bluuebunny/crossref_metadata_2025 huggingface dataset:
Latino advanced cancer patients’ prognostic awareness and familial cultural influences on advance care planning engagement: a qualitative study
Authors: Torres Blasco Normarie , Rosario Lianel , Shen Megan J.
Published: August 2023

Background:

Advanced cancer patients need an accurate understanding of their prognoses in order to engage in informed end-of-life care treatment decision-making. Latino cancer patients experience disparities around prognostic understanding, in part due to a lack of culturally competent communication around prognosis and advance care planning (ACP).

Objective:

The objective of the present study of Latino patients with advanced, terminally ill cancer is to examine their understanding of prognosis, and how cultural factors may influence this understanding and engagement in ACP.

Methods:

A mixed methods study was conducted, which consisted of surveys and semi-structured interviews. Descriptive statistics were used for sociodemographic information and self-reported prognostic understanding. Interviews around prognostic understanding and cultural influences on this understanding and engagement in ACP were recorded, transcribed, and then coded and analyzed using thematic content analysis.

Findings:

Latino patients with advanced cancer ( n = 20) completed a self-reported survey and participated in a semi-structured interview. Results indicate that among terminally ill patients, 50% of the patients inaccurately believed they had early-stage cancer, 85% did not believe their cancer was terminal, and 70% believed their cancer was curable. Moreover, interviews yielded two main themes: varying levels of awareness of the incurability of their cancer and diverse end-of-life care decision-making and treatment preferences based on prognostic understanding. Within these themes, patients expressed denial or acceptance of their prognosis through communication with the oncologist, the importance of family, and incorporating their pre-existing beliefs.

Conclusion:

Findings indicate the importance of communication, family involvement, and incorporation of beliefs for promoting an accurate prognostic understanding among Latino patients. It is imperative to address disparities in Latino advanced cancer patients’ prognostic understanding so they can engage in informed treatment decision-making around end-of-life care.
The spatial-temporal evolution of public bike-sharing systems in China: The disruption of dockless bike-sharing emergence
Authors: Zhou Ziyu , Jin Scarlett Ting , Jiang Jinzheng , Kong Hui
Published: August 2023

Many Chinese cities have implemented the station-based public bike-sharing systems (PBSs). However, the recent spread of the dockless bike-sharing systems (DBSs) has significantly impacted PBSs, which has not been thoroughly investigated in previous research. This study bridges this research gap by examining the spatiotemporal evolution of China’s PBSs, with a particular focus on the changes brought by the entry of DBSs, by analyzing data on the start and end dates of PBSs and DBSs across the country. We utilized logistic regression to identify factors that may influence the decision to discontinue PBS operations, and examined selected representative cities to uncover the underlying structural and political factors affecting PBSs’ persistency. Findings reveal that the entry of DBSs disrupts PBS operations in many cities. PBSs are less likely to cease operation in cities with subways and in coastal areas, but more likely to do so in densely populated cities. Furthermore, technical advancements, operational consistency, adherence to government guidelines, and a well-planned station layout contribute to the continued viability of PBSs amidst the challenges posed by DBSs. Based on these results, we suggest that cities should improve the competitiveness of PBSs through better integration with public transit and optimization of PBS operations.
Crucial roles of red blood cells and platelets in whole blood thrombin generation
Authors: Sun Siyu , Campello Elena , Zou Jinmi , Konings Joke , Huskens Dana , Wan Jun , Fernández Delia I. , Reutelingsperger Chris P. M. , ten Cate Hugo , Toffanin Serena , Bulato Cristiana , de Groot Philip G. , de Laat Bas , Simioni Paolo , Heemskerk Johan W. M. , Roest Mark
Published: August 2023

Red blood cells (RBCs) and platelets contribute to the coagulation capacity in bleeding and thrombotic disorders. The thrombin generation (TG) process is considered to reflect the interactions between plasma coagulation and the various blood cells. Using a new high-throughput method capturing the complete TG curve, we were able to compare TG in whole blood and autologous platelet-rich and platelet-poor plasma to redefine the blood cell contributions to the clotting process. We report a faster and initially higher generation of thrombin and shorter coagulation time in whole blood than in platelet-rich plasma upon low concentrations of coagulant triggers, including tissue factor, Russell viper venom factor X, factor Xa, factor XIa, and thrombin. The TG was accelerated with increased hematocrit and delayed after prior treatment of RBC with phosphatidylserine-blocking annexin A5. RBC treatment with ionomycin increased phosphatidylserine exposure, confirmed by flow cytometry, and increased the TG process. In reconstituted blood samples, the prior selective blockage of phosphatidylserine on RBC with annexin A5 enhanced glycoprotein VI–induced platelet procoagulant activity. For patients with anemia or erythrocytosis, cluster analysis revealed high or low whole-blood TG profiles in specific cases of anemia. The TG profiles lowered upon annexin A5 addition in the presence of RBCs and thus were determined by the extent of phosphatidylserine exposure of blood cells. Profiles for patients with polycythemia vera undergoing treatment were similar to that of control subjects. We concluded that RBC and platelets, in a phosphatidylserine-dependent way, contribute to the TG process. Determination of the whole-blood hypo- or hyper-coagulant activity may help to characterize a bleeding or thrombosis risk.
CD38 antibody re-treatment in daratumumab-refractory multiple myeloma after time on other therapies
Authors: Perez de Acha Olivia , Reiman Lauren , Jayabalan David S. , Walker Zachary J. , Bosma Grace , Keller Alana L. , Parzych Sarah E. , Abbott Diana , Idler Beau M. , Ribadeneyra Drew , Niesvizky Ruben , Forsberg Peter A. , Mark Tomer M. , Sherbenou Daniel W.
Published: August 2023

Monoclonal antibodies targeting CD38 are important for treatment of both newly diagnosed and relapsed multiple myeloma (MM). Daratumumab and isatuximab are anti-CD38 antibodies with the US Food and Drugs Administration approval in multiple different combinations. Despite good initial efficacy, patients inevitably develop drug resistance. Whether patients can be effectively re-treated with these antibodies in subsequent lines of therapy is unclear. Thus far, studies have mostly been limited to clinical retrospectives with short washout periods. To answer whether patients regain sensitivity after longer washouts, we used ex vivo sensitivity testing to isolate the anti-CD38 antibody-specific cytotoxicity in samples obtained from patients who had been exposed to and then off daratumumab for up to 53 months. MM cells from patients who had been off daratumumab for >1 year showed greater sensitivity than those with <1 year, although they still were less sensitive than those who were daratumumab naïve. CD38 expression on MM cells gradually recovered, although, again, not to the level of anti-CD38 antibody–naïve patients. Interestingly, low MM CD38 explained only 45% of cases identified to have daratumumab resistance. With clinical follow-up, we found ex vivo sensitivity predicted subsequent clinical response but CD38 overexpression did not. Patients clinically re-treated with anti-CD38 antibodies had <6 months of clinical benefit, but 1 patient who was daratumumab exposed but not refractory achieved complete response lasting 13 months. We conclude that transient efficacy can be achieved by waiting 1 year before CD38 antibody rechallenge, but this approach may be best used as a bridge to, or after, chimeric antigen receptor T-cell therapy.
Real-world effectiveness of airway clearance techniques in children with cystic fibrosis
Authors: Filipow Nicole , Stanojevic Sanja , Raywood Emma , Shannon Harriet , Tanriver Gizem , Kapoor Kunal , Douglas Helen , Davies Gwyneth , O'Connor Rachel , Murray Nicky , Main Eleanor
Published: August 2023

Background

Cystic fibrosis (CF) is commonly characterised by thick respiratory mucus. From diagnosis, people with CF are prescribed daily physiotherapy, including airway clearance techniques (ACTs). ACTs consume a large proportion of treatment time, yet the efficacy and effectiveness of ACTs are poorly understood. This study aimed to evaluate associations between the quality and quantity of ACTs and lung function in children and young people with CF.

Methods

Project Fizzyo, a longitudinal observational cohort study in the UK, used remote monitoring with electronic pressure sensors attached to four different commercial ACT devices to record real-time, breath-by-breath pressure data during usual ACTs undertaken at home over 16 months in 145 children. ACTs were categorised either as conformant or not with current ACT recommendations based on breath pressure and length measurements, or as missed treatments if not recorded. Daily, weekly and monthly associations between ACT category and lung function were investigated using linear mixed effects regression models adjusting for clinical confounders.

Results

After exclusions, 45 224 ACT treatments (135 individuals) and 21 069 days without treatments (141 individuals) were analysed. The mean±sdage of participants was 10.2±2.9 years. Conformant ACTs (21%) had significantly higher forced expiratory volume in 1 s (FEV1) (mean effect size 0.23 (95% CI 0.19–0.27) FEV1% pred per treatment) than non-conformant (79%) or missed treatments. There was no benefit from non-conformant or missed treatments and no significant difference in FEV1between them (mean effect size 0.02 (95% CI −0.01–0.05) FEV1% pred per treatment).

Conclusions

ACTs are beneficial when performed as recommended, but most people use techniques that do not improve lung function. Work is needed to monitor and improve ACT quality and to increase the proportion of people doing effective airway clearance at home.
The impact of the immune system on lung injury and regeneration in COPD
Authors: Kapellos Theodore S. , Conlon Thomas M. , Yildirim Ali Önder , Lehmann Mareike
Published: August 2023

COPD is a devastating respiratory condition that manifestsviapersistent inflammation, emphysema development and small airway remodelling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations, and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the micro-environment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarise recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes: 1) the mechanismsviawhich myeloid cells cause alveolar degradation; 2) the formation of tertiary lymphoid structures and the production of autoreactive antibodies; 3) the consequences of inefficient apoptotic cell removal; and 4) the effects of innate and adaptive immune cell signalling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and humanex vivolung models can delineate immune cell–epithelium cross-talk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.
Role of bronchoscopy for respiratory involvement in granulomatosis with polyangiitis and microscopic polyangiitis
Authors: Villeneuve Thomas , Prévot Grégoire , Pugnet Grégory , Plat Gavin , Héluain Valentin , Faguer Stanislas , Guibert Nicolas
Published: August 2023

Objectives

This study describes data from bronchoscopy performed at the diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods

We conducted a retrospective study between 2004 and 2019 in patients aged >18 years with a diagnosis of microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) who underwent bronchoscopy at onset of the disease. We collected bronchoalveolar lavage (BAL) and histological findings obtained during bronchoscopy.

Results

274 patients with AAV were identified. Among 92 bronchoscopies, 62 were performed at diagnosis, and 58 procedures were finally analysed. Cough was more frequent in patients with MPA than GPA (p=0.02). The presence of endobronchial lesions (24.1%) was found to be significantly associated with GPA (p<0.0001) and proteinase 3-ANCA (p=0.01). The most frequent endobronchial lesions were inflammation and hyperaemia of the bronchial mucosa (50%), followed by stenoses (28%), ulcerations (21%) and mass-like granulomatosis (7%). The diagnostic yield of bronchial biopsies was useful for visible lesions (66.6%versus0%; p=0.006). On BAL, diffuse alveolar haemorrhage (DAH) was detected in 31 (53.4%) patients and was more frequent in MPA patients (70.4%versus38.7%; p=0.016). In 16.1% of DAH cases, BAL confirmed the diagnosis despite the absence of clinical or biological arguments. The incidence of microbial infections on BAL (38%) was similar between MPA and GPA (p=0.54).

Conclusion

Bronchoscopy is an informative procedure at the onset of AAV disease in patients with respiratory manifestations. Endobronchial lesions are more frequently found in GPA and should be biopsied. BAL can be used to confirm DAH or diagnose superadded infection.
Update on metabolomic findings in COPD patients
Authors: Gea Joaquim , Enríquez-Rodríguez César J. , Agranovich Bella , Pascual-Guardia Sergi
Published: August 2023

COPD is a heterogeneous disorder that shows diverse clinical presentations (phenotypes and “treatable traits”) and biological mechanisms (endotypes). This heterogeneity implies that to carry out a more personalised clinical management, it is necessary to classify each patient accurately. With this objective, and in addition to clinical features, it would be very useful to have well-defined biological markers. The search for these markers may either be done through more conventional laboratory and hypothesis-driven techniques or relatively blind high-throughput methods, with the omics approaches being suitable for the latter. Metabolomics is the science that studies biological processes through their metabolites, using various techniques such as gas and liquid chromatography, mass spectrometry and nuclear magnetic resonance. The most relevant metabolomics studies carried out in COPD highlight the importance of metabolites involved in pathways directly related to proteins (peptides and amino acids), nucleic acids (nitrogenous bases and nucleosides), and lipids and their derivatives (especially fatty acids, phospholipids, ceramides and eicosanoids). These findings indicate the relevance of inflammatory-immune processes, oxidative stress, increased catabolism and alterations in the energy production. However, some specific findings have also been reported for different COPD phenotypes, demographic characteristics of the patients, disease progression profiles, exacerbations, systemic manifestations and even diverse treatments. Unfortunately, the studies carried out to date have some limitations and shortcomings and there is still a need to define clear metabolomic profiles with clinical utility for the management of COPD and its implicit heterogeneity.
Positive airway pressure treatment affects respiratory symptoms and gastro-oesophageal reflux: the Icelandic Sleep Apnea Cohort Study
Authors: Emilsson Össur Ingi , Aspelund Thor , Janson Christer , Benediktsdottir Bryndis , Juliusson Sigurdur , Maislin Greg , Pack Allan I. , Keenan Brendan T. , Gislason Thorarinn
Published: August 2023

Aim

To study the effect of positive airway pressure (PAP) treatment on nocturnal gastro-oesophageal reflux (nGOR) and respiratory symptoms among clinical obstructive sleep apnoea (OSA) patients.

Methods

822 patients newly diagnosed with OSA referred for PAP treatment were recruited. 732 patients had a 2-year follow-up visit with continuous PAP compliance data (366 full PAP users, 366 partial/non-PAP users). They answered questionnaires, including reporting of nGOR, sleep and respiratory symptoms and general health. Patients with nGOR symptoms once a week or more were defined as “with nGOR”. Those without nGOR symptoms and nGOR medication were defined as “no nGOR”. Others were defined as “possible nGOR”.

Results

At 2-year follow-up, PAP treatment among full users resulted in decreased nGOR (adjusted OR 0.58, 95% CI 0.40–0.86) and wheezing (adjusted OR 0.56, 95% CI 0.35–0.88) compared with partial/non-PAP users. Decreased nGOR, among both full and partial/non-users of PAP treatment, was associated with a decrease in productive morning cough (adjusted OR 4.70, 95% CI 2.22–9.99) and a decrease in chronic bronchitis (adjusted OR 3.86, 95% CI 1.74–8.58), but not decreased wheezing (adjusted OR 0.90, 95% CI 0.39–2.08). A mediation analysis found that PAP treatment directly led to a decrease in wheezing, not mediated through nGOR. Conversely, PAP treatment decreased productive cough mediated through a decrease in nGOR.

Conclusion

In an unselected group of OSA patients, PAP treatment for 2 years was associated with a decrease in nGOR and respiratory symptoms. The PAP treatment itself was associated with less wheezing. A decrease in nGOR through PAP treatment was associated with a decrease in productive cough.
The hospital-to-home care transition experience of home care clients: an exploratory study using patient journey mapping
Authors: Saragosa Marianne , Nizzer Sonia , McKay Sandra , Kuluski Kerry
Published: August 2023

Background

Care transitions have a significant impact on patient health outcomes and care experience. However, there is limited research on how clients receiving care in the home care sector experience the hospital-to-home transition. An essential strategy for improving client care and experience is through client engagement efforts. The study's aim was to provide insight into the care transition experiences and perspectives of home care clients and caregivers of those receiving home care who experienced a hospital admission and returned to home care services by thematically and illustratively mapping their collective journey.

Methods

This study applied a qualitative descriptive exploratory design using a patient journey mapping approach. Home care clients and their caregivers with a recent experience of a hospital discharge back to the community were recruited. A conventional inductive approach to analysis enabled the identification of categories and a collective patient journey map. Follow-up interviews supported the validation of the map.

Results

Seven participants (five clients and two caregivers) participated in 11 interviews. Participants contributed to the production of a collective journey map and the following four categories and themes: (1) Touchpoints as interactions with the health system; Life is changing; (2) Pain points as barriers in the health system: Sensing nobody is listening and Trying to find a good fit; (3) Facilitators to positive care transitions: Developing relationships and gaining some continuity and Trying to advocate, and (4) Emotional impact: Having only so much emotional capacity.

Conclusions

The patient journey map enabled a collective illustration of the care transition depicted in touchpoints, pain points, enablers, and feelings experienced by home care recipients and their caregivers. Patient journey mapping offers an opportunity to acknowledge home care clients and their caregivers as critical to quality care delivery across the continuum.
ATF2-driven osteogenic activity of enoxaparin sodium-loaded polymethylmethacrylate bone cement in femoral defect regeneration
Authors: Ding Luobin , Hao Kangning , Sang Linchao , Shen Xiaoyu , Zhang Ce , Fu Dehao , Qi Xiangbei
Published: August 2023

Background

Polymethylmethacrylate (PMMA) bone cement loaded with enoxaparin sodium (PMMA@ES) has been increasingly highlighted to affect the bone repair of bone defects, but the molecular mechanisms remain unclear. We addressed this issue by identifying possible molecular mechanisms of PMMA@ES involved in femoral defect regeneration based on bioinformatics analysis and network pharmacology analysis.

Methods

The upregulated genes affecting the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were selected through bioinformatics analysis, followed by intersection with the genes of ES-induced differentiation of BMSCs identified by network pharmacology analysis. PMMA@ES was constructed. Rat primary BMSCs were isolated and cultured in vitro in the proliferation medium (PM) and osteogenic medium (OM) to measure alkaline phosphatase (ALP) activity, mineralization of the extracellular matrix, and the expression of RUNX2 and OCN using gain- or loss-of-function experiments. A rat femoral bone defect model was constructed to detect the new bone formation in rats.

Results

ATF2 may be a key gene in differentiating BMSCs into osteoblasts. In vitro cell assays showed that PMMA@ES promoted the osteogenic differentiation of BMSCs by increasing ALP activity, extracellular matrix mineralization, and RUNX2 and OCN expression in PM and OM. In addition, ATF2 activated the transcription of miR-335-5p to target ERK1/2 and downregulate the expression of ERK1/2. PMMA@ES induced femoral defect regeneration and the repair of femoral defects in rats by regulating the ATF2/miR-335-5p/ERK1/2 axis.

Conclusion

The evidence provided by our study highlighted the ATF2-mediated mechanism of PMMA@ES in the facilitation of the osteogenic differentiation of BMSCs and femoral defect regeneration.
Active versus passive distraction for reducing procedural pain and anxiety in children: a meta-analysis and systematic review
Authors: Shen Ting , Wang Xixi , Xue Qiaoyun , Chen Dan
Published: August 2023

Background

Procedural pain is very important in clinical children care. We aimed to evaluate the effects of active versus passive distraction for reducing procedural pain and anxiety in children.

Methods

Two researchers searched the Web of Science, PubMed, EMBASE, Cochrane, SinoMed, Wanfang, China National Knowledge Infrastructure, Weipu databases for the randomized controlled trials(RCTs) on the active versus passive distraction affecting procedural pain and anxiety in children until May 18, 2023. The literature screening and data extraction were carried out by two researchers independently. Review Manager 5.3 software was used for data analysis.

Results

13 RCTs were finally included. 553 children received active distraction intervention and 551 children received passive distraction intervention. There were no significant differences in the children self-reported procedural pain betweent active and passive distraction. The parent-reported procedural pain, medical staff-reported procedural pain, children-reported procedural anxiety, parent-reported procedural anxiety, medical staff-reported procedural anxiety in the active distraction were significant less than that of active distraction. Egger regression analysis showed that there was no publication bias in the results.

Conclusions

Existing evidence suggests that active distraction may be more effective in reducing operational pain and anxiety in children than passive distraction. More studies on the effects of active distraction versus passive distraction in children with larger sample size are needed in the future.
Wolbachia wMel strain-mediated effects on dengue virus vertical transmission from Aedes aegypti to their offspring
Authors: Duong Thi Hue Kien , da Silva Goncalves Daniela , Tran Thuy Vi , Thi Vo Long , Le Thi Dui , Vu Tuyet Nhu , Nguyen Thi Giang , Huynh Thi Xuan Trang , Nguyen Minh Nguyet , Nguyen Thanh Phong , Yacoub Sophie , Simmons Cameron P.
Published: August 2023

Background

Dengue virus serotypes (DENV-1 to -4) can be transmitted vertically in Aedes aegpti mosquitoes. Whether infection with the wMel strain of the endosymbiont Wolbachia can reduce the incidence of vertical transmission of DENV from infected females to their offspring is not well understood.

Methods

A laboratory colony of Vietnamese Ae. aegypti, both with and without wMel infection, were infected with DENV-1 by intrathoracic injection (IT) to estimate the rate of vertical transmission (VT) of the virus. VT in the DENV-infected mosquitoes was calculated via the infection rate estimation from mosquito pool data using maximum likelihood estimation (MLE).

Results

In 6047 F1 Vietnamese wild-type Ae. aegypti, the MLE of DENV-1 infection was 1.49 per 1000 mosquitoes (95% confidence interval [CI] 0.73–2.74). In 5500 wMel-infected Ae. aegypti, the MLE infection rate was 0 (95% CI 0–0.69). The VT rates between mosquito lines showed a statistically significant difference.

Conclusions

The results reinforce the view that VT is a rare event in wild-type mosquitoes and that infection with wMel is effective in reducing VT.

Graphical Abstract
Recent increase in low complexity polygenomic infections and sialic acid-independent invasion pathways in Plasmodium falciparum from Western Gambia
Authors: Nganyewo Nora Nghochuzie , Bojang Fatoumata , Oriero Eniyou Cheryll , Drammeh Ndey Fatou , Ajibola Olumide , Mbye Haddijatou , Jawara Aminata Seedy , Corea Simon , Awandare Gordon Akanzuwine , D’Alessandro Umberto , Amenga-Etego Lucas N. , Amambua-Ngwa Alfred
Published: August 2023

Background

The malaria parasitePlasmodium falciparumutilizes multiple alternative receptor-ligand interactions for the invasion of human erythrocytes. While someP. falciparumclones make use of sialic acid (SA) residues on the surface of the human glycophorin receptors to invade the erythrocyte, others use alternative receptors independent of sialic acid residues. We hypothesized that over the years, intensified malaria control interventions and declining prevalence in The Gambia have resulted in a selection of parasites with a dominant invasion pathways and ligand expression profiles.

Methods

Blood samples were collected from 65 malaria-infected participants with uncomplicated malaria across 3 years (2015, 2016, and 2021). Genetic diversity was determined by genotyping the merozoite surface protein 2 (msp2) polymorphic gene ofP. falciparum.Erythrocyte invasion phenotypes were determined using neuraminidase, trypsin, and chymotrypsin enzymes, known to cleave different receptors from the surface of the erythrocyte. Schizont-stage transcript levels were obtained for a panel of 6P. falciparuminvasion ligand genes (eba175, eba181, Rh2b, Rh4, Rh5, andclag2) using 48 successfully cultured isolates.

Results

Though the allelic heterozygosity ofmsp2repeat region decreased as expected with reduced transmission, there was an increase in infections with more than a singlemsp2allelotype from 2015 to 2021. The invasion phenotypes of these isolates were mostly SA independent with a continuous increase from 2015 to 2021. Isolates from 2021 were highly inhibited by chymotrypsin treatment compared to isolates from 2015 and 2016. Higher invasion inhibition for 2021 isolates was further obtained following erythrocyte treatment with a combination of chymotrypsin and trypsin. The transcript levels of invasion ligand genes varied across years. However, levels ofclag2, a rhoptry-associated protein, were higher in 2015 and 2016 isolates than in 2021 isolates, whileRh5levels were higher in 2021 compared to other years.

Conclusions

Overall, these findings suggest increasing mixed infections with an increase in the use of sialic-acid independent invasion pathways byP. falciparumclinical isolates in the Western part of Gambia.

Graphical Abstract
Fathers’ preconception smoking and offspring DNA methylation
Authors: Kitaba Negusse Tadesse , Knudsen Gerd Toril Mørkve , Johannessen Ane , Rezwan Faisal I. , Malinovschi Andrei , Oudin Anna , Benediktsdottir Bryndis , Martino David , González Francisco Javier Callejas , Gómez Leopoldo Palacios , Holm Mathias , Jõgi Nils Oskar , Dharmage Shyamali C. , Skulstad Svein Magne , Watkins Sarah H. , Suderman Matthew , Gómez-Real Francisco , Schlünssen Vivi , Svanes Cecilie , Holloway John W.
Published: August 2023

Background

Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father’s preconception smoking.

Methods

We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7–50 years) on father’s any preconception smoking (n = 875 offspring) and father’s pubertal onset smoking < 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father’s smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure.

Results

Father’s smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) < 0.05) inPRR5andCENPP. Father’s pubertal onset smoking was associated with 19 CpGs (FDR < 0.05) mapped to 14 genes (TLR9,DNTT,FAM53B,NCAPG2,PSTPIP2,MBIP,C2orf39,NTRK2,DNAJC14,CDO1,PRAP1,TPCN1,IRS1andCSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p < 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father’s smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR < 0.05), and all sites remained significant (p < 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure.

Conclusion

Father’s preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity.
Engineered clinical-grade mesenchymal stromal cells combating SARS-CoV-2 omicron variants by secreting effective neutralizing antibodies
Authors: Wang Yanning , Gao Tianyun , Li WanTing , Tai Chenxu , Xie Yuanyuan , Chen Dong , Liu Shuo , Huang Feifei , Wang Wenqing , Chen Yuxin , Wang Bin
Published: August 2023

Background

The emergence of SARS-CoV-2 becomes life-threatening for the older and immunocompromised individuals, whereas limited treatment is available on these populations. Mesenchymal stromal cells (MSCs) have been reported to be useful in SARS-CoV-2 treatment and reduce SARS-CoV-2-related sequelae.

Results

In this study, we developed an autonomous cellular machine to secret neutralizing antibody in vivo constantly based on the clinical-grade MSCs, to combat SARS-CoV-2 infections. First, various modified recombinant plasmids were constructed and transfected into clinical-grade MSCs by electroporation, for assembly and expression of neutralizing anti-SARS-CoV-2 antibodies. Second, the stable antibody secreting MSCs clones were screened through pseudovirus neutralization assay. Finally, we investigated the pharmacokinetics and biodistribution of neutralizing antibody secreted by engineered MSCs in vivo. The stable clinical-grade MSCs clones, expressing XGv347-10 and LY-CoV1404-5 neutralizing antibodies, exhibited their feasibility and protective efficacy against SARS-CoV-2 infection. Transplanted engineered clinical-grade MSCs effectively delivered the SARS-CoV-2 antibodies to the lung, and the immune hyperresponsiveness caused by COVID-19 was coordinated by MSC clones through inhibiting the differentiation of CD4 + T cells into Th1 and Th17 subpopulations.

Conclusions

Our data suggested that engineered clinical-grade MSCs secreting effective neutralizing antibodies as cellular production machines had the potential to combat SARS-CoV-2 infection, which provided a new avenue for effectively treating the older and immunocompromised COVID-19 patients.
Diagnostic yield, safety and therapeutic consequences of myocardial biopsy in clinically suspected fulminant myocarditis unweanable from mechanical circulatory support
Authors: Marquet Yann , Hékimian Guillaume , Lebreton Guillaume , Kerneis Mathieu , Rouvier Philippe , Bay Pierre , Mathian Alexis , Bréchot Nicolas , Chommeloux Juliette , Petit Matthieu , Gautier Melchior , Lefevre Lucie , Saura Ouriel , Levy David , Quentric Paul , Moyon Quentin , Ortuno Sofia , Schmidt Matthieu , Leprince Pascal , Luyt Charles-Edouard , Combes Alain , Pineton de Chambrun Marc
Published: August 2023

Background

Fulminant myocarditis is a rare and severe disease whose definite and etiological diagnoses rely on pathological examination. Albeit, myocardial biopsy can be associated with significant morbidity and mortality, its therapeutic consequences are unclear. We conducted a study to determine the diagnostic yield, the safety and the therapeutic consequences of myocardial biopsy in patients with fulminant clinically suspected myocarditis unweanable from mechanical circulatory support (MCS).

Methods

Monocenter, retrospective, observational cohort study in a 26-bed French tertiary ICU between January 2002 and February 2019. Inclusion of all fulminant clinically suspected myocarditis patients undergoing in-ICU myocardial biopsy while being on MCS. The primary endpoint was the proportion of patients classified as definite myocarditis using Bonaca criteria before and after including myocardial biopsy results.

Results

Forty-seven patients (median age 41 [30–47], female 53%) were included: 55% died before hospital discharge, 34% could be bridged-to-recovery and 15% bridged-to-transplant. Myocardial biopsy was endomyocardial or surgical in 36% and 64% cases respectively. Tamponade requiring emergency pericardiocentesis occurred in 29% patients after endomyocardial biopsy. After adding the biopsy results in the Bonaca classification algorithm the percentage of definite myocarditis raised from 13 to 55% (p < 0.0001). The rate of biopsy-related treatments modifications was 13%, leading to patients’ recovery in only 4% patients.

Conclusions

In clinically suspected myocarditis unweanable from MCS, myocardial biopsy increased the rate of definite myocarditis but was associated with a low rate of treatment modification and a significant proportion of adverse events. We believe the benefit/risk ratio of myocardial biopsy should be more carefully weighted in these frail and selected patients than suggested by actual guidelines. Further prospective studies are now needed to determine its value in patients under MCS.

Graphical Abstract
Multiple solutions for a class of anisotropic p⃗-Laplacian problems
Authors: Bonanno G. , D’Aguì G. , Sciammetta A.
Published: August 2023

In this paper we present some existence and multiplicity results for a class of anisotropic p⃗-Laplacian problems with Dirichlet boundary conditions. In particular, the existence of three solutions is pointed out. The approach is based on variational methods and our main tool is a three critical point theorem.
The association between Urban and Rural Resident Basic Medical Insurance and instrumental activity of daily living disability among middle-aged and older adults in China
Authors: Sun Jian , Yu Shui , Lu Wanjun , Liu Yujiang
Published: August 2023

Background

Previous studies have not investigated the association between medical insurance and instrumental activity of daily living (IADL) disability. To fulfill this research gap, this study aims to explore the association between Urban and Rural Resident Basic Medical Insurance (URRBMI) and IADL disability among middle-aged and older adults in China.

Methods

The data of this study were sourced from the 2018 wave of China Health and Retirement Longitudinal Study (CHARLS). Logit regression models were used to analyze the association between URRBMI and odds of suffering from IADL disability. Furthermore, we used IV-Probit regression model to address the potential endogeneity problem. Moreover, propensity score matching and generalized random forest model were employed to conduct robustness checks.

Results

The logit regression results reveal that URRBMI participation was significantly related to reduced odds of suffering from IADL disability by 39.86% after adjusting for the control variables (p < 0.01). The results of IV-Probit estimation show that URRBMI was an exogenous variable. Further robustness checks reported similar estimation results. The results of heterogeneity analysis reveal that URRBMI produced a statistically stronger effect on IADL disability for the older adults (OR = 0.5815,p < 0.01) when compared with the middle-aged adults (OR = 0.5690,p < 0.05). The results of impact channel analysis indicate that physical exercise was a channel involving the effect of URRBMI on IADL disability.

Conclusion

This study finds that the middle-aged and older adults who were covered by URRBMI had a reduced possibility of suffering from IADL disability when compared with those without URRBMI. Furthermore, it is found that URRBMI produced a statistically stronger effect on IADL disability for the older adults when compared with the middle-aged adults. Moreover, we obtain evidence indicating that physical exercise was a channel involving the effect of URRBMI on IADL disability.
Consumers' preferences for processed meat: a best–worst scaling approach in three European countries
Authors: Török Áron , Yeh Ching-Hua , Menozzi Davide , Balogh Péter , Czine Péter
Published: August 2023

Processed meat products are a staple part of the typical European diet. Product packaging can include a considerable amount of information and, with other intrinsic and extrinsic attributes, substantially influence consumers' preferences and purchasing decisions. This study investigates 14 product attributes of processed meat products using a cross-country analysis. Based on an online survey conducted in Hungary (n = 410), Italy (n = 268), and Serbia (n = 402), an object-case best–worst scaling approach was applied. Results reveal both international and country-specific characteristics of preferences. Best-Worst scores reveal that taste and best-before date are among the most significant considerations in all three countries, while brand is among the attributes considered least important. Comparisons indicate significant differences according to country and socioeconomic characteristics. The study provides managerial implications.
Predicting moose behaviors from tri-axial accelerometer data using a supervised classification algorithm
Authors: Kirchner Theresa M. , Devineau Olivier , Chimienti Marianna , Thompson Daniel P. , Crouse John , Evans Alina L. , Zimmermann Barbara , Eriksen Ane
Published: August 2023

Background

Monitoring the behavior of wild animals in situ can improve our understanding of how their behavior is related to their habitat and affected by disturbances and changes in their environment. Moose (Alces alces) are keystone species in their boreal habitats, where they are facing environmental changes and disturbances from human activities. How these potential stressors can impact individuals and populations is unclear, in part due to our limited knowledge of the physiology and behavior of moose and how individuals can compensate for stress and disturbances they experience. We collected data from collar-mounted fine-scale tri-axial accelerometers deployed on captive moose in combination with detailed behavioral observations to train a random forest supervised classification algorithm to classify moose accelerometer data into discrete behaviors. To investigate the generalizability of our model to collared new individuals, we quantified the variation in classification performance among individuals.

Results

Our machine learning model successfully classified 3-s accelerometer data intervals from 12 Alaskan moose (A. a. gigas) and two European moose (A. a. alces) into seven behaviors comprising 97.6% of the 395 h of behavioral observations conducted in summer, fall and spring. Classification performance varied among behaviors and individuals and was generally dependent on sample size. Classification performance was highest for the most common behaviors lying with the head elevated, ruminating and foraging (precision and recall across all individuals between 0.74 and 0.90) comprising 79% of our data, and lower and more variable among individuals for the four less common behaviors lying with head down or tucked, standing, walking and running (precision and recall across all individuals between 0.28 and 0.79) comprising 21% of our data.

Conclusions

We demonstrate the use of animal-borne accelerometer data to distinguish among seven main behaviors of captive moose and discuss generalizability of the results to individuals in the wild. Our results can support future efforts to investigate the detailed behavior of collared wild moose, for example in the context of disturbance responses, time budgets and behavior-specific habitat selection.
Testing the effects of passive integrated transponder (PIT) tags on survival, growth, and tag retention of common nase (Chondrostoma nasus L.) and European barbel (Barbus barbus L.)
Authors: Nagel Christoffer , Droll Jan , Kroemer Katharina , Pander Joachim , Geist Juergen
Published: August 2023

Freshwater fish populations are in steep decline, prompting conservation measures and a need for their evaluation. Fish are increasingly monitored with passive integrated transponders (PIT), although the suitability of this tagging technique has not yet been validated for most European target species of conservation. Consequently, this study tested the effect of commonly used 12 mm full-duplex (FDX) PIT tags implanted into the abdominal cavity of common nase (Chondrostoma nasus L.) and European barbel (Barbus barbus L.). A controlled laboratory setup was used to compare survival, growth (both length and weight) and tag retention for two different size classes of sub-adults over 61 days. Survival in the treatment groups was high (96.7–100%) and not statistically different from the control groups (97.5–100%). Highest mortality occurred in small tagged barbel (n = 4; 96.7% survival), while no mortality occurred in large tagged nase. Mean growth rates for tagged fish (2.28 mm, 3.26 g) were similar to those of control fish (2.77 mm, 3.59 g). Overall tag retention rate was 99.0% and tag loss only occurred in nase. The results of this study demonstrate the suitability of PIT injection in the body cavity of nase and barbel > 100 mm TL, which is of high methodological importance given the increasing role these species play in PIT tag-based assessments of freshwater fish conservation in European rivers.
Novel histotypes of sporadic Creutzfeldt–Jakob disease linked to 129MV genotype
Authors: Cracco Laura , Puoti Gianfranco , Cornacchia Antonio , Glisic Katie , Lee Seong‑Ki , Wang Zerui , Cohen Mark L. , Appleby Brian S. , Cali Ignazio
Published: August 2023

The MV1 and MV2 subtypes of sporadic Creutzfeldt–Jakob disease (sCJD) are linked to the heterozygous methionine (M)/valine (V) polymorphism at codon 129 of the prion protein (PrP) gene. MV2 is phenotypically heterogeneous, whereas MV1, due to its low prevalence, is one of the least well characterized subtypes. In this study, we investigated the biochemical properties of PrPSc and phenotypic expression of cases diagnosed as sCJD MV1 and MV2. We describe four MV2 histotypes: 2C, with cortical (C) coarse pathology; 2K, with kuru (K) plaque deposits; 2C-K, with co-existing C and K histotypic features; and the novel histotype 2C-PL that mimics 2C in the cerebral cortex and cerebellum, but exhibits plaque-like (PL) PrP deposits in subcortical regions (e.g., basal nuclei, thalamus and midbrain). Histotype prevalence is highest for 2C-K (55%), intermediate for 2C (31%), and lowest for 2C-PL and 2K (7%). Nearly every MV2 case expressed both PrPSc types, with T2 being the predominant type (“MV2-1”). MV1 cases typically show a rapid disease course (≤ 4 months), and feature the 1C histotype, phenotypically identical to sCJDMM1. Co-existing PrPSc types, with T1 significantly exceeding T2 (“MV1-2”), are detected in patients diagnosed as MV1 with longer disease courses. We observed four histotypes among MV1-2 cases, including two novel histotypes: 1V, reminiscent of sCJDVV1; 1C-2C, resembling sCJDMM1-2 with predominant MM1 histotypic component; and novel histotypes 1C-2PL and 1C-2K, overall mimicking 1C in the cerebral cortex, but harboring T2 and plaque-like PrP deposits in subcortical regions (1C-2PL), and T2 and kuru plaques in the cerebellum (1C-2K). Lesion profiles of 1C, 1V, and 1C-2C are similar, but differ from 1C-2PL and 1C-2K, as the latter two groups show prominent hippocampal and nigral degeneration. We believe that the novel “C-PL” histotypes are distinct entities rather than intermediate forms between “C” and “C-K” groups, and that 1C-2PL and 1C-2K histotypes may be characterized by different T1 variants of the same size.
Big data decision tree for continuous-valued attributes based on unbalanced cut points
Authors: Ma Shixiang , Zhai Junhai
Published: August 2023

The decision tree is a widely used decision support model, which can quickly mine effective decision rules based on the dataset. The decision tree induction algorithm for continuous-valued attributes, based on unbalanced cut points, is efficient for mining decision rules; however, extending it to big data remains an unresolved. In this paper, two solutions are proposed to solve this problem: the first one is based on partitioning instance subsets, whereas the second one uses partitioning attribute subsets. The crucial of these two solutions is how to find the global optimal cut point from the set of local optimal cut points. For the first solution, the calculation of the Gini index of the cut points between computing nodes and the selection of the global optimal cut point by communication between these computing nodes is proposed. However, in the second solution, the division of the big data into subsets using attribute subsets in a way that all cut points of an attribute are on the same map node is proposed, the local optimal cut points can be found in this map node, then the global optimal cut point can be obtained by summarizing all local optimal cut points in the reduce node. Finally, the proposed solutions are implemented with two big data platforms, Hadoop and Spark, and compared with three related algorithms on four datasets. Experimental results show that the proposed algorithms can not only effectively solve the scalability problem, but also have lowest running time, the fastest speed and the highest efficiency under the premise of preserving the classification performance.