bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway-derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD
Authors: Hu Yan , Hu Qianjiang , Ansari Meshal , Riemondy Kent , Pineda Ricardo , Sembrat John , Leme Adriana S. , Ngo Kenny , Morgenthaler Olivia , Ha Kellie , Gao Bifeng , Janssen William J. , Basil Maria C. , Kliment Corrine R. , Morrisey Edward , Lehmann Mareike , Evans Christopher M. , Schiller Herbert B. , Königshoff Melanie
Published: August 2024

Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of COPD that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific subpopulation of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single-cell RNA sequencing andin situlocalisation revealed that asATII cells co-express the alveolar marker surfactant protein C and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII subpopulation derived from club cells was also identified in mouse COPD models using lineage labelling. Human and mouse ATII subpopulations formed 80–90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.
Exacerbation history and blood eosinophil count prior to diagnosis of COPD and risk of subsequent exacerbations
Authors: Halpin David M.G. , Healey Heath , Skinner Derek , Carter Victoria , Pullen Rachel , Price David
Published: August 2024

Background

Prior exacerbation history is used to guide initial maintenance therapy in COPD; however, the recommendations were derived from patients already diagnosed and treated.

Methods

We assessed the rates of moderate (i.e.treated with antibiotics and/or systemic corticosteroids) and severe (i.e.hospitalised) exacerbations in the year following diagnosis in patients newly diagnosed with COPD according to their prior history of exacerbations, blood eosinophil count (BEC) and whether maintenance therapy was started. Data were extracted from the Optimum Patient Care Research Database.

Results

73 189 patients were included. 61.9% had no exacerbations prior to diagnosis, 21.5% had 1 moderate, 16.5% had ≥2 moderate and 0.3% had ≥1 severe. 50% were started on maintenance therapy. In patients not started on maintenance therapy the rates of moderate exacerbations in the year after diagnosis in patients with no, 1 moderate, ≥2 moderate and ≥1 severe prior exacerbations were 0.34 (95% CI 0.33–0.35), 0.59 (95% CI 0.56–0.61), 1.18 (95% CI 1.14–1.23) and 1.21 (95% CI 0.73–1.69), respectively. Similar results were seen in patients started on maintenance therapy. BEC did not add significantly to the prediction of future exacerbation risk.

Conclusions

A single moderate exacerbation in the year prior to diagnosis increases the risk of subsequent exacerbations, and more frequent or severe exacerbations prior to diagnosis are associated with a higher risk.
A computationally feasible multi-trait single-step genomic prediction model with trait-specific marker weights
Authors: Strandén Ismo , Jenko Janez
Published: August 2024

Background

Regions of genome-wide marker data may have differing influences on the evaluated traits. This can be reflected in the genomic models by assigning different weights to the markers, which can enhance the accuracy of genomic prediction. However, the standard multi-trait single-step genomic evaluation model can be computationally infeasible when the traits are allowed to have different marker weights.

Results

In this study, we developed and implemented a multi-trait single-step single nucleotide polymorphism best linear unbiased prediction (SNPBLUP) model for large genomic data evaluations that allows for the use of precomputed trait-specific marker weights. The modifications to the standard single-step SNPBLUP model were minor and did not significantly increase the preprocessing workload. The model was tested using simulated data and marker weights precomputed using BayesA. Based on the results, memory requirements and computing time per iteration slightly increased compared to the standard single-step model without weights. Moreover, convergence of the model was slower when using marker weights, which resulted in longer total computing time. The use of marker weights, however, improved prediction accuracy.

Conclusions

We investigated a single-step SNPBLUP model that can be used to accommodate trait-specific marker weights. The marker-weighted single-step model improved prediction accuracy. The approach can be used for large genomic data evaluations using precomputed marker weights.
The costs and benefits of symbiotic interactions: variable effects of rhizobia and arbuscular mycorrhizae on Vigna radiata accessions
Authors: Chien Chih-Cheng , Tien Shang-Ying , Yang Shu-Yi , Lee Cheng-Ruei
Published: August 2024

Background

The symbiosis among plants, rhizobia, and arbuscular mycorrhizal fungi (AMF) is one of the most well-known symbiotic relationships in nature. However, it is still unclear how bilateral/tripartite symbiosis works under resource-limited conditions and the diverse genetic backgrounds of the host.

Results

Using a full factorial design, we manipulated mungbean accessions/subspecies, rhizobia, and AMF to test their effects on each other. Rhizobia functions as a typical facilitator by increasing plant nitrogen content, plant weight, chlorophyll content, and AMF colonization. In contrast, AMF resulted in a tradeoff in plants (reducing biomass for phosphorus acquisition) and behaved as a competitor in reducing rhizobia fitness (nodule weight). Plant genotype did not have a significant effect on AMF fitness, but different mungbean accessions had distinct rhizobia affinities. In contrast to previous studies, the positive relationship between plant and rhizobia fitness was attenuated in the presence of AMF, with wild mungbean being more responsive to the beneficial effect of rhizobia and attenuation by AMF.

Conclusions

We showed that this complex tripartite relationship does not unconditionally benefit all parties. Moreover, rhizobia species and host genetic background affect the symbiotic relationship significantly. This study provides a new opportunity to re-evaluate the relationships between legume plants and their symbiotic partners.
Scale up of the learning circles: a participatory action approach to support local food systems in four diverse First Nations school communities within Canada
Authors: Domingo Ashleigh , Yessis Jennifer , Zupko Barbara , McEachern Louise Watson , Valaitis Renata , Skinner Kelly , Hanning Rhona M.
Published: August 2024

Background

Addressing Indigenous food security and food sovereignty calls for community-driven strategies to improve access to and availability of traditional and local food. Participatory approaches that integrate Indigenous leadership have supported successful program implementation. Learning Circles: Local Healthy Food to School is a participatory program that convenes a range of stakeholders including food producers, educators and Knowledge Keepers to plan, implement and monitor local food system action. Pilot work (2014–2015) in Haida Gwaii, British Columbia (BC), showed promising results of the Learning Circles (LC) approach in enhancing local and traditional food access, knowledge and skills among youth and adolescents. The objective of the current evaluation was therefore to examine the process of scaling-up the LC vertically within the Haida Nation; and horizontally across three diverse First Nations contexts: Gitxsan Nation, Hazelton /Upper Skeena, BC; Ministikwan Lake Cree Nation, Saskatchewan; and Black River First Nation, Manitoba between 2016 and 2019.

Methods

An implementation science framework, Foster-Fishman and Watson’s (2012) ABLe Change Framework, was used to understand the LC as a participatory approach to facilitate community capacity building to strengthen local food systems. Interviews (n = 52), meeting summaries (n = 44) and tracking sheets (n = 39) were thematically analyzed.

Results

The LC facilitated a collaborative process to: (1) build on strengths and explore ways to increase readiness and capacity to reclaim traditional and local food systems; (2) strengthen connections to land, traditional knowledge and ways of life; (3) foster community-level action and multi-sector partnerships; (4) drive actions towards decolonization through revitalization of traditional foods; (5) improve availability of and appreciation for local healthy and traditional foods in school communities; and (6) promote holistic wellness through steps towards food sovereignty and food security. Scale-up within Haida Gwaii supported a growing, robust local and traditional food system and enhanced Haida leadership. The approach worked well in other First Nations contexts, though baseline capacity and the presence of champions were enabling factors.

Conclusions

Findings highlight LC as a participatory approach to build capacity and support iterative planning-to-action in community food systems. Identified strengths and challenges support opportunities to expand, adopt and modify the LC approach in other Indigenous communities with diverse food systems.
Insights into the cardiovascular benefits of taurine: a systematic review and meta-analysis
Authors: Tzang Chih-Chen , Lin Wei-Chen , Lin Long-Huei , Lin Ting-Yu , Chang Ke-Vin , Wu Wei-Ting , Özçakar Levent
Published: August 2024

Background

Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance.

Methods

We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted.

Results

The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases.

Conclusions

Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.
LATCHES – a memory aide for the principles of attachment for effective breastfeeding: findings of a regional pilot in the Northeast of England and North Cumbria
Authors: Shotton Lynette Harland , Elliot Cheryl , Nunn Roslyn , Lane Kathryn
Published: August 2024

Background

This paper outlines a pilot of a new memory aide for breastfeeding conducted in the Northeast of England and North Cumbria between April and August 2023. The United Kingdom has some of the lowest rates of breastfeeding, particularly in the Northeast of England, and as such more needs to be done to support mothers to breastfeed for as long as they would like to. Good support from health professionals can be effective in influencing decisions to breastfeed as well as helping to ensure initiation and continuation of breastfeeding but there is evidence to suggest that professionals and students do not always feel adequately trained and it is here, where memory aides may have value.

Methods

Key breastfeeding practitioners and educators were brought together to select one of two memory aides for principles of attachment for effective breastfeeding. The selected memory aide, LATCHS, was piloted with 57 participants with a key role in promotion and support of breastfeeding in the Northeast of England and North Cumbria.

Results

Participants conveyed mixed views about the proposed memory aide with more experienced staff reporting more favourable opinions than student midwives and early years practitioners. Experienced staff felt the new memory aide would complement an early memory aide, CHINS, which focused on principles of positioning.

Discussion

Findings of the pilot indicate there is a role for a mnemonic to help practitioners understand, recall, and retain theory around attachment for effective breastfeeding and that memory aides can play an important role in complementing existing approaches to education and practice. The participants felt the proposed memory aide had some limitations and suggested important ways for it to be improved, particularly in adding an E to reflect the expecting wording. This produced the final memory aide: LATCHES.

Conclusion

Using data from the pilot, the memory aide was refined, and the final version LATCHES agreed for wider dissemination. Future research is needed to understand the value of LATCHES on the wider breastfeeding workforce and whether any future improvements can be made to enhance its utility.
Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease
Authors: Liu Meng-Ke , Chen Xu-Yang , Tang Juan-Juan , Liu Zhi-Peng , Lin Gui-Ying , Cai Jun-Ling , Chen Zuo-Ming , Yan Yu-Yun , Ji Xiao-Fang , Yang Zhong-Jin , Li Zi
Published: August 2024

Background

Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART.

Methods

We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment.

Results

ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms’ surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART.

Conclusion

ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.

Graphical Abstract
Exploring immediate cardiorespiratory responses: low-intensity blood flow restricted cycling vs. moderate-intensity traditional exercise in a randomized crossover trial
Authors: Kuhn Manuel , Clarenbach Christian F. , Kläy Adrian , Kohler Malcolm , Mayer Laura C. , Lüchinger Martin , Andrist Belinda , Radtke Thomas , Haile Sarah R. , Sievi Noriane A. , Kohlbrenner Dario
Published: August 2024

Purpose

Blood-flow restriction (BFR) endurance training may increase endurance performance and muscle strength similar to traditional endurance training while requiring a lower training intensity. We aimed to compare acute cardiorespiratory responses to low-intensity interval exercise under BFR with moderate-intensity traditional interval exercise (TRA).

Methods

We conducted a randomized crossover study. The protocol involved three cycling intervals interspersed with 1 min resting periods. With a 48-h washout period, individuals performed the protocol twice in random order: once as BFR-50 (i.e., 50% incremental peak power output [IPPO] and 50% limb occlusion pressure [LOP]) and once as TRA-65 (65% IPPO without occlusion). TRA-65 intervals lasted 2 min, and time-matched BFR-50 lasted 2 min and 18 s. Respiratory parameters were collected by breath-by-breath analysis. The ratings of perceived breathing and leg exertion (RPE, 0 to 10) were assessed. Linear mixed models were used for analysis.

Results

Out of the 28 participants initially enrolled in the study, 24 healthy individuals (18 males and 6 females) completed both measurements. Compared with TRA-65, BFR-50 elicited lower minute ventilation (VE, primary outcome) (-3.1 l/min [-4.4 to -1.7]), oxygen consumption (-0.22 l/min [-0.28 to -0.16]), carbon dioxide production (-0.25 l/min [-0.29 to -0.20]) and RPE breathing (-0.9 [-1.2 to -0.6]). RPE leg was significantly greater in the BFR-50 group (1.3 [1.0 to 1.7]).

Conclusion

BFR endurance exercise at 50% IPPO and 50% LOP resulted in lower cardiorespiratory work and perceived breathing effort compared to TRA at 65% IPPO. BFR-50 could be an attractive alternative for TRA-65, eliciting less respiratory work and perceived breathing effort while augmenting perceived leg muscle effort.

Trial registration

NCT05163600; December 20, 2021.
Fluid boluses and infusions in the early phase of resuscitation from septic shock and sepsis-induced hypotension: a retrospective report and outcome analysis from a tertiary hospital
Authors: Messina Antonio , Albini Marco , Samuelli Nicolò , Brunati Andrea , Costantini Elena , Lionetti Giulia , Lubian Marta , Greco Massimiliano , Matronola Guia Margherita , Piccirillo Fabio , De Backer Daniel , Teboul Jean Louis , Cecconi Maurizio
Published: August 2024

Background

Fluid administration is the first line treatment in intensive care unit (ICU) patients with sepsis and septic shock. While fluid boluses administration can be titrated by predicting preload dependency, the amount of other forms of fluids may be more complex to be evaluated. We conducted a retrospective analysis in a tertiary hospital, to assess the ratio between fluids given as boluses and total administered fluid intake during early phases of ICU stay, and to evaluate the impact of fluid strategy on ICU mortality. Data related to fluid administration during the first four days of ICU stay were exported from an electronic health records system (ICCA®, Philips Healthcare). Demographic data, severity score, norepinephrine dose at ICU admission, overall fluid balance and the percentage of different fluid components of the overall volume administered were included in a multivariable logistic regression model, evaluating the association with ICU survival.

Results

We analyzed 220 patients admitted with septic shock and sepsis-induced hypotension from 1st July 2021 to 31st December 2023. Fluid boluses and maintenance represented 49.3% ± 22.8 of the overall fluid intake, being balanced solution the most represented (40.4% ± 22.0). The fluid volume for drug infusion represented 34.0% ± 2.9 of the total fluid intake, while oral or via nasogastric tube fluid intake represented 18.0% ± 15.7 of the total fluid intake. Fluid volume given as boluses represented 8.6% of the total fluid intake over the four days, with a reduction from 25.1% ± 24.0 on Day 1 to 4.8% ± 8.7 on Day 4. A positive fluid balance [OR 1.167 (1.029–1.341); p = 0.021] was the most important factor associated with ICU mortality. Non-survivors (n = 66; 30%) received a higher amount of overall inputs than survivors only on Day 1 [2493 mL vs. 1855 mL; p = 0.022].

Conclusions

This retrospective analysis of fluids given over the early phases of septic shock and sepsis-induced hypotension showed that the overall volume given by boluses ranges from about 25% on Day 1 to about 5% on Day 4 from ICU admission. Our data confirms that a positive fluid balance over the first 4 days of ICU is associated with mortality.
Nutritional implications of substituting plant-based proteins for meat: evidence from home scan data
Authors: Dogbe Wisdom , Wang Yihan , Revoredo-Giha Cesar
Published: August 2024

There is growing concern among policymakers and researchers about the negative health and climate impacts of meat consumption. Consumers are encouraged to re-evaluate their dietary choices to preserve our ecosystem and reduce the burden of diet-related diseases. However, limited information is available about how price changes in animal protein sources affect plant-based protein demand and the consequences for nutrient intake and/or diet quality. The goal of the present paper is to fill this gap by explaining how consumers react to price changes in animal protein types and to present the implications for nutrition or diet quality. This paper applied the exact affine stone index implicit (EASI) Marshallian demand system to 2021 home scan panel data collated by the Kantar Worldpanel to estimate both price and expenditure elasticities. Twelve food groups of seven animal-based protein products and five plant-based protein products were considered. The results revealed that dairy and eggs are daily necessities for the people of Scotland. The demand for fish and non-dairy milk are the most sensitive to price. Estimates based on expenditure elasticities show that beef is considered a luxury and a highly substitutable product in the Scottish diet. Peas are relatively basic, essential foodstuffs. In general, increasing the price of animal protein sources will shift demand towards plant protein. On the positive side, there will be a significant reduction in cholesterol and fat purchases. However, there would also be a significant reduction in the total amount of protein, carbohydrates, and healthy fats, such as unsaturated fatty acids, purchased by the average household. This shows that increases in plant-based protein are not enough to compensate for the reductions in essential macro- and micronutrient purchases from animal protein. From the climate perspective, reductions in meat purchases could reduce emissions from production and consumption.
Enhanced depletion of MLL-fusion proteins in acute leukemia: potential for improved therapeutic outcomes
Authors: Che Noelia , Cantilena Sandra , Looi-Somoye Remi , Sundar Danesh , Fung Kent , de Boer Jasper , Williams Owen
Published: August 2024

Rearrangements of the MLL (KMT2A) locus are associated with aggressive leukaemia of both myeloid and lymphoid lineages, that present profound therapeutic challenges in pediatric and adult patient populations. MLL-fusion genes resulting from these rearrangements function as driving oncogenes and have been the focus of research aimed at understanding mechanisms underlying their leukemogenic activity and revealing novel therapeutic opportunities. Inspired by the paradigm of depleting the PML-RARA fusion protein in acute promyelocytic leukemia using all-trans retinoic acid and arsenic trioxide, we conducted a screen to identify FDA-approved drugs capable of depleting MLL-fusion protein expression in leukemia cells. Previously, we reported potent anti-leukemia effects of disulfiram (DSF), identified through this screen. In the present study, we demonstrate that another hit compound, niclosamide (NSM), is also able to deplete MLL-fusion proteins derived from a range of different MLL-fusion genes in both acute myeloid (AML) and acute lymphoid (ALL) leukemias. Loss of MLL-fusion protein appeared to result from inhibition of global protein translation by NSM. Importantly, combination of DSF with NSM enhanced MLL-fusion protein depletion. This led to more profound inhibition of downstream transcriptional leukemogenic programs regulated by MLL-fusion proteins and more effective killing of both MLL-rearranged AML and ALL cells. In contrast, DSF/NSM drug combination had little impact on normal hematopoietic progenitor cell differentiation. This study demonstrates that two FDA-approved drugs with excellent safety profiles can be combined to increase the efficacy of MLL-fusion protein depletion and elimination of MLL-rearranged leukaemia.
The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy
Authors: Zhang Mingming , Chen Han , Liu Huan , Tang Hong
Published: August 2024

The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.
Naldemedine-induced perforation of a diverticulum in the sigmoid colon of a patient with opioid-related constipation: a case report
Authors: Yokota Hayato , Akamine Yumiko , Kobayashi Mizuki , Kitabayashi Takuro , Horie Misato , Endo Tentaro , Yamada Takechiyo , Kikuchi Masafumi
Published: August 2024

Background

Naldemedine is an orally available peripherally acting μ-opioid receptor antagonist approved to treat opioid-induced constipation (OIC). It is contraindicated for patients with known or suspected gastrointestinal obstruction to protect against naldemedine-induced perforation. Here, we report a clinical case of suspected perforation of a diverticulum in the sigmoid colon associated with naldemedine.

Case presentation

The patient was a 65-year-old man with a history of oral cancer who had been prescribed oxycodone (20 mg/day) for cancer pain. On day 0, the patient started naldemedine 0.2 mg once daily before bedtime for OIC. The dose of oxycodone was increased for pain control up to 60 mg/day. On day 35 of naldemedine treatment, the patient developed fever and abdominal pain, and his frequency of defecation had decreased. Initial laboratory results showed a C-reactive protein (CRP) level of 28.5 mg/dL and white blood cell (WBC) count of 13,500/µL. On day 37, the patient still had tenderness in his lower abdomen. Abdominal computed tomography revealed free air in the abdominal cavity suggesting an intestinal perforation. A Hartmann procedure was performed. Histopathological findings showed numerous diverticula in the sigmoid colon, some of which were perforated.

Conclusions

These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints.
Stressing the Relevance of Differentiating between Systematic and Random Measurement Errors in Ultrasound Muscle Thickness Diagnostics
Authors: Lohmann Lars Hubertus , Hillebrecht Martin , Schiemann Stephan , Warneke Konstantin
Published: August 2024

Background

The majority of studies that explore changes in musculature following resistance training interventions or examine atrophy due to immobilization or sarcopenia use ultrasound imaging. While most studies assume acceptable to excellent reliability, there seems to be unawareness of the existing absolute measurement errors. As early as 1998, methodological research addressed a collective unawareness of the random measurement error and its practical indications. Referring to available methodological approaches, within this work, we point out the limited value of focusing on relative, correlation-based reliability indices for the interpretability in scientific research but also for clinical application by assessing 1,512 muscle thickness values from more than 400 ultrasound images. To account for intra- and inter-day repeatability, data were collected on two consecutive days within four testing sessions. Commonly-stated reliability values (ICC, CV, SEM and MDC) were calculated, while evidence-based agreement analyses were applied to provide the accompanied systematic and random measurement error.

Results

While ICCs in the range of 0.832 to 0.998 are in accordance with the available literature, the mean absolute percentage error ranges from 1.34 to 20.38% and the mean systematic bias from 0.78 to 4.01 mm (all p ≤ 0.013), depending on the measurement time points chosen for data processing.

Conclusions

In accordance with prior literature, a more cautious interpretation of relative reliability values should be based on included systematic and random absolute measurement scattering. Lastly, this paper discusses the rationale for including different measurement error statistics when determining the validity of pre-post changes, thus, accounting for the certainty of evidence.
The interplay among Chinese EFL teachers’ enthusiasm, engagement, and foreign language teaching enjoyment: a structural equation modelling approach
Authors: Chen Xiaoming , Guo Shufa , Zhao Xiaomei , Fekri Neda , Azari Noughabi Mostafa
Published: August 2024

Teacher enthusiasm is receiving remarkable scholarly attention in L2 education, and its effect on students’ language learning outcomes has been extensively investigated. Nevertheless, exploring the antecedents of language teacher enthusiasm has received scant attention in foreign language education, particularly within the Chinese context. Thus, informed by the principles of positive psychology, the present study investigated the extent to which English as a foreign (EFL) teachers’ enthusiasm can be predicted by their work engagement and foreign language teaching enjoyment (FLTE) in the context of China. The study involved three online questionnaires completed by 576 EFL teachers in China. The results of structural equation modeling revealed that teacher work engagement and FLTE were strong predictors of Chinese EFL teachers’ enthusiasm. In addition, EFL teachers’ FLTE was a better predictor of their enthusiasm than their work engagement. The findings highlighted the importance of applying positive psychology in foreign language education. Finally, the paper concludes with avenues for future research.
Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials
Authors: Rassi Tiago N. O. , Barbosa Lucas M. , Pereira Sacha , Novais Eduardo A. , Penha Fernando , Roisman Luiz , Maia Mauricio
Published: August 2024

Background

Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated.

Methods

We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI).

Results

We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias.

Conclusion

This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM’s therapeutic potential for dry AMD.
Social environment influences microbiota and potentially pathogenic bacterial communities on the skin of developing birds
Authors: Martínez-Renau Ester , Martín-Platero Antonio M. , Bodawatta Kasun H. , Martín-Vivaldi Manuel , Martínez-Bueno Manuel , Poulsen Michael , Soler Juan José
Published: August 2024

Background

Animal bacterial symbionts are established early in life, either through vertical transmission and/or by horizontal transmission from both the physical and the social environment, such as direct contact with con- or heterospecifics. The social environment particularly can influence the acquisition of both mutualistic and pathogenic bacteria, with consequences for the stability of symbiotic communities. However, segregating the effects of the shared physical environment from those of the social interactions is challenging, limiting our current knowledge on the role of the social environment in structuring bacterial communities in wild animals. Here, we take advantage of the avian brood-parasite system of Eurasian magpies (Pica pica) and great spotted cuckoos (Clamator glandarius) to explore how the interspecific social environment (magpie nestlings developing with or without heterospecifics) affects bacterial communities on uropygial gland skin.

Results

We demonstrated interspecific differences in bacterial community compositions in members of the two species when growing up in monospecific nests. However, the bacterial community of magpies in heterospecific nests was richer, more diverse, and more similar to their cuckoo nest-mates than when growing up in monospecific nests. These patterns were alike for the subset of microbes that could be considered core, but when looking at the subset of potentially pathogenic bacterial genera, cuckoo presence reduced the relative abundance of potentially pathogenic bacterial genera on magpies.

Conclusions

Our findings highlight the role of social interactions in shaping the assembly of the avian skin bacterial communities during the nestling period, as exemplified in a brood parasite—host system.
The implementation of exercise therapy within hospital-based mental healthcare: Delphi study
Authors: McMahen Caleb , Wright Kemi , Jackson Ben , Stanton Robert , Lederman Oscar , McKeon Grace , Rosenbaum Simon , Furzer Bonnie
Published: August 2024

Background

The physical health comorbidities and premature mortality experienced by people with mental illness has led to an increase in exercise services embedded as part of standard care in hospital-based mental health services. Despite the increase in access to exercise services for people experiencing mental illness, there is currently a lack of guidelines on the assessment and triage of patients into exercise therapy.

Aims

To develop guidelines for the pre-exercise screening and health assessment of patients engaged with exercise services in hospital-based mental healthcare and to establish an exercise therapy triage framework for use in hospital-based mental healthcare.

Method

A Delphi technique consisting of two online surveys and two rounds of focus group discussions was used to gain consensus from a multidisciplinary panel of experts.

Results

Consensus was reached on aspects of pre-exercise health screening, health domain assessment, assessment tools representing high-value clinical assessment, and the creation and proposed utilisation of an exercise therapy triage framework within exercise therapy.

Conclusions

This study is the first of its kind to provide guidance on the implementation of exercise therapy within Australian hospital-based mental healthcare. The results provide recommendations for appropriate health assessment and screening of patients in exercise therapy, and provide guidance on the implementation and triage of patients into exercise therapy via a stepped framework to determine (a) the timeliness of exercise therapy required and (b) the level of support required in the delivery of their exercise therapy.
Selecting Immune Checkpoint Inhibitor Side Effects for Real-Time Monitoring in Routine Cancer Care: A Modified Delphi Study
Authors: Lai-Kwon Julia , Jefford Michael , Best Stephanie , Zhang Iris , Rutherford Claudia
Published: August 2024

PURPOSE

Electronic patient-reported outcome (ePRO) symptom monitoring may support the safe delivery of immune checkpoint inhibitors (ICI). There is no consensus on which side effects should be monitored in routine care. We aimed to develop a prioritized list of ICI side effects to include in ePRO systems and compare this to existing ICI-specific patient-reported outcome measures (PROMs).

METHODS

We conducted a two-round modified Delphi survey. Participants were patients (or their carers) who had received/were receiving ICI or managing health care professionals (HCPs). Round 1 (R1) side effects were generated from a literature review and existing PROMs. In R1, participants rated the importance of 63 ICI side effects in an ePRO system on a five-point Likert scale. In round 2 (R2), participants ranked the 10 most important side effects from 36 side effects. Content mapping of the prioritized list against existing PROMs was conducted.

RESULTS

In R1, 47 patients, nine carers, and 58 HCPs responded. Twenty-eight side effects were rated important (I)/very important (VI) by >75% of participants and included in R2. Ten were rated I/VI by <50% of participants and excluded. Twenty-five were rated I/VI by 50%-75% of participants and discussed at an HCP roundtable to determine inclusion in R2. In R2, 39 patients, 11 carers, and 42 HCPs ranked seizures, shortness of breath, chest pain, diarrhea, and rash as the most important side effects for monitoring. Content mapping showed significant differences between the prioritized list and existing PROMs.

CONCLUSION

We developed a consumer- and clinician-driven prioritized list of 36 ICI side effects to include in future ePRO systems. This process highlights the importance of broad stakeholder engagement in side-effect selection and rigorously identifying clinically important side effects to ensure content validity and clinical utility.
Statin Use and Development and Progression of Nonalcoholic Fatty Liver Disease Based on Ultrasonography
Authors: Feng Baoyu , Li Fengde , Lan Yanqi , Wang Xiaomo , Chen Shuohua , Yang Chenlu , Yin Meihua , Cui Feipeng , Wang Guodong , Zhou Di , Zhou Yang , Wu Shutong , Wang Li , Wu Shouling
Published: August 2024

Context

Nonalcoholic fatty liver disease (NAFLD) has emerged as a public health issue, while no drugs have been specifically approved for treatment.

Objective

This study aimed to examine the association between statin use and NAFLD occurrence, progression, and regression.

Methods

A cohort study was designed based on the Kailuan Study and electronic medical records from the Kailuan General Hospital. Participants aged 18 years with statin indication, including statin and nonstatin users, were enrolled from 2010 to 2017. Propensity score (PS)-matched cohorts were also used.

Results

In the entire cohort, 21 229 non-NAFLD and 22 419 NAFLD patients (including 12 818 mild NAFLD patients) were included in the final analysis. After a median follow-up of about 4 years, the incidence of NAFLD occurrence and progression for statin users was lower than those for nonstatin users (occurrence: 84.7 vs 106.5/1000 person-years; progression: 60.7 vs 75.5/1000 person-years). Compared with nonstatin users, the risk of NAFLD occurrence (hazard ratio [HR]: 0.78; 95% CI, 0.70-0.87) and regression (HR [95% CI]; 0.71 [0.60-0.84]) was decreased in statin users. The significantly negative association was observed only in those with cumulative statin duration of 2 years or more (HR [95% CI] for occurrence 0.56 [0.46-0.69] vs 0.52 [0.30-0.90] for progression) and those with low or moderate atherosclerosis cardiovascular disease (ASCVD) risk (HR [95% CI] for occurrence 0.74 [0.66-0.82] vs 0.68 [0.57-0.80] for progression). No statistically significant correlation was observed between statin use, statin use duration, and NAFLD regression. The PS-matched cohort had similar results.

Conclusion

Taking statin may decrease the risk of NAFLD occurrence and progression in the population with statin indication, suggesting the potential role of statin both in primary and secondary prevention strategies for NAFLD, especially among those with low or moderate ASCVD risk.
Myosteatosis Predicts Bariatric Surgery Response: A Longitudinal Study in Patients With Morbid Obesity
Authors: Han Eugene , Kim Mi Kyung , Lee Hye Won , Ryu Seungwan , Kim Hye Soon , Jang Byoung Kuk , Suh Youngsung
Published: August 2024

Context

Data on the preoperative factors for bariatric surgery response in patients with morbid obesity are limited, and there are no studies on the relationship between myosteatosis and surgery response.

Object

We investigated the preoperative factors determining bariatric surgery response and the impact of preoperative muscle fat infiltration on bariatric surgery response.

Methods

This retrospective longitudinal cohort study included 125 individuals (37 men, 88 women) with morbid obesity who underwent bariatric surgery. Muscle fat infiltration [skeletal muscle fat index (SMFI)] was evaluated using computed tomography-based psoas muscle mass and density at the fourth lumbar level. A bariatric surgery response was defined as ≥50% excessive weight loss at 1 year postoperatively.

Results

Before bariatric surgery, the patient’s mean body weight and body mass index (BMI) were 107.0 kg and 39.0 kg/m2, respectively. After 1 year, the mean body weight was 79.6 kg. The mean excessive weight loss at 1 year was 75.6%, and 102 (81.6%) patients were categorized as responders. There were no statistically significant differences in initial BMI, age, sex, or proportion of diabetes between responders and nonresponders. Responders were more likely to have lower SMFI and triglyceride and glycated hemoglobin A1c levels than nonresponders at baseline (P < .05). Multiple logistic regression analysis showed that a lower baseline SMFI was associated with bariatric surgery response (odds ratio = 0.31, 95% confidence interval = 0.14-0.69, P = .004).

Conclusion

Preoperative myosteatosis may determine the response to bariatric surgery.
Platelet indices as diagnostic and prognostic markers in acute coronary syndrome
Authors: Krishnan Gokul , Prabhu M Mukhyaprana , Stanley Weena
Published: August 2024

Background Acute coronary syndromes refer to STEMI, NSTEMI and unstable angina. The preferred biomarkers for assessing myocardial damage are cTnI and cTnT, and high-sensitivity cardiac troponin assays are recommended in clinical practice. Other biomarkers such as CK-MB have lower sensitivity and specificity. Platelets play a major role in thrombosis, which is a causative factor for most acute coronary syndromes. In our study, we attempted to analyze the effectiveness of platelet indices (mean platelet volume, platelet count, and platelet distribution width) as diagnostic and prognostic markers in acute coronary syndromes. Our data suggest that mean platelet volume and platelet distribution width are potential diagnostic markers, and plateletcrits can serve as prognostic markers. Methods A total of 290 subjects were recruited for the study, including 145 cases and 145 controls matched for sex and age. Cases presented with the first episode of acute coronary syndrome. Controls are those without acute coronary syndrome during present admission or in the past. Results MPV and plateletcrit correlated with both troponin T and pro-BNP, whereas PDW showed a positive correlation only with troponin T. The only significant correlation was between the plateletcrit and pro-BNP levels. The plateletcrit showed a positive correlation with other parameters (degree of ventricular dysfunction, severity of coronary artery disease, and presence of arrhythmia). On comparing platelet indices with risk factors for coronary artery disease, such as diabetes mellitus and dyslipidemia, MPV showed a positive correlation with HbA1c and the entire lipid profile, whereas PDW showed a positive correlation only with HbA1c and triglycerides. The plateletcrit was positively correlated with HbA1c and total cholesterol levels. Conclusions Our data suggest that mean platelet volume and platelet distribution width are potential diagnostic markers, whereas plateletcrits can serve as prognostic markers.