bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Cognitive Performance and Nutritional Status: Analysis From LASI-DAD
Authors: Bhagwasia Manjusha , Rao Abhijith R. , Banerjee Joyita , Bajpai Swati , Raman Aruna V. , Talukdar Arunanshu , Jain Arvind , Rajguru Chhaya , Sankhe Lalit , Goswami Debabrata , Shanthi Ganapathy Sankaralingam , Kumar Govind , Varghese Mathew , Dhar Minakshi , Gupta Monica , A-Koul Parvaiz , Mohanty Rashmi Ranjan , Chakrabarti Sankha Shubhra , Yadati Sathyanarayana Raju , Dey Sharmistha , Dey Aparajit Ballav
Published: September 2023

Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p < .001), at risk of malnutrition (adjusted OR: 1.89, p < .001) and malnourished (adjusted OR: 2.86, p < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p-.03), hemoglobin (adjusted OR: 0.91, p-.006), and serum albumin (adjusted OR: 0.38, p < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults.
‘Where is the new constitution?’ Activist art and the politics of space in Iceland
Authors: O’Farrell Liam , Oddsdóttir Katrín
Published: September 2023

In 2008, Iceland experienced one of the largest banking crashes in history. Protests against the government emerged, and as a response the country set in motion a process to rewrite its constitution. In 2011 the world’s first ‘crowdsourced constitution’ was presented to Parliament, following which two-thirds of voters in a national referendum said “yes” to the document being the basis for the Constitution of Iceland. Despite this, successive governments have repeatedly failed to implement constitutional reform. In this context, grassroots activists have campaigned to keep the issue of the new constitution alive, including through an artistic campaign. This article is the first study of this art and consideration of how Iceland’s political struggles have played out in space. Applying Duncombe’s methodology of affective effect, we present an evidence-based case of art achieving quantifiable goals, suggesting broader social change. Given that policies pursued by the government have changed the nature and use of space in the country, activist art is shown to have a significant capacity to reinvigorate the democratic functions of space, with effects that can be observed both within and without political institutions.
How Many Participants Do I Need to Test an Interaction? Conducting an Appropriate Power Analysis and Achieving Sufficient Power to Detect an Interaction
Authors: Sommet Nicolas , Weissman David L. , Cheutin Nicolas , Elliot Andrew J.
Published: September 2023

Power analysis for first-order interactions poses two challenges: (a) Conducting an appropriate power analysis is difficult because the typical expected effect size of an interaction depends on its shape, and (b) achieving sufficient power is difficult because interactions are often modest in size. This article consists of three parts. In the first part, we address the first challenge. We first use a fictional study to explain the difference between power analyses for interactions and main effects. Then, we introduce an intuitive taxonomy of 12 types of interactions based on the shape of the interaction (reversed, fully attenuated, partially attenuated) and the size of the simple slopes (median, smaller, larger), and we offer mathematically derived sample-size recommendations to detect each interaction with a power of .80/.90/.95 (for two-tailed tests in between-participants designs). In the second part, we address the second challenge. We first describe a preregistered metastudy (159 studies from recent articles in influential psychology journals) showing that the median power to detect interactions of a typical size is .18. Then, we use simulations (≈900,000,000 data sets) to generate power curves for the 12 types of interactions and test three approaches to increase power without increasing sample size: (a) preregistering one-tailed tests (+21% gain), (b) using a mixed design (+75% gain), and (c) preregistering contrast analysis for a fully attenuated interaction (+62% gain). In the third part, we introduce INT×Power ( www.intxpower.com ), a web application that enables users to draw their interaction and determine the sample size needed to reach the power of their choice with the option of using/combining these approaches.
Achieving a restorative Just Culture through the patient safety incident response framework
Authors: Lounsbury Olivia , Sujan Mark
Published: September 2023

Despite years of calls for adoption of a Just Culture, it is evident that taking this concept from paper to practice has been slower than expected. Many have cited the subpar application of the Just Culture framework and, recently, questions have been raised regarding how the Just Culture framework is perceived by those impacted by harm, including patients, family members, and staff. Though this framework is one tool that can be used to guide inquiry after harm events, its use, independent of active efforts toward restoration of relationships with patients, families, and staff, could compromise engagement and therefore learning. A lack of focus on restoring the trust of those affected by harm in parallel with the event investigation introduces a risk of further compounding the harm for all involved. Those involved in safety work at NHS England have recognized the need to apply a systems mindset within a concerted effort toward more compassionate engagement for optimal learning and improvement. In response, they have included compassionate engagement and involvement of those affected by patient safety incidents as a foundational pillar in the NHS England Patient Safety Incident Response Framework.
A thematic analysis of National Institute for Health and Care Excellence responses to coroners’ concerns’
Authors: Southall Sara , Tariq Alison , Patrick Hannah , Harris Kevin , Bird Chris
Published: September 2023

In England and Wales, law requires that coroners issue a Prevention of Future Death (PFD) report when they believe that action should be taken to prevent future deaths. Prevention of Future Death reports therefore provide an opportunity to learn and prevent harm. This study thematically analyses PFD reports received by the National Institute for Health and Care Excellence (NICE) along with the organisation's response. We undertook a framework analysis of PFD reports, the organisation's response, and supporting documents or correspondence. Our framework was developed with a deductive approach, with themes pre-selected using areas of interest to the inquiry, including NHS England's national standards for patient safety investigation. The review includes 39 reports dated from 2012 to 2020. Common health areas involved were intrapartum care and head injuries. Coroners frequently raised the issue of a lack of relevant NICE guidance, with NICE most often committing to reflecting on the issues raised through its established processes. Recent responses demonstrated greater consideration of implementation and engagement actions, along with a more collaborative approach and person-centred tone. This report provides insight into the PFD report practices of a national guidance producing and standard setting body in the UK. The report supports system-level understanding of current practices in relation to PFD reports. However, there are no means to assess if the Chief Coroner's Office and the wider safety system considered them an adequate response or whether the actions taken were effective. Recommendations are made to support transparency, learning and collaboration in an evolving patient safety landscape.
‘Completely by accident’: a qualitative analysis of service providers motivations to practice palliative care
Authors: Okyere Joshua
Published: September 2023

Background:

The lack of clarity about the factors that motivate service providers to take a career in palliative care presents a significant knowledge gap that must be filled. This is because gaining knowledge about the motivations for taking a career in palliative care would provide valuable insights that can potentially increase buy-in and interest among prospective healthcare professionals. By elucidating the motivations of service providers, the study aims to contribute to the broader field of palliative care research and inform the development of tailored interventions and training programmes to increase the pool of specialized palliative care providers.

Objective:

To explore palliative care service providers’ motivations to practice palliative care.

Design:

Exploratory descriptive design.

Methods:

In all, seven in-depth interviews were conducted using a semi-structured interview guide. Data were managed using NVivo-12. Inductive thematic analysis was performed by following Hasse’s adaptation of Colaizzi’s approach to qualitative thematic analysis.

Results:

Two main factors motivated service providers to take a career in palliative care. The first was the influence of professional training while the second motivation was from their personal experiences regarding providing care to a family member with palliative care needs.

Conclusion:

The study concludes that personal experiences with caring for a loved one with palliative care needs play a pivotal role in shaping the decision of service providers to pursue a career in palliative care. Also, investment in palliative care education and training is crucial to ensure a skilled workforce capable of meeting the growing needs of patients and families facing serious illnesses.
Hydrosocial geographies: Cycles, spaces and spheres of concern
Authors: Liao Yu-Kai , Schmidt Jeremy J
Published: September 2023

Over recent decades, hydrosocial scholarship focusing on the plural, often contested relations of waters and societies has advanced significantly. This article reviews hydrosocial scholarship in three steps that are contextualized by geography's long-standing efforts to use water to ‘think geography’. The article begins by revisiting critiques of the hydrological cycle as circulating free of anthropogenic forces and wholly on the ‘nature’ side of the society/nature dualism. We consider how this critique shapes engagement with other fields where human–water relations are crucial, such as socio-hydrology and those focused on climate change. The article then examines the extension of hydrosocial scholarship from critiques of the hydrological cycle to its use in explaining social spaces, such as territory, urban processes and citizenship. Finally, we consider how hydrosocial scholarship from Black, Indigenous and anti-colonial praxis challenges epistemologies and ontologies that, even in their critiques, recentre Eurocentric notions of water.
Fluvial geomorphic factors affecting liquefaction-induced lateral spreading
Authors: Ingabire Abayo Nancy , Cabas Ashly , Chamberlin Ellen , Montoya Brina
Published: September 2023

Liquefaction-induced lateral displacements represent a major geohazard in earthquake-prone regions, yet the uncertainty associated with their prediction remains notoriously high. Documented observations after recent earthquakes provide evidence that depositional environment-specific geologic conditions play a crucial role in liquefaction susceptibility, and in the severity and spatial extent of liquefaction-induced ground deformations. However, this evidence is largely qualitative in nature, which limits the potential to incorporate the effects of depositional processes and environments in the next generation of lateral spreading predictive models. This study provides a framework to quantitatively assess the relationship between depositional environment-specific geologic factors and lateral spreading by means of simple fluvial geomorphic facies models, geotechnical engineering data (e.g. Cone Penetration Test data), and geospatial analytics. Three hypotheses are introduced and tested using lateral spreading ground deformations observed following the 2011 Christchurch earthquake along the Avon and Heathcote rivers in New Zealand. The results from this study indicate that the presence of an active (i.e. with active sediment deposition) compared to inactive (e.g. abandoned) channels is the most important fluvial geomorphologic variable out of the three tested. The other two are associated with the location relative to the meander bend position, including location within the point bar (inside) or the cut bank (outside), and upstream versus downstream within a given point bar. Findings from this study show that more lateral spreading occurs within point bars, and upstream (within a given point bar) in simple meander bends. However, the presence of geomorphic complexities (e.g. cut banks connected to an incised channel or tributary and/or channel confinement) can challenge the unbiased quantification of the contribution of a single geomorphic variable to the observed lateral displacements. These findings can be applied to other fluvial environments outside of New Zealand, and the proposed framework can be implemented for other non-fluvial depositional settings.
De novo hematopoiesis from the fetal lung
Authors: Yeung Anthony K. , Villacorta-Martin Carlos , Lindstrom-Vautrin Jonathan , Belkina Anna C. , Vanuytsel Kim , Dowrey Todd W. , Ysasi Alexandra B. , Bawa Pushpinder , Wang Feiya , Vrbanac Vladimir , Mostoslavsky Gustavo , Balazs Alejandro B. , Murphy George J.
Published: September 2023

Hemogenic endothelial cells (HECs) are specialized cells that undergo endothelial-to-hematopoietic transition (EHT) to give rise to the earliest precursors of hematopoietic progenitors that will eventually sustain hematopoiesis throughout the lifetime of an organism. Although HECs are thought to be primarily limited to the aorta-gonad-mesonephros (AGM) during early development, EHT has been described in various other hematopoietic organs and embryonic vessels. Though not defined as a hematopoietic organ, the lung houses many resident hematopoietic cells, aids in platelet biogenesis, and is a reservoir for hematopoietic stem and progenitor cells (HSPCs). However, lung HECs have never been described. Here, we demonstrate that the fetal lung is a potential source of HECs that have the functional capacity to undergo EHT to produce de novo HSPCs and their resultant progeny. Explant cultures of murine and human fetal lungs display adherent endothelial cells transitioning into floating hematopoietic cells, accompanied by the gradual loss of an endothelial signature. Flow cytometric and functional assessment of fetal-lung explants showed the production of multipotent HSPCs that expressed the EHT and pre-HSPC markers EPCR, CD41, CD43, and CD44. scRNA-seq and small molecule modulation demonstrated that fetal lung HECs rely on canonical signaling pathways to undergo EHT, including TGFβ/BMP, Notch, and YAP. Collectively, these data support the possibility that post-AGM development, functional HECs are present in the fetal lung, establishing this location as a potential extramedullary site of de novo hematopoiesis.
CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216
Authors: Gress Verena , Roussy Mathieu , Boulianne Luc , Bilodeau Mélanie , Cardin Sophie , El-Hachem Nehme , Lisi Véronique , Khakipoor Banafsheh , Rouette Alexandre , Farah Azer , Théret Louis , Aubert Léo , Fatima Furat , Audemard Éric , Thibault Pierre , Bonneil Éric , Chagraoui Jalila , Laramée Louise , Gendron Patrick , Jouan Loubna , Jammali Safa , Paré Bastien , Simpson Shawn M. , Tran Thai Hoa , Duval Michel , Teira Pierre , Bittencourt Henrique , Santiago Raoul , Barabé Frédéric , Sauvageau Guy , Smith Martin A. , Hébert Josée , Roux Philippe P. , Gruber Tanja A. , Lavallée Vincent-Philippe , Wilhelm Brian T. , Cellot Sonia
Published: September 2023

Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted, and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two-thirds of the cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest-fatality subgroups. We established CD34+ cord blood–derived CG2 models (n = 6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia-initiating cell frequencies, comutational landscape, and gene expression signature, with distinct upregulation of the prosurvival factor B-cell lymphoma 2 (BCL2). Cell membrane proteomic analyses highlighted CG2 surface markers preferentially expressed on leukemic cells compared with CD34+ cells (eg, NCAM1 and CD151). AMKL differentiation block in the mega-erythroid progenitor space was confirmed by single-cell profiling. Although CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with venetoclax, they were vulnerable to strategies that target the megakaryocytic prosurvival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor navitoclax and DT2216, a selective BCL-XL proteolysis-targeting chimera degrader developed to limit thrombocytopenia in patients. NUP98r AMKL were also sensitive to BCL-XL inhibition but not the NUP98r monocytic leukemia, pointing to a lineage-specific dependency. Navitoclax or DT2216 treatment in combination with low-dose cytarabine further reduced leukemic burden in mice. This work extends the cellular and molecular diversity set of human AMKL models and uncovers BCL-XL as a therapeutic vulnerability in CG2 and NUP98r AMKL.
Neurocognitive impairment associated with chronic morbidity in long-term survivors of Hodgkin Lymphoma
Authors: Phillips Nicholas S. , Mulrooney Daniel A. , Williams AnnaLynn M. , Liu Wei , Khan Raja B. , Ehrhardt Matthew J. , Folse Tim , Krasin Matthew , Srivastava Deo Kumar , Ness Kirsten K. , Hudson Melissa M. , Sabin Noah D. , Krull Kevin R.
Published: September 2023

Thoracic radiation is associated with significant cardiopulmonary morbidities in survivors of long-term Hodgkin lymphoma and may affect neurocognitive outcomes. Survivors (N = 204; 52.5% female; mean [standard deviation] age, 36.6 [8.01] years) treated with thoracic radiation and age-, sex-, and race/ethnicity-matched community controls (N = 205; 51.7% female; age, 36.7 [9.17] years) completed standardized neurocognitive testing, echocardiography, pulmonary function tests, and vascular studies during the same visit. Treatments were abstracted from medical records. Cardiac (ie, left ventricular ejection fraction [LVEF], global longitudinal strain [GLS]), vascular (ie, large and small artery elasticity [SAE]), pulmonary (ie, diffusing capacity of the lungs for carbon monoxide [DLCO] and forced expiratory volume [FEV1]), and chronic health conditions were evaluated for associations with age-adjusted neurocognitive performance using multivariable linear regression. Compared with controls, survivors had lower performance (P < 0.05) in visuomotor (0.11 vs 0.41), visual processing speed (0.25 vs 0.64), short-term recall (−0.24 vs 0.12), and flexibility (−0.04 vs 0.28). Survivors had lower pulmonary (FEV1, DLCOcorr), cardiac (LVEF, GLS), and vascular function (SAE) than controls (all P < 0.001). FEV1 was associated with visuomotor (P = .008) and visual processing speed (P = .05), and flexibility (P = .05). GLS was associated with short-term recall (P = .03). SAE was associated with flexibility (P = .007). Neurocognitive outcomes were also associated with moderate-to-severe neurologic chronic conditions (P < .05). Findings suggest a link between subclinical cardiopulmonary and vascular findings, neurologic morbidity, and neurocognitive impairments. Prevention of health morbidity may benefit neurocognitive outcomes.
Dupilumab leads to better-controlled asthma and quality of life in children: the VOYAGE study
Authors: Fiocchi Alessandro G. , Phipatanakul Wanda , Zeiger Robert S. , Durrani Sandy R. , Cole Jeremy , Msihid Jérôme , Gall Rebecca , Jacob-Nara Juby A. , Deniz Yamo , Rowe Paul J. , Lederer David J. , Hardin Megan , Zhang Yi , Khan Asif H.
Published: September 2023

Background

Dupilumab has shown long-term treatment benefits in children with uncontrolled asthma. We assessed in more detail the impact of dupilumab on asthma control and health-related quality of life (HRQoL) in children and their caregivers.

Methods

Children aged 6–11 years with uncontrolled moderate-to-severe type 2 asthma (baseline blood eosinophils ≥150 cells·µL−1or fractional exhaled nitric oxide ≥20 ppb; n=350) were treated with dupilumab or placebo for 52 weeks in the VOYAGE study. Primary outcomes of these analyses were asthma control (change from baseline in Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) and achieving a clinically meaningful response of ≥0.5 points); proportion of patients achieving well-controlled asthma or better (ACQ-7-IA ≤0.75 points); effect on patients’ (Standardised Paediatric Asthma Quality of Life Questionnaire Interviewer-Administered (PAQLQ(S)-IA)) and caregivers’ (Paediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ)) HRQoL; and allergic rhinitis-related QoL.

Results

Dupilumabversusplacebo significantly improved children's ACQ-7-IA scores by week 4 with sustained improvements through week 52 (least squares mean difference at week 52: −0.44, 95% CI −0.59– −0.30; p<0.0001); a higher proportion achieved a clinically meaningful response (week 52: 86%versus75%; p=0.0051). At weeks 24 and 52, more children who received dupilumab achieved well-controlled asthma (ACQ-7-IA ≤0.75 points: 61%versus43%; p=0.0001 and 70%versus46%; p<0.0001, respectively). Significant improvements in PAQLQ(S)-IA and PACQLQ scores were observed by week 52.

Conclusions

In children aged 6–11 years with moderate-to-severe type 2 asthma, dupilumab treatment was associated with rapid, sustained improvements in asthma control. HRQoL was significantly improved for children and their caregivers.
Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose
Authors: Domingo Christian , Rabe Klaus F. , Price David , Brusselle Guy , Wechsler Michael E. , Xia Changming , Pandit-Abid Nami , Gall Rebecca , Rowe Paul J. , Deniz Yamo , Jacob-Nara Juby A. , Radwan Amr
Published: September 2023

Background

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. Thispost hocanalysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day−1) on long-term outcomes of dupilumab treatment.

Methods

Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), measures of asthma control and quality of life, and OCS dose were evaluated in patients from the phase 3 VENTURE trial with severe OCS-dependent asthma, further categorised by OCS dose ≤10 or >10 mg·day−1at parent study baseline (PSBL), who enrolled in TRAVERSE.

Results

Dupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202–0.265 (OCS ≤10 mg·day−1at PSBL) and 0.221–0.366 (OCS >10 mg·day−1at PSBL)). Improvements in pre-bronchodilator FEV1, asthma control and quality of life observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1upon initiating dupilumab in TRAVERSE, which were sustained to the end of TRAVERSE. Reductions in OCS dose observed in VENTURE were maintained throughout TRAVERSE, with more than two-thirds of patients achieving reductions in OCS doses to ≤5 mg·day−1by TRAVERSE week 48.

Conclusions

Improvements in clinical outcomes and reductions in OCS dose with dupilumab observed in VENTURE were maintained throughout TRAVERSE, regardless of baseline disease severity. Patients who switched from placebo in VENTURE to dupilumab in TRAVERSE had improved clinical outcomes and reductions in OCS dose comparable to those given dupilumab in VENTURE.
Virtual reality intervention alleviates dyspnoea in patients recovering from COVID-19 pneumonia
Authors: Betka Sophie , Kannape Oliver Alan , Fasola Jemina , Lance Florian , Cardin Sylvain , Schmit Aline , Similowski Thomas , Soccal Paola Marina , Herbelin Bruno , Adler Dan , Blanke Olaf
Published: September 2023

Background

Immersive virtual reality (iVR)-based digital therapeutics are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnoea, we investigated the effects of visual respiratory feedback on persistent dyspnoea in patients recovering from coronavirus disease 2019 (COVID-19) pneumonia.

Methods

We performed a controlled, randomised, single-blind, crossover proof-of-concept study (feasibility and initial clinical efficacy) to evaluate an iVR-based intervention to alleviate dyspnoea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnoea (≥5 on a 10-point scale) and preserved cognitive function (Montreal Cognitive Assessment score >24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodiedviaa gender-matched virtual body. The virtual body flashed in a waxing and waning visual effect that could be synchronous or asynchronous to the patient's respiratory movements. Outcomes were assessed using questionnaires and breathing recordings.

Results

Study enrolment was open between November 2020 and April 2021. 26 patients were enrolled (27% women; median age 55 years, interquartile range (IQR) 18 years). Data were available for 24 of 26 patients. The median rating on a 7-point Likert scale of breathing comfort improved from 1 (IQR 2) at baseline to 2 (IQR 1) for synchronous feedback, but remained unchanged at 1 (IQR 1.5) for asynchronous feedback (p<0.05 between iVR conditions). Moreover, 91.2% of all patients were satisfied with the intervention (p<0.0001) and 66.7% perceived it as beneficial for their breathing (p<0.05).

Conclusion

Our iVR-based digital therapy presents a feasible and safe respiratory rehabilitation tool that improves breathing comfort in patients recovering from COVID-19 infection presenting with persistent dyspnoea. Future research should investigate the intervention's generalisability to persistent dyspnoea with other aetiologies and its potential for preventing chronification.
Multiple stressor effects of insecticide exposure and increased fine sediment deposition on the gene expression profiles of two freshwater invertebrate species
Authors: Brasseur Marie V. , Buchner Dominik , Mack Leoni , Schreiner Verena C. , Schäfer Ralf B. , Leese Florian , Mayer Christoph
Published: September 2023

Background

Freshwater ecosystem degradation and biodiversity decline are strongly associated with intensive agricultural practices. Simultaneously occurring agricultural stressors can interact in complex ways, preventing an accurate prediction of their combined effects on aquatic biota. Here, we address the limited mechanistic understanding of multiple stressor effects of two globally important stressors, an insecticide (chlorantraniliprole), and increased fine sediment load and assessed their impact on the transcriptomic profile of two stream macroinvertebrates: the amphipod Gammarus pulex and the caddisfly Lepidostoma basale.

Results

We identified mainly antagonistic stressor interactions at the transcriptional level, presumably because the insecticide adsorbed to fine sediment particles. L. basale, which is phylogenetically more closely related to the insecticide’s target taxon Lepidoptera, exhibited strong transcriptional changes when the insecticide stressor was applied, whereas no clear response patterns were observed in the amphipod G. pulex. These differences in species vulnerability can presumably be attributed to molecular mechanisms determining the cellular affinity toward a stressor as well as differential exposure patterns resulting from varying ecological requirements between L. basale and G. pulex. Interestingly, the transcriptional response induced by insecticide exposure in L. basale was not associated with a disruption of the calcium homeostasis, which is the described mode of action for chlorantraniliprole. Instead, immune responses and alterations of the developmental program appear to play a more significant role.

Conclusions

Our study shows how transcriptomic data can be used to identify multiple stressor effects and to explore the molecular mechanisms underlying stressor-induced physiological responses. As such, stressor effects assessed at the molecular level can inform about modes of action of chemicals and their interplay with non-chemical stressors. We demonstrated that stressor effects vary between different organismic groups and that insecticide effects are not necessarily covered by their described mode of action, which has important implications for environmental risk assessment of insecticides in non-target organisms.
ECL 3.0: a sensitive peptide identification tool for cross-linking mass spectrometry data analysis
Authors: Zhou Chen , Dai Shuaijian , Lai Shengzhi , Lin Yuanqiao , Zhang Xuechen , Li Ning , Yu Weichuan
Published: September 2023

Background

Cross-linking mass spectrometry (XL-MS) is a powerful technique for detecting protein–protein interactions (PPIs) and modeling protein structures in a high-throughput manner. In XL-MS experiments, proteins are cross-linked by a chemical reagent (namely cross-linker), fragmented, and then fed into a tandem mass spectrum (MS/MS). Cross-linkers are either cleavable or non-cleavable, and each type requires distinct data analysis tools. However, both types of cross-linkers suffer from imbalanced fragmentation efficiency, resulting in a large number of unidentifiable spectra that hinder the discovery of PPIs and protein conformations. To address this challenge, researchers have sought to improve the sensitivity of XL-MS through invention of novel cross-linking reagents, optimization of sample preparation protocols, and development of data analysis algorithms. One promising approach to developing new data analysis methods is to apply a protein feedback mechanism in the analysis. It has significantly improved the sensitivity of analysis methods in the cleavable cross-linking data. The application of the protein feedback mechanism to the analysis of non-cleavable cross-linking data is expected to have an even greater impact because the majority of XL-MS experiments currently employs non-cleavable cross-linkers.

Results

In this study, we applied the protein feedback mechanism to the analysis of both non-cleavable and cleavable cross-linking data and observed a substantial improvement in cross-link spectrum matches (CSMs) compared to conventional methods. Furthermore, we developed a new software program, ECL 3.0, that integrates two algorithms and includes a user-friendly graphical interface to facilitate wider applications of this new program.

Conclusions

ECL 3.0 source code is available at https://github.com/yuweichuan/ECL-PF.git. A quick tutorial is available at https://youtu.be/PpZgbi8V2xI.
Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits
Authors: Cheng Youshu , Justice Amy , Wang Zuoheng , Li Boyang , Hancock Dana B. , Johnson Eric O. , Xu Ke
Published: September 2023

Background

Cocaine use (CU) is associated with psychiatric and medical diseases. Little is known about the mechanisms of CU-related comorbidities. Findings from preclinical and clinical studies have suggested that CU is associated with aberrant DNA methylation (DNAm) that may be influenced by genetic variants [i.e., methylation quantitative trait loci (meQTLs)]. In this study, we mapped cis-meQTLs for CU-associated DNAm sites (CpGs) in an HIV-positive cohort (Ntotal = 811) and extended the meQTLs to multiple traits.

Results

We conducted cis-meQTL analysis for 224 candidate CpGs selected for their association with CU in blood. We identified 7,101 significant meQTLs [false discovery rate (FDR) < 0.05], which mostly mapped to genes involved in immunological functions and were enriched in immune pathways. We followed up the meQTLs using phenome-wide association study and trait enrichment analyses, which revealed 9 significant traits. We tested for causal effects of CU on these 9 traits using Mendelian Randomization and found evidence that CU plays a causal role in increasing hypertension (p-value = 2.35E-08) and decreasing heel bone mineral density (p-value = 1.92E-19).

Conclusions

These findings suggest that genetic variants for CU-associated DNAm have pleiotropic effects on other relevant traits and provide new insights into the causal relationships between cocaine use and these complex traits.
Drug-target binding affinity prediction using message passing neural network and self supervised learning
Authors: Xia Leiming , Xu Lei , Pan Shourun , Niu Dongjiang , Zhang Beiyi , Li Zhen
Published: September 2023

Background

Drug-target binding affinity (DTA) prediction is important for the rapid development of drug discovery. Compared to traditional methods, deep learning methods provide a new way for DTA prediction to achieve good performance without much knowledge of the biochemical background. However, there are still room for improvement in DTA prediction: (1) only focusing on the information of the atom leads to an incomplete representation of the molecular graph; (2) the self-supervised learning method could be introduced for protein representation.

Results

In this paper, a DTA prediction model using the deep learning method is proposed, which uses an undirected-CMPNN for molecular embedding and combines CPCProt and MLM models for protein embedding. An attention mechanism is introduced to discover the important part of the protein sequence. The proposed method is evaluated on the datasets Ki and Davis, and the model outperformed other deep learning methods.

Conclusions

The proposed model improves the performance of the DTA prediction, which provides a novel strategy for deep learning-based virtual screening methods.
In-vitro antibacterial activity and mechanism of Monarda didyma essential oils against Carbapenem-resistant Klebsiella pneumoniae
Authors: Chen Ying , Zhao Jinda , Liu Chenyu , Wu Dongmei , Wang Xianhe
Published: September 2023

To fight the global epidemic of drug-resistant bacteria, essential oils have gained increasing attention as a new source of antibiotics. The antimicrobial activity of Monarda didyma essential oils (MDEO) for the Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were determined by agar disc diffusion assay and broth microdilution assay. To further understand MDEO efficacy, a time-growth curve was performed. The biofilm formation of CRKP were determined by crystalline violet staining method, additionally, changes in intracellular Adenosine triphosphate (ATP), protein, Alkaline phosphatase (AKP) activities, and membrane integrity were investigated to assess the influence of MDEO on cell membrane damage. Finally, the activities of key enzymes in the tricarboxylic acid (TCA) pathways and pentose phosphate (PPP) pathways were examined to determine the effect of MDEO on the respiratory metabolism of CRKP. This study presents the antibacterial mechanism of MDEO against CRKP with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1.25 mg/ml. To understand MDEO efficacy, a time-kill kinetics approach was performed. The bactericidal effect of MDEO was evident at 2 h compared to the control at its MIC and 2MIC. Surface electron microscopic and ATP assay studies provided evidence for the multi-target action of MDEO against CRKP. MDEO could inhibit CRKP biofilm formation. MDEO could also cause irreversible damage to the CRKP cell membrane, resulting in the leakage of biological macromolecules (protein, ATP) and the reduction of intracellular enzymes (AKP) activities. Finally, MDEO affected the pathways of respiratory metabolism, such as PPP and TCA pathways. MDEO could reduce the activity of key enzymes (Glucose-6-phosphate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) in the PPP and TCA pathways to exert its biological effects against CRKP. These results suggest MDEO can exert inhibitory effects on CRKP, and potential mechanisms of action including inhibition of biofilm formation, damage of cell membrane structure and inhibition of energy metabolism.
Thrombotic microangiopathies after kidney transplantation in modern era: nosology based on chronology
Authors: Von Tokarski Florent , Fillon Alexandre , Maisons Valentin , Thoreau Benjamin , Bayer Guillaume , Gatault Philippe , Longuet Hélène , Sautenet Bénédicte , Buchler Matthias , Vigneau Cécile , Fakhouri Fadi , Halimi Jean-Michel
Published: September 2023

Background

Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant.

recipients (KTR).

Methods

We analysed the epidemiology of adjudicated TMA in consecutive KTR during the.

2009–2021 period.

Results

TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1–8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5–6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9–15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features.

Conclusions

TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.
Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study
Authors: Fang Tian , Zhang Zhihao , Zhou Huijie , Wu Wanchun , Ji Fuqing , Zou Liqun
Published: September 2023

Background

The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis.

Methods

We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements.

Results

Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035–1.110, P = 8.78 × 10− 5, false discovery rate (FDR) = 7.36 × 10− 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023–1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019–1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis.

Conclusion

This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.
Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms
Authors: Wang Hui , Liu Shu , Xie Liqing , Wang Jinhui
Published: September 2023

Background

Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it’s essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.

Methods

In this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.

Results

The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.

Conclusions

Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.
The role of the cultural environment in the development of physical literacy and physical activity of Iranian children
Authors: Mohammadi Majid , Elahipanah Farzaneh , Amani-shalamzari Sadegh
Published: September 2023

Background

The investigation of physical literacy (PL) and physical activity (PA) should be done in an ecological context because the socio-cultural situation can encourage or inhibit children’s activity. The present study aimed to study the role of the cultural environment in the development of PL and PA in Iranian children.

Methods

The statistical population consisted of Iranian children aged 8 to 12, of whom 270 students were recruited by cluster sampling from six provinces. They complete the Canadian Assessment of Physical Literacy 2 (CAPL-2) and the International Physical Activity Survey. To examine the cultural environment, the components of geographic location (west, south, central, east, and northwest), place of residence (downtown, suburban, and village), and gender (boys and girls) were used. A multivariate ANOVA analysis was used to analyze the data.

Results

From the geographic location, the findings showed that students inhabit in the west and east of Iran have significantly higher scores than their counterparts living in the central, south, and northwest at PA and PL (P < 0.001). From the place of residence, we observed a higher level of PA and PL in children living in the village than in those living in the suburbs and downtown (P < 0.001). In terms of gender, boys have higher PL and PA scores (P < 0.001).

Conclusion

The findings demonstrate that socio-cultural factors, geographic location, place of residence, and gender have different impacts on children’s PL and physical activity. Therefore, we suggest using ecologically appropriate decentralized planning in a physical education curriculum.