bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated social sustainability assessment framework: the case of construction industry
Authors: Taherkhani Roohollah
Published: September 2022

Purpose

The discourse of construction practitioners and decision-makers worldwide has begun to appreciate and acknowledge the advantages of sustainable building. Toward this goal, one of the main steps is creating a control mechanism, which provides the context for moving to sustainable buildings by monitoring the environmental, economic and social dimensions of sustainability. The previous research studies indicate the social dimension has received far less attention than the economic and environmental aspects. Therefore, this study aims at developing a social sustainability framework to evaluate building systems.

Design/methodology/approach

This research has chosen the Parsons sociological theory as its theoretical framework basis and acquires the research theoretical framework with its modification and completion by grounded theory (GT). In the next step, to realize the GT structure validity and model fitting, the confirmatory factor analysis (CFA) was used and the research hypotheses were tested.

Findings

An integrated social sustainable framework is presented with five subsystems: socio-political, socio-cultural, socio-institutional, socio-economic and socio-environmental. This research addresses the void of a comprehensive social sustainability framework in the construction industry, and the findings can contribute to construction industry practitioners and decision-makers to evaluate building systems socially.

Originality/value

The application of this framework is not limited to the construction industry and building systems. It can deliver a general use for integrating social perspectives into decision-making on various subjects. Localization and specialization of current research's social sustainability components and factors can be a high potential research topic for future studies, in all fields and scopes. This framework can be a significant contribution to the sustainable development goals (SDGs) as a basis for creating comparable models to assess social aspects of buildings, campuses and urban sustainability.
Chemical and microbiological stability and sensorial properties of traditional Iranian butter incorporated with pomegranate peel extract
Authors: Ebrahimian Maryam , Mehdizadeh Tooraj , Aliakbarlu Javad
Published: September 2022

In this study, the antioxidant activity of pomegranate peel extract (PPE) and its potential effect on the chemical and microbiological stability of traditional butter was investigated. The PPE having total phenol content of 327.48 ± 1.43 mg gallic acid equivalent/g showed significantly greater (64.34 ± 0.32%) radical scavenging activity than butylated hydroxy toluene. Butter treated with PPE had significantly lower levels of peroxide value, free fatty acids, Totox, Schaal value and microbial population. The work concluded that PPE could be an excellent natural source of antimicrobial and antioxidant substances, which can be used for traditional butter preservation.
Chronological analysis of the gut microbiome for efficacy of atezolizumab‐based immunotherapy in non‐small cell lung cancer: Protocol for a multicenter prospective observational study
Authors: Shoji Fumihiro , Miura Naoko , Tagawa Tetsuzo , Tsukamoto Shuichi , Okamoto Tatsuro , Yamazaki Koji , Hamatake Motoharu , Takeo Sadanori
Published: September 2022

Background

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is an innovative treatment for non‐small cell lung cancer (NSCLC). Recently, the specific composition of the gut microbiome before initiation of cancer immunotherapy has been highlighted as a predictive biomarker in patients undergoing cancer immunotherapy, mainly in the US or Europe. However, the fact gut microbiome status is completely different in races or countries has been revealed. In addition, how the microbiome composition and diversity chronologically change during cancer immunotherapy is still unclear.

Methods

This multicenter, prospective observational study will analyze the association between the gut microbiome and therapeutic response in NSCLC patients who received atezolizumab‐based immunotherapy. The aim of the present study is to clarify not only how the specific composition of the gut microbiome influences clinical response in NSCLC patients but the chronological changes of gut microbiota during atezolizumab‐based immunotherapy. The gut microbiota will be analyzed using 16S rRNA gene sequencing. The main inclusion criteria are as follows: (1) Pathologically‐ or cytologically‐confirmed stage IV or postoperative recurrent NSCLC. (2) Patients ≥20 years old at the time of informed consent. (3) Planned to treat with atezolizumab‐based immunotherapy combined with platinum‐based chemotherapy (cohort 1) and monotherapy (cohort 2) as a first immunotherapy. (4) Patients to provide fecal samples. A total of 60 patients will be enrolled prospectively. Enrollment will begin in 2020 and the final analyses will be completed by 2024.

Discussion

This trial will provide more evidence of how gut microbiota composition and diversity chronologically change during cancer immunotherapy and contribute to the development of biomarkers to predict ICI response as well as biotic therapies which enhance the ICI response.
A randomized, double‐blind, placebo‐controlled, pharmacogenetic study of ondansetron for treating alcohol use disorder
Authors: Seneviratne Chamindi , Gorelick David A. , Lynch Kevin G. , Brown Clayton , Romer Danielle , Pond Timothy , Kampman Kyle , Kranzler Henry R.
Published: September 2022

Background

In a previous study, ondansetron, a serotonin 5‐HT3 receptor antagonist, reduced drinking intensity (drinks/drinking day [DPDD]) among European‐ancestry (EA) participants with moderate‐to‐severe alcohol use disorder (AUD) and variants in genes encoding the serotonin transporter (SLC6A4) and 5‐HT3A (HTR3A), and 5‐HT3B (HTR3B) receptors. We tested whether (1) ondansetron reduces DPDD among individuals of either European or African ancestry (AA), and (2) that reductions in DPDD are greatest among ondansetron‐treated individuals with population‐specific combinations of genotypes at SLC6A4, HTR3A, and HTR3B.

Methods

In this 16‐week, double‐blind, placebo‐controlled, parallel‐group clinical trial, adults with AUD were randomized to receive low‐dose oral ondansetron (0.33 mg twice daily) or placebo stratified by “responsive” versus “nonresponsive” genotype defined using population‐specific genotypes at the three genetic loci. Generalized estimating equation regression models and a modified intent‐to‐treat analysis were used to compare the treatment groups on the primary outcome—DPDD—and two secondary outcomes—heavy drinking days per week [HDD] and drinks per day [DPD] across the 16 weeks of treatment.

Results

Of 296 prospective participants screened, 95 (58 EA and 37 AA) were randomized and received at least one dose of study medication. In the modified intent‐to‐treat analysis, the ondansetron group averaged 0.40 more DPDD (p = 0.51), 1.35 times as many HDD (p = 0.16), and 1.06 times as many DPD (p = 0.59) as the placebo group. There were no significant interactions with genotype. There were no study‐related serious adverse events (AEs) and similar proportions of participants in the two treatment groups experienced AEs across organ systems.

Conclusions

We found no evidence that low‐dose oral ondansetron is beneficial in the treatment of AUD, irrespective of genotype, thus failing to confirm prior study findings. However, the study was underpowered to identify medication by genotype interactions.
Fetal alcohol spectrum disorders and access to regional center services in San Diego County
Authors: Montag Annika C. , Jones Kenneth Lyons , del Campo Miguel , Akshoomoff Natacha , Coles Claire D. , Kable Julie A. , Hernandez John‐Gregorey , Chambers Christina D.
Published: September 2022

Background

Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2–5% of elementary school children and that negatively impact a child's ability to function without support. Timely diagnosis‐informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown.

Methods

An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5‐ to 7‐year‐old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria.

Results

Among 216 eligible caregiver‐child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol‐related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services.

Conclusions

The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5‐ to 7‐year‐old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD.
Drought and stand susceptibility to attacks by the European spruce bark beetle: A remote sensing approach
Authors: Nardi Davide , Jactel Hervé , Pagot Elodie , Samalens Jean‐Charles , Marini Lorenzo
Published: September 2022

Several time‐series analyses have demonstrated that after extreme summer drought bark beetle damage increased. However, studies predicting stand susceptibility over large spatial extents are limited by technical constraints in obtaining detailed, spatially‐explicit data on infestation spot occurrence.

Using a unique dataset of georeferenced bark beetle infestation data, we tested whether the spatial variation of local growing conditions of forest stands, topography, and landscape variables modified the local occurrence of Ips typographus infestations after a severe hot drought in Central Europe.

Bark beetle infestation occurrence depended on soil‐related aridity intensity, elevation, slope, and soil conditions. We showed that elevation interacted with growing conditions and topography. At low elevations, spruce forests growing on flat areas and wetter soils were more sensitive to the infestations. On the contrary, forests on steep slopes and soils with low water availability were rarely attacked. At the landscape scale, bark beetle damage increased with host tree cover but decreased with compositional diversity.

Our findings are generally consistent with the growth‐differentiation balance hypothesis that predicts that trees growing under chronic dry conditions tend to be more resistant against biotic disturbances.

Spruce stands at low elevations located in homogeneous landscapes dominated by spruce were those more exposed to bark beetles in the initial phase of a drought‐induced outbreak.
Causes of platelet loss during extracorporeal life support
Authors: Atchison Christie , Widdershins Afton , Chandler Wayne L.
Published: September 2022

Background

Most pediatric patients show a decline in platelet counts while on extracorporeal life support (ECLS) and require multiple platelet transfusions. To better understand platelet loss during ECLS, this study estimated platelet loss rates due to diagnostic phlebotomy, platelet activation, bleeding and other causes.

Methods

We collected data on 91 patients (1d‐20y, 50 M, 41F). Platelet losses were estimated based on changes in platelet count, patient+circuit blood volume, and transfused platelet volumes. Platelet extracellular vesicles were measured by flow cytometry.

Results

Median platelet loss was 2.8 × 109/L/hr, more than twice the normal rate of platelet removal and equivalent to a 67 000/μl decrease in platelet count per day. While platelet loss was correlated with platelet transfusion (r2 = 0.51), transfusion underestimated platelet loss in patients with large decreases in platelet count and over‐estimated platelet loss in neonates where the circuit volume > patient blood volume. Patients with disseminated intravascular coagulation before or significant bleeding during ECLS have double the rate of platelet loss. Platelet activation accounted for ~32% of total platelet loss, bleeding ~36% and phlebotomy 4%, with the remaining one‐third due to other causes. Annexin‐negative platelet extracellular vesicle release, a measure of platelet damage, was increased 9‐fold during ECLS.

Conclusion

Our study is the first to quantitate total, phlebotomy and activation related platelet loss during ECLS. Platelet activation accounts for ~32% of total platelet loss, while bleeding doubles the platelet loss rate. The etiology of the remaining platelet loss is unknown.
Neonatal outcomes of foetal micrognathia: An 11‐year review
Authors: Sammut Audrienne , Knight Caroline L. , O'Sullivan Hannah Rosen , Meau‐Petit Virginie
Published: September 2022

Aim

To identify antenatal features associated with foetal micrognathia that can predict a challenging postnatal management, including difficult airway at delivery, feeding problems and impaired neurological outcomes.

Methods

Single‐centre retrospective observational study. Data for antenatally diagnosed cases of micrognathia over 11 years were obtained and analysed.

Results

A total of 38 cases were identified, 20 were live births. Of the 16 inborn infants, all had associated congenital anomalies: 14 were diagnosed antenatally, two postnatally. Six of the 16 infants had difficult intubation at birth and three required a tracheostomy. Three died in the neonatal period. The risk of requiring respiratory support at discharge or death was increased if any anomaly was diagnosed antenatally (p = 0.05). There were no differences in respiratory or gastrointestinal morbidities for infants where polyhydramnios was detected antenatally. Of the 13 survivors, two were orally fed, five required a gastrostomy and six were fed by nasogastric/nasojejunal tube. Ten infants were followed up after discharge and seven had normal neurological outcomes.

Conclusion

There remains no predictive tool available antenatally to anticipate neonatal outcomes. Our associated mortality rate was 64%. Foetal micrognathia rarely occurs in isolation and each case should be referred to a specialist centre for optimal counselling and careful planning.
Climate change shocks and socially responsible investments
Authors: Fiordelisi Franco , Galloppo Giuseppe , Paimanova Viktoriia
Published: September 2022

Climate change's impact on investor behavior is a scantly investigated area in finance. This paper examines the performance of socially responsible exchange trade funds (ETFs) concerning conventional ETFs, in response to climate change events. We proxy climate change signals with a list of natural disaster events that NASA scientists relate to climate change. We contribute to existing literature, by using a very extensive information set of ETF strategies, not influenced by rating agencies' subjective evaluation policies, and covering almost 90% of the universe of worldwide sustainability thematic‐oriented ETFs. This sample allows us to identify the socially responsible investment behavior in response to unpredictable climate change shocks. Our identification strategy accounts for endogeneity concerns and relies on two‐stage least square (2SLS) approach finding that responsible investors react to climate change events by purchasing socially responsible investments. The relationship between climate change signals and return of investment in themes linked to the development of sustainability is positive. Interestingly enough, the sign of this relationship is different, when we disentangle the empirical results according to the asset type, confirming that investors shift their investments from equity funds to bond funds when market sentiment worsens. Our results indicate that policymakers should increase the support of firms adopting environmentally conscious business practices, while managers should boost a sustainable business strategy.
Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments
Authors: Zhang Feipeng , Li Qunhua
Published: September 2022

High-throughput biological experiments are essential tools for identifying biologically interesting candidates in large-scale omics studies. The results of a high-throughput biological experiment rely heavily on the operational factors chosen in its experimental and data-analytic procedures. Understanding how these operational factors influence the reproducibility of the experimental outcome is critical for selecting the optimal parameter settings and designing reliable high-throughput workflows. However, the influence of an operational factor may differ between strong and weak candidates in a high-throughput experiment, complicating the selection of parameter settings. To address this issue, we propose a novel segmented regression model, called segmented correspondence curve regression, to assess the influence of operational factors on the reproducibility of high-throughput experiments. Our model dissects the heterogeneous effects of operational factors on strong and weak candidates, providing a principled way to select operational parameters. Based on this framework, we also develop a sup-likelihood ratio test for the existence of heterogeneity. Simulation studies show that our estimation and testing procedures yield well-calibrated type I errors and are substantially more powerful in detecting and locating the differences in reproducibility across workflows than the existing method. Using this model, we investigated an important design question for ChIP-seq experiments: How many reads should one sequence to obtain reliable results in a cost-effective way? Our results reveal new insights into the impact of sequencing depth on the binding-site identification reproducibility, helping biologists determine the most cost-effective sequencing depth to achieve sufficient reproducibility for their study goals.
LAMP‐2A ablation in hippocampal CA1 astrocytes confers cerebroprotection and ameliorates neuronal injury after global brain ischemia
Authors: Fu Han‐Yu , Cui Yang , Li Qiao , Wang Ding , Li Hui , Yang Long , Wang De‐Juan , Zhou Jing‐Wei
Published: September 2022

Reactive astrogliosis and neuronal death are major features of brain tissue damage after transient global cerebral ischemia/reperfusion (I/R). The CA1 subfield in the hippocampus is particularly susceptible to cell death after I/R. Recently, attention has focused on the relationship between the autophagy–lysosomal pathway and cerebral ischemia. Lysosomal‐associated membrane protein type‐2A (LAMP‐2A) is a key protein in chaperone‐mediated autophagy (CMA). However, LAMP‐2A expression in astrocytes of the hippocampus and its influence on brain injury following I/R remain unknown. Here, we show that LAMP‐2A is elevated in astrocytes of the CA1 hippocampal subfield after I/R and in primary cultured astrocytes after transient oxygen–glucose deprivation (OGD). Conditional LAMP‐2A knockdown in CA1 astrocytes inhibited astrocyte activation and prevented neuronal death by inhibiting the mitochondrial pathway of apoptosis after I/R, suggesting that elevated astrocytic LAMP‐2A contributes to regional ischemic vulnerability. Furthermore, astrocytic LAMP‐2A ablation ameliorated the spatial learning and memory deficits caused by I/R. Conditional astrocytic LAMP‐2A knockdown also prevented the loss of hippocampal synapses and dendritic spines, improved the synaptic ultrastructure, and inhibited the reduced expression of synaptic proteins after ischemia. Thus, our findings demonstrate that astrocytic LAMP‐2A expression increases upon I/R and that LAMP‐2A ablation specifically in hippocampal astrocytes contributes to cerebroprotection, suggesting a novel neuroprotective strategy for patients with global ischemia.
Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model
Authors: Sora Shota , Sukhbaatar Ariunbuyan , Fukushige Shinichi , Mori Shiro , Sakamoto Maya , Kodama Tetsuya
Published: September 2022

Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high‐frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT‐PCR of spleens after combination therapy revealed increased expression of CD4, CD8, and IL‐12b, indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.
Adjuvant atezolizumab in Japanese patients with resected stage IB‐IIIA non‐small cell lung cancer (IMpower010)
Authors: Kenmotsu Hirotsugu , Sugawara Shunichi , Watanabe Yasutaka , Saito Haruhiro , Okada Morihito , Chen‐Yoshikawa Toyofumi Fengshi , Ohe Yuichiro , Nishio Wataru , Nakagawa Shizuka , Nagao Haruka
Published: September 2022

The global phase 3 IMpower010 study evaluated adjuvant atezolizumab versus best supportive care (BSC) following platinum‐based chemotherapy in patients with resected stage IB–IIIA non‐small cell lung cancer (NSCLC). Here, we report a subgroup analysis in patients enrolled in Japan. Eligible patients had complete resection of histologically or cytologically confirmed stage IB (tumors ≥4 cm)–IIIA NSCLC. Upon completing 1–4 cycles of adjuvant cisplatin‐based chemotherapy, patients were randomized 1:1 to receive atezolizumab (fixed dose of 1200 mg every 21 days; 16 cycles or 1 year) or BSC. The primary endpoint of the global IMpower010 study was investigator‐assessed disease‐free survival, tested hierarchically first in patients with stage II–IIIA NSCLC whose tumors expressed programmed death‐ligand 1 (PD‐L1) on ≥1% of tumor cells, then in all randomized patients with stage II–IIIA NSCLC, and finally in the intention‐to‐treat (ITT) population (stage IB–IIIA NSCLC). Safety was evaluated in all patients who received atezolizumab or BSC. The study comprised 149 enrolled patients in three populations: ITT (n = 117; atezolizumab, n = 59; BSC, n = 58), all‐randomized stage II–IIIA (n = 113; atezolizumab, n = 56; BSC, n = 57), and PD‐L1 tumor cells ≥1% stage II–IIIA (n = 74; atezolizumab, n = 41; BSC, n = 33). At the data cutoff date (January 21, 2021), a trend toward disease‐free survival improvement with atezolizumab vs BSC was observed in the PD‐L1 tumor cells ≥1% stage II–IIIA (unstratified hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.25–1.08), all‐randomized stage II–IIIA (unstratified HR, 0.62; 95% CI, 0.35–1.11), and ITT (unstratified HR, 0.61; 95% CI, 0.34–1.10) populations. Atezolizumab‐related grade 3/4 adverse events occurred in 16% of patients; no treatment‐related grade 5 events occurred. Adjuvant atezolizumab showed disease‐free survival improvement and a tolerable toxicity profile in Japanese patients in IMpower010, consistent with the global study results.
MiR‐22‐3p in exosomes increases the risk of heart failure after down‐regulation of FURIN
Authors: Lu Wenlin , Liu Xuhui , Zhao Linghui , Yan Shirong , Song Qingyun , Zou Cao , Li Xun
Published: September 2022

Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR‐22‐3p is a marker in heart failure. Therefore, miR‐22‐3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real‐time polymerase chain reaction detected miR‐22‐3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR‐22‐3p in cells, cell viability, apoptosis, and apoptosis‐associated markers were detected. Bioinformatic analysis screened the target gene of miR‐22‐3p, which was verified by dual‐luciferase assay. Regulation of miR‐22‐3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR‐22‐3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR‐22‐3p was overexpressed in HF‐treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF‐treated exosomes were cytotoxic. By regulating apoptosis‐related genes, overexpressed miR‐22‐3p inhibited cell activity and promoted cell apoptosis. Silenced miR‐22‐3p with opposite effects counteracted effects of HF‐treated exosomes. FURIN, target gene of miR‐22‐3p, was negatively regulated by miR‐22‐3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR‐22‐3p in exosomes increases the risk of HF damage.
Variation in caregivers' references to their toddlers: Child‐directed speech in Vanuatu and Canada
Authors: Cebioğlu Senay , Marin Kelly A. , Broesch Tanya
Published: September 2022

The authors examined similarities and differences in Canadian and ni‐Vanuatu caregivers' child‐directed speech to their toddlers (N = 35, Mage: 21 months, 20 girls). Speech samples were collected (2013–2016) during free play and analyzed with a focus on describing parents' references to their toddlers. Canadian caregivers referred significantly more to toddlers' tangible characteristics (relative risk, RR = 2.12) and internal states (RR = 2.31), whereas ni‐Vanuatu caregivers referred more to actions (RR = 2.04). When referring to internal states, Canadian mothers referred significantly more to mind‐minded states, whereas ni‐Vanuatu caregivers referred more to body‐minded states (RR = 7.98). These findings are interpreted as capturing meaningful differences in toddlers' opportunities to attend to themselves. Implications for self‐concept development are discussed.
Finding methods for the inclusion of all children: Advancing participatory research with children with disabilities
Authors: Tiefenbacher Rebecka
Published: September 2022

This method‐focused article continues the discussion of how methodological challenges in research with children with disabilities can be overcome. By examining the difficulties in introducing walk‐and‐talk conversations in an ethnographic study with young children (3–11 years) with disabilities, it asks what doing research ‘with’ means and on whose terms research should take place. The article argues for a shift in the understanding of doing ‘with’, from a researcher‐controlled research encounter to the focusing of children's own activities. This ensures the participation of all children in research, by recognizing and listening to the many different ways in which children communicate.
Lung function in Lolland‐Falster Health Study (LOFUS)
Authors: Jacobsen Katja Kemp , Jepsen Randi , Bodtger Uffe , Rasmussen Knud , St‐Martin Gry
Published: September 2022

Background

COPD prevalence in Denmark is estimated at 18% based on data from urban populations. However, studies suggest that using the clinical cut‐off for airway obstruction in population studies may overestimate prevalence. The present study aims to compare estimated prevalence of airway obstruction using different cut‐offs and to present lung function data from the Lolland‐Falster Health Study, set in a rural‐provincial area.

Methods

Descriptive analysis of participant characteristics and self‐reported respiratory disease and of spirometry results in the total population and in subgroups defined by these characteristics. Airway obstruction was assessed using previously published Danish reference values and defined according to either FEV1/FVC below lower limit of normal (LLN) 5% (as in clinical diagnosis) or 2.5% (suggested for population studies), or as FEV1/FVC < 70%.

Results

Using either FEV1/FVC < 70% or LLN 5% cut‐off, 19.0% of LOFUS participants aged 35 years or older had spirometry, suggesting airway obstruction. By the LLN 2.5% criterion, the proportion was considerably lower, 12.2%. The prevalence of airway obstruction was higher among current smokers, in participants with short education or reporting low leisure‐time physical activity and in those with known respiratory disease. Approximately 40% of participants reporting known respiratory disease had normal spirometry, and 8.7% without known respiratory disease had airway obstruction.

Conclusion

Prevalence of airway obstruction in this rural population was comparable to previous estimates from urban Danish population studies. The choice of cut‐off impacts the estimated prevalence, and using the FEV1/FVC cut‐off may overestimate prevalence. However, many participants with known respiratory disease had normal spirometry in this health study.
Endoscopic ultrasound‐guided biliary drainage for complete obstruction of hepaticojejunostomy using a forward‐viewing echoendoscope and novel spiral dilator
Authors: Nakatsubo Ryosuke , Yamamoto Kenjiro , Itoi Takao
Published: September 2022

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Clinical significance of prediabetes, undiagnosed diabetes and diagnosed diabetes on critical outcomes in COVID‐19: Integrative analysis from the JapanCOVID‐19 task force
Authors: Fukushima Takahiro , Chubachi Shotaro , Namkoong Ho , Asakura Takanori , Tanaka Hiromu , Lee Ho , Azekawa Shuhei , Okada Yukinori , Koike Ryuji , Kimura Akinori , Imoto Seiya , Miyano Satoru , Ogawa Seishi , Kanai Takanori , Fukunaga Koichi ,   The Japan COVID‐19 Task Force
Published: September 2022

Aim

Diabetes mellitus (DM) is a known risk factor for severe coronavirus disease 2019 (COVID‐19), but the clinical impact of undiagnosed diabetes and prediabetes in COVID‐19 are unclear particularly in Japan. We clarify the difference in clinical characteristics, including age, sex, body mass index and co‐morbidities, laboratory findings and critical outcomes, in a large Japanese COVID‐19 cohort without diabetes, with prediabetes, undiagnosed diabetes and diagnosed diabetes, and to identify associated risk factors.

Materials and Methods

This multicentre, retrospective cohort study used the Japan COVID‐19 Task Force database, which included data on 2430 hospitalized COVID‐19 patients from over 70 hospitals from February 2020 to October 2021. The prevalence of prediabetes, undiagnosed diabetes and diagnosed diabetes were estimated based on HbA1c levels or a clinical diabetes history. Critical outcomes were defined as the use of high‐flow oxygen, invasive positive‐pressure ventilation or extracorporeal membrane oxygenation, or death during hospitalization.

Results

Prediabetes, undiagnosed diabetes and diagnosed diabetes were observed in 40.9%, 10.0% and 23.0%, respectively. Similar to diagnosed diabetes, prediabetes and undiagnosed diabetes were risk factors for critical COVID‐19 outcomes (adjusted odds ratio [aOR] [95% CI]: 2.13 [1.31‐3.48] and 4.00 [2.19‐7.28], respectively). HbA1c was associated with COVID‐19 severity in prediabetes patients (aOR [95% CI]: 11.2 [3.49‐36.3]), but not other groups.

Conclusions

We documented the clinical characteristics and outcomes of Japanese COVID‐19 patients according to HbA1c levels or diabetes co‐morbidity. As well as undiagnosed and diagnosed diabetes, physicians should be aware of prediabetes related to COVID‐19 severity.
From dogmatic slumber to rationalist nightmares: Kant among the dreamers of reason
Authors: Stratmann Joe
Published: September 2022

What awakened Kant from his dogmatic slumber? On the traditional narrative, he was awakened by Hume's challenge to our cognition of causal connections. A more recent narrative claims that he was awakened by Hume's challenge to our cognition of non‐logical connections more generally. In this paper, I argue that a key part of Kant's awakening was far wider‐reaching: he came to realize that all dogmas must be abandoned. An oft‐overlooked technical notion, dogmas are non‐logical principles cognizable to unaided human reason. I detail how Kant repudiated dogmas by the mid‐1760's in engaging with his German predecessor, Christian Crusius. This repudiation lays the foundation for his critical project. For once liberated of dogmas, reason must look beyond itself for the principles that would enable rational cognitionof non‐logical connections.
Risk of future stroke in patients with a diagnosis of peripheral vertigo in the emergency department
Authors: Choi Jeong‐Yoon , Kim Seok , Boo Dachung , Yoo Sooyoung , Kim Hyo‐Jung , Kim Jun Yup , Lee Keon‐Joo , Kang Jihoon , Kim Beom Joon , Han Moon‐Ku , Bae Hee‐Joon , Kim Ji‐Soo
Published: September 2022

Background and purpose

The temporal characteristics of stroke risks were evaluated in emergency department patients who had a diagnosis of peripheral vertigo. It was also attempted to reveal the stroke risk factor amongst those with peripheral vertigo.

Methods

This is a parallel‐group cohort study in a tertiary referral hospital. After assigning each of 4367 matched patients to the comparative set of peripheral vertigo and appendicitis‐ureterolithiasis groups and each of 4911 matched patients to the comparative set of peripheral vertigo and ischaemic stroke groups, the relative stroke risk was evaluated. In addition, to predict the individual stroke risk in patients with peripheral vertigo, any association between the demographic factors and stroke events was evaluated in the peripheral vertigo group.

Results

The peripheral vertigo group had a higher stroke risk than the appendicitis‐ureterolithiasis group (hazard ratio 1.73, 95% confidence interval 1.18–2.55) but a lower risk than the ischaemic stroke group (hazard ratio 0.30, 95% confidence interval 0.24–0.37). The stroke risk of the peripheral vertigo group was just below that of small vessel stroke. The stroke risk of the peripheral vertigo group differed markedly by time: higher within 7 days, moderate between 7 days and 1 year, and diminished thereafter. Old age (>65 years), male gender and diabetes mellitus were the risk factors for stroke in the peripheral vertigo group.

Conclusion

Patients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk and so a stroke preventive strategy tailored to the timing of symptom onset and individual risk is required.
Cutting edge technologies in chronic inflammation research
Authors: Laman Jon D.
Published: September 2022

This concise review provides the broad background and selection from the literature for a Keynote lecture at EHSF 2022 on state of the art technologies in inflammation research, with an emphasis on disease of the skin and the nervous system. The value of ex vivo skin explant models is discussed, as well as the innovative use of animal models, wherein the crucial roles of antigen experience and “wild” microbiota are emphasized. Spectral flow cytometry allowing large surface marker panels to be explored is touched upon, as well as multiplex technology for cytokines and other analytes important for inflammation and tissue damage. Single‐cell sequencing and in situ transcriptomics (spatial profiling) now provide exciting granular information on functional cell subsets, interactions and plasticity. A selection of novel research and diagnostic tools for antibodies against linear peptides or gangliosides is presented. Finally, the review discusses a new anti‐inflammatory strategy against skin inflammation with a panel of protease inhibitors derived from the protein fraction of industrial starch potatoes.
Unexpected expansion of the voltage‐gated proton channel family
Authors: Chaves Gustavo , Ayuyan Artem G. , Cherny Vladimir V. , Morgan Deri , Franzen Arne , Fieber Lynne , Nausch Lydia , Derst Christian , Mahorivska Iryna , Jardin Christophe , DeCoursey Thomas E. , Musset Boris
Published: September 2022

Voltage‐gated ion channels, whose first identified function was to generate action potentials, are divided into subfamilies with numerous members. The family of voltage‐gated proton channels (HV) is tiny. To date, all species found to express HV have exclusively one gene that codes for this unique ion channel. Here we report the discovery and characterization of three proton channel genes in the classical model system of neural plasticity, Aplysia californica. The three channels (AcHV1, AcHV2, and AcHV3) are distributed throughout the whole animal. Patch‐clamp analysis confirmed proton selectivity of these channels but they all differed markedly in gating. AcHV1 gating resembled HV in mammalian cells where it is responsible for proton extrusion and charge compensation. AcHV2 activates more negatively and conducts extensive inward proton current, properties likely to acidify the cytosol. AcHV3, which differs from AcHV1 and AcHV2 in lacking the first arginine in the S4 helix, exhibits proton selective leak currents and weak voltage dependence. We report the expansion of the proton channel family, demonstrating for the first time the expression of three functionally distinct proton channels in a single species.
Climate drives the spatiotemporal dynamics of scrub typhus in China
Authors: Ding Fangyu , Wang Qian , Hao Mengmeng , Maude Richard James , John Day Nicholas Philip , Lai Shengjie , Chen Shuai , Fang Liqun , Ma Tian , Zheng Canjun , Jiang Dong
Published: September 2022

Scrub typhus is a climate‐sensitive and life‐threatening vector‐borne disease that poses a growing public health threat. Although the climate‐epidemic associations of many vector‐borne diseases have been studied for decades, the impacts of climate on scrub typhus remain poorly understood, especially in the context of global warming. Here we incorporate Chinese national surveillance data on scrub typhus from 2010 to 2019 into a climate‐driven generalized additive mixed model to explain the spatiotemporal dynamics of this disease and predict how it may be affected by climate change under various representative concentration pathways (RCPs) for three future time periods (the 2030s, 2050s, and 2080s). Our results demonstrate that temperature, precipitation, and relative humidity play key roles in driving the seasonal epidemic of scrub typhus in mainland China with a 2‐month lag. Our findings show that the change of projected spatiotemporal dynamics of scrub typhus will be heterogeneous and will depend on specific combinations of regional climate conditions in future climate scenarios. Our results contribute to a better understanding of spatiotemporal dynamics of scrub typhus, which can help public health authorities refine their prevention and control measures to reduce the risks resulting from climate change.
Phosphorus additions imbalance terrestrial ecosystem C:N:P stoichiometry
Authors: Sun Yuan , Wang Cuiting , Chen Xinli , Liu Shirong , Lu Xingjie , Chen Han Y. H. , Ruan Honghua
Published: September 2022

Carbon (C):nitrogen (N):phosphorus (P) stoichiometry in plants, soils, and microbial biomass influences productivity and nutrient cycling in terrestrial ecosystems. Anthropogenic inputs of P to ecosystems are increasing; however, our understanding of the impacts of P addition on terrestrial ecosystem C:N:P ratios remains elusive. By conducting a meta‐analysis with 1413 paired observations from 121 publications, we showed that P addition significantly decreased plant, soil, and microbial biomass N:P and C:P ratios, but had negligible effects on C:N ratios. The reductions in N:P and C:P ratios became more evident as the P application rates and experimental duration increased. The P addition effects on terrestrial ecosystem C:N:P stoichiometry did not vary with ecosystem types or climates. Moreover, the responses of N:P and C:P ratios in soil and microbial biomass were associated with the responses of soil pH and fungi:bacteria ratios. Additionally, P additions increased net primary productivity, microbial biomass, soil respiration, N mineralization, and N nitrification, but decreased ammonium and nitrate contents. Decreases in plant N:P and C:P ratios were both negatively correlated to net primary productivity and soil respiration, but positively correlated to ammonium and nitrate contents; microbial biomass, soil respiration, ammonium contents, and nitrate contents all increased with declining soil N:P and C:P ratios. Our findings highlight that P additions could imbalance C:N:P stoichiometry and potentially impact the terrestrial ecosystem functions.
Cluster headache – The worst possible pain on YouTube
Authors: Chaudhry Basit Ali , Do Thien Phu , Ashina Håkan , Ashina Messoud , Amin Faisal Mohammad
Published: September 2022

In clinical practice, patients with cluster headache often ask questions or mention information that they have seen or heard on the Internet. Because YouTube (www.youtube.com) is the second most visited Web site worldwide and offers a plethora of video content, we found it timely to ascertain the quality of information on cluster headache that is freely available on YouTube. We conducted an inquiry on YouTube on January 24, 2022, with the search term “cluster headache.” Eligible YouTube videos included those with ≥10,000 views and content related to cluster headache. We assessed the quality and reliability of the videos with the Global Quality Scale and DISCERN, respectively. The search strategy identified 644 videos of which 134 were eligible for inclusion. The sources of the included videos were categorized as “healthcare professional/institution” (n = 45), “personal experience” (n = 52), and “other” (n = 37). According to the Global Quality Scale, 70 (52%) were low quality, 34 (25%) were of moderate quality, and 30 (22%) were of high quality. According to DISCERN, 104 (78%) were of low reliability, 28 (21%) were of moderate reliability, and 2 (1%) were of high reliability. The quality and reliability of cluster headache‐related information on YouTube has room for improvement, even the content provided by healthcare providers. These findings should incentivize stakeholders, for example, government services, professional societies, healthcare providers, to provide accessible and better information on cluster headache.
Preoperative serum brain‐derived neurotrophic factor as a predictive biomarker for sepsis after living‐donor liver transplantation
Authors: Tsutsui Yuriko , Yoshio Sachiyo , Tomiyama Takahiro , Shimagaki Tomonari , Itoh Shinji , Harada Noboru , Yoshida Yuichi , Yoshikawa Shiori , Kakazu Eiji , Kanto Tatsuya , Yoshizumi Tomoharu
Published: September 2022

Aim

Although the survival rate after living‐donor liver transplantation (LDLT) is improving, sepsis still limits the prognosis. Immune dysfunction and sarcopenia are often observed in LDLT patients, and increase susceptibility to infection. Brain‐derived neurotrophic factor (BDNF) is a myokine produced by immune cells and skeletal muscle. We aimed to determine whether serum BDNF could be a feasible biomarker for sepsis of LDLT patients.

Methods

We measured serum samples from 124 patients who underwent LDLT and 9 healthy volunteers for BDNF. We examined its correlation with incidence rate of sepsis. To clarify the source of BDNF, we examined its expression in lymphocytes, skeletal muscle cells, and hepatocytes.

Results

Patients who experienced sepsis showed worse short‐term survival. Preoperative serum BDNF was lower in LDLT patients compared with healthy volunteers, and was also lower in Child–Pugh C compared with Child–Pugh A or B. Serum BDNF was inversely correlated with Model for End‐Stage Liver Disease and controlling nutritional status (CONUT) scores, but had a weak positive correlation with skeletal muscle mass index (SMI). Multivariate analysis revealed that serum BDNF was independently associated with sepsis. Preoperative serum BDNF was a better predictor of sepsis in LDLT patients than CONUT score or SMI. Serum BDNF was positively correlated with lymphocyte counts, especially T cells. In vitro, T cells and skeletal muscle cells produced BDNF.

Conclusions

Preoperative serum BDNF could be a predictive biomarker for sepsis after LDLT, by reflecting the systemic condition including hepatic function, nutritional status, and immune status.