bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unseen Strain: Investigating the Awareness of Rhinoplasty Surgeons Regarding Their Spine Health
Authors: Alzayadneh Islam , Hamdan Omar , Alzayadneh Lana , Al-Zu’bi Belal , Glikson Eran , Almusaileem Nisreen , Rival Ella , Solomon Philip
Published: January 2024

Background

Musculoskeletal pain is a common occupational health problem among surgeons that can affect work productivity and quality of life.

Objectives

The aim of the study was to investigate the prevalence and causes of back pain among rhinoplasty surgeons, evaluate their routine practice, and identify unique risk factors. A further goal was to measure functional disabilities with the Total Disability Index (TDI) questionnaire.

Methods

A structured online questionnaire was distributed to plastic surgeons performing rhinoplasty internationally. The questionnaire comprised sections on biodata, routine practice posture, length of practice, surgical duration, and the history of surgery or hospitalization related to these issues. In the second part of the survey, participants were asked to complete the TDI questionnaire.

Results

The prevalence of back pain was reported by 93.6% of surgeons, with low back pain being the most common (76.7%). The average pain intensity for low back pain was 44.8 ± 26.8. The mean TDI score was calculated as 31 ± 12.1, with 58.2% of surgeons experiencing mild to moderate disability. Significant associations were found between musculoskeletal pain severity and disability index and factors such as BMI, exercise, years of rhinoplasty practice, number of surgeries performed per week, and average procedure length. Interestingly, only 16.4% of rhinoplasty surgeons had previous ergonomic training or education.

Conclusions

Musculoskeletal issues related to the spine are prevalent among rhinoplasty surgeons. It is imperative to educate surgeons about this underestimated health problem, provide proper physical rehabilitation targeting ergonomic concerns, and make changes to current practices to address this issue effectively.

Level of Evidence: 5
Testing ‘bigger is better’ and maternal effects hypotheses in hatchlings of the sexually dimorphic spiny softshell turtle (Apalone spinifera)
Authors: Porter Eden , Paterson James E , Davy Christina M
Published: January 2024

The ‘bigger is better’ hypothesis (BIBH) predicts that fitness increases with body size. Eastern spiny softshell turtles (Apalone spinifera) exhibit sexual size dimorphism (SSD) at maturity, and the much larger female body size is attributed to selection favouring greater reproductive output. Hatchlings exhibit sexually dimorphic markings, but hatchling SSD has not been investigated. The BIBH predicts that hatchlings will not exhibit SSD because reproductive benefits to larger, mature females drive size dimorphism at maturity, but selection on hatchlings relates only to survival. We tested this prediction with A. spinifera hatchlings (N = 2630) incubated in controlled conditions to avoid confounding environmental effects on phenotype. Hatchling mass was similar between sexes, suggesting similar nutritional allocation to male and female offspring. Hatchling size (carapace length) was also similar between sexes. Hatchling mass and body size varied among clutches and were positively related to maternal size, suggesting morphological constraints on egg size. Surprisingly, clutch size was related only weakly to maternal size. Taken together, our results suggest that hatchling size in A. spinifera is consistent with the BIBH and that offspring quality increases with maternal age, but that maternal effects drive a large proportion of the variation in clutch size and offspring quality.
Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation
Authors: Muñoz-Oreja Mikel , Sandoval Abigail , Bruland Ove , Perez-Rodriguez Diego , Fernandez-Pelayo Uxoa , de Arbina Amaia Lopez , Villar-Fernandez Marina , Hernández-Eguiazu Haizea , Hernández Ixiar , Park Yohan , Goicoechea Leire , Pascual-Frías Nerea , Garcia-Ruiz Carmen , Fernandez-Checa Jose , Martí-Carrera Itxaso , Gil-Bea Francisco Javier , Hasan Mazahir T , Gegg Matthew E , Bredrup Cecilie , Knappskog Per-Morten , Gereñu-Lopetegui Gorka , Varhaug Kristin N , Bindoff Laurence A , Spinazzola Antonella , Yoon Wan Hee , Holt Ian J
Published: January 2024

Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, and mitochondria have been linked to perturbed cholesterol homeostasis via the study of pathological mutations in the ATAD3 gene cluster. However, whether the cholesterol changes were compensatory or contributory to the disorder was unclear, and the effects on cell membranes and the wider cell were also unknown.

Using patient-derived cells, we show that cholesterol perturbation is a conserved feature of pathological ATAD3 variants that is accompanied by an expanded lysosome population containing membrane whorls characteristic of lysosomal storage diseases. Lysosomes are also more numerous in Drosophila neural progenitor cells expressing mutant Atad3, which exhibit abundant membrane-bound cholesterol aggregates, many of which co-localize with lysosomes. By subjecting the Drosophila Atad3 mutant to nutrient restriction and cholesterol supplementation, we show that the mutant displays heightened cholesterol dependence.

Collectively, these findings suggest that elevated cholesterol enhances tolerance to pathological ATAD3 variants; however, this comes at the cost of inducing cholesterol aggregation in membranes, which lysosomal clearance only partly mitigates.
British Association of Dermatologists national clinical audit on the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in adults
Authors: Tasker Fiona , Smith Stephen P , Mohd Mustapa M Firouz , de Berker David A R
Published: January 2024

Background

UK guidelines for managing adults with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), published by the British Association of Dermatologists (BAD) in 2016, outline a set of audit standards.

Objectives

To audit current management of SJS/TEN in adults against standards in the BAD guidelines.

Methods

BAD members were invited to submit data on five consecutive adults with SJS/TEN per department over an 8-week period in 2022.

Results

Thirty-nine dermatology centres in the UK (29%) participated, and data for 147 adults with SJS/TEN were collected. Within 24 h of the diagnosis being made or suspected, the following were documented, per 147 submitted cases: Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN) for 76 (52%), list of medications for 113 (77%) and timelines for commencement/alterations of medications for 104 (71%). The initial assessment was documented of the eyes by an ophthalmologist in 71 (48%), of the mouth in 130 (88%), of the genital skin in 103 (70%) and of the urinary tract in 93 (63%). During the first 10 days after a suspected or confirmed diagnosis of SJS/TEN, daily assessments of the mouth were documented in 26 of 147 cases (18%), of the eyes in 12 (8%), and of the urinary tract and genital skin in 14 (10%). At discharge, a drug was declared to be the cause of SJS/TEN for 130 of 147 cases (88%), while 9 (6%) were thought to be secondary to infection. Eleven of 147 (8%) had no response to this question. Documentation regarding advice was present on avoidance of the culprit drug in 76 of 130 declared SJS/TEN cases (58%), and on requesting a MedicAlert® bracelet/amulet in 9 of the 147 cases (6%).

Conclusions

This audit suggests that a clinical review checklist might be needed to enable colleagues to maintain standards outlined in the guidelines, including documentation of SCORTEN, daily assessments of mucosal areas, and advice to avoid culprit drug(s) and to request a MedicAlert® bracelet/amulet.
Proposal of a new model of national skin audit and data submission
Authors: Ali Stephen R , Dobbs Thomas D , Whitaker Iain S
Published: January 2024

This article discusses the role of multidisciplinary teams in improving data flow to cancer registries and the inefficiencies of current retrospective data entry methods. It proposes a novel model using a rule-based natural language processing technique for basal cell carcinoma, integrating real-time analysis and structured data presentation to enhance national skin audit and data submission. The model faces challenges like varied reporting styles and the need for common ontologies but aims to fill a gap in dermatology and plastic surgery audits, improving healthcare quality through precise and timely data analysis.
Glucose–oxygen coupling can serve as a biomarker for neuroinflammation-related genetic variants
Authors: Yang Ze , Sheng Jinhua ,   IET Fellow, Zhang Qiao , Xin Yu , Wang Luyun , Zhang Qian , Wang Binbing
Published: January 2024

The single-nucleotide polymorphism rs3197999 in the macrophage-stimulating protein 1 gene is a missense variant. Studies have indicated that macrophage-stimulating protein 1 mediates neuronal loss and synaptic plasticity damage, and overexpression of the macrophage-stimulating protein 1 gene leads to the excessive activation of microglial cells, thereby resulting in an elevation of cerebral glucose metabolism. Traditional diagnostic models may be disrupted by neuroinflammation, making it difficult to predict the pathological status of patients solely based on single-modal images. We hypothesize that the macrophage-stimulating protein 1 rs3197999 single-nucleotide polymorphism may lead to imbalances in glucose and oxygen metabolism, thereby influencing cognitive resilience and the progression of Alzheimer’s disease. In this study, we found that among 121 patients with mild cognitive impairment, carriers of the macrophage-stimulating protein 1 rs3197999 risk allele showed a significant reduction in the coupling of glucose and oxygen metabolism in the dorsolateral prefrontal cortex region. However, the rs3197999 variant did not induce significant differences in glucose metabolism and neuronal activity signals. Furthermore, the rs3197999 risk allele correlated with a higher rate of increase in clinical dementia score, mediated by the coupling of glucose and oxygen metabolism.

Highlight
Cortical and subcortical substrates of minutes and days-long object value memory in humans
Authors: Farmani Sepideh , Sharifi Kiomars , Ghazizadeh Ali
Published: January 2024

Obtaining valuable objects motivates many of our daily decisions. However, the neural underpinnings of object processing based on human value memory are not yet fully understood. Here, we used whole-brain functional magnetic resonance imaging (fMRI) to examine activations due to value memory as participants passively viewed objects before, minutes after, and 1–70 days following value training. Significant value memory for objects was evident in the behavioral performance, which nevertheless faded over the days following training. Minutes after training, the occipital, ventral temporal, interparietal, and frontal areas showed strong value discrimination. Days after training, activation in the frontal, temporal, and occipital regions decreased, whereas the parietal areas showed sustained activation. In addition, days-long value responses emerged in certain subcortical regions, including the caudate, ventral striatum, and thalamus. Resting-state analysis revealed that these subcortical areas were functionally connected. Furthermore, the activation in the striatal cluster was positively correlated with participants’ performance in days-long value memory. These findings shed light on the neural basis of value memory in humans with implications for object habit formation and cross-species comparisons.
The Influence of Subclinical Active Inflammation on IFX Pharmacokinetic Modeling and Disease Progression Assessment: Findings from a Prospective Real-World Study in Inflammatory Bowel Disease Patients
Authors: Magro Fernando , Fernandes Samuel , Patita Marta , Arroja Bruno , Lago Paula , Rosa Isadora , Tavares de Sousa Helena , Ministro Paula , Mocanu Irina , Vieira Ana , Castela Joana , Moleiro Joana , Roseira Joana , Cancela Eugénia , Sousa Paula , Portela Francisco , Correia Luís , Moreira Paula , Dias Sandra , Afonso Joana , Danese Silvio , Peyrin-Biroulet Laurent , Vucicevic Katarina M , Santiago Mafalda
Published: January 2024

Background and aims

Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study’s primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.

Methods

The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.

Results

The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression.

Conclusion

In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.
Dust and Death: Evidence from the West African Harmattan
Authors: Adhvaryu Achyuta , Bharadwaj Prashant , Fenske James , Nyshadham Anant , Stanley Richard
Published: January 2024

Using two decades of data from 12 low-income countries in West Africa, we show that dust carried by harmattan trade winds increases infant and child mortality. Health investments respond to dust exposure, consistent with compensating behaviours. Despite these efforts, surviving children still exhibit negative health impacts. Our data allow us to investigate differential impacts over time and across countries. We find declining impacts over time, suggesting adaptation. Using national-level measures of macroeconomic conditions and health resources, we find suggestive evidence that both economic development and public health improvements have contributed to this adaptation, with health improvements playing a larger role.
Advanced considerations in survival analysis
Authors: Carnero-Alcázar Manuel , Montero-Cruces Lourdes , Cobiella-Carnicer Javier , Pérez-Camargo Daniel , Maroto Castellanos Luis
Published: January 2024

Investigation of survival during the follow-up period is common in cardiovascular research and has intrinsic issues that require precise knowledge, such as survival or censoring. Besides, as the follow-up period lengthens and events other than mortality are studied, the analysis becomes more complex, so Kaplan–Meier analyses or Cox models are not always sufficient. In this primer, we provide the reader with detailed information on the interpretation of the most common survival analyses and delve into methods to analyse competing risks or alternatives to the conventional methods when the proportional hazards assumption is not met.
The non to moderately dilated root in acute type A aortic dissection: outcomes of the PENN–BERN registry in young, non-syndromic patients
Authors: Mosbahi Selim , Siepe Matthias , Desai Nimesh D , Pregaldini Fabio , Nucera Maria , Berezowski Mikolaj , Kelly John J , Jiang Fei , Zhao Yu , Szeto Wilson Y , Schoenhoff Florian S , Bavaria Joseph E
Published: January 2024

OBJECTIVES

There is an ongoing debate regarding whether patients benefit more from root replacement compared to a reconstruction of the sinuses of Valsalva in acute type A aortic dissection (aTAAD). In those with known or suspected connective tissue disorders, root replacement is considered appropriate. However, there are currently no diameter-based guidelines regarding the best approach in patients with minimally to moderately dilated root and no connective tissue disorders.

METHODS

From January 2005 to December 2022, a two-centre registry of aTAAD was created. Patients were included based on their age (≤60 years), the absence of root entry and dilatation >50 mm and the absence of syndromic hereditable aortic disease. Patients were divided into 2 groups based on the proximal procedure, root reconstruction and root replacement. Propensity score pair matching was performed based on preoperative characteristics.

RESULTS

Cumulative incidence of reintervention at 10 years was slightly higher after root reconstruction 13% vs 3.9% in the matched group (P = 0.040). Survival at 10 years was not affected by the procedure independently of the matching 72.1% vs 71.4% (P = 0.2). Uni- and multivariate Cox regressions showed that a root diameter of >40 mm was associated with a hazard ratio of 7.7 (95% confidence interval 2.6–23) and 5.4 (7–17), respectively, for reoperation for aneurysm and pseudoaneurysm.

CONCLUSIONS

Rate of reoperation due to proximal pseudoaneurysm and aneurysm could be significantly reduced with a lower threshold of 40 mm to replace the aortic root in aTAAD than in elective cases.
‘When age is not a barrier’: an explorative study of nonagenarian patients’ experiences of undergoing percutaneous coronary intervention
Authors: Instenes Irene , Fridlund Bengt , Borregaard Britt , Larsen Alf Inge , Allore Heather , Bendz Bjørn , Deaton Christi , Rotevatn Svein , Fålun Nina , Norekvål Tone M
Published: January 2024

Aims

The recent rise in the number of nonagenarians (age ≥ 90 years) undergoing percutaneous coronary intervention (PCI) has revealed gaps in research, in particular on patients’ experiences. Therefore, the aim of the study was to explore and describe nonagenarians’ internal resources and their experiences of the in-hospital pathway.

Methods and results

Nineteen nonagenarian patients (women n = 9), mean age 91 years, 9 acutely, and 10 electively treated, were consecutively enrolled from a tertiary university hospital from June 2021 to February 2023. In-depth interviews were conducted during hospitalization, audiotaped and transcribed. The interviews were analysed using qualitative content analysis. Three sub-themes emerged from the nonagenarians’ experiences with the PCI treatment trajectory: (i) Taking lifelong responsibility for own physical and mental health describes a population striving to live a healthy life and to stay independent. Physical and mental activities including healthy food choices had been an integral aspect of their lives from early childhood. (ii) Individual internal resources influenced the PCI pathway describes how their internal resources were used, from actively engaging in the decision-making process to withstanding discomfort during the PCI procedure. (iii) The post-PCI pathway was multifaceted describes a short stay at the cardiac ward with individual post-procedural experiences, close monitoring, and preparation for discharge including cardiac rehabilitation.

Conclusion

Nonagenarians undergoing PCI demonstrated a personal incentive to stay healthy and independent. Their internal resources of independence, stoicism, and resilience were used during their in-hospital stay contributing to a successful PCI procedure. Individual cardiac rehabilitation strategies were highlighted after discharge from hospital.
Preferences for innovations in healthcare delivery models in the Swiss elderly population: a latent class, choice modelling study
Authors: Nicolet Anna , Perraudin Clémence , Krucien Nicolas , Wagner Joël , Peytremann-Bridevaux Isabelle , Marti Joachim
Published: January 2024

Background

With the increasing number of people affected by multiple chronic conditions, it is essential for public-health professionals to promote strategies addressing patient needs for coordinated care. We aim to explore preference heterogeneity for better-coordinated care delivery models in Swiss older adults, and identify profiles of individuals more open to healthcare reforms.

Methods

A DCE (discrete choice experiment) survey was developed online and on paper for the Swiss adults aged 50+, following best practice. To elicit preferences, we estimated a latent class model allowing grouping individuals with similar preferences into distinct classes, and examined what background characteristics contributed to specific class membership.

Results

The optimal model identified three classes with different openness to reforms. Class 1 (49%) members were concerned with premium increases and were in favour of integrated care structures with care managed by interprofessional teams. Individuals in class 2 (19%) were younger, open to reforms, and expressed the needs for radical changes within the Swiss healthcare system. Class 3 respondents (32%) were strongly reluctant to changes.

Conclusions

Our study goes beyond average preferences and identifies three distinct population profiles, a majority open to reforms on specific aspects of care delivery, a smallest group in favour radical changes, and a third strongly against changes. Therefore, tailored approaches around healthcare reforms are needed, e.g. explaining the role of interprofessional teams in coordinating care, electronic health records and insurance premium variation.
Analysis of CRISPR–Cas loci distribution in Xanthomonas citri and its possible control by the quorum sensing system
Authors: Martins Paula Maria Moreira , Granato Laís Moreira , Morgan Túlio , Nalin Julia Lopes , Takita Marco Aurélio , Alfenas-Zerbini Poliane , de Souza Alessandra Alves
Published: January 2024

Xanthomonas is an important genus of plant-associated bacteria that causes significant yield losses of economically important crops worldwide. Different approaches have assessed genetic diversity and evolutionary interrelationships among the Xanthomonas species. However, information from clustered regularly interspaced short palindromic repeats (CRISPRs) has yet to be explored. In this work, we analyzed the architecture of CRISPR–Cas loci and presented a sequence similarity-based clustering of conserved Cas proteins in different species of Xanthomonas. Although absent in many investigated genomes, Xanthomonas harbors subtype I-C and I-F CRISPR–Cas systems. The most represented species, Xanthomonas citri, presents a great diversity of genome sequences with an uneven distribution of the CRISPR–Cas systems among the subspecies/pathovars. Only X. citri subsp. citri and X. citri pv. punicae have these systems, exclusively of subtype I-C system. Moreover, the most likely targets of the X. citri CRISPR spacers are viruses (phages). At the same time, few are plasmids, indicating that CRISPR/Cas system is possibly a mechanism to control the invasion of foreign DNA. We also showed in X. citri susbp. citri that the cas genes are regulated by the diffusible signal factor, the quorum sensing (QS) signal molecule, according to cell density increases, and under environmental stress like starvation. These results suggest that the regulation of CRISPR–Cas by QS occurs to activate the gene expression only during phage infection or due to environmental stresses, avoiding a possible reduction in fitness. Although more studies are needed, CRISPR–Cas systems may have been selected in the Xanthomonas genus throughout evolution, according to the cost-benefit of protecting against biological threats and fitness maintenance in challenging conditions.
ProbBreed: a novel tool for calculating the risk of cultivar recommendation in multienvironment trials
Authors: Chaves Saulo F S , Krause Matheus D , Dias Luiz A S , Garcia Antonio A F , Dias Kaio O G
Published: January 2024

Neglecting genotype-by-environment interactions in multienvironment trials (MET) increases the risk of flawed cultivar recommendations for growers. Recent advancements in probability theory coupled with cutting-edge software offer a more streamlined decision-making process for selecting suitable candidates across diverse environments. Here, we present the user-friendly ProbBreed package in R, which allows breeders to calculate the probability of a given genotype outperforming competitors under a Bayesian framework. This article outlines the package’s basic workflow and highlights its key features, ranging from MET model fitting to estimating the per se and pairwise probabilities of superior performance and stability for selection candidates. Remarkably, only the selection intensity is required to compute these probabilities. By democratizing this complex yet efficient methodology, ProbBreed aims to enhance decision-making and ultimately contribute to more accurate cultivar recommendations in breeding programs.
Flatworm Transcriptomes Reveal Widespread Parasitism by Histophagous Ciliates
Authors: Woodcock M Ryan , Powers Kaleigh , Snead Kirsten , Pellettieri Jason
Published: January 2024

Unicellular ciliates like Tetrahymena are best known as free-living bacteriovores, but many species are facultative or obligate parasites. These “histophages” feed on the tissues of hosts ranging from planarian flatworms to commercially important fish and the larvae of imperiled freshwater mussels. Here, we developed a novel bioinformatics pipeline incorporating the nonstandard ciliate genetic code and used it to search for Ciliophora sequences in 34 publicly available Platyhelminthes EST libraries. From 2,615,036 screened ESTs, we identified nearly 6,000 high-confidence ciliate transcripts, supporting parasitism of seven additional flatworm species. We also cultured and identified Tetrahymena from nine terrestrial and freshwater planarians, including invasive earthworm predators from the genus Bipalium and the widely studied regeneration models Dugesia japonica and Schmidtea mediterranea. A co-phylogenetic reconstruction provides strong evidence for the coevolution of histophagous Ciliophora with their Platyhelminthes hosts. We further report the antiprotozoal aminoglycoside paromomycin expels Tetrahymena from S. mediterranea, providing new opportunities to investigate the effects of this relationship on planarian biology. Together, our findings raise the possibility that invasive flatworms constitute a novel dispersal mechanism for Tetrahymena parasites and position the Platyhelminthes as an ideal model phylum for studying the ecology and evolution of histophagous ciliates.
Enhancing the health knowledge and health literacy of recently resettled refugees through classroom-based instructional methods
Authors: Agrawal Pooja , Phadke Manali , Du Nan , Hosain Fatima , Koons Leslie , Brown Camille , O’Malley Shannon , Cheng Frances Y
Published: January 2024

Health education can elevate health literacy, which is associated with health knowledge, health-seeking behaviors and overall improved health outcomes. Refugees are particularly vulnerable to the effects of low health knowledge and literacy, which can exacerbate already poor health stemming from their displacement experience. Traditional learning methods including classroom-based instruction are typically how health-related information is presented to refugees. Through a series of interactive classes focused on specific health topics relevant to the resettled refugee population, this study evaluated the effectiveness of a classroom-based health education model in enhancing the health knowledge of recently resettled refugees. We used the Wilcoxon signed-rank test to evaluate differences in pre- and post-class knowledge through test performance. We found a significant improvement in health knowledge in two refugee groups: females and those who were employed. Culturally and socially sensitive considerations including language inclusiveness, class timing, transportation and childcare provisions are important when creating an educational program for individuals with refugee backgrounds. Developing focused approaches to instruction that enhance health knowledge could lead to better health literacy and ultimately improve health-related behaviors and outcomes in the refugee population.
Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy
Authors: Liu Zhou , Julius Peter , Himwaze Cordilia Maria , Mucheleng’anga Luchenga Adam , Chapple Andrew G , West John T , Wood Charles
Published: January 2024

Background

Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis’s effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored.

Methods

To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use.

Results

The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower.

Conclusions

Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.
Loratadine as an Anti-inflammatory Agent Against Clostridium difficile Toxin B
Authors: Xie Ying , Irwin Sophie , Chupina Estrada Andrea , Nelson Becca , Bullock Ashlen , Fontenot Lindsey , Feng Hanping , Sun Mingjun , Koon Hon Wai
Published: January 2024

Background

Clostridium difficile infection (CDI) is a debilitating nosocomial infection. C. difficile produces toxins A and B, which cause inflammation. Existing therapies have issues with recurrence, cost, and safety. We aim to discover a safe, effective, and economical nonmicrobiological therapeutic approach against CDI.

Methods

We included human primary peripheral blood mononuclear cells (PBMCs), fresh human colonic explants, and humanized HuCD34-NCG mice. Toxin A+B+ VPI 10463 and A−B+ ribotype 017 C. difficile strains were used. We used single-cell RNA profiling and high-throughput screening to find actionable toxin B–dependent pathways in PBMCs.

Results

Histamine 1 receptor–related drugs were found among the hit compounds that reversed toxin-mediated macrophage inflammatory protein (MIP) 1α expression in PBMCs. We identified loratadine as the safest representative antihistamine for therapeutic development. Loratadine inhibited toxin B–induced MIP-1α secretion in fresh human colonic tissues. Oral loratadine (10 mg/kg/d) maintained survival, inhibited intestinal CCl3 messenger RNA expression, and prevented vancomycin-associated recurrence in the VPI 10463–infected mice and ribotype 017-infected hamsters. Splenocytes from loratadine-treated mice conferred anti-inflammatory effects to the VPI 10463–infected T/B-cell­–deficient Rag−/− mice. Oral loratadine suppressed human MIP-1α expression in monocytes/macrophages in toxin B–expressing ribotype 017-infected humanized HuCD34-NCG mice.

Conclusions

Loratadine may be repurposed to optimize existing therapies against CDI.
Toward Pedagogies of Decoloniality: Evaluating Teaching Practice and Syllabus Design in IR Undergraduate Modules
Authors: Clarke Helen
Published: January 2024

Undergraduate teaching in international relations (IR) primarily focuses on state-centric topics of sovereignty, anarchy, and power politics, its dominant theories governed by Western interests. However, the implementation of decolonial pedagogies requires more than simply “adding” non-Western theories to curricula. The myth of Europe must be ruptured, revealing its idealized and partisan foundations, uncovering knowledges from the interstices. This article contributes to the pedagogic literature by exploring attempts to decenter the discipline, evaluating teaching practice and syllabus design in three IR undergraduate modules. Drawing on thirty-five semi-structured interviews with lecturers and students, it argues that students benefit from the introduction of decolonial pedagogies, developing broader curricula knowledge, and, crucially, epistemic criticality. Despite these benefits, implementing decolonial praxis in 12-week modules can be challenging. The article suggests starting-points for lecturers seeking to decenter their teaching, calling for pedagogies of decoloniality to be implemented at a departmental level, with faculty and institutional support.
Measuring quality-of-care in treatment of young children with attention-deficit/hyperactivity disorder using pre-trained language models
Authors: Pillai Malvika , Posada Jose , Gardner Rebecca M , Hernandez-Boussard Tina , Bannett Yair
Published: January 2024

Objective

To measure pediatrician adherence to evidence-based guidelines in the treatment of young children with attention-deficit/hyperactivity disorder (ADHD) in a diverse healthcare system using natural language processing (NLP) techniques.

Materials and Methods

We extracted structured and free-text data from electronic health records (EHRs) of all office visits (2015-2019) of children aged 4-6 years in a community-based primary healthcare network in California, who had ≥1 visits with an ICD-10 diagnosis of ADHD. Two pediatricians annotated clinical notes of the first ADHD visit for 423 patients. Inter-annotator agreement (IAA) was assessed for the recommendation for the first-line behavioral treatment (F-measure = 0.89). Four pre-trained language models, including BioClinical Bidirectional Encoder Representations from Transformers (BioClinicalBERT), were used to identify behavioral treatment recommendations using a 70/30 train/test split. For temporal validation, we deployed BioClinicalBERT on 1,020 unannotated notes from other ADHD visits and well-care visits; all positively classified notes (n = 53) and 5% of negatively classified notes (n = 50) were manually reviewed.

Results

Of 423 patients, 313 (74%) were male; 298 (70%) were privately insured; 138 (33%) were White; 61 (14%) were Hispanic. The BioClinicalBERT model trained on the first ADHD visits achieved F1 = 0.76, precision = 0.81, recall = 0.72, and AUC = 0.81 [0.72-0.89]. Temporal validation achieved F1 = 0.77, precision = 0.68, and recall = 0.88. Fairness analysis revealed low model performance in publicly insured patients (F1 = 0.53).

Conclusion

Deploying pre-trained language models on a variable set of clinical notes accurately captured pediatrician adherence to guidelines in the treatment of children with ADHD. Validating this approach in other patient populations is needed to achieve equitable measurement of quality of care at scale and improve clinical care for mental health conditions.
Glutamine Supplementation on Burn Patients: A Systematic Review and Meta-analysis
Authors: Tao Wei , Xu Gang , Zhou Jie , Luo Yi , Li Ping-Song
Published: January 2024

To evaluate the effect of glutamine supplement on patients with burns, we conducted a systematic review and meta-analysis via synthesizing up-to-date studies. Databases including PubMed, Cochrane Central Register, EMBASE, Google scholar, Wanfang data, and ClinicalTrials.gov were searched up to October 2023 to find randomized trials evaluating glutamine supplement on patients with burns. The main outcomes included hospital stay, in-hospital mortality, infection, and wound healing. Twenty-two trials that randomized a total of 2170 patients were included in this meta-analysis. Pooled the length of hospital stay was shortened by glutamine supplement (weighted mean differences [WMD] = −7.95, 95% confidence interval [CI] −10.53 to −5.36, I2 = 67.9%, 16 trials). Both pooled wound healing rates (WMD = 9.15, 95% CI 6.30 to 12.01, I2 = 82.7%, 6 studies) and wound healing times (WMD = −5.84, 95% CI −7.42 to −4.27, I2 = 45.7%, 7 studies) were improved by glutamine supplement. Moreover, glutamine supplement reduced wound infection (risk ratios [RR] = 0.38, 95% CI 0.21 to 0.69, I2 = 0%, 3 trials), but not nonwound infection (RR = 0.88, 95% CI 0.73 to 1.05, I2 = 39.6%, 9 trials). Neither in-hospital mortality (RR = 0.95, 95% CI 0.74 to 1.22, I2 = 36.0%, 8 trials) nor the length of intensive care unit stay (WMD = 1.85, 95% CI −7.24 to 10.93, I2 = 78.2%, 5 studies) was improved by glutamine supplement. Subgroup analysis showed positive effects were either influenced by or based on small-scale, single-center studies. Based on the current available data, we do not recommend the routine use of glutamine supplement for burn patients in hospital. Future large-scale randomized trials are still needed to give a conclusion about the effect of glutamine supplement on burn patients.
The Fundamentals of Inflammatory Bowel Disease Management in Pregnancy: A Practical Review for the Gastroenterologist
Authors: Squirell Elizabeth , Meade Susanna , Leung Yvette
Published: January 2024

This narrative review explores the management of Inflammatory Bowel Disease (IBD) during pregnancy, emphasizing its unique challenges to maternal and fetal health, particularly within the Canadian Gastroenterology setting. Seven key principles are highlighted: 1) Preconception counselling, aiming for steroid-free remission confirmed by objective markers, should be routine for female IBD patients. 2) Medication safety, with an eye to future pregnancies, should be addressed upon initiation. Methotrexate and small molecules are contraindicated during pregnancy, while most 5-ASA therapies, biologics, and thiopurines can be continued throughout pregnancy and breastfeeding. Steroids, though not without risks, can be utilized if necessary. 3) Routine monitoring during remission should include serum biomarkers and fecal calprotectin each trimester. 4) Routine endoscopy and imaging are not required, but if indicated, lower GI endoscopy, ultrasound, and unenhanced MRI can be used. Computed tomography and gadolinium enhanced MRI should be avoided. 5) Caesarean section is advised for patients with previous ileal pouch surgeries or active perianal disease, but other patients should follow obstetric indications for delivery. 6) Postpartum period may see more active disease, requiring continued monitoring. Breastfeeding is encouraged, and routine childhood vaccinations are advised, but live vaccinations in the first 6 months warrant detailed review. 7) Complex IBD patients may benefit from a multidisciplinary approach with robust communication between gastroenterologists and obstetricians.
Habitat heterogeneity limits prey colour polymorphism maintained via negative frequency-dependent selection
Authors: Murali Gopal , Kodandaramaiah Ullasa , Merilaita Sami
Published: January 2024

The persistence of non-neutral trait polymorphism is enigmatic because stabilizing selection is expected to deplete variation. In cryptically coloured prey, negative frequency-dependent selection due to search image formation by predators has been proposed to favour rare variants, promoting polymorphism. However, in a heterogeneous environment, locally varying disruptive selection favours patch type-specific optima, resulting in spatial segregation of colour variants. Here, we address whether negative frequency-dependent selection can overcome selection posed by habitat heterogeneity to promote local polymorphism using an individual-based model. In addition, we compare how prey and predator mobility may modify the outcome. Our model revealed that frequency-dependent predation could strongly promote local prey polymorphism, but only when differences between morphs in patch-specific fitness were small. The effect of frequency-dependent predation depended on the predator adjustment of search image and was hampered by the prey population structure. Gene flow due to prey movement counteracted local selection, promoted local polymorphism to some extent, and relaxed the conditions for polymorphism due to frequency-dependent predation. Importantly, abrupt spatial changes in morph frequencies decreased the probability that mobile frequency-dependent predators could maintain local prey polymorphism. Overall, our study suggests that in a spatially heterogeneous environment, negative frequency-dependent selection may help maintain local polymorphism but only under a limited range of conditions.
Agency in Hierarchies: Middle Managers and Performance Evaluations
Authors: Castro-Pires Henrique
Published: January 2024

This paper studies the optimal joint design of incentives and performance rating scales in a principal-manager-worker hierarchy. The principal wants to motivate the worker to exert unobservable effort at the minimum feasible cost. Given the worker’s effort, two signals are realized: public and verifiable output and a private non-verifiable signal known only to the manager. The principal may try to elicit the manager’s private information by requiring her to evaluate the worker’s performance. Payments may depend on output and the manager’s evaluation. I show that the principal can achieve no more than what is feasible with a binary rating scale. I also identify scenarios where subjective evaluations are valuable (non-valuable), reduced transparency is advantageous, and forced ranking outperforms individual evaluations.
The regulation of health data sharing in Africa: a comparative study
Authors: Nienaber McKay Annelize G , Brand Dirk , Botes Marietjie , Cengiz Nezerith , Swart Marno
Published: January 2024

The sharing of health data is an essential component in the provision of healthcare, in medical research, and disease surveillance. Health data sharing is subject to regulatory frameworks that vary across jurisdictions. In Africa, numerous factors complicate the regulation of health data sharing, including technological, motivational, economic, and political barriers, as well as ethical and legal challenges. This comparative study examines the regulation of health data sharing in Africa by comparing and contrasting the legal and policy frameworks of five African countries. The study identifies gaps and inconsistencies in the current regulatory regimes and provides recommendations for improving the regulation of health data sharing in Africa.
Correlation between tumor size change and outcome in a rare cancer immunotherapy basket trial
Authors: Othus Megan , Patel Sandip P , Chae Young K , Dietrich Eliana , Streicher Howard , Sharon Elad , Kurzrock Razelle
Published: January 2024

Background

RECIST criteria for progressive disease, partial response, and complete response, reflecting +20%, −30%, and −100% tumor size changes, respectively, are critical outcome variables in oncology clinical trials. Herein, we evaluated post-immunotherapy tumor size change correlation with outcomes.

Methods

We used a unique clinical trial data resource, a multicenter basket trial in patients with rare solid tumors treated with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) between 2017 and 2023 (National Cancer Institute/Southwest Oncology Group-sponsored DART trial [NCT02834013]) (open at 1083 sites at its peak). Outcome associations were evaluated by survival analysis techniques including Martingale residuals.

Results

In 638 evaluable patients, we found strong linear relationships between percent change in tumor measurement up to a 40%-50% increase and progression-free (PFS) and overall survival (OS) (both Cox regression P < .001; landmark analyses based on day 65). Pearson R correlation between survival estimates and tumor change category were −0.94, −0.89, and −0.89 (PFS) and −0.84, −0.90, and −0.90 (OS) for median, 6-month (PFS), and 1-year (OS) and for 1-year (PFS) and 2-year (OS) estimates.

Conclusions

Percent change in tumor measurement per RECISTv1.1 (the sum of longest dimensions of target lesions) has a linear association with PFS and OS up to a 40% to 50% increase in tumor measurement in this cohort of patients with rare cancers who received combination immune checkpoint blockade. Quantitative first scan tumor measurement changes include important information to evaluate the potential efficacy of a therapy beyond the proportion of patients who achieve an objective response.
Association between exposure to technological advances in the workplace and work engagement: a prospective cohort study
Authors: Adi Nuri Purwito , Nagata Tomohisa , Odagami Kiminori , Nagata Masako , Mori Koji
Published: January 2024

Objectives: The study objective was to measure the association between exposure to technological advances and work engagement, adjusting for personal and workplace factors.

Methods: We conducted a nationwide online longitudinal survey study in Japan. The sample was stratified to represent Japanese workforce conditions. Work engagement was measured using the Japanese version of the Utrecht Work Engagement Scale-9. Exposure to technological advances was measured using a single question with Likert scale responses. Industry characteristics that were more/less likely to be replaced by automation were also measured. Linear regression was used for statistical analysis.

Results: There were 16 629 participants. We found that exposure to technological advances was associated with work engagement after adjustment for age, sex, education, income, and industry characteristics. We observed a significant interaction between age and exposure to technological advances (coefficient 0.891, P < .001), and conducted an age-stratified linear regression analysis. The significant association between age and exposure to technological advances reduced as age increased, and disappeared after adjustment for baseline work engagement.

Conclusions: Longitudinal observations showed that exposure to technological advances was not significantly associated with work engagement.
Emile’s inquiry-based science education
Authors: Dimopoulou Georgia , Gasparatou Renia
Published: January 2024

Over the past decades, science education researchers have suggested Inquiry-Based Science Education (IBSE) teaching interventions for science classes. In this article, we argue that IBSE’s basic principles can be traced back to Jean-Jacques Rousseau’s work Emile or On Education (1762). First, we will look at IBSE’s rationale. Then we will turn to Emile and outline Rousseau’s educational ideas concerning science education. We will show that Rousseau’s suggested practices for science education are very similar to those of IBSE. Yet despite their vivid similarities, Rousseau seems to pursue epistemic virtues, whilst IBSE aims at epistemic skills. However, nurturing epistemic skills might be seen as the first step for cultivating an epistemically virtuous character. So, embracing Rousseau’s ideal for full character development could further inspire IBSE’s proposals.