bluuebunny/crossref_metadata_2025 huggingface dataset:
Perception of nudge interventions to mitigate medication errors risk in healthcare service delivery
Authors: Chew Keng Sheng , Ooi Say Keat , Abdul Rahim Noor Fareen , Wong Shirly Siew-Ling , Kandasamy Vanitha , Teo Shin-Shin
Published: November 2023

Background

Conventional cognitive interventions to reduce medication errors have been found to be less effective as behavioural change does not always follow intention change. Nudge interventions, which subtly steer one’s choices, have recently been introduced.

Methods

Conducted from February to May 2023, this study aimed to determine the relationships between perceived effectiveness and perceived ease of implementation of six nudge interventions to reduce medication errors, i.e., provider champion, provider’s commitment, peer comparison, provider education, patient education and departmental feedback, and the moderating effects of seniority of job positions and clinical experience on nudge acceptability. Partial Least Square Structural Equation Modelling was used for data analysis.

Results and discussion

All six nudge strategies had significant positive relationships between perceived effectiveness and acceptability. In three out of six interventions, perceived ease of implementation was shown to have positive relationships with perceived acceptability. Only seniority of job position had a significant moderating effect on perceived ease of implementation in peer comparison intervention. Interventions that personally involve senior doctors appeared to have higher predictive accuracy than those that do not, indicating that high power-distance culture influence intervention acceptability.

Conclusion

For successful nudge implementations, both intrinsic properties of the interventions and the broader sociocultural context is necessary.
Challenges and experience of the Ethiopian rural health extension program: implications for reform and revitalization
Authors: Zerfu Taddese Alemu , Tareke Amare Abera , Biadgilign Sibhatu
Published: November 2023

Background

Despite remarkable gains over the past decade, mounting evidence suggests that Ethiopia’s rural health extension program (HEP) is facing serious implementation challenges. We investigated the current and potential future program design and implementation challenges of Ethiopia’s rural HEP based on the lived experiences of health extension workers (HEW) implementing the program at the grassroots level.

Methods

We employed a longitudinal qualitative exploration linked to a larger cluster-randomized trial (RCT) which was implemented in 282 villages randomly selected from 18 Kebeles of the Gedeo zone, southern Ethiopia. Data were collected using in-depth interviews with key informants, focus group discussion, and passive observation of program implementation. The data were analyzed manually using a thematic framework analysis approach. Themes and sub-themes were generated by condensing, summarizing, and synthesizing data collected in the field in the form of extended notes and field observation checklists.

Findings

Despite considerable gains in availing basic health services to the rural population, HEP seems to suffer serious design and implementation flaws that demand thoughtful and immediate adjustment. The design constraints span from the number and type of intervention packages to the means of dissemination (vehicle) as well as the target population emphasized. As such, some low-cost high-impact interventions that were strongly desired by the community were overlooked, while others were inappropriately packed. The means of distribution - female health extension workers trained with basic prevention skills, were lacking essential skills. They also had high burnout rates and with little engagement with men, were repeatedly mentioned flaws of the program demanding revitalization. Furthermore, the sheer structure of HEP precluded adult and adolescent men, non-reproductive women, and the elderly.

Conclusion

Despite significant gains over the last couple of months, Ethiopia’s rural HEP appears to have reached a tipping point that requires a comprehensive revamp of the program package, means of distribution, and target beneficiaries rather than the “usual” tweaks to reap maximum benefits.
Willingness, perceived facilitators and barriers to use remote care among healthcare professionals – a cross-sectional study
Authors: Thomassen Emil Eirik Kvernberg , Berg Inger Jorid , Kristianslund Eirik Klami , Tveter Anne Therese , Østerås Nina
Published: November 2023

Background

Remote care has the potential of improving access to timely care for people with inflammatory joint diseases (IJD), but there is limited knowledge on how this approach is regarded by healthcare professionals (HCP). This study aimed to examine willingness, perceived facilitators, and barriers to use remote care among HCP.

Methods

Employees at 20 rheumatology departments in Norway received a digital survey containing 16 statements regarding willingness, perceived facilitators and barriers to use remote care. Statements were scored using numeric rating scales (NRS, 0–10, 10 = strongly agree), and analysed in linear regression models. Open-ended responses with participant-defined facilitators and barriers were analysed using qualitative manifest analysis.

Results

A total of 130 participants from 17 departments completed the survey. The majority of participants were 45 years or older (n = 84, 54%), 54 (42%) were medical doctors, 48 (37%) nurses, and 27 (21%) were allied healthcare professionals, clinical leaders, or secretaries. A high willingness to use remote care was observed (median NRS: 9, IQR 8–10). The facilitator statement with the highest score was that patients save time and costs by using remote care, whereas the barrier statement with the highest score was the lack of physical examination. Willingness to use remote care was positively associated with the belief that patients wish to use it (β: 0.18, 95% CI: 0.00, 0.34), that patients in remission need less hospital visits (β: 0.30, 95% CI: 0.16, 0.43), and if remote care is widely adopted by co-workers (β: 0.27, 95% CI: 0.15, 0.39). Willingness was negatively associated with mistrust in the technical aspects of remote care (β: -0.26, 95% CI:-0.40, -0.11), and lack of physical examination (β: -0.24, 95% CI: -0.43, -0.06). The open-ended responses showed that technological equipment, eligible patients, user-friendly software, adequate training and work flow could be facilitators, but also that lack of these factors were considered barriers to use remote care.

Conclusion

This study showed that HCP have a high willingness to use remote care, and provides important new knowledge on perceived facilitators and barriers among HCP relevant for implementation of remote care for eligible patients with IJD.
Therapeutic effect and transcriptome-methylome characteristics of METTL3 inhibition in liver hepatocellular carcinoma
Authors: Liu Qingbin , Qi Jingjing , Li Weiyang , Tian Xinchen , Zhang Jiaqi , Liu Fen , Lu Xiulian , Zang Hengchang , Liu Chenqiao , Ma Changlin , Yu Yong , Jiang Shulong
Published: November 2023

Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC.
Exploiting innate immunity for cancer immunotherapy
Authors: Yi Ming , Li Tianye , Niu Mengke , Mei Qi , Zhao Bin , Chu Qian , Dai Zhijun , Wu Kongming
Published: November 2023

Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have already achieved great success, only a tiny percentage of patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined by multiple components in the tumor microenvironment beyond adaptive immunity. Cells from the innate arm of the immune system, such as macrophages, dendritic cells, myeloid-derived suppressor cells, neutrophils, natural killer cells, and unconventional T cells, also participate in cancer immune evasion and surveillance. Considering that the innate arm is the cornerstone of the antitumor immune response, utilizing innate immunity provides potential therapeutic options for cancer control. Up to now, strategies exploiting innate immunity, such as agonists of stimulator of interferon genes, CAR-macrophage or -natural killer cell therapies, metabolic regulators, and novel immune checkpoint blockade, have exhibited potent antitumor activities in preclinical and clinical studies. Here, we summarize the latest insights into the potential roles of innate cells in antitumor immunity and discuss the advances in innate arm-targeted therapeutic strategies.
Role of surgery in T4N0-3M0 esophageal cancer
Authors: Qi Chen , Hu Liwen , Zhang Chi , Wang Kang , Qiu Bingmei , Yi Jun , Shen Yi
Published: November 2023

Background

This study aimed to investigate an unsettled issue that whether T4 esophageal cancer could benefit from surgery.

Methods

Patients with T4N0-3M0 esophageal cancer from 2004 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Kaplan–Meier method, Cox proportional hazard regression, and propensity score matching (PSM) were used to compare overall survival (OS) between the surgery and no-surgery group.

Results

A total of 1822 patients were analyzed. The multivariable Cox regression showed the HR (95% CI) for surgery vs. no surgery was 0.492 (0.427–0.567) (P < 0.001) in T4N0-3M0 cohort, 0.471 (0.354–0.627) (P < 0.001) in T4aN0-3M0 cohort, and 0.480 (0.335–0.689) (P < 0.001) in T4bN0-3M0 cohort. The HR (95% CI) for neoadjuvant therapy plus surgery vs. no surgery and surgery without neoadjuvant therapy vs. no surgery were 0.548 (0.461–0.650) (P < 0.001) and 0.464 (0.375–0.574) (P < 0.001), respectively. No significant OS difference was observed between neoadjuvant therapy plus surgery and surgery without neoadjuvant therapy: 0.966 (0.686–1.360) (P = 0.843). Subgroup analyses and PSM-adjusted analyses showed consistent results.

Conclusion

Surgery might bring OS improvement for T4N0-3M0 esophageal cancer patients, no matter in T4a disease or in T4b disease. Surgery with and without neoadjuvant therapy might both achieve better OS than no surgery.
Hypoxia-inducible factor 1α modulates interstitial pneumonia-mediated lung cancer progression
Authors: Shimoji Kiyofumi , Nakashima Taku , Masuda Takeshi , Namba Masashi , Sakamoto Shinjiro , Yamaguchi Kakuhiro , Horimasu Yasushi , Mimae Takahiro , Miyamoto Shintaro , Iwamoto Hiroshi , Fujitaka Kazunori , Hamada Hironobu , Okada Morihito , Hattori Noboru
Published: November 2023

Background

The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents.

Methods

A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings.

Results

In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis.

Conclusions

The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.
6mA-StackingCV: an improved stacking ensemble model for predicting DNA N6-methyladenine site
Authors: Huang Guohua , Huang Xiaohong , Luo Wei
Published: November 2023

DNA N6-adenine methylation (N6-methyladenine, 6mA) plays a key regulating role in the cellular processes. Precisely recognizing 6mA sites is of importance to further explore its biological functions. Although there are many developed computational methods for 6mA site prediction over the past decades, there is a large root left to improve. We presented a cross validation-based stacking ensemble model for 6mA site prediction, called 6mA-StackingCV. The 6mA-StackingCV is a type of meta-learning algorithm, which uses output of cross validation as input to the final classifier. The 6mA-StackingCV reached the state of the art performances in the Rosaceae independent test. Extensive tests demonstrated the stability and the flexibility of the 6mA-StackingCV. We implemented the 6mA-StackingCV as a user-friendly web application, which allows one to restrictively choose representations or learning algorithms. This application is freely available at http://www.biolscience.cn/6mA-stackingCV/. The source code and experimental data is available at https://github.com/Xiaohong-source/6mA-stackingCV.
Upregulated expression of miR-4443 and miR-4488 in drug resistant melanomas promotes migratory and invasive phenotypes through downregulation of intermediate filament nestin
Authors: Castaldo Vittorio , Minopoli Michele , Di Modugno Francesca , Sacconi Andrea , Liguoro Domenico , Frigerio Rachele , Ortolano Arianna , Di Martile Marta , Gesualdi Luisa , Madonna Gabriele , Capone Mariaelena , Cirombella Roberto , Catizone Angiolina , Del Bufalo Donatella , Vecchione Andrea , Carriero Maria Vincenza , Ascierto Paolo Antonio , Mancini Rita , Fattore Luigi , Ciliberto Gennaro
Published: November 2023

Background

BRAF-mutant melanoma patients benefit from the combinatorial treatments with BRAF and MEK inhibitors. However, acquired drug resistance strongly limits the efficacy of these targeted therapies in time. Recently, many findings have underscored the involvement of microRNAs as main drivers of drug resistance. In this context, we previously identified a subset of oncomiRs strongly up-regulated in drug-resistant melanomas. In this work, we shed light on the molecular role of two as yet poorly characterized oncomiRs, miR-4443 and miR-4488.

Methods

Invasion and migration have been determined by wound healing, transwell migration/invasion assays and Real Time Cell Analysis (RTCA) technology. miR-4488 and miR-4443 have been measured by qRT-PCR. Nestin levels have been tested by western blot, confocal immunofluorescence, immunohistochemical and flow cytometry analyses.

Results

We demonstrate that the two oncomiRs are responsible for the enhanced migratory and invasive phenotypes, that are a hallmark of drug resistant melanoma cells. Moreover, miR-4443 and miR-4488 promote an aberrant cytoskeletal reorganization witnessed by the increased number of stress fibers and cellular protrusions-like cancer cell invadopodia. Mechanistically, we identified the intermediate filament nestin as a molecular target of both oncomiRs. Finally, we have shown that nestin levels are able to predict response to treatments in melanoma patients.

Conclusions

Altogether these findings have profound translational implications in the attempt i) to develop miRNA-targeting therapies to mitigate the metastatic phenotypes of BRAF-mutant melanomas and ii) to identify novel biomarkers able to guide clinical decisions.

Graphical Abstract
Hsa_circ_0009092/miR-665/NLK signaling axis suppresses colorectal cancer progression via recruiting TAMs in the tumor microenvironment
Authors: Song Jialin , Liu Qing , Han Lei , Song Tiantian , Huang Sihao , Zhang Xinyao , He Qiuming , Liang Chenxi , Zhu Shuai , Xiong Bin
Published: November 2023

Background

It has been demonstrated that circularRNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain.

Methods

Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth.

Results

Circ_0009092 was downregulated in CRCand predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/β-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME).

Conclusion

EIF4A3 suppressed circ_0009092 biogenesis, whichinhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/β-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC.
RSK3 switches cell fate: from stress-induced senescence to malignant progression
Authors: Huna Anda , Flaman Jean-Michel , Lodillinsky Catalina , Zhu Kexin , Makulyte Gabriela , Pakulska Victoria , Coute Yohann , Ruisseaux Clémence , Saintigny Pierre , Hernandez-Vargas Hector , Defossez Pierre-Antoine , Boissan Mathieu , Martin Nadine , Bernard David
Published: November 2023

Background

TGFβ induces several cell phenotypes including senescence, a stable cell cycle arrest accompanied by a secretory program, and epithelial-mesenchymal transition (EMT) in normal epithelial cells. During carcinogenesis cells lose the ability to undergo senescence in response to TGFβ but they maintain an EMT, which can contribute to tumor progression. Our aim was to identify mechanisms promoting TGFβ-induced senescence escape.

Methods

In vitro experiments were performed with primary human mammary epithelial cells (HMEC) immortalized by hTert. For kinase library screen and modulation of gene expression retroviral transduction was used. To characterize gene expression, RNA microarray with GSEA analysis and RT-qPCR were used. For protein level and localization, Western blot and immunofluorescence were performed. For senescence characterization crystal violet assay, Senescence Associated-β-Galactosidase activity, EdU staining were conducted. To determine RSK3 partners FLAG-baited immunoprecipitation and mass spectrometry-based proteomic analyses were performed. Proteosome activity and proteasome enrichment assays were performed. To validate the role of RSK3 in human breast cancer, analysis of METABRIC database was performed. Murine intraductal xenografts using MCF10DCIS.com cells were carried out, with histological and immunofluorescence analysis of mouse tissue sections.

Results

A screen with active kinases in HMECs upon TGFβ treatment identified that the serine threonine kinase RSK3, or RPS6KA2, a kinase mainly known to regulate cancer cell death including in breast cancer, reverted TGFβ-induced senescence. Interestingly, RSK3 expression decreased in response to TGFβ in a SMAD3-dependent manner, and its constitutive expression rescued SMAD3-induced senescence, indicating that a decrease in RSK3 itself contributes to TGFβ-induced senescence. Using transcriptomic analyses and affinity purification coupled to mass spectrometry-based proteomics, we unveiled that RSK3 regulates senescence by inhibiting the NF-κΒ pathway through the decrease in proteasome-mediated IκBα degradation. Strikingly, senescent TGFβ-treated HMECs display features of epithelial to mesenchymal transition (EMT) and during RSK3-induced senescence escaped HMECs conserve EMT features. Importantly, RSK3 expression is correlated with EMT and invasion, and inversely correlated with senescence and NF-κΒ in human claudin-low breast tumors and its expression enhances the formation of breast invasive tumors in the mouse mammary gland.

Conclusions

We conclude that RSK3 switches cell fate from senescence to malignancy in response to TGFβ signaling.
Psychoactive substances and previous hospital admissions, triage and length of stay in rural injuries: a prospective observational study
Authors: Wilson Thomas , Wisborg Torben , Vindenes Vigdis , Jamt Ragnhild Elèn Gjulem , Bogstrand Stig Tore
Published: November 2023

Background

Patients admitted to hospital after an injury are often found to have used psychoactive substances prior to the injury. The aim of this study was to investigate the associations between psychoactive substances (alcohol, psychoactive medicinal drugs and illicit drugs) and previous hospital admissions, triage and length of stay in the arctic Norwegian county of Finnmark.

Methods

Patients ≥ 18 years admitted due to injury to trauma hospitals in Finnmark from January 2015 to August 2016 were approached. Parameters regarding admittance and hospital stay were collected from 684 patients and blood was analysed for psychoactive substances. Using a prospective, observational design, time, triage, length of stay in hospital, use of intensive care unit (ICU), injury severity, Alcohol Use Disorder Identification Test—Consumption (AUDIT-C) and number of previous admittances were investigated by bivariable testing and logistical regression analysis.

Results

Of 943 patients approached, 81% consented and 684 were included in the study. During the weekend, 51.5% tested positive for any substance versus 27.1% Monday–Friday. No associations were identified between testing positive and either triage or injury severity for any substance group although triage level was lower in patients with AUDIT-C ≥ 5. Short length of stay was associated with alcohol use prior to injury [odds ratio (OR) 0.48 for staying > 12 h, confidence interval (CI) 0.25–0.90]. The OR for staying > 24 h in the ICU when positive for an illicit substance was 6.33 (CI 1.79–22.32) while negatively associated with an AUDIT-C ≥ 5 (OR 0.30, CI 0.10–0.92). Patients testing positive for a substance had more often previously been admitted with the strongest association for illicit drugs (OR 6.43 (CI 1.47–28.08), compared to patients in whom no substances were detected.

Conclusions

Triage level and injury severity were not associated with psychoactive substance use. Patients using alcohol are more often discharged early, but illicit substances were associated with longer ICU stays. All psychoactive substance groups were associated with having been previously admitted.
Patient and process factors associated with opportunities for improvement in trauma care: a registry-based study
Authors: Albaaj Hussein , Attergrim Jonatan , Strömmer Lovisa , Brattström Olof , Jacobsson Martin , Wihlke Gunilla , Västerbo Liselott , Joneborg Elias , Gerdin Wärnberg Martin
Published: November 2023

Background

Trauma is one of the leading causes of morbidity and mortality worldwide. Morbidity and mortality review of selected patient cases is used to improve the quality of trauma care by identifying opportunities for improvement (OFI). The aim of this study was to assess how patient and process factors are associated with OFI in trauma care.

Methods

We conducted a registry-based study using all patients between 2017 and 2021 from the Karolinska University Hospital who had been reviewed regarding the presence of OFI as defined by a morbidity and mortality conference. We used bi- and multivariable logistic regression to assess the associations between the following patient and process factors and OFI: age, sex, respiratory rate, systolic blood pressure, Glasgow Coma Scale (GCS), Injury Severity Score (ISS), survival at 30 days, highest hospital care level, arrival on working hours, arrival on weekends, intubation status and time to first computed tomography (CT).

Results

OFI was identified in 300 (5.8%) out of 5182 patients. Age, missing Glasgow Coma Scale, time to first CT, highest hospital care level and ISS were statistically significantly associated with OFI.

Conclusion

Several patient and process factors were found to be associated with OFI, indicating that patients with moderate to severe trauma and those with delays to first CT are at the highest odds of OFI.
Extending the ‘host response’ paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities
Authors: Buckel Marie , Maclean Patrick , Knight Julian C. , Lawler Patrick R. , Proudfoot Alastair G.
Published: November 2023

Recent clinical and research efforts in cardiogenic shock (CS) have largely focussed on the restoration of the low cardiac output state that is the conditio sine qua non of the clinical syndrome. This approach has failed to translate into improved outcomes, and mortality has remained static at 30–50%. There is an unmet need to better delineate the pathobiology of CS to understand the observed heterogeneity of presentation and treatment effect and to identify novel therapeutic targets. Despite data in other critical illness syndromes, specifically sepsis, the role of dysregulated inflammation and immunity is hitherto poorly described in CS. High-dimensional molecular profiling, particularly through leukocyte transcriptomics, may afford opportunity to better characterise subgroups of patients with shared mechanisms of immune dysregulation. In this state-of-the-art review, we outline the rationale for considering molecular subtypes of CS. We describe how high-dimensional molecular technologies can be used to identify these subtypes, and whether they share biological features with sepsis and other critical illness states. Finally, we propose how the identification of molecular subtypes of patients may enrich future clinical trial design and identification of novel therapies for CS.

Graphical Abstract
Discovery of novel alkaline-tolerant xylanases from fecal microbiota of dairy cows
Authors: Zhang Xiaoling , Miao Qin , Tang Bingling , Mijakovic Ivan , Ji Xiao-Jun , Qu Lingbo , Wei Yongjun
Published: November 2023

Xylo-oligosaccharides (XOS) are considered as a promising type of prebiotics that can be used in foods, feeds, and healthcare products. Xylanases play a key role in the production of XOS from xylan. In this study, we conducted a metagenomic analysis of the fecal microbiota from dairy cows fed with different types of fodders. Despite the diversity in their diets, the main phyla observed in all fecal microbiota were Firmicutes and Bacteroidetes. At the genus level, one group of dairy cows that were fed probiotic fermented herbal mixture-containing fodders displayed decreased abundance of Methanobrevibacter and increased growth of beneficial Akkermansia bacteria. Additionally, this group exhibited a high microbial richness and diversity. Through our analysis, we obtained a comprehensive dataset comprising over 280,000 carbohydrate-active enzyme genes. Among these, we identified a total of 163 potential xylanase genes and subsequently expressed 34 of them in Escherichia coli. Out of the 34 expressed genes, two alkaline xylanases with excellent temperature stability and pH tolerance were obtained. Notably, CDW-xyl-8 exhibited xylanase activity of 96.1 ± 7.5 U/mg protein, with an optimal working temperature of 55 ℃ and optimal pH of 8.0. CDW-xyl-16 displayed an activity of 427.3 ± 9.1 U/mg protein with an optimal pH of 8.5 and an optimal temperature at 40 ℃. Bioinformatic analyses and structural modeling suggest that CDW-xyl-8 belongs to GH10 family xylanase, and CDW-xyl-16 is a GH11 family xylanase. Both enzymes have the ability to hydrolyze beechwood xylan and produce XOS. In conclusion, this metagenomic study provides valuable insights into the fecal microbiota composition of dairy cows fed different fodder types, revealing main microbial groups and demonstrating the abundance of xylanases. Furthermore, the characterization of two novel xylanases highlights their potential application in XOS production.
Efficacy of a chewable tablet containing sarolaner, moxidectin, and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange caused by Sarcoptes scabiei mite infestations in dogs
Authors: Becskei Csilla , Liebenberg Julian , Fernandes Tiago , Borowski Stasia , D’Hanis Lina , Mahabir Sean P.
Published: November 2023

Background

Infestation with Sarcoptes scabiei in dogs is a debilitating disease if left untreated and is transmissible to humans. Two field studies were conducted to confirm the efficacy of orally administered sarolaner in combination with moxidectin and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange in dogs.

Methods

Client-owned dogs with S. scabiei infestation were enrolled and received 2 monthly treatments. In the first, small-scale study, 12 dogs each were allocated randomly to treatment with either placebo or Simparica Trio®. Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, 44, and 60. Efficacy was calculated based on the percent reduction in arithmetic mean live mite counts relative to placebo. In the second, large-scale study, 75 dogs were allocated randomly to treatment with Simparica Trio® and 37 to treatment with afoxolaner + milbemycin oxime (NexGard Spectra®). Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, and 60. The parasitological cure rate (percentage of dogs without live mites) was determined and non-inferiority of Simparica Trio® to the control product was assessed.

Results

In the small-scale study, 2 monthly doses of Simparica Trio® resulted in a significant reduction (P ≤ 0.0050) in live S. scabiei mite numbers and provided a 99.2% reduction relative to placebo by Day 60. Clinical signs of sarcoptic mange improved throughout the study in Simparica Trio®-treated dogs. In the large-scale study, the parasitological cure rate on Days 30 and 60 was 97.3% and 100% in the Simparica Trio® group and 91.9% and 100% in the afoxolaner + milbemycin oxime group, respectively. The parasitological cure rate for Simparica Trio® was non-inferior to afoxolaner + milbemycin oxime at both time points. Clinical signs of sarcoptic mange improved throughout the study in both groups.

Conclusions

Two-monthly doses of Simparica Trio® reduced S. scabiei mite counts by 99.2% relative to placebo in one study and eliminated S. scabiei mites in 100% of dogs in the second study, thus confirming that Simparica Trio® is highly effective in the treatment of sarcoptic mange in dogs caused by S. scabiei var. canis.

Graphical abstract
Systematic review of sporozoite infection rate of Anopheles mosquitoes in Ethiopia, 2001–2021
Authors: Aschale Yibeltal , Getachew Aklilu , Yewhalaw Delenasaw , De Cristofaro Antonio , Sciarretta Andrea , Atenafu Getnet
Published: November 2023

Background

Adult mosquitoes of the genus Anopheles are important vectors of Plasmodium parasites, causative agents of malaria. The aim of this review was to synthesize the overall and species-specific proportion of Anopheles species infected with sporozoites and their geographical distribution in the last 2 decades (2001–2021).

Methods

A comprehensive search was conducted using databases (PubMed, Google Scholar, Science Direct, Scopus, African Journals OnLine) and manual Google search between January 1 and February 15, 2022. Original articles describing work conducted in Ethiopia, published in English and reporting infection status, were included in the review. All the required data were extracted using a standardized data extraction form, imported to SPSS-24, and analyzed accordingly. The quality of each original study was assessed using a quality assessment tool adapted from the Joanna Briggs Institute critical appraisal checklist. This study was registered on PROSPERO (International Prospective Register of Systematic Reviews; registration no. CRD42022299078).

Results

A search for published articles produced a total of 3086 articles, of which 34 met the inclusion criteria. Data on mosquito surveillance revealed that a total of 129,410 anophelines comprising 25 species were captured, of which 48,365 comprising 21 species were tested for sporozoites. Anopheles arabiensis was the dominant species followed by An. pharoensis and An. coustani complex. The overall proportion infected with sporozoites over 21 years was 0.87%. Individual proportions included Anopheles arabiensis (1.09), An. pharoensis (0.79), An. coustani complex (0.13), An. funestus (2.71), An. demeilloni (0.31), An. stephensi (0.70), and An. cinereus (0.73). Plasmodium falciparum sporozoites accounted 79.2% of Plasmodium species. Mixed infection of Plasmodium vivax and P. falciparum was only reported from one An. arabiensis sample.

Conclusions

Anopheles arebiensis was the dominant malaria vector over the years, with the highest sporozoite infection proportion of 2.85% and an average of 0.90% over the years. Other species contributing to malaria transmission in the area were An. pharoensis, An. coustani complex, An. funestus, An. stephensi, and An. coustani. The emergence of new vector species, in particular An. stephensi, is particularly concerning and should be investigated further.

Graphical Abstract
Data of whole-genome sequencing of Karakul, Zel, and Kermani sheep breeds
Authors: Saadatabadi Leila Mohammadipour , Mohammadabadi Mohammadreza , Ghanatsaman Zeinab Amiri , Babenko Olena , Stavetska Ruslana Volodymyrivna , Kalashnik Oleksandr Mikolayovich , Afanasenko Volodymyr , Kochuk-Yashchenko Oleksandr Anatoliiovych , Kucher Dmytro Mykolaiovych , Nanaei Hojjat Asadollahpour
Published: November 2023

Objective

The data provided herein represent the whole-genome sequencing data associated with three sheep breeds of Iranian native breeds. Sheep are the first domesticated animals that, during the long path of the evolution process, have created gene variants with desirable phenotypic effects, so they can be suitable models for biomedical research. In addition, sheep have a vital role in providing protein to a notable part of the human population around the world.

Data description

Ten blood samples were taken from three Iranian native sheep breeds, the Zel, Karakul, and Kermani kinds. Blood samples genomes were extracted using the salting-out technique. The Illumina NovaSeq 6000 platform was used to carry out sequencing of the whole genome in a laboratory in China. All sequence information is available through the NCBI database in the sequence read archive (SRA) format under the accession number PRJNA904537. The dataset presented here can provide a useful resource for genome analysis of livestock breeds adapted to hot and dry regions.
Exploring shared neural substrates underlying cognition and gait variability in adults without dementia
Authors: Byun Seonjeong , Lee Hyang Jun , Kim Jun Sung , Choi Euna , Lee Subin , Kim Tae Hui , Kim Jae Hyoung , Han Ji Won , Kim Ki Woong
Published: November 2023

Background

High gait variability is associated with neurodegeneration and cognitive impairments and is predictive of cognitive impairment and dementia. The objective of this study was to identify cortical or subcortical structures of the brain shared by gait variability measured using a body-worn tri-axial accelerometer (TAA) and cognitive function.

Methods

This study is a part of a larger population-based cohort study on cognitive aging and dementia. The study included 207 participants without dementia, with a mean age of 72.6, and 45.4% of them are females. We conducted standardized diagnostic interview including a detailed medical history, physical and neurological examinations, and laboratory tests for cognitive impairment. We obtained gait variability during walking using a body-worn TAA along and measured cortical thickness and subcortical volume from brain magnetic resonance (MR) images. We cross-sectionally investigated the cortical and subcortical neural structures associated with gait variability and the shared neural substrates of gait variability and cognitive function.

Results

Higher gait variability was associated with the lower cognitive function and thinner cortical gray matter but not smaller subcortical structures. Among the clusters exhibiting correlations with gait variability, one that included the inferior temporal, entorhinal, parahippocampal, fusiform, and lingual regions in the left hemisphere was also associated with global cognitive and verbal memory function. Mediation analysis results revealed that the cluster’s cortical thickness played a mediating role in the association between gait variability and cognitive function.

Conclusion

Gait variability and cognitive function may share neural substrates, specifically in regions related to memory and visuospatial navigation.
Human placental extract suppresses mast cell activation and induces mast cell apoptosis
Authors: Wu Tongqian , He Jingjing , Yan Shirong , Li Jing , Chen Ke , Zhang Dingshan , Cheng Mingliang , Xiang Zou , Fang Yu
Published: November 2023

Background

Human placental extract (HPE) has been documented to facilitate the healing of certain disorders including allergy. However, the effects of HPE on the functionality of mast cells, a critical cell type in allergic diseases, have not been reported.

Methods

To investigate the effects of HPE on the regulation of allergy with respect to the biological functions of mast cells, the mast cell line C57 or HMC-1 cells were treated with HPE followed by the assessment of cell proliferation, apoptosis, activation, chemotaxis and phagocytosis. Mouse peritoneal mast cells were also investigated for their responses to induction of apoptosis by HPE in vivo. Furthermore, the effect of HPE on mast cell degranulation was confirmed using the passive cutaneous anaphylaxis (PCA) assay, an acute allergy model.

Results

HPE was capable of suppressing mast cell proliferation and inducing mast cell apoptosis. Mast cell degranulation in response to compound 48/80- or anti-DNP IgE and DNP-mediated activation was suppressed. In addition, treatment with HPE compromised the production of cytokines by mast cells and cell chemotaxis. These observations were consistent with the dampened passive cutaneous anaphylaxis (PCA) assay following treatment with HPE.

Conclusion

This study revealed a suppressive effect of HPE on overall mast cell activities, suggesting a potential regulatory role of HPE on the alleviation of allergic diseases through mast cells.
Quality of life is lower in food allergic adolescents compared to young children at a community educational symposium
Authors: Nguyen Diem-Tran I. , Pitts Kathleen , Staggers Kristen A. , Davis Carla M.
Published: November 2023

Introduction

Food allergies (FA) can detrimentally impact physical, emotional, and psychological quality of life (QoL) among pediatric patients. Given the changes from childhood into adolescence, the impact of FA on QoL likely evolves with age. The purpose of this study was to determine whether QoL differed between adolescents and children with FA who participated in a Food Allergy Symposium (FAS).

Methods

Patients with confirmed FA were recruited at an educational community symposium in September 2018 and September 2019. Patients and/or their parents were invited to complete the Food Allergy Quality of Life Questionnaires (FAQLQ). The Food Allergy Independent Measure (FAIM) reflects concerns about accidental food exposure and disease severity. Higher FAIM and FAQLQ scores reflect worse QoL. Summary scores were compared using the Wilcoxon rank sum test, Fisher’s exact test, or the Chi-square test.

Results

Seventy-four surveys (82% children, 18% adolescents) were included. The FAQLQ total score was higher among adolescents than children (median 5.2 vs 4.2; p = 0.045), and the FAIM was lower in adolescents (median 2.2 vs 2.8; p = 0.037). More adolescents reported previous anaphylaxis than children (91.7% vs 51.8%; p = 0.011). The percentage reassured by having epinephrine was higher in adolescents (81.8% vs 45.8%; p = 0.046). No other QoL scores and survey responses were significantly different.

Discussion

In this study, adolescents were more concerned about their disease and more reassured by epinephrine carriage than younger children, which may reflect increased autonomy and responsibility. Community events are an important way to assess QoL and provide FA-related education to pediatric patients.
Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications
Authors: Lefebvre Aline , Traut Nicolas , Pedoux Amandine , Maruani Anna , Beggiato Anita , Elmaleh Monique , Germanaud David , Amestoy Anouck , Ly-Le Moal Myriam , Chatham Christopher , Murtagh Lorraine , Bouvard Manuel , Alisson Marianne , Leboyer Marion , Bourgeron Thomas , Toro Roberto , Dumas Guillaume , Moreau Clara , Delorme Richard
Published: November 2023

Background

Repetitive and restricted behaviors and interests (RRBI) are core symptoms of autism with a complex entity and are commonly categorized into ‘motor-driven’ and ‘cognitively driven’. RRBI symptomatology depends on the individual’s clinical environment limiting the understanding of RRBI physiology, particularly their associated neuroanatomical structures. The complex RRBI heterogeneity needs to explore the whole RRBI spectrum by integrating the clinical context [autistic individuals, their relatives and typical developing (TD) individuals]. We hypothesized that different RRBI dimensions would emerge by exploring the whole spectrum of RRBI and that these dimensions are associated with neuroanatomical signatures—involving cortical and subcortical areas.

Method

A sample of 792 individuals composed of 267 autistic subjects, their 370 first-degree relatives and 155 TD individuals was enrolled in the study. We assessed the whole patterns of RRBI in each individual by using the Repetitive Behavior Scale-Revised and the Yale-Brown Obsessive Compulsive Scale. We estimated brain volumes using MRI scanner for a subsample of the subjects (n = 152, 42 ASD, 89 relatives and 13 TD). We first investigated the dimensionality of RRBI by performing a principal component analysis on all items of these scales and included all the sampling population. We then explored the relationship between RRBI-derived factors with brain volumes using linear regression models.

Results

We identified 3 main factors (with 30.3% of the RRBI cumulative variance): Factor 1 (FA1, 12.7%) reflected mainly the ‘motor-driven’ RRBI symptoms; Factor 2 and 3 (respectively, 8.8% and 7.9%) gathered mainly Y-BOCS related items and represented the ‘cognitively driven’ RRBI symptoms. These three factors were significantly associated with the right/left putamen volumes but with opposite effects: FA1 was negatively associated with an increased volume of the right/left putamen conversely to FA2 and FA3 (all uncorrected p < 0.05). FA1 was negatively associated with the left amygdala (uncorrected p < 0.05), and FA2 was positively associated with the left parietal structure (uncorrected p = 0.001).

Conclusion

Our results suggested 3 coherent RRBI dimensions involving the putamen commonly and other structures according to the RRBI dimension. The exploration of the putamen’s integrative role in RSBI needs to be strengthened in further studies.
Real-world application of a discrete feedback control system for flexible biogas production
Authors: Putra Lingga Aksara , Huber Bernhard , Gaderer Matthias
Published: November 2023

Using renewable energy is increasingly prevalent as part of a global effort to safeguard the environment, with a reduction in $${\mathrm{CO}}_{2}$$

CO
2

being one of the primary objectives. A biogas plant provides an opportunity to produce green energy, but its profitability prevents it from being utilized more frequently. A suitable response to this economic issue would be flexible biogas production to exploit fluctuating energy prices. Nevertheless, the complex nature of the anaerobic digestion process that proceeds within the biogas plant and the wide range of substrates that may be utilized as the plant’s feeds make it challenging to achieve flexible biogas production truly. Most plant operators will rely on their experience and intuition to run the plant without knowing exactly how much biogas they will produce with the feed substrate. This work combines a system model estimation and feedback controller to provide an intuitive yet precise feedback control system. The system model estimation represents the biogas plant mathematically, and a total of six distinct approaches have been compared and evaluated. A PT1 model most accurately approximated the step-down and the step-up by the time percentage method, with the Akaike Information Criterion as the primary evaluation criterion for selecting the best model. The downward model was controlled by a discrete PI controller modified with the Root Locus Method and an Anti-Windup scheme, and the upward model was controlled by a state space controller. The quality of the controller was evaluated in both simulation and at the actual biogas plant in Grub, and the controller was able to reduce the biogas production rate approaching the setpoint in the expected period. Furthermore, the developed feedback control system is effortless enough to be installed in many biogas plants.