Background:

Altered cerebral cortex’s structural organization has been found in individuals with betel quid dependence (BQD). However, the neurological underpinnings of the BQD-related abnormalities in cortical thickness and brain circuitry deficit are largely unknown.

Objective:

This study aimed to investigate potential abnormalities of brain circuitry in the cortical thickness of BQD individuals by applying the surface-based morphometry (SBM) method.

Design:

Cross-sectional study.

Methods:

High spatial resolution, three-dimensional T1-weighted structural imaging data were collected from 53 individuals with BQD and 37 healthy controls (HCs) who were similar to the BQD group in terms of age, sex, and educational level. The SBM method was applied to analyze the cortical thickness alterations in BQD-related areas. Independent-samples t-test was used to assess the cortical thickness difference between the two groups. Pearson correlation analysis was used to investigate the correlation between cortical thickness changes and clinical characteristics, including BQD scale scores and duration of BQD.

Results:

The BQD group had a higher cortical thickness than the HC group at the lateral orbitofrontal ( t = 4.703, p = 0.0028) and pars opercularis ( t = 3.602, p = 0.0403) clusters in the right cerebral hemisphere, with age, sex, and education duration as covariates ( p < 0.05, Monte Carlo). There were no significant differences in age, sex, or education duration-adjusted cortical thickness of the left cerebral hemisphere between BQD chewers and HCs ( p > 0.05, Monte Carlo). Correlation analysis revealed that the cortical thickness of the right pars opercularis was negatively correlated with the BQD duration ( r = −0.274, p = 0.047). The cortical thickness of the right lateral orbitofrontal cluster was not significantly correlated with Betel Quid Dependence Scale (BQDS) or BQD duration ( p > 0.05).

Conclusion:

This study demonstrated that BQD might be associated with changes in the orbitofrontal and pars opercularis cortical thickness, which may be related to the neurobiological basis of BQD.
Hyperthyroidism and fulminant myocarditis in an adolescent with iodine-induced hyperthyroidism: A case report
Authors: Lai Teng Fang , Liu ZhengJiang
Published: December 2024

This paper describes the case of a 15-year-old male patient who exhibited chest distress and pain following an upper respiratory tract infection. Upon admission, the patient exhibited elevated levels of myocardial enzymes and troponin I. Electrocardiography revealed an acute inferior myocardial infarction. Coronary computed tomography angiography ruled out coronary stenosis; however, cardiac magnetic resonance imaging revealed myocardial congestion and edema. Subsequent examinations revealed increased thyroid hormone levels and decreased thyroid-stimulating hormone levels, which is consistent with the manifestations of hyperthyroidism. The patient was diagnosed with acute fulminant myocarditis accompanied by iodine-induced hyperthyroidism. The patient received no pharmacologic treatment for hyperthyroidism but was prescribed a low-iodine diet, medication, and supportive treatment. His myocardial enzymes and troponin I levels gradually decreased, his electrocardiography and echocardiography results improved, and his cardiac function returned to normal. The patient was discharged and advised to maintain a low-iodine diet. At the 6-month follow-up, the patient’s thyroid function and cardiac indicators had returned to normal. This case demonstrates that myocardial injury can result from myocarditis and iodine-induced hyperthyroidism and highlights the importance of closely monitoring and assessing thyroid function during treatment.
The impact of digital skills on health: Evidence from the China General Social Survey
Authors: Qin Cheng , Zhu Yuchen , Li Donglin , Liu Can
Published: December 2024

Objective

The widespread penetration of the internet and digital technology have profoundly impacted the global economy and people's lives. Although the impact of digital skills on social development and personal lifestyles is well-documented, their influence on health and health inequalities remains underexplored. This study aims to analyze the impact of digital skills on health and health inequalities and to investigate the underlying mechanisms.

Methods

This study utilized cross-sectional data from the 2017 China General Social Survey ( N = 2195). We employed the Ordered Probit (O-Probit) model and ordinary least squares regression to examine the impact of digital skills on health and explore the underlying mechanisms. Health inequalities across different groups were measured using the health concentration index.

Results

Enhancing digital skills enhances population health by boosting economic status, increasing social participation, and improving access to information. However, the impact varies by age and residence. Digital skills have a stronger effect on the health of young and middle-aged individuals, as well as urban residents, compared to older adults and rural populations. Furthermore, digital skills exacerbate health inequalities, benefiting high-income groups and widening the gap between income levels.

Conclusions

Widespread promotion and continuous improvement of digital skills are key to enhancing public health. We need to focus on the popularization of digital skills and the construction of digital infrastructure for low-income disadvantaged groups and rural areas, as well as use various means to reduce group and regional differences in the impact of digital skills on health conditions.
Exploring the complexities of epigenetics in multiple sclerosis: A study involving meta-analysis of DNA methylation profiles, epigenetic drift, and rare epivariations
Authors: Baldrighi Giulia Nicole , Cavagnola Rebecca , Sacco Davide , Costantino Lucy , Bernardinelli Luisa , Gentilini Davide
Published: December 2024

Background

Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory and neurodegenerative traits. Recently, DNA methylation has emerged as a promising field of investigation for elucidating dynamics characterizing MS development and progression.

Objectives

This study aimed to comprehensively investigate the role of epigenetics in MS by analyzing the methylation profiles from blood and brain tissues from public datasets.

Methods

Employing a meta-analytical framework for differential methylation analyses, the study extended beyond conventional analyses to explore additional dimensions of epigenetic regulation, including epigenetic drift, age acceleration, and rare epivariations.

Results

Results of the differential methylation analysis were in line with previously reported findings. No significant differences were observed in age acceleration or global epigenetic drift between MS cases and controls. However, upon closer analysis at the gene level, distinctive patterns of epigenetic drift emerged, particularly within genes implicated in neural biological functions.

Conclusions

These findings underscore the role of epigenetic modifications in shaping MS pathology. Furthermore, the study unveiled the exclusive presence of rare epivariations within the MS cases, some of which involved genes previously linked to MS or other autoimmune diseases. This highlights the potential significance of rare genetic aberrations in driving MS susceptibility and progression.
Lumbar Spinal Fusion Outcomes in Patients With Cancer Compared to Matched Peers Without Cancer
Authors: Gallagher Ryan S. , Karsalia Ritesh , Xu Emily , Wathen Connor A. , Borja Austin J. , Na Jianbo , Collier Tara , McClintock Scott , Malhotra Neil R.
Published: December 2024

Study Design

Retrospective Matched Cohort Study.

Objectives

Optimization of medical comorbidities is an essential part of preoperative management. However, the isolated effects of individual comorbidities have not been evaluated within a homogenous spine surgery population. This exact matching study aims to assess the independent effects of cancer on outcomes following single-level lumbar fusions for non-cancer surgery.

Methods

4680 consecutive patients undergoing single-level posterior-only lumbar fusion were retrospectively enrolled. Univariate statistics and coarsened exact matching (CEM) were computed to evaluate outcomes between cancer patients and those without comorbidities.

Results

By logistic regression, malignancy conferred a higher risk of surgical complication ( P = 0.016, OR = 2.64, CI = [1.200,5.790]), 30- and 90- day readmission ( P = 0.012, OR = 2.025, CI = [1.170-3.510]; P < 0.001, OR = 2.34, CI = [1.430, 3.830], respectively), 90-day reoperation ( P < 0.001, OR = 2.16, [1.110, 4.200]), and death at 90-days ( P = 0.032, OR = 8.27, CI = [1.200, 56.850]). After matching, malignancy was associated with increased odds of incidental durotomy (6 vs 0 cases, P = 0.048) and death at both 30 and 90 days (both: OR = 8.0, P = 0.020, CI = [1.00, 63.960]). No cases of durotomy occurred in cases with mortality in the matched sample, suggesting independent relationships. There were no differences in length of stay, non-home discharge, ED evaluation, readmission, or reoperations.

Conclusion

Among otherwise exact-matched patients undergoing single level lumbar fusion, history of malignancy conferred a higher risk of short-term mortality, but not other outcomes suggestive of surgical failure. Increased mortality after lumbar fusion should be studied further and may play a role in surgical decision-making and patient discussions.
Inclusive Marketing Communication with Specific Reference to LGBTQ: A Review of Literature and Directions for Future Research
Authors: Srivastava Juhi , Malik Nishtha , Tripathi Shalini Nath
Published: December 2024

The purpose of this study is to explore the existing literature on how inclusive marketing communication targets LGBTQ individuals (lesbian, gay, bisexual, transgender and queer). This study has used SLR and bibliometric analysis to gain in-depth understanding of the topic. Data were extracted from Scopus database as it is one of the most widely used databases across the world and a total of 174 papers qualified the criteria. The findings of this study stated important insights on information like country collaborations, growth of topic undertaken across years, trending topics and so on. Clusters were also identified which helped in identifying trending topics and area of studies which yet needs to be focused. Moving forward, this study compiled all the information to identify future research gaps and implications for academicians as well as practitioners. It is among the few studies which have explored the importance of inclusive marketing specially focusing on LGBTQ individuals. This study has suggested agendas for future advertising research. Also, with evolving role of inclusive marketing, organizations need to re-think and re-position themselves in the market to survive; hence, this study also provides future research agendas for practitioners to understand global trends of consumer behaviour.
Risk and Prognosis of Hamstring Injuries in the National Football League: A 12-Year Review
Authors: Jenkins Ryne , Bianchi John , Watson Jeremy , Shinners Jason , Jaisinghani Pooja , Spain Brett , Ruotolo Charles
Published: December 2024

Background:

Hamstring injuries can have a significant burden on a professional football player's career and performance. One in 4 players will suffer a lower extremity strain in their career, with the hamstring being the most common. These injuries are often fraught with extended periods of recovery and reinjury rates varying between 16% and 38%.

Purpose:

To determine the progression and duration of hamstring injury as well as risk factors and probability of reinjury in the National Football League (NFL).

Study Design:

Descriptive epidemiology study.

Methods:

Data were extracted from the official publicly accessible NFL database of injuries. NFL players suffering a hamstring injury during the study period of 2008-2020 were identified. Injuries were reported weekly as mandated by the NFL. Players were deemed cleared from injury when no longer listed in the injury report (IR). Reinjury was defined as any subsequent hamstring injury after a player's initial injury. The duration of injury and factors associated with injury were analyzed. Secondary objectives included team-specific injury rates and timing of injury.

Results:

A total of 2101 hamstring injuries occurred among 1354 players. The mean duration of the IR was 2.4 ± 2.1 weeks. A total of 442 (33%) players suffered subsequent reinjury, 27% of which occurred during the same season. The mean duration on the IR for reinjury was 2.4 ± 1.8 weeks, with no significant difference in duration compared with initial injury (2.4 ± 1.8 vs 2.2 ± 1.7; P = .138). Defensive skill players were most frequently injured (50.4%) followed by offensive skill players (37.7%). Of the 4812 total IR listings, 1806 (38%) did not participate in practice. A total of 1590 (33.5%) had limited participation in practice, and 1353 (28.5%) had full participation in practice. Injury rates among teams varied and ranged from 0.6% (Baltimore Ravens) to 5.7% (Houston Texans), with a median of 3.1% ( P < .0001).

Conclusion:

Hamstring injuries can have a lasting impact on a player's career with more than a third of players suffering subsequent reinjury. Although suffering a hamstring injury predisposes a player to reinjury, previous injury was not associated with longer recovery times. Rates of injury among organizational teams vary; thus, further research to understand the difference in preventive measures and treatment protocols may be warranted.
Comparison of Clinical Outcomes Between Arthroscopic Rotator Cuff Repair and Reverse Total Shoulder Arthroplasty in Patients With Massive Rotator Cuff Tears and High-Grade Fatty Atrophy Without Glenohumeral Osteoarthritis
Authors: Gonzalez-Morgado Diego , Hoffman Tammy R. , Ardebol Javier , Noble Matthew B. , Galasso Lisa A. , Nugent Matthew , Phillips Cameron , Denard Patrick J.
Published: December 2024

Background:

Despite the effectiveness of reverse total shoulder arthroplasty (RSA) and arthroscopic rotator cuff repair (ARCR) for treating massive rotator cuff tears (MRCTs), controversies remain in patients without glenohumeral osteoarthritis (GHOA).

Purpose:

To compare clinical outcomes of ARCR or RSA in patients with MRCT with high-grade fatty atrophy without GHOA.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

This was a retrospective study on patients with MRCTs without GHOA and with grades 3 or 4 Goutallier muscle changes who underwent ARCR or RSA, with a minimum 2-year follow-up. Range of motion (ROM) and patient-reported outcomes (PROs) were collected—including visual analog scale for pain, American Shoulder and Elbow Surgeons score, Veterans Rand 12-Item Health survey, and Subjective Shoulder Value. Postoperative results were compared based on rotator cuff tendon healing in the ARCR group.

Results:

A total of 81 patients met the study criteria—56 underwent ARCR and 25 underwent RSA. Patients in the RSA (age, 71.7 ± 7.7 years) group were older than those in the ARCR (age, 66.7 ± 7.4 years) group ( P = .01) and more likely to have pseudoparalysis (52% vs 21.4%; P = .016). The mean follow-up for the ARCR and RSA groups was 56.5 ± 19 months and 36.1 ± 7.6 months, respectively ( P < .001). The rate of patients with ≥2 tendons with grade 3 or 4 changes was higher in the RSA group compared with the ARCR group: 96% versus 47% ( P < .001). PROs significantly improved after surgery in both groups ( P < .05). Postoperative forward flexion (FF) and internal rotation were higher after ARCR compared with RSA—144°± 22° versus 113°± 25° and L3 ± L4 versus S1 ± S2, respectively ( P <.001 and P = .002, respectively). Also, 31 of the rotator cuff repairs (55%) healed. PROs were similar between the healed and unhealed ARCR groups, with the only difference observed in postoperative FF—150°± 18° in the healed group versus 136°± 26° in the unhealed group ( P = .044).

Conclusion:

Both ARCR and RSA improved functional outcomes in patients with MRCT without GHOA. While healing was moderate after ARCR, the postoperative ROM was greater after ARCR compared with RSA in appropriately selected patients. Moreover, healed rotator cuffs demonstrated improved postoperative FF compared with unhealed repairs.
Implementation of a Privilege and Resilience Walk in Health Professions Education: Experiences, Insights, and Reflections
Authors: Patel Premal , Kutac Julie
Published: December 2024

The privilege walk (PW) has gained traction as a method to raise awareness of privilege and vulnerability across various settings. This experiential activity involves participants responding to statements about their identities and backgrounds by stepping forward or backward, illustrating disparities in social advantage. The PW can contribute to self-awareness, the recognition of diversity, and the cultivation of compassion among health profession students. However, concerns about potential emotional and moral harms have prompted strong criticism. To address these concerns, the authors have integrated a resilience walk (RW) alongside the PW as a curricular addition for healthcare learners. The RW focuses on strengths and protective skills individuals have developed to overcome challenges, providing a balanced perspective. By conducting the PW and RW sequentially and facilitating a brave discussion afterward, facilitators can offer learners a more comprehensive opportunity to reflect on their identities, privileges, and strengths within a supportive environment. The authors provide insights into curricular integration of the PW and RW, effective facilitator training, and navigating the possible range of student reactions during the debrief. Further qualitative research should assess student perceptions and outcomes, enabling educators to optimize their use within healthcare education.
A conceptual framework for assessing implementation strategy integrity
Authors: Molfenter Todd , Ducharme Lori , Stein Lynda , Belenko Steven , Mitchell Shannon Gwin , Watson Dennis P. , Aalsma Matthew C. , Friedmann Peter D. , Becan Jennifer E. , Garner Bryan R. , Vechinski Jessica , Bouris Alida , Claypool Emily , Elkington Kate
Published: December 2024

Background

The outcomes of planned implementation efforts have been mixed, with some applications failing to achieve the desired change or impact. While reasons for mixed findings in implementation research are multifaceted (e.g., Damschroder et al., 2009, 2022), how the implementation strategy (IS) was deployed (i.e., integrity) and its impact on the implementation outcomes of evidence-based innovations (EBIs) is under-studied and warrants further clarification.

Method

This article builds on the IS fidelity and mechanisms of change literature to create the Implementation Strategy Integrity Framework (ISIF). The ISIF was developed by a set of implementation science researchers in the Justice Community Opioid Innovation Network seeking to document the role of implementation strategies in influencing EBI outcomes.

Results

The authors identified four areas of documentation and measurement to examine the role of IS integrity on EBI outcomes. (a) Implementation Strategy Rigor (i.e., adherence, dose, and quality) requires those implementing the strategy/strategies to specify them, document adherence to the planned strategies, quality of execution, and any adaptations made. (b) Target User Responsiveness documents the extent and quality of targeted users’ participation in IS activities and how well the target users perform their roles in conducting actions intended by the implementation strategies. (c) Target Mechanism Activation notes to what degree the implementation strategies achieved the intended impact(s) on targeted factors that facilitate EBI use. Finally, (d) these three areas are combined with selected Inner and Outer Context variables to explain IS integrity’s potential moderating and mediating effects on EBI outcomes.

Conclusions

A framework that can define the integrity of an IS and allow for its subsequent use as an explanatory variable in EBI outcomes is necessary for better elucidating mechanisms of action. The ISIF offers a structured approach to operationalize, measure, and evaluate the application and related impacts of implementation strategies.
Whose values? From the discrete to the continuous in how place and space matter in valuation studies
Authors: Keith Michael
Published: December 2024

This collection provides some invaluable insight on the interface between the academic discipline of Geography and studies of values and valuation. This article suggests that the tension between the normative and the analytical dimensions of these terms in man pieces is best rooted in the subdiscipline of economic sociology associated with scholars such as Boltanski and Thevenot, Mackenzie, Muniesa and Stark. It goes on to highlight how the geographical tradition might be best served by developing less an argument about why ‘space matters’ and more the sense in which affordances and propensities invoke the temporal and the spatial simultaneously, a framing that echoes Latour’s characterisation of ‘timespace’. This argument is illustrated with reference to the notion of urban fabric as an exemplar of what Latour characterises as the ‘fifth dimension’.
Impact of Malnutrition on Patients with Sickle Cell Anemia Hospitalized with Vaso-Occlusive Crisis: A US Collaborative Network Cohort Study
Authors: Byfield Karecia , Jones Colton Frisco , Obomanu Elvis , Syal Arshi , Arya Yajur , Mayo Ryan J
Published: December 2024

Background

Malnutrition is frequently seen in patients with sickle cell anemia (SCA). It is associated with a weakened immune system and reduced pain threshold, increasing the risk of vaso-occlusive pain crises (VOC). However, its impact on the clinical outcomes of patients hospitalized for vaso-occlusive crises remains unclear. Therefore, we conducted a national-level cohort study to elucidate these outcomes.

Methods

We used data from the US Collaborative Network-TriNetX to evaluate the impact of malnutrition on patients with SCA who were hospitalized for VOC. Patients were divided into two cohorts: those with malnutrition, identified by the relevant ICD-10 codes, and those without. The malnutrition cohort was propensity score matched with a control group based on age, sex, gender, and various comorbidities. They were followed for 30 days post-hospitalization to assess outcomes such as mortality, need for transfusion, splenic infarction, stroke, myocardial infarction, acute kidney injury, and readmission.

Results

After propensity score matching, each cohort consisted of 1,517 patients with similar baseline characteristics. The mean age for both cohorts was 32 years, with the malnutrition cohort being 51% female and the non-malnutrition cohort 53% female. The ethnic distribution was 67% Black, 12% White, and the remainder of unknown ethnicity. Our analysis found that within 30 days post-hospitalization, the cohort with malnutrition had a significantly higher risk of mortality (RR: 3.05, 95% CI: 1.93-4.81, P<0.001), need for blood transfusion (RR: 2.17, 95% CI: 1.68-2.81, P<0.001), ischemic stroke (RR: 1.98, 95% CI: 1.07-3.69, P<0.001), and myocardial infarction (RR: 1.97, 95% CI: 1.12-3.46, P<0.001). There was also an increased risk of acute kidney injury (RR: 2.57, 95% CI: 1.94-3.41, P<0.001) and readmission (RR: 2.34, 95% CI: 2.00-2.74, P<0.001). There was no significant difference in the occurrence of acute chest syndrome or splenic infarction.

Conclusion

Our study reveals that malnutrition in patients with SCA hospitalized for VOC is significantly associated with a heightened risk of adverse outcomes, including increased mortality, ischemic stroke, myocardial infarction, and acute kidney injury. A multidisciplinary approach to managing malnutrition in sickle cell anemia is essential to improving survival and outcomes in these patients.