bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis immune responses triggered by cellulose‐ and mixed‐linked glucan‐derived oligosaccharides require a group ofleucine‐rich repeat malectinreceptor kinases
Authors: Martín‐Dacal Marina , Fernández‐Calvo Patricia , Jiménez‐Sandoval Pedro , López Gemma , Garrido‐Arandía María , Rebaque Diego , del Hierro Irene , Berlanga Diego José , Torres Miguel Ángel , Kumar Varun , Mélida Hugo , Pacios Luis F. , Santiago Julia , Molina Antonio 
Published: December 2022

SUMMARYThe plant immune system perceives a diversity of carbohydrate ligands from plant and microbial cell walls through the extracellular ectodomains (ECDs) of pattern recognition receptors (PRRs), which activate pattern‐triggered immunity (PTI). Among these ligands are oligosaccharides derived from mixed‐linked β‐1,3/β‐1,4‐glucans (MLGs; e.g. β‐1,4‐D‐(Glc)2‐β‐1,3‐D‐Glc, MLG43) and cellulose (e.g. β‐1,4‐D‐(Glc)3, CEL3). The mechanisms behind carbohydrate perception in plants are poorly characterized except for fungal chitin oligosaccharides (e.g. β‐1,4‐d‐(GlcNAc)6, CHI6), which involve several receptor kinase proteins (RKs) with LysM‐ECDs. Here, we describe the isolation and characterization ofArabidopsis thalianamutants impaired in glycan perception (igp) that are defective in PTI activation mediated by MLG43 and CEL3, but not by CHI6.igp1–igp4are altered in three RKs – AT1G56145 (IGP1), AT1G56130 (IGP2/IGP3) and AT1G56140 (IGP4) – with leucine‐rich‐repeat (LRR) and malectin (MAL) domains in their ECDs.igp1harbors point mutation E906K andigp2andigp3harbor point mutation G773E in their kinase domains, whereasigp4is a T‐DNA insertional loss‐of‐function mutant. Notably, isothermal titration calorimetry (ITC) assays with purified ECD‐RKs of IGP1 and IGP3 showed that IGP1 binds with high affinity to CEL3 (with dissociation constantKD = 1.19 ± 0.03 μm) and cellopentaose (KD = 1.40 ± 0.01 μM), but not to MLG43, supporting its function as a plant PRR for cellulose‐derived oligosaccharides. Our data suggest that these LRR‐MAL RKs are components of a recognition mechanism for both cellulose‐ and MLG‐derived oligosaccharide perception and downstream PTI activation in Arabidopsis.
ABSCISIC ACID INSENSITIVE 4 coordinates eoplast formation to ensure acquisition of seed longevity during maturation in Medicago truncatula
Authors: Zinsmeister Julia , Lalanne David , Ly Vu Benoit , Schoefs Benoît , Marchand Justine , Dang Thi Thu , Buitink Julia , Leprince Olivier 
Published: December 2022

SUMMARYSeed longevity, the capacity to remain alive during dry storage, is pivotal to germination performance and is essential for preserving genetic diversity. It is acquired during late maturation concomitantly with seed degreening and the de‐differentiation of chloroplasts into colorless, non‐photosynthetic plastids, called eoplasts. As chlorophyll retention leads to poor seed performance upon sowing, these processes are important for seed vigor. However, how these processes are regulated and connected to the acquisition of seed longevity remains poorly understood. Here, we show that such a role is at least provided by ABSCISIC ACID INSENSITIVE 4 (ABI4) in the legume Medicago truncatula. Mature seeds of Mtabi4 mutants contained more chlorophyll than wild‐type seeds and exhibited a 75% reduction in longevity and reduced dormancy. MtABI4 was necessary to stimulate eoplast formation, as evidenced by the significant delay in the dismantlement of photosystem II during the maturation of mutant seeds. Mtabi4 seeds also exhibited transcriptional deregulation of genes associated with retrograde signaling and transcriptional control of plastid‐encoded genes. Longevity was restored when Mtabi4 seeds developed in darkness, suggesting that the shutdown of photosynthesis during maturation, rather than chlorophyll degradation per se, is a requisite for the acquisition of longevity. Indeed, the shelf life of stay green mutant seeds that retained chlorophyll was not affected. Thus, ABI4 plays a role in coordinating the dismantlement of chloroplasts during seed development to avoid damage that compromises the acquisition of seed longevity. Analysis of Mtabi4 Mtabi5 double mutants showed synergistic effects on chlorophyll retention and longevity, suggesting that they act via parallel pathways.
Organoids of patient‐derived medullary thyroid carcinoma: The first milestone towards a new in vitro model in dogs
Authors: Scheemaeker Stephanie , Inglebert Marine , Daminet Sylvie , Dettwiler Martina , Letko Anna , Drögemüller Cord , Kessler Martin , Ducatelle Richard , Rottenberg Sven , Campos Miguel 
Published: December 2022

AbstractOrganoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period. This cMTC N°2 organoid line was further compared to the primary tumour regarding morphology and IHC expression of thyroid transcription factor‐1 (TTF‐1), thyroglobulin, calcitonin, synaptophysin, vimentin, Ki‐67, cyclooxygenase‐2 (COX‐2), P‐glycoprotein and vascular endothelial growth factor (VEGF). Quality control of the cMTC N°2 organoid line was achieved by a single nucleotide polymorphism (SNP) array of the organoids, primary tumour and healthy blood cells of the same dog. The effect of carboplatin, meloxicam and toceranib phosphate (TOC) on cMTC N°2 organoids' viability was evaluated. The cMTC N°2 organoid line was cultured for 94 days and showed similar histological features with the primary tumour. Immunolabelling for TTF‐1, thyroglobulin, calcitonin and VEGF was similar between the primary tumour and cMTC N°2 organoids. Compared to the primary tumour, organoids showed higher immunolabelling for vimentin and Ki‐67, and lower immunolabelling for synaptophysin, COX‐2 and P‐glycoprotein. The SNP genotype was similar for each chromosome between healthy blood cells, primary tumour and cMTC N°2 organoids. Carboplatin, meloxicam and TOC had no effect on cMTC N°2 organoid cell viability within achievable in vivo concentration range. In conclusion, the cMTC N°2 organoid line is a promising first milestone towards an established in vitro organoid model to explore pathophysiology and new treatment modalities in cMTC.
Influence of feline brachycephaly on respiratory, gastrointestinal, sleep, and activity abnormalities
Authors: Gleason Hadley E. , Phillips Heidi , McCoy Annette M. 
Published: December 2022

AbstractObjectiveTo determine the influence of brachycephaly on respiratory, gastrointestinal, sleep, and activity‐related parameters in cats.Study designProspective questionnaire‐based study.AnimalsA total of 194 BC and 1003 non‐BC cats.MethodsOwners completed an online questionnaire regarding respiratory, gastrointestinal, sleep, and activity‐related parameters. Response options were scored, and individual scores summed to give a total clinical severity score for each cat.ResultsBrachycephalic cats had more frequent snoring (odds ratio [OR] 6.89; 95% confidence interval [CI]: 5.06–9.41), sneezing (OR 6.52; CI: 4.75–8.98), nasal discharge (OR 8.26; 95% CI 5.77–11.85), coughing (OR 1.75; CI: 1.17–2.59), and dyspnea (OR 5.32; CI: 3.42–8.28); shorter activity before becoming dyspneic (OR 2.71; CI: 1.93–3.79), slower recovery from activity (OR 3.17; CI: 2.19–4.57), lower activity levels (OR 2.16; CI: 1.59–2.95), and increased respiratory noise (OR 6.68; CI: 4.71–9.52); and more hypersalivation (OR 2.50; CI: 1.47–4.16), halitosis (OR 1.40; CI: 1.00–1.95), and difficulty chewing (OR 5.19; CI: 3.65–7.38). Median clinical severity scores were higher for BC cats than non‐BC cats (p < .0001).ConclusionsBrachycephalic cats (BC) were at risk for respiratory, gastrointestinal, and activity‐related symptoms compared to non‐BC cats.Clinical relevanceSome BC cats exhibit clinically relevant symptoms and behaviors as reported by owners. Medical or surgical interventions may improve these symptoms and warrant investigation.
Treatment patterns and satisfaction in patients with type 2 diabetes newly initiating oral monotherapy with antidiabetic drugs in Japan: results from the prospective Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND)
Authors: Tajima Atsushi , Tobe Keisuke , Eiki Jun-ichi , Origasa Hideki , Watada Hirotaka , Shimomura Iichiro , Tokita Shigeru , Kadowaki Takashi 
Published: December 2022

IntroductionTo present longitudinal data from the Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) in Japan.Research design and methodsIn this multicenter, prospective, observational cohort study, patients with type 2 diabetes mellitus (T2DM) newly initiated on monotherapy were followed up for 2 years. Primary outcomes included changes in treatment pattern over time, target hemoglobin A1c (HbA1c) attainment and treatment satisfaction per Oral Hypoglycaemic Agent Questionnaire (OHA-Q).ResultsAmong 1474 enrolled patients (male, 62.1%; mean age, 59.7 years; HbA1c, 8.08%), the oral antidiabetic drug (OAD) monotherapy prescription rate decreased to 47.2% and that of 2 and ≥3 OADs increased to 14.8% and 5.4% at 24 months, respectively. Switch/add-on OAD was associated with higher HbA1c and body mass index (BMI), baseline OAD being non-dipeptidyl peptidase-4 inhibitor (DPP-4i)/non-sodium glucose cotransporter-2 inhibitor (SGLT2i), diabetes complications, no comorbidities and consulting a diabetes specialist. The mean (SD) HbA1c (%) was 6.73 (0.85) at 24 months. Higher HbA1c, diabetes complications, cardiovascular disease, being employed, no hypertension and younger treating physician were associated with ≥2 OAD classes prescription or target HbA1c non-attainment at 24 months. OHA-Q subscale scores were significantly higher in patients achieving (vs not achieving) target HbA1c and in those continuing monotherapy (vs combination therapy). Baseline age (<65 years), sex (female), HbA1c, alcohol use, use of non–‍DPP-4i OADs or non-T2DM drugs, diabetes complications and cardiovascular disease had a significant negative impact, while EuroQol five-dimensional five-level and Summary of Diabetes Self-Care Activities-specific diet scores, BMI and unemployment had a significant positive impact on OHA-Q scores at 24 months.ConclusionsPrimary outcomes show real-world treatment patterns and glycemic control over 2 years in patients with T2DM newly initiated on OAD monotherapy in Japan. Key factors associated with durability of initial monotherapy, target achievement or treatment satisfaction included baseline HbA1c, comorbidity and initial OAD choice.
The Effect of high temperature on the stability of basal insulin in a pen: a randomized controlled, crossover, equivalence trial
Authors: Kongmalai Tanawan , Orarachin Patima , Dechates Bothamai , Chanphibun Pornnapa , Junnu Sarawut , Srisawat Chatchawan , Sriwijitkamol Apiradee 
Published: December 2022

IntroductionInsulin is an essential medicine in the management of diabetes. When stored at high temperatures(HTs), its efficacy could rapidly decline. Therefore, appropriate storage of in-use insulin is necessary to achieve its maximum therapeutic effects. However, the ambient temperature in tropical countries is normally relatively high. This study aimed to compare the efficacies of basal insulin in a pen previously kept at 37°C for 21 days and basal insulin in a refrigerated pen (2°C–8°C). Continuous glucose monitoring (CGM) was used to evaluate daily mean glucose levels (MGLs).Research design and methodsThis randomized controlled, crossover, equivalence trial recruited adults with type 2 diabetes mellitus and glycated hemoglobin levels <8% who had used insulin glargine for >3 months. Subjects were randomized for sequential use of refrigerated basal insulin followed by basal insulin kept at HT, with a 2-week washout between phases. The HT insulin pens were stored in a 37°C incubator for 21 days before use, while the refrigerated insulin pens were stored at 2°C–8°C. Study patients received 7-day CGM. The primary outcome was the difference in the groups’ MGLs. The secondary outcome parameters were glucose variability represented by the standard deviation (SD), mean amplitude of glycemic excursion (MAGE), and percentage of time in range (TIR). The remaining quantity of insulin was evaluated by ultrahigh-performance liquid chromatography (UHPLC) assay.ResultsForty patients completed the study. The MGLwas 158.7±30.5 mg/dL and 157.0±40.9 mg/dL in the HT and refrigerated insulin pen groups, respectively (p=0.72). The groups had no significant differences in MAGE7day, SD, percentage of TIR, carryover period, or treatment effects (all p>0.05). There was also no significant difference in the remaining quantity of insulin evaluated by UHPLC (p=0.97).ConclusionsHT basal insulin pens retain their potency and have biological activity comparable to that of refrigerated pens.Trial registration numberTCTR20210611002.
Child Health, Agriculture and Integrated Nutrition (CHAIN): protocol for a randomised controlled trial of improved infant and young child feeding in rural Zimbabwe
Authors: Smith Laura E , Chagwena Dexter. T , Bourke Claire , Robertson Ruairi , Fernando Shamiso , Tavengwa Naume V , Cairns Jill , Ndhlela Thokozile , Matumbu Exhibit , Brown Tim , Datta Kavita , Mutasa Batsirai , Tengende Alice , Chidhanguro Dzivaidzo , Langhaug Lisa , Makanza Maggie , Chasekwa Bernard , Mutasa Kuda , Swann Jonathan , Kelly Paul , Ntozini Robert , Prendergast Andrew 
Published: December 2022

IntroductionOver one-quarter of children in sub-Saharan Africa are stunted; however, commercial supplements only partially meet child nutrient requirements, cannot be sustainably produced, and do not resolve physiological barriers to adequate nutrition (eg, inflammation, microbiome dysbiosis and metabolic dysfunction). Redesigning current infant and young child feeding (IYCF) interventions using locally available foods to improve intake, uptake and utilisation of nutrients could ameliorate underlying pathogenic pathways and improve infant growth during the critical period of complementary feeding, to reduce the global burden of stunting.Methods and analysisChild Health Agriculture Integrated Nutrition is an open-label, individual household randomised trial comparing the effects of IYCF versus ‘IYCF-plus’ on nutrient intake during infancy. The IYCF intervention comprises behaviour change modules to promote infant nutrition delivered by community health workers, plus small-quantity lipid-based nutrient supplements from 6 to 12 months of age which previously reduced stunting at 18 months of age by ~20% in rural Zimbabwe. The ‘IYCF-plus’ intervention provides these components plus powdered NUA-45 biofortified sugar beans, whole egg powder, moringa leaf powder and provitamin A maize. The trial will enrol 192 infants between 5 and 6 months of age in Shurugwi district, Zimbabwe. Research nurses will collect data plus blood, urine and stool samples at baseline (5–6 months of age) and endline (9–11 months of age). The primary outcome is energy intake, measured by multipass 24-hour dietary recall at 9–11 months of age. Secondary outcomes include nutrient intake, anthropometry and haemoglobin concentration. Nested laboratory substudies will evaluate the gut microbiome, environmental enteric dysfunction, metabolic phenotypes and innate immune function. Qualitative substudies will explore the acceptability and feasibility of the IYCF-plus intervention among participants and community stakeholders, and the effects of migration on food production and consumption.Ethics and disseminationThis trial is registered at ClinicalTrials.gov (NCT04874688) and was approved by the Medical Research Council of Zimbabwe (MRCZ/A/2679) with the final version 1.4 approved on 20 August 2021, following additional amendments. Dissemination of trial results will be conducted through the Community Engagement Advisory Board in the study district and through national-level platforms.Trial registration numberNCT04874688.
Acupuncture combined with cognitive–behavioural therapy for insomnia (CBT-I) in patients with insomnia: study protocol for a randomised controlled trial
Authors: Pei Wenya , He Te , Yang Pei , Lv Xiaozhou , Jiao Boyu , Meng Fanqi , Yan Yingshuo , Cui Liqian , He Guanheng , Zhou Xin , Wen Guihua , Ruan Jingwen , Lu Liming 
Published: December 2022

IntroductionInsomnia affects physical and mental health due to the lack of continuous and complete sleep architecture. Polysomnograms (PSGs) are used to record electrical information to perform sleep architecture using deep learning. Although acupuncture combined with cognitive–behavioural therapy for insomnia (CBT-I) could not only improve sleep quality, solve anxiety, depression but also ameliorate poor sleep habits and detrimental cognition. Therefore, this study will focus on the effects of electroacupuncture combined with CBT-I on sleep architecture with deep learning.Methods and analysisThis randomised controlled trial will evaluate the efficacy and effectiveness of electroacupuncture combined with CBT-I in patients with insomnia. Participants will be randomised to receive either electroacupuncture combined with CBT-I or sham acupuncture combined with CBT-I and followed up for 4 weeks. The primary outcome is sleep quality, which is evaluated by the Pittsburgh Sleep Quality Index. The secondary outcome measures include a measurement of depression severity, anxiety, maladaptive cognitions associated with sleep and adverse events. Sleep architecture will be assessed using deep learning on PSGs.Ethics and disseminationThis trial has been approved by the institutional review boards and ethics committees of the First Affiliated Hospital of Sun Yat-sun University (2021763). The results will be disseminated through peer-reviewed journals. The results of this trial will be disseminated through peer-reviewed publications and conference abstracts or posters.Trial registration numberCTR2100052502.
Exploration of the health needs of patients with poorly controlled type 2 diabetes using a user-centred co-production approach in the area of mHealth: an exploratory sequential mixed-method protocol
Authors: Xie Qinqin , Hu Xiling , Wang Yarui , Peng Junsheng , Cheng Li 
Published: December 2022

IntroductionResearch on the needs and preferences of patients with poorly controlled type 2 diabetes mellitus (T2DM) with mobile health (mHealth) service is limited. With the principles of co-production, this study aims to address this research gap by exploring the health needs of Chinese patients with poorly controlled T2DM.Methods and analysisThis study uses a three-phase, exploratory sequential mixed-method design. Phase 1 aims to assess the health needs of patients with poorly controlled T2DM by conducting semi-structured interviews with patients, doctors and nurses. Participants will be recruited by purposive sampling with maximum variation. Content analysis will be employed. Phase 2 will form item generation and develop the mHealth need scale. The scale will be subject to pilot testing and psychometric evaluation, including content validity, construct validity, discriminant validity, internal validity and test–retest reliability. Phase 3 will explore the priority of health needs perceived by patients with poorly controlled T2DM through a cross-sectional study. The measurement tools include an mHealth needs scale, the Summary of Diabetes Self-care Activities Questionnaire, the Diabetes Empowerment Scale-Short Form, the Diabetes Health Literacy Scale and the eHealth Literacy Scale. Multiple regression techniques with a hierarchical block design will be used for the model building to identify the factors contributing to the heterogeneity of the perceived mHealth needs. The findings of phase 1 and phase 3 will be integrated using data correlation, comparison and consolidation.Ethics and disseminationThe Ethics Committee of the School of Nursing, Sun Yat-sen University, has approved this study (No. 2021ZSLYEC). The results of this study will be disseminated through conference presentations and peer-reviewed publications.
Burn-out, emotional labour and psychological resilience among gastroenterology nurses during COVID-19: a cross-sectional study
Authors: Lin Huayan , Li Zhangjie , Yan Mengting 
Published: December 2022

ObjectivesTo investigate the relationship between burn-out, emotional labour and psychological resilience of gastroenterology nurses during the COVID-19 pandemic and explore the factors associated with these specific variables.DesignA multicentre cross-sectional study with anonymous self-reporting was conducted from 24 November 2021 to 26 December 2021.SettingThe study was conducted in Fujian Province, China.ParticipantsThe participants were 345 gastroenterology nurses from 7 tertiary hospitals.Primary and secondary outcome measuresBurn-out, emotional labour and psychological resilience were the primary outcome measures. Using a convenience sampling method, the data were collected using Questionnaire Star (a tool for questionnaire surveys) via WeChat. The Chinese version of the Maslach Burnout Inventory, the Chinese version of the Emotional Labour Scale and the Chinese version of the Psychological Resilience Scale were used to evaluate burn-out, emotional labour and psychological resilience, respectively.ResultsThe total scores for burn-out, emotional labour and psychological resilience in gastroenterology nurses were 53.07±19.63, 38.79±12.22 and 69.97±22.38, respectively, with less use of deep acting and more use of surface acting. Pearson correlation analysis showed that burn-out was positively correlated with two dimensions of emotional labour; surface acting and emotional expression, and negatively correlated with deep acting. There was a negative correlation between emotional labour and all three dimensions of psychological resilience.ConclusionsGreater adoption of deep acting by nurses can be promoted by improving their psychological resilience during events such as the COVID-19 pandemic, which can help improve emotional labour, thereby reducing burn-out and decreasing turnover rates. Senior management in hospitals must pay attention to nurses’ psychological status. Further interventional studies could be conducted in the future to explore relevant measures.