bluuebunny/crossref_metadata_2025 huggingface dataset:
TREM‐1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4/NEMO pathway
Authors: Yang Zilong , Pan Xiaoyan , Wu Xiaoxia , Lin Qiuyun , Chen Yongxia , Cai Shuting , Zhang Yuanli , Mai Zhenhua , Ahmad Niall , Ma Daqing , Deng Liehua
Published: October 2022

Sepsis often causes cell death via pyroptosis and hence results in septic cardiomyopathy. Triggering receptors expressed in myeloid cells‐1 (TREM‐1) may initiate cellular cascade pathways and, in turn, induce cell death and vital organ dysfunction in sepsis, but the evidence is limited. We set to investigate the role of TREM‐1 on nucleotide‐binding oligomerization domain‐like receptors with pyrin domain‐3 (NLRP3) inflammasome activation and cardiomyocyte pyroptosis in sepsis models using cardiac cell line (HL‐1) and mice. In this study, TREM‐1 was found to be significantly increased in HL‐1 cells challenged with lipopolysaccharide (LPS). Pyroptosis was also significantly increased in the HL‐1 cells challenged with lipopolysaccharide and an NLRP3 inflammasome activator, nigericin. The close interaction between TREM‐1 and structural maintenance of chromosome 4 (SMC4) was also identified. Furthermore, inhibition of TREM‐1 or SMC4 prevented the upregulation of NLRP3 and decreased Gasdermin‐D, IL‐1β and caspase‐1 cleavage. In mice subjected to caecal ligation and puncture, the TREM‐1 inhibitor LR12 decreased the expression of NLRP3 and attenuated cardiomyocyte pyroptosis, leading to improved cardiac function and prolonged survival of septic mice. Our work demonstrates that, under septic conditions, TREM‐1 plays a critical role in cardiomyocyte pyroptosis. Targeting TREM‐1 and its associated molecules may therefore lead to novel therapeutic treatments for septic cardiomyopathy.
Reevaluation of Makuuchi’s criteria for resecting hepatocellular carcinoma: A Japanese nationwide survey
Authors: Aramaki Osamu , Takayama Tadatoshi , Matsuyama Yutaka , Kubo Shoji , Kokudo Norihiro , Kurosaki Masayuki , Murakami Takamichi , Shiina Shuichiro , Kudo Masatoshi , Sakamoto Michiie , Nakashima Osamu , Fukumoto Takumi , Iijima Hiroko , Eguchi Susumu , Soejima Yuji , Makuuchi Masatoshi
Published: October 2022

Aim

Although Makuuchi’s criteria are widely used to determine the cut‐off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi’s criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria.

Methods

A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi’s criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long‐term survival were compared between the two groups.

Results

The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p < 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23–3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18–1.36; p < 0.001).

Conclusion

Makuuchi’s criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.
Ultrasound‐assisted microemulsions of anthocyanins extracted from black carrot pomace and its utilisation as functional component in kulfi: implication on in vitro release, bio‐functional components and rheological characteristics
Authors: Kaur Gurkirat , Sharma Neha , Singh Arashdeep , Kapoor Swati , Khatkar Sunil Kumar
Published: October 2022

The present study explores the possibility of encapsulating anthocyanins from black carrot pomace (BCP) into water in oil (w/o) type emulsion via two‐stage emulsification (high‐speed shear homogenisation and ultrasonication). Anthocyanin‐loaded emulsions (Antho‐Es) with different extract to oil (EO) ratio (50:50, 40:60, 30:70, 20:80 and 10:90) exhibits particle size, zeta potential, dispersibility index in the range of 1132 to 2709 nm, −21.02 to −29.64 mV, 0.617 to 1.120 respectively. Anth‐Es exhibits linear visco‐elastic behaviour with high loss modulus than storage modulus. Anth‐Es with 30% EO ratio exhibits higher encapsulation efficiency (88.07%) and anthocyanin release (81.56%) after 4 h of in vitro gastrointestinal incubation. Increasing the EO ratio in Antho‐Es decreased the lightness (86.46–79.12) and increased the redness values (7.46–15.35), antioxidant activities (33.08–79.12%) and phenolic content (31.37–90.56 mg GAE/100 g). FTIR spectra also confirmed the successful enclosure of anthocyanins into the NEs. The best characterised Antho‐Es (30%) was used as anthocyanins fortification in functional kulfi and compared with BCP and its extract. Kulfi with Antho‐Es exhibits highest anthocyanins stability (86.40%), antioxidant activity (75.60%). Antho‐Es also help to reduce the melting rate of kulfi and enhance redness value which further enhances the sensory attribute and overall acceptability of the kulfi.
Infant locomotion shapes proximity to adults during everyday play in the U.S.
Authors: Chen Qi , Schneider Joshua L. , West Kelsey L. , Iverson Jana M.
Published: October 2022

Learning to walk expands infants’ access to the physical environment and prompts changes in their communicative behaviors. However, little is known about whether walking also shapes infants’ proximity to their adult social partners during everyday activities at home. Here we followed 89 infants (42 boys, 47 girls; 92% White, not Hispanic or Latino) longitudinally and documented connections between infant locomotion and infant‐adult proximity on two timescales: (1) across developmental time, by comparing data from a session when infants could only crawl to a later session when they could walk (M walk onset = 12.15 months, range = 8‐15); and (2) in real time, by testing whether the amount of time that infants spent in motion (regardless of their locomotor status) related to their interpersonal distance to adults. The developmental transition to walking corresponded to a significant, but modest, decrease in infant‐adult proximity. Infants’ moment‐to‐moment locomotion, however, was strongly related to patterns of interpersonal distance: infants who spent more time in motion spent less time near adults and instigated more proximity transitions, resulting in shorter and more dispersed bouts of proximity throughout sessions. Findings shed new light on how infants’ motor achievements can reverberate across other domains of development, and how changes in infant development that researchers often observe over months arise from infants’ moment‐to‐moment experiences.
Characterisation of key biomarkers in diabetic ulcers via systems bioinformatics
Authors: Zhang Zhan , Zhang Ying , Yang Dan , Luo Yue , Luo Ying , Ru Yi , Song Jiankun , Fei Xiaoya , Chen Yiran , Li Bin , Jiang Jingsi , Kuai Le
Published: October 2022

Diabetic ulcers (DUs) are characterised by a high incidence and disability rate. However, its pathogenesis remains elusive. Thus, a deep understanding of the underlying mechanisms for the pathogenesis of DUs has vital implications. The weighted gene co‐expression network analysis was performed on the main data from the Gene Expression Omnibus database. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were adopted to analyse the potential biological function of the most relevant module. Furthermore, we utilised CytoHubba and protein–protein interaction network to identify the hub genes. Finally, the hub genes were validated by animal experiments in diabetic ulcer mice models. The expression of genes from the turquoise module was found to be strongly related to DUs. GO terms, KEGG analysis showed that biological functions are closely related to immune response. The hub genes included IFI35, IFIT2, MX2, OASL, RSAD2, and XAF1, which were higher in wounds of DUs mice than that in normal lesions. Additionally, we also demonstrated that the expression of hub genes was correlated with the immune response using immune checkpoint, immune cell infiltration, and immune scores. These data suggests that IFI35, IFIT2, MX2, OASL, RSAD2, and XAF1 are crucial for DUs.
Let's Not Do Responsibility Skepticism
Authors: Levy Ken M.
Published: October 2022

I argue for three conclusions. First, responsibility skeptics are committed to the position that the criminal justice system should adopt a universal nonresponsibility excuse. Second, a universal nonresponsibility excuse would diminish some of our most deeply held values, further dehumanize criminals, exacerbate mass incarceration, and cause an even greater number of innocent people (nonwrongdoers) to be punished. Third, while Saul Smilansky's ‘illusionist’ response to responsibility skeptics – that even if responsibility skepticism is correct, society should maintain a responsibility‐realist/retributivist criminal justice system – is generally compelling, it would not work if a majority of society were to convert, theoretically and psychologically, to responsibility skepticism. In this (highly improbable) scenario, and only in this (highly improbable) scenario, the criminal justice system would need to be reformed in such a way that it aligned with the majority's responsibility‐skeptical beliefs and attitudes.
SNARE‐binding protein synaptosomal‐associated protein of 29 kDa (SNAP29) regulates the intracellular sequestration of glucose transporter 4 (GLUT4) vesicles in adipocytes
Authors: Matsui Kumiko , Emoto Masahiro , Fukuda Naofumi , Nomiyama Ryuta , Yamada Kyoko , Tanizawa Yukio
Published: October 2022

Aims/Introduction

Insulin stimulates translocation of glucose transporter 4 (GLUT4) from the perinuclear location to the plasma membrane. In the unstimulated state, intracellular vesicles containing GLUT4 are sequestered into specialized storage vesicles that have come to be known as the insulin‐responsive compartment (IRC). The IRC is a functional compartment in the perinuclear region that is a target of the insulin signaling cascade, although its precise nature is unclear. Here, we report a novel molecular mechanism facilitating formation of the IRC.

Materials and Methods

We determined synaptosomal‐associated protein of 29 kDa (SNAP29) by mass spectrometry to be an EH domain‐containing protein 1 (EHD1)‐binding protein. Then, its expression was confirmed by western blotting. Subcellular localization of SNAP29 was determined by immunofluorescent microscopy. Interactions between SNAP29 and syntaxins were determined by immunoprecipitation. We measured glucose uptake and GLUT4 translocation in 3T3‐L1 adipocyte expressing SNAP29 or silencing SNAP29.

Results

We found SNAP29 to be localized in the perinuclear region and to show partial co‐localization with GLUT4 under basal conditions. We also found that SNAP29 binds to syntaxin6, a Qc‐SNARE, in adipocytes. In SNAP29‐expressing cells, vesicles containing GLUT4 were observed to aggregate around the perinuclear region. In contrast, when SNAP29 was silenced, perinuclear GLUT4 vesicles were dispersed throughout the cytosol. Insulin‐stimulated glucose uptake was inhibited in both SNAP29‐expressing and SNAP29‐silenced cells.

Conclusions

These data suggest that SNAP29 sequesters and anchors GLUT4‐containing vesicles in the perinuclear region, and might have a role in the biogenesis of the perinuclear IRC.
Association between diabetes mellitus and post‐stroke cognitive impairment
Authors: Lee Kang‐Po , Chen Jung‐Sheng , Wang Chih‐Yuan
Published: October 2022

Stroke survivors suffer from various physical, emotional, and cognitive impairments. These changes are dynamic and depend on multiple factors, including underlying diseases, baseline brain function and pathology, the site of the stroke and the post‐stroke inflammation, neurogenesis as well as the subsequent remodeling of the neuro‐network. First we review the structural and pathological changes of the brain in stroke survivors with diabetes mellitus, which may lead to post‐stroke cognitive dysfunction. Second, we provide evidence of hyperglycemia, diabetes mellitus, hypoglycemia, and their relationship with post‐stroke cognitive impairment (PSCI) and post‐stroke dementia (PSD). In addition to conventional biomarkers, such as HbA1c, we also provide other novel tools to predict PSCI/PSD, such as glycemic variability, receptor for advanced glycation end products, and gut microbiota. Finally, we attempt to provide some modifying methods for glycemic control, focusing on the prevention of PSCI/PSD.
Illuminating otoliths: New insights for life history of Balistes triggerfishes
Authors: Shervette Virginia R. , Rivera Hernández Jesús M.
Published: October 2022

Our understanding of fish life‐history strategies is informed by key biological processes, such as growth, survival/mortality, recruitment and sexual maturation, used to characterize fish stocks (populations). Characterizing the life‐history traits of fish populations requires the application of accurate age estimation for managed species. Grey triggerfish Balistes capriscus and queen triggerfish Balistes vetula are important reef‐associated species for commercial and recreational fisheries in the Atlantic Ocean. Both species exhibit a unique reproductive strategy for large‐bodied fisheries‐targeted reef fishes in that they are nesting benthic spawners and invest substantial energy in defence and care of their benthic nests and fertilized eggs. Until recently, our understanding of the life‐history strategies of triggerfishes assumed the main method used to obtain age estimates, increments counted from thin sections of the first dorsal spine, provided an accurate characterization of population age‐based parameters. However, results from bomb radiocarbon validation studies on the two Balistes species demonstrated that spines do not provide accurate ages, but sagittal otoliths do. The main goal of the current study was to provide an updated understanding for triggerfish life‐history strategies by using otolith‐based age estimates to characterize population age structure and growth for grey triggerfish and queen triggerfish from waters of the south‐eastern U.S. Atlantic. The current study is the first to report on sex‐specific age and growth information for grey triggerfish using the Δ14C‐validated otolith‐based age estimation method and the results indicate that the previous characterization of Balistes species as exhibiting moderately rapid growth and as relatively short‐lived, based on spine‐derived age estimates, are flawed. Otolith‐based ages indicated that grey triggerfish and queen triggerfish are moderately slow‐growing and long‐lived species, attaining maximum ages of 21 and 40 years, respectively. Management efforts for triggerfishes should evaluate these new insights and incorporate the results of otolith‐based age estimation into future population monitoring efforts.
Superiority of a preparation‐related model for predicting inadequate bowel preparation in patients undergoing colonoscopy: A multicenter prospective study
Authors: Chen Long , Ren Gui , Luo Hui , Zhang Linhui , Wang Limei , Zhao Jianghai , Zhang Rongchun , Zhang Xiaoying , Kang Xiaoyu , Pan Yanglin
Published: October 2022

Background and Aim

Three models based on patient‐related factors have been developed to predict inadequate bowel preparation (BP). However, the performance of the models seems suboptimal. This study aimed to develop a novel preparation‐related model and compare it with the available patient‐related models.

Methods

Patients receiving standard BP were prospectively enrolled from five endoscopic centers. Patient‐related and preparation‐related factors for inadequate BP (defined by segmental Boston Bowel Preparation Scale score < 2) were identified by logistic regression. A preparation‐related model was derived and internally validated in 906 patients. The comparisons of models were assessed by discrimination and calibration. The preparation‐related model was also externally validated.

Results

Several patient‐related factors (male and American Society of Anesthesiologists Physical Status Classification System score ≥ 3) and preparation‐related factors (drinking‐to‐stool interval ≥ 3 h, preparation‐to‐colonoscopy interval ≥ 6 h, and poor rectal effluent) were found to be independently associated with inadequate BP (all P < 0.05). C‐statistics was 0.81 for the preparation‐related model in the training cohort (n = 604), significantly higher than three available patient‐based models (0.58–0.61). Similar results were observed in the validation cohort (n = 302). Calibration curves showed close agreement in the preparation‐related model (R2 = 0.315 in the training cohort and 0.279 in the validation cohort). The preparation‐related model was externally validated in another 606 patients with C‐index of 0.80.

Conclusions

A new preparation‐related model (consisting of drinking‐to‐stool interval ≥ 3 h, preparation‐to‐colonoscopy interval ≥ 6 h, and poor last rectal effluent) was developed and performed better than three available patient‐related models. This easy‐to‐use model may be a useful decision‐support tool on individualized plans in patients undergoing BP.
A comparison of efficacy and safety of potassium‐competitive acid blocker and proton pump inhibitor in gastric acid‐related diseases: A systematic review and meta‐analysis
Authors: Simadibrata Daniel Martin , Syam Ari Fahrial , Lee Yeong Yeh
Published: October 2022

Background and Aim

Potassium‐competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta‐analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid‐related diseases.

Methods

We searched up to June 5, 2022, for randomized controlled trials of gastric acid‐related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment‐emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings.

Results

Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03–1.14), 1.03 (95% CI 1.00–1.07), and 1.02 (95% CI 1.00–1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first‐line treatment (RR 1.13; 95% CI 1.04–1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89–1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion.

Conclusion

Vonoprazan is superior to PPI in first‐line H. pylori eradication and erosive esophagitis but non‐inferior in other gastric acid‐related diseases. Likewise, short‐term safety is comparable in both treatment groups.
Design and development of tranexamic acid loaded film‐forming gel to alleviate melasma
Authors: Chevala Naga Thirumalesh , Dsouza Jenica Alwin , Saini Hitesh , Kumar Lalit
Published: October 2022

Background

Melasma is a skin condition that causes increased epidermal pigmentation, enlarged melanocytes, increased melanosomes, solar elastosis, dermal blood vessels, and, occasionally, perivascular lymph histiocytic infiltrates.

Objective

To develop the film‐forming gel to alleviate melasma. Tranexamic acid was used as a model drug to evaluate the suitability of formulation to prevent symmetric hyperpigmentation.

Methods

FFG is a hydrophilic polymeric cross‐linked system loaded with an active moiety. Nine different formulations of 2% TXA were formulated using polyvinyl alcohol and hydroxypropyl methylcellulose 50 cP as film‐forming polymers. Sodium carboxymethylcellulose, methylcellulose, and carbopol were used as gelling agents.

Results

F7, F8, and F9 showed shorter DT, that is, 11, 8, and 12 min, respectively. The folding endurance of F7, F8, and F9 was >100 folds, and the pH of F7, F8, and F9 was >6. Among three formulations, F8 was further analyzed for in vitro drug diffusion, which showed >95% drug diffusion within 48 h. In vivo, the skin irritation potential of F8 was estimated using BAL/C mice, which confirmed the absence of skin irritation.

Conclusion

From the obtained results, we conclude that the FFG can be a strategic attempt to deliver the cosmeceutical drugs like TXA to alleviate Melasma with improved sustainability of the drug.
Status of cosmetic safety in Malaysia market: Mercury contamination in selected skin whitening products
Authors: Wan Mohamed Radzi Che Wan Jasimah , Nordin Fatin Nur Majdina
Published: October 2022

Background

Concern on cosmetic safety has been a subject of interest in recent years and is commonly associated with the exposure of the consumers to chemicals and impurities such as mercury contamination. Moreover, cancellations of notified cosmetic products were recurrently being reported by the Malaysia authority, namely the National Pharmaceutical Regulatory Authority (NPRA). Among the cosmetic categories was skin whitening product, which is still in high demand whilst reported to cause health risks. Besides, low number of studies on cosmetic safety and mercury contamination were recorded in Malaysia. The lack of scientific evidence on the safety and risks of the ingredients used in cosmetic formulation is a major concern to many consumers.

Objective

The aim of this study was to identify the presence of mercury in skin whitening products, and to identify products containing mercury with the concentration exceeding the limitation of 1 ppm.

Methodology

A total of 104 whitening products were selected from the market via random sampling technique. The mercury concentration was determined by accredited laboratory, and the results were later compared with the cosmetic guideline of Malaysia and the list of banned products issued by NPRA.

Results

A total of 51.9% (n = 54) whitening products were found registered under the NPRA Quest system and remaining 48.1% (n = 50) were non‐registered products. None of the whitening products listed mercury as an ingredient, but laboratory analysis showed 15.4% (n = 16) of the products contained mercury with the concentration exceeding the maximum limit of 1 ppm. A total of 87.5% of the whitening products (14 out of 16) containing high mercury concentration were non‐registered products which were not registered in NPRA Quest system. The exceeded concentration recorded ranged between 1.81 ppm and 838 123 ppm. Besides that, 50% (8 out of 16) of the products were found in the list of banned products issued by the NPRA of Malaysia.

Conclusions

This study presents the status of cosmetic products, particularly the skin whitening products available in Malaysia market. Concern arises when some of the products were found to have presence of harmful substances such as mercury. Even though the presence of mercury in a cosmetic product can either be non‐intentional or intentionally used by the manufacturer in the cosmetic formulation, the impact of the ingredient can cause health risk to the users.
The other COVID‐19 survivors: Timing, duration, and health impact of post‐acute sequelae of SARS‐CoV‐2 infection
Authors: Lambert Natalie ,   Survivor Corps, El‐Azab Sarah A. , Ramrakhiani Nathan S. , Barisano Anthony , Yu Lu , Taylor Kaitlyn , Esperança Álvaro , Mendiola Christian , Downs Charles A. , Abrahim Heather L. , Hughes Thomas , Rahmani Amir M. , Borelli Jessica L. , Chakraborty Rana , Pinto Melissa D.
Published: October 2022

Aims and Objectives

To determine the frequency, timing, and duration of post‐acute sequelae of SARS‐CoV‐2 infection (PASC) and their impact on health and function.

Background

Post‐acute sequelae of SARS‐CoV‐2 infection is an emerging major public health problem that is poorly understood and has no current treatment or cure. PASC is a new syndrome that has yet to be fully clinically characterised.

Design

Descriptive cross‐sectional survey (n = 5163) was conducted from online COVID‐19 survivor support groups who reported symptoms for more than 21 days following SARS‐CoV‐2 infection.

Methods

Participants reported background demographics and the date and method of their covid diagnosis, as well as all symptoms experienced since onset of covid in terms of the symptom start date, duration, and Likert scales measuring three symptom‐specific health impacts: pain and discomfort, work impairment, and social impairment. Descriptive statistics and measures of central tendencies were computed for participant demographics and symptom data.

Results

Participants reported experiencing a mean of 21 symptoms (range 1–93); fatigue (79.0%), headache (55.3%), shortness of breath (55.3%) and difficulty concentrating (53.6%) were the most common. Symptoms often remitted and relapsed for extended periods of time (duration M = 112 days), longest lasting symptoms included the inability to exercise (M = 106.5 days), fatigue (M = 101.7 days) and difficulty concentrating, associated with memory impairment (M = 101.1 days). Participants reported extreme pressure at the base of the head, syncope, sharp or sudden chest pain, and “brain pressure” among the most distressing and impacting daily life.

Conclusions

Post‐acute sequelae of SARS‐CoV‐2 infection can be characterised by a wide range of symptoms, many of which cause moderate‐to‐severe distress and can hinder survivors' overall well‐being.

Relevance to Clinical Practice

This study advances our understanding of the symptoms of PASC and their health impacts.
Gadolinium‐based contrast agent exposures and physical and cognitive disability in multiple sclerosis
Authors: Nakamura Kunio , McGinley Marisa P. , Jones Stephen E. , Lowe Mark J. , Cohen Jeffrey A. , Ruggieri Paul M. , Ontaneda Daniel
Published: October 2022

Background and Purpose

The clinical correlation of gadolinium‐based contrast agents (GBCAs) has not been well studied in multiple sclerosis (MS). We investigated the extent to which the number of GBCA administrations relates to self‐reported disability and performance measures.

Methods

A cohort of MS patients was analyzed in this retrospective observational study. The main outcome was the association between the cumulative number of GBCA exposures (linear or macrocyclic GBCA), Patient‐Determined Disease Steps (PDDS), and measures of physical and cognitive performance (walking speed test, manual dexterity test [MDT], and processing speed test [PST]). The analysis was performed first cross‐sectionally and then longitudinally.

Results

The cross‐sectional data included 1059 MS patients with a mean age of 44.0 years (standard deviation = 11.2). While the contrast ratio in globus pallidus weakly correlated with PDDS, MDT, and PST in a univariate correlational analysis (coefficients, 95% confidence interval [CI] = 0.11 [0.04, 0.18], 0.15 [0.08, 0.21], and –0.16 [–0.10, –0.23], respectively), the associations disappeared after covariate adjustment. A significant association was found between number of linear GBCA administrations and PDDS (coefficient [CI] = –0.131 [–0.196, –0.067]), and MDT associated with macrocyclic GBCA administrations (–0.385 [–0.616, –0.154]), but their signs indicated better outcomes in patients with greater GBCA exposures. The longitudinal data showed no significant detrimental effect of macrocyclic GBCA exposures.

Conclusion

No detrimental effects were observed between GBCA exposure and self‐reported disability and standardized objective measures of physical and cognitive performance. While several weak associations were found, they indicated benefit on these measures.
What does the term childhood behavioural disorders mean in the context of Aboriginal culture within Australia? Part 2: Historical and social context
Authors: Rungan Santuri , Liu Huei M , Edwige Vanessa , Smith‐Merry Jennifer , Eastwood John
Published: October 2022

Childhood behavioural disorders (CBDs) are a common reason for referral to paediatric services and are associated with negative individual and societal outcomes. This article addresses how childhood became a distinct entity and how historical changes shaped its definition. Thereafter, the evolution of diagnostic criteria for CBD and associated limitations will be summarised. This will be followed by a discussion about Aboriginal culture, and the impact of colonisation on social and emotional well‐being. This will provide a contextual frame for understanding how social and cultural context influences diagnoses of CBD in Aboriginal children. From this, a conversation about the journey moving forward will begin.
The influence of road networks on brown bear spatial distribution and habitat suitability in a human‐modified landscape
Authors: González‐Bernardo E. , Delgado M. d. M. , Matos D. G. G. , Zarzo‐Arias A. , Morales‐González A. , Ruiz‐Villar H. , Skuban M. , Maiorano L. , Ciucci P. , Balbontín J. , Penteriani V.
Published: October 2022

Roads are human infrastructure that heavily affect wildlife, often with marked impacts on carnivores, including brown bears Ursus arctos. Here, we assessed the potential impact of road networks on the distribution of brown bears in the small, isolated and endangered Cantabrian population of north‐western Spain. To ascertain whether local road networks affect brown bear spatial distribution, we first assessed potential influences on the distance of bear locations to roads using candidate models which included topographic variables, landcover types, bear age and reproductive status, traffic volume and road visibility. Then, we built two sets of habitat suitability models, both with and without roads, to discern the possible loss of habitat suitability caused by roads. The mean distance of bear locations to the nearest road was 968 ± 804 m and the closest road was a low traffic road in 72.5% of cases. Candidate models showed little influence of our variables on bear distance to the nearest road, with the exception of elevation. Habitat suitability models revealed that road networks in our study area seem to have almost no effect on brown bear habitat suitability, except for females with yearlings during the denning season. However, this result may also be a consequence of the fact that only a small proportion (16.5%) of the cells classified as suitable bear habitats were crossed by roads, that is, most of the roads are primarily located in unsuitable bear habitats in the Cantabrian Mountains. Compared to previous studies conducted in other populations, mainly North American ones, our findings might suggest a different response of Eurasian brown bears to roads due to a longer bear‐human coexistence in Europe versus North America. However, the indirect approach used in our study does not exclude other detrimental effects, for example, road mortality, increased stress and movement pattern disruption, only detectable by more direct approaches such as telemetry.
Goal co‐construction and dialogue in an internal medicine longitudinal coaching programme
Authors: Farrell Laura , Cuncic Cary , Hartford Wendy , Hatala Rose , Ajjawi Rola
Published: October 2022

Background

Longitudinal coaching in residency programmes is becoming commonplace and requires iterative and collaborative discussions between coach and resident, with the shared development of goals. However, little is known about how goal development unfolds within coaching conversations over time and the effects these conversations have. We therefore built on current coaching theory by analysing goal development dialogues within resident and faculty coaching relationships.

Methods

This was a qualitative study using interpretive description methodology. Eight internal medicine coach–resident dyads consented to audiotaping coaching meetings over a 1‐year period. Transcripts from meetings and individual exit interviews were analysed thematically using goal co‐construction as a sensitising concept.

Results

Two themes were developed: (i) The content of goals discussed in coaching meetings focused on how to be a resident, with little discussion around challenges in direct patient care, and (ii) co‐construction mainly occurred in how to meet goals, rather than in prioritising goals or co‐constructing new goals.

Conclusions

In analysing goal development in the coach–resident relationships, conversations focused mainly around how to manage as a resident rather than how to improve direct patient care. This may be because academic coaching provides space separate from clinical work to focus on the stage‐specific professional identity development of a resident. Going forward, focus should be on how to optimise longitudinal coaching conversations to ensure co‐regulation and reflection on both clinical competencies and professional identity formation.
Real‐time automatic crack detection method based on drone
Authors: Meng Shiqiao , Gao Zhiyuan , Zhou Ying , He Bin , Djerrad Abderrahim
Published: October 2022

Real‐time automated drone‐based crack detection can be used for efficient building damage assessment. This paper proposes an automated real‐time crack detection method based on a drone. Using a lightweight classification algorithm, a lightweight segmentation algorithm, a high‐precision segmentation algorithm, and a crack width measurement algorithm, the cracks are classified, roughly segmented, finely segmented, and the maximum width is extracted. A crack information‐assisted drone flight automatic control algorithm for automatic crack detection guides the drone toward the crack position. The effectiveness of the crack detection algorithm and the crack information‐assisted drone flight automatic control algorithm was tested on two different datasets, a two‐story building, and a 16‐m‐high shaking table test building. The results show that crack detection can be finished in real‐time during the flight. Using the proposed method can significantly improve the MIoU of crack edge detection and the accuracy of maximum crack width measurement under the non‐ideal shooting conditions of the actual inspection situation by automatically approaching the vicinity of the crack.
The northern corn leaf blight resistance gene Ht1 encodes an nucleotide‐binding, leucine‐rich repeat immune receptor
Authors: Thatcher Shawn , Leonard April , Lauer Marianna , Panangipalli Gayathri , Norman Bret , Hou Zhenglin , Llaca Victor , Hu Wang‐Nan , Qi Xiuli , Jaqueth Jennifer , Severns Dina , Whitaker David , Wilson Bill , Tabor Girma , Li Bailin
Published: October 2022

Northern corn leaf blight, caused by the fungal pathogen Exserohilum turcicum, is a major disease of maize. The first major locus conferring resistance to E. turcicum race 0, Ht1, was identified over 50 years ago, but the underlying gene has remained unknown. We employed a map‐based cloning strategy to identify the Ht1 causal gene, which was found to be a coiled‐coil nucleotide‐binding, leucine‐rich repeat (NLR) gene, which we named PH4GP‐Ht1. Transgenic testing confirmed that introducing the native PH4GP‐Ht1 sequence to a susceptible maize variety resulted in resistance to E. turcicum race 0. A survey of the maize nested association mapping genomes revealed that susceptible Ht1 alleles had very low to no expression of the gene. Overexpression of the susceptible B73 allele, however, did not result in resistant plants, indicating that sequence variations may underlie the difference between resistant and susceptible phenotypes. Modelling of the PH4GP‐Ht1 protein indicated that it has structural homology to the Arabidopsis NLR resistance gene ZAR1, and probably forms a similar homopentamer structure following activation. RNA sequencing data from an infection time course revealed that 1 week after inoculation there was a threefold reduction in fungal biomass in the PH4GP‐Ht1 transgenic plants compared to wild‐type plants. Furthermore, PH4GP‐Ht1 transgenics had significantly more inoculation‐responsive differentially expressed genes than wild‐type plants, with enrichment seen in genes associated with both defence and photosynthesis. These results demonstrate that the NLR PH4GP‐Ht1 is the causal gene underlying Ht1, which represents a different mode of action compared to the previously reported wall‐associated kinase northern corn leaf blight resistance gene Htn1/Ht2/Ht3.
CircHOMER1 aggravates oxidative stress, inflammation and extracellular matrix deposition in high glucose‐induced human mesangial cells
Authors: Shu Shi , Xu Zhongju , Lu Haiying , Li Zhijie , Zhang Yue
Published: October 2022

Background

Circular RNAs (circRNAs) play an important regulatory role in human diseases, including diabetic nephropathy (DN). The purpose of this study was to investigate the role and mechanism of circHOMER1 action in DN.

Methods

Human mesangial cells (HMCs) were tested with high glucose (HG) to mimic DN cell models. Quantitative real‐time PCR was performed to determine circHOMER1, microRNA (miR)‐137 and SRY‐box transcription factor 6 (SOX6) expression. SOD activity and MDA level were detected to evaluate cell oxidative stress. ELISA assay was used to analyse the levels of inflammation factors. The protein levels of extracellular matrix (ECM) deposition‐related markers and SOX6 were assessed by western blot analysis. The interaction between miR‐137 and circHOMER1 or SOX6 was analysed by dual‐luciferase reporter assay and RNA pull‐down assay.

Results

CircHOMER1 was highly expressed in HG‐induced HMCs and DN patients. Downregulation of circHOMER1 suppressed oxidative stress, inflammation and ECM deposition in HMCs induced by HG. In terms of mechanism, circHOMER1 could sponge miR‐137 to regulate SOX6. Function assays showed that miR‐137 inhibitor or SOX6 overexpression revoked the negative regulation of circHOMER1 knockdown on HG‐induced HMCs injury. In addition, miR‐137 expression was negatively correlated with circHOMER1 and SOX6 expression in DN patients.

Conclusion

CircHOMER1 promoted HG‐induced HMCs oxidative stress, inflammation and ECM accumulation via the miR‐137/SOX6 axis, suggesting that circHOMER1 might be a target for DN treatment.
PM2.5,PM10 and bronchiolitis severity: A cohort study
Authors: Milani Gregorio P. , Cafora Marco , Favero Chiara , Luganini Anna , Carugno Michele , Lenzi Erica , Pistocchi Anna , Pinatel Eva , Pariota Luigi , Ferrari Luca , Bollati Valentina
Published: October 2022

Background

A few studies suggest that particulate matter (PM) exposure might play a role in bronchiolitis. However, available data are mostly focused on the risk of hospitalization and come from retrospective studies that provided conflicting results. This prospective study investigated the association between PM (PM2.5 and PM10) exposure and the severity of bronchiolitis.

Methods

This prospective cohort study was conducted between November 2019 and February 2020 at the pediatric emergency department of the Fondazione IRCCS Ca′ Ospedale Maggiore Policlinico, Milan, Italy. Infants <1 year of age with bronchiolitis were eligible. The bronchiolitis severity score was assessed in each infant and a nasal swab was collected to detect respiratory viruses. The daily PM10 and PM2.5 exposure in the 29 preceding days were considered. Adjusted regression models were employed to evaluate the association between the severity score and PM10 and PM2.5 exposure.

Results

A positive association between the PM2.5 levels and the severity score was found at day‐2 (β 0.0214, 95% CI 0.0011–0.0417, p = .0386), day‐5 (β 0.0313, 95% CI 0.0054–0.0572, p = .0179), day‐14 (β 0.0284, 95% CI 0.0078–0.0490, p = .0069), day‐15 (β 0.0496, 95% CI 0.0242–0.0750, p = .0001) and day‐16 (β 0.0327, 95% CI 0.0080–0.0574, p = .0093).Similar figures were observed considering the PM10 exposure and limiting the analyses to infants with respiratory syncytial virus.

Conclusion

This study shows for the first time a direct association between PM2.5 and PM10 levels and the severity of bronchiolitis.
Mediators linking obesity to childhood asthma
Authors: Chen Yang‐Ching , Huang Yen‐Tsung , Pan Wen‐Harn , Lee Yungling L.
Published: October 2022

Background

Obesity and asthma are highly associated, but the mechanisms underlying the association remain unknown. We examined five mediators linking obesity with childhood asthma: (1) pulmonary function impairment, (2) airway inflammation, (3) physical fitness, (4) sleep‐disordered breathing (SDB), and (5) early puberty.

Methods

A Mendelian randomization (MR) study with mediation analysis of data obtained from 5965 children as part of the Taiwan Children Health Study. Observational analysis, MR two‐stage least‐squares method, and MR sensitivity analysis were carried out to investigate each causal pathway. Prospective cohort analyses were used to strengthen the findings.

Results

The increased asthma risk associated with obesity was found to be mostly mediated through impaired pulmonary function, low physical fitness, and early puberty. In the MR analysis, body mass index was negatively associated with FEV1/FVC and physical fitness index (β = −2.17 and −0.71; 95% CI, −3.92 to −0.42 and −1.30 to −0.13, respectively) and positively associated with early puberty (OR, 1.09; 95% CI, 1.02–1.17). High FEV1/FVC and physical fitness index reduced asthma risk (OR, 0.98 and 0.93; 95% CI, 0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and 1.05–1.42, respectively). Temporal causality was strengthened in prospective cohort analyses. The three main mediators were low physical fitness, impaired pulmonary function, and early puberty, with mediation proportions of 73.76%, 61.63%, and 27.66%, respectively.

Conclusions

Interventions promoting physical fitness and pulmonary function might effectively reduce obesity‐induced asthma risk.
Wellness of patients with chronic pain is not only about pain intensity
Authors: Gershoni Tamar , Pud Dorit , Aviram Joshua , Eisenberg Elon
Published: October 2022

Objective

Attaining good outcomes in the management of chronic pain remains a clinical challenge. This study aimed to investigate the relationships between – and the contribution of – pain and related conditions to the wellness of these patients.

Design

A secondary analysis of database of patients with chronic pain treated with medical cannabis (MC) to carry out a one‐year prospective follow‐up study was conducted. Questionnaires were completed before (T0), six (T6), and twelve (T12) months after MC initiation. Data included patients' demographics and questionnaires related to three latent factors: pain intensity measures, related conditions (catastrophizing, sleep disturbance, anxiety, and depression), and wellness parameters (quality‐of‐life, disability, subjective‐health‐state). Weighted average of the observed variables (WOBs) were calculated for each latent factor. Longitudinal structural equation modeling (SEM) and mediation analyses were performed to identify predictors and interrelations between the WOBs, respectively.

Results

Participants included 510 patients. All variables were significantly improved from T0 to T6 and T12. SEM revealed that related conditions, and to a lesser extent pain, predicted wellness at T0, T6, and T12 (related conditions: β0 = 0.55, p < 0.001; β6 = 0.54, p < 0.001; and β12 = 0.51, p < 0.001; pain: β0 = 0.42, p < 0.001; β6 = 0.18, p < 0.001; and β12 = 0.25, p < 0.001). Mediation analyses demonstrated that the effect of WOB‐related conditions was greater than WOB‐pain on wellness.

Conclusion

Wellness of patients with chronic pain can be determined not only by pain itself but even more so by the severity of related conditions. Thus, considering a broad spectrum of pain measures and related conditions seems relevant for improving the wellness of patients with chronic pain.
Increased abundance of patatins, lipoxygenase and miraculins in a thaxtomin A‐habituated potato Russet Burbank somaclone with enhanced resistance to common scab
Authors: Isayenka Iauhenia , Duque‐Yate Juan , Goulet Marie‐Claire , Michaud Dominique , Beaulieu Carole , Beaudoin Nathalie
Published: October 2022

Potato common scab caused by the actinobacterium Streptomyces scabiei is characterized by the formation of corky lesions on tubers that reduce their marketability. Management of common scab is very complex and often ineffective under various environmental conditions. Using potato varieties that are more resistant to common scab remains one of the most efficient strategies to control this disease. However, very little is known about the factors associated with resistance to common scab. Somaclone RB9 regenerated from thaxtomin A‐habituated potato Russet Burbank calli produced tubers more resistant to common scab than the original variety. Comparison of the RB9 tuber proteome with that of Russet Burbank using label‐free quantitative proteomic analysis revealed changes in the accumulation of defence‐related proteins from the patatin and lipoxygenase (LOX) families, which are involved in the metabolism of lipids, and of two miraculins of the Kunitz‐type protease inhibitors family. The implication of LOX during common scab infection was studied using synchronized minitubers developed from leaf‐bud cuttings. S. scabiei infection stimulated the accumulation of LOX in both Russet Burbank and RB9 minitubers, but this accumulation was intensified in RB9 minitubers. Infection also increased LOX activity in Russet Burbank and RB9 minitubers. However, LOX activity measured in noninfected RB9 minitubers was similar to that of infected Russet Burbank minitubers, indicating endogenous activation of LOX activity in RB9 minitubers. We discuss how increased LOX abundance and activity in the somaclone RB9 may contribute to improving tuber defence against common scab.
No evidence of three herbicides and one surfactant impacting biological soil crusts
Authors: Slate Mandy L. , Durham Rebecca A. , Casper Chuck , Mummey Daniel , Ramsey Philip , Pearson Dean E.
Published: October 2022

Land managers rely heavily on herbicides to mitigate exotic plant invasions but the nontarget effects of herbicides on treated plant, animal, and soil communities are often overlooked. Biological soil crusts (biocrusts) are important components of ecosystems yet the effects of different herbicides on biocrusts are rarely considered. We tested the impact of three widely used herbicides, indaziflam, imazapic, aminocyclopyrachlor, and chlorsulfuron, two of which were applied with or without a surfactant, on biocrusts dominated by mosses or lichens in intermountain grasslands. We found that neither the herbicides nor surfactant impacted biocrust moss or lichen cover within 2 years of their application.