bluuebunny/crossref_metadata_2025 huggingface dataset:
From Latin QUO(D) VELLES to Romagnol Cvël: A Case of Degrammaticalisation from a Free‐choice Indefinite to the Noun ‘Thing’1
Authors: D’Antuono Nicola
Published: November 2023

Degrammaticalisation is an oft‐dismissed category of language change. In this paper evidence is provided for its existence, its triggers, and its conditions. This case study details the development of an understudied Old Italo‐Romance indefinite, covelle, a polarity‐sensitive item roughly translating as ‘anything’ which originated from a Latin free relative with Free‐Choice interpretation. It is shown that in Old Italo‐Romance the original Free Choice use was expanded to further nonveridical contexts. Subsequently, a curious development of covelle in Old Romagnol, a 16th‐century Gallo‐Italic variety, is examined whereby polar neutralisation (loss of sensitivity to polarity) of the indefinite was taking place. Contextually, a process of degrammaticalisation had begun through which the indefinite pronoun developed into the classifier ‘thing’. In Modern and Contemporary Romagnol cvël is almost exclusively employed as a noun/classifier. It is argued that two parallel processes have initiated a cycle that led cvël to complete degrammaticalisation: (i) the grammaticalization of the old noun for ‘thing’, co(n)sa, into a wh‐word, calling for lexical replacement, and (ii) competition from the Negative Concord Item gnit. The development of covelle in Romagnol represents a well‐documented case of degrammaticalisation, whose causes and conditions can be thoroughly described and motivated within an interaction with cyclical change.
Impact of COVID‐19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study
Authors: Mclennan Niamh‐Maire , Lindsay Robert , Saravanan Ponnusamy , Sukumar Nithya , White Sara L. , von Dadelszen Peter , Burden Christy , Hunt Kathryn , George Priya , Hirst Jane E. , Lattey Katherine , Lee Tara T. M. , Murphy Helen R. , Scott Eleanor M. , Magee Laura A. , Reynolds Rebecca M. ,   the Diabetes in Pregnancy Working Group
Published: November 2023

Objective

To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID‐19.

Design

Retrospective multicentre cohort.

Setting

Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland.

Population

4915 women with GDM pre‐pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021).

Methods

We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia.

Main Outcome Measures

Intervention at birth, perinatal mortality, large‐for‐gestational‐age infants and neonatal unit admission.

Results

The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre‐existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre‐ and during the pandemic.

Conclusions

Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre‐existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.
A pilot study of intensive short‐time continuous renal replacement therapy to substitute maintenance hemodialysis during transitional period of COVID‐19
Authors: Xu Jing , Xue Cheng , Cui Fangzheng , Lv Jiayi , Jie Yanqing , Liu Lingling , Zheng Qianwen , Fang Haigu , Li Xiangdong , Dai Bing , Chen Jing , Mao Zhiguo
Published: November 2023

Introduction

There is a lack of perfect solutions for maintenance hemodialysis (MHD) in patients with a high transmission risk of SARS‐CoV‐2.

Methods

MHD patients with a high risk of SARS‐CoV‐2 transmission from April 1 to June 30, 2022, were recruited. We performed 4‐h continuous renal replacement therapy with Prismaflex dialysis machine and ST100 suite using continuous venovenous hemodiafiltration (CVVHDF) mode with a fluid exchange volume of 8000 mL/h.

Results

Forty‐five MHD patients were included with a median dialysis age of 91 months. Overall spKt/V reached 0.96 ± 0.19. Urea reduction ratio was 50.29 ± 7.60% with the ultrafiltration of 2.18 ± 0.79 kg. Dry weight was significantly inversely correlated with spKt/V (R = −0.563, p < 0.001). Female gender was a significant positive factor of spKt/V. Preheating of replacement solution using an incubator solved the complication of shivering in most patients.

Conclusion

Intensive short‐time CVVHDF may be considered as an alternative for routine MHD during COVID‐19 transitional period.
Declination affects geomagnetic field‐modulated geotaxis in fruit flies
Authors: Bae JunYong , Kim Na‐Hyeon , Kim Soo‐Chan , Chae Kwon‐Seok
Published: November 2023

Decades of research have established that the Earth’s magnetic field (geomagnetic field, GMF) is broadly used as a sensory cue for magnetic orientation in various animal taxa, including insects. In contrast to the investigation of the total intensity or inclination of the GMF, the effect of declination on horizontal magnetic movement has been explored in a few species, including flies, cockroaches, and dogs. However, the potential role of declination in the vertical movement in magnetosensitive organisms is yet to be reported. In this study, we provide the first evidence that declination within a natural range of change can affect static geotaxis in fruit flies, as assessed using the tube‐positioning assay. In open‐field measurements conducted at 22 domestic and foreign locations, the variation in declination was notably dependent upon the specific location, regardless of altitude, with similar variation in total intensity. Flies subjected to a geographic range of declination under the same total intensity and inclination exhibited remarkably different geotactic positioning scores, irrespective of GMF polarity. Notably, we observed a significant negative correlation between the geotactic score and the absolute value of declination, indicating that declination can induce negative geotaxis effects in flies. These results reveal that flies have evolved to incorporate a declination compass into their multimodal sensorimotor system and suggest that declination may be complementary to gravity in terms of environmental factor‐driven negative geotaxis in flies.
Species delimitation with limited sampling: An example from rare trapdoor spider genus Cyclocosmia (Mygalomorphae, Halonoproctidae)
Authors: Opatova Vera , Bourguignon Kellie , Bond Jason E.
Published: November 2023

The outcome of species delimitation depends on many factors, including conceptual framework, study design, data availability, methodology employed and subjective decision making. Obtaining sufficient taxon sampling in endangered or rare taxa might be difficult, particularly when non‐lethal tissue collection cannot be utilized. The need to avoid overexploitation of the natural populations may thus limit methodological framework available for downstream data analyses and bias the results. We test species boundaries in rare North American trapdoor spider genus Cyclocosmia Ausserer (1871) inhabiting the Southern Coastal Plain biodiversity hotspot with the use of genomic data and two multispecies coalescent model methods. We evaluate the performance of each methodology within a limited sampling framework. To mitigate the risk of species over splitting, common in taxa with highly structured populations, we subsequently implement a species validation step via genealogical diversification index (gdi), which accounts for both genetic isolation and gene flow. We delimited eight geographically restricted lineages within sampled North American Cyclocosmia, suggesting that major river drainages in the region are likely barriers to dispersal. Our results suggest that utilizing BPP in the species discovery step might be a good option for datasets comprising hundreds of loci, but fewer individuals, which may be a common scenario for rare taxa. However, we also show that such results should be validated via gdi, in order to avoid over splitting.
Human lung vascular endothelium may limit infection with HRV16viaIFN‐β‐dependent mechanisms
Authors: Gawrysiak Mateusz , Szewczyk Robert , Kobierecki Mateusz , Szymański Michał , Gajewski Adrian , Gulbas Izabela , Michlewska Sylwia , Chałubiński Maciej
Published: November 2023

Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC‐L) was infected with HRV16. IFN‐β, OAS‐1, and PKR expression was assessed by real‐time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN‐β in the limitation of HRV16 replication, HMVEC‐Ls were preincubated with anti‐IFN‐β Abs. To prove the involvement of OAS‐1 and PKR in the IFN‐dependent limitation of HRV16 replication, HMVEC‐Ls were transfected with respective siRNA. HRV16 stimulated IFN‐β production and activated intracellular mechanisms of antiviral immunity based on OAS‐1 and PKR activation. Blocking of IFN‐β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS‐1, PKR) and boosted replication of HRV16. Effective OAS‐1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN‐β‐dependent intracellular mechanisms based on OAS‐1 and PKR activity.
Livestock grazing promotes legume abundance under increased nutrient loads: Mechanistic evidence from a temperate grassland
Authors: Ciavattini Mariana , Tognetti Pedro M. , Campana Sofía , Yahdjian Laura
Published: November 2023

Question

Legumes are a key component of rangelands because they play an important role in animal nutrition and the entrance of nitrogen (N) into ecosystems through symbiotic fixation. Legume abundance is commonly low in N‐enriched environments because of competition with grasses and non‐legume forbs. Both haying and livestock grazing remove plant biomass and reduce light limitation to plant growth, with the difference that livestock may selectively consume legumes. This study examines how legumes respond to grazing, haying and fertilization, and what mechanisms explain legume abundance in rangelands.

Location

Flooding Pampa, Argentina.

Methods

We performed two manipulation field experiments over 3 years. First, a factorial of rangeland management (intact, haying, or grazing) under two nutrient levels (ambient and increased N, phosphorus [P] and potassium [K]); and second, a factorial of rangeland management (intact or haying) and N × P addition. We evaluated legume, grass and non‐legume forb abundance and ground‐level light in three to five replicates of our experiments over 3 years.

Results

NPK fertilization increased legume abundance consistently under grazing, and temporarily under haying, but had no effect in the intact grassland. Also, P addition increased legume abundance only under haying when N was not added. Temporal changes in legume abundance were positively associated with changes in ground‐level light, which increased with haying and grazing, but decreased with fertilization in the intact grassland, and negatively with grass abundance.

Conclusions

The negative effects of nutrients on legume abundance were offset by the positive effects of livestock. The reduction in grass competition and increase in ground‐level light due to grazing and haying explained the positive responses of legume abundance to nutrients in this temperate grassland. Our results highlight the importance of considering the interactive response of legume abundance to grazing and fertilization, which are becoming common practices in rangelands.
The effect of competition on children's merit‐based resource allocation: The difference between interpersonal and intergroup competition
Authors: Xiao Xue , Zhang Miaomiao , Li Yanfang
Published: November 2023

Competition usually exists in groups in everyday interactions, but how children allocate according to competition outcomes (e.g., merit‐based allocation) after intergroup competition and the difference in children's allocations of rewards between interpersonal and intergroup competition remain unclear. Children aged 3–8 years were asked to complete interpersonal or intergroup competitive games and were further asked to allocate rewards between themselves and their partners (Study 1) or between their group and the other group (Studies 2 and 3) and to reason about their decisions. We found that after interpersonal competition, children tended to conduct merit‐based allocations when they won but were more inclined to conduct equal allocations when they lost; after intergroup competition, children were more inclined to make equal allocations regardless of whether they won or lost, only less than half of children followed meritorious principles. However, children conducted more merit‐based allocations with age after both interpersonal and intergroup competitions. In addition, children showed less bias towards their own side after intergroup competition than after interpersonal competition. Finally, they demonstrated an earlier proclivity towards being influenced by winning outcomes than by losing outcomes after interpersonal competition, whereas a converse tendency was found after intergroup competition.
The effect of simulated seasonal temperatures on Metarhizium brunneum‐associated mortality in Agriotes spp. click beetles, and a degree‐day infection model
Authors: Kabaluk Todd , Ruau Sophie , Poon Anita
Published: November 2023

Entomopathogens tend to have a slow speed of kill when used for targeting agricultural insect pests. Relating temperature as a driver of this speed is important to predict pest mortality, and extending this to a degree‐day infection model has rarely been studied. Many species of wireworms (Coleoptera: Elateridae), the larvae of click beetles, are subterranean and generalist agricultural pests that can be difficult to control with pesticides. Targeting adult beetles, however, may be an effective method to reduce larval recruitment. Metarhizium brunneum Petch (Hypocreales), an entomopathogenic fungus, kills click beetles but the mortality rate and speed of kill are expected to vary according to temperature. Using a thermal gradient plate to simulate daily oscillating temperatures in Agassiz, British Columbia, Canada, for April, May, and June, the effectiveness of M. brunneum strains LRC112 and F52 in causing mortality to Agriotes obscurus (L.) and Agriotes lineatus (L.) click beetles was studied in the laboratory. Mortality was fastest in beetles exposed to June temperatures and slowest in those exposed to April temperatures, with differences among beetle species × M. brunneum strain combinations. Higher temperatures resulted in more rapid mycelial outgrowth and conidiation in beetle cadavers, with only A. obscurus infected with M. brunneum LRC112 attaining near 100% conidiation. The number of degree days required to kill 50% of the beetles (LDD50) was least for A. obscurus infected with M. brunneum LRC112 (176) followed by A. obscurus × M. brunneum F52 (212), A. lineatus × M. brunneum LRC112 (215), and A. lineatus × M. brunneum F52 (292). Hypothetical calculations showed that M. brunneum exposure earlier in the season resulted in a longer time to kill 50% of the beetles (LT50) but the earliest LT50 calendar date. Later M. brunneum exposure dates resulted in lower LT50's, but later LT50 dates. This conceptual work demonstrates that daily temperature oscillations, seasonality, and degree days must be considered to predict the efficacy and speed of kill of different fungal entomopathogen strains when targeting different click beetle species.
Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta‐analysis
Authors: Pham James P. , Rodrigues Anthony , Goldinger Simone M. , Sim Hao‐Wen , Liu Jia
Published: November 2023

Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti‐PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single‐arm trials or retrospective studies. A systematic review and meta‐analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression‐free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18–36), median PFS was 4.8 months (95% CI 3.9–6.6) and median OS was 11.7 months (95% CI 9.2–14.1). Any grade AEs occurred in 93% of patients (95% CI 85–97) while grade 3 and higher AEs occurred in 30% (95% CI 14–54). These results were similar between anti‐EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first‐line anti‐PD1 immunotherapy. Future studies should evaluate their activity and safety following anti‐PD1, identify predictive biomarkers for their efficacy and explore combination approaches.
Carbon storage in old hedgerows: The importance of below‐ground biomass
Authors: Drexler Sophie , Thiessen Eiko , Don Axel
Published: November 2023

Ambitious climate change mitigation goals require novel carbon (C) sinks in agricultural systems. Thus, the establishment of new hedgerows is increasingly attracting attention as a C sequestration measure. Despite hedgerows being a traditional agroforestry system, few studies have been conducted on hedgerow C stocks. Data on below‐ground biomass (BGB) in particular are limited. The aim of this study was therefore to quantify both above‐ground biomass (AGB) and BGB C stocks, as well as litter and soil organic C stocks, of established hedgerow systems by destructive sampling at three sites in northern Germany. The total biomass C (TBC) stock of the sampled hedgerows was 105 ± 11 Mg ha−1 on average. An additional 11 ± 2 Mg ha−1 were found in hedgerow litter and dead roots. Coarse roots (34% of TBC), stumps (22%) and harvestable biomass (20%) were the largest biomass C pools of the hedgerows. The BGB:AGB ratio was 0.7 ± 0.1, showing the importance of BGB in old hedgerow systems. Compared with other woody systems, these old hedgerows seem to have a different biomass distribution, with more biomass allocated below‐ground. About 15% of BGB C stock was stored in fine roots, whereas 85% was stored in coarse roots. The topsoil (0–30 cm) contained 85% of coarse root biomass C and 51% of fine root biomass C. Hedgerow C stock exceeded that of average German forests, and thus demonstrated their large potential for C sequestration when newly planted. This study provides detailed empirical data on C stocks in old hedgerow systems, and thus can be used to take hedgerow C sinks into account in C farming frameworks.
Advances in Helicobacter pylori vaccine research: From candidate antigens to adjuvants—A review
Authors: Yunle Kuang , Tong Wu , Jiyang Liu , Guojun Wu
Published: November 2023

Background

Helicobacter pylori is a Gram‐negative, spiral‐shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa‐associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric‐related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection.

Methods

PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms—H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed.

Results

Most of the candidate antigens used as H. pylori vaccines in these literatures are whole‐cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible.

Conclusions

This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers.
Effects of compassion satisfaction and compassion fatigue on posttraumatic growth of psychiatric nurses: A cross‐sectional study
Authors: Zeng Li , Liu Guiling , Feng Fen , Qiu Yinong , Wang Shuping , Yu Meng , Wang Jialin
Published: November 2023

Aims

This study aimed to explore the effects of compassion satisfaction and compassion fatigue on the posttraumatic growth of psychiatric nurses.

Background

Psychiatric nurses' prolonged and repeated exposure to trauma and complex situations in the work environment can lead to negative emotions such as compassion fatigue, but they also experience positive consequences such as posttraumatic growth, and the relationship between compassion fatigue and posttraumatic growth is not unclear.

Methods

A total of 336 nurses from psychiatry departments of seven tertiary hospitals in Sichuan Province, China, were administered an online questionnaire. Participants were recruited through convenience sampling. The posttraumatic growth level was measured with the Simplified Chinese version of the Posttraumatic Growth Inventory. The Professional Quality of Life Scale‐Chinese version was used to assess compassion satisfaction, burnout and secondary traumatic stress. T‐test and one‐way variance analysis, Pearson correlation analysis and hierarchical linear regression were used for data analysis. A STROBE checklist was used to guide the reporting of the research.

Results

Psychiatric nurses' posttraumatic growth is at a low level, influenced by demographic and occupational factors, whereas compassion satisfaction, burnout and secondary traumatic stress are at a moderate level. Hierarchical regression analysis suggested that compassion satisfaction and secondary traumatic stress had a positive impact on posttraumatic growth, whereas burnout had a negative impact on posttraumatic growth.

Conclusions

Findings suggest that nursing managers should attach importance to the mental health of psychiatric nurses, improve compassion satisfaction, alleviate burnout and promote posttraumatic growth.
Descriptive epidemiology of SARS‐CoV‐2 Beta (B.1.351) variant cases in England, December 2020 to June 2022
Authors: Sinnathamby Mary A. , Zaidi Asad , Twohig Katherine A. , Aliabadi Shirin , Aziz Nurin Abdul , Groves Natalie , Gallagher Eileen , Thelwall Simon , Dabrera Gavin
Published: November 2023

The emergence of the SARS‐CoV‐2 Beta (B.1.351) variant in November 2020 raised concerns of increased transmissibility and severity. We describe the epidemiology of 949 confirmed SARS‐CoV‐2 Beta variant cases in England, identified between December 2020 and June 2022. Most cases were detected in the first 3 months. A total of 10 deaths (1.1%; 10/949) were identified among all cases and of those with travel information, 38 (4.9%; 38/781) cases with hospital admissions within 14 days of a positive test being detected. 52.9% (413/781) cases were imported. This study reinforces the importance of monitoring of travel‐associated cases to inform public health response and reduce transmissibility of new variants.
Facilitating the identification of intellectual disability in schools: A qualitative study of stakeholder views
Authors: McKenzie Karen , Tanfield Yasmin , Murray George , Sandhu Rinku
Published: November 2023

Background

Many children experience delayed or missed identification of an intellectual disability diagnosis, meaning that key opportunities for early educational intervention may be lost.

Methods

Semi‐structured interviews were used to explore the views of teachers, parents, and clinicians (n = 22), about the use of the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS‐Q) and what could improve screening and identification of intellectual disability in schools. Thematic analysis was used to identify relevant themes.

Results

Three themes were identified: the need for, and role of, screening in the context of limited knowledge about intellectual disability; the impact of screening and subsequent identification of intellectual disability; and the context within which participants felt screening should take place in order to maximise its benefits.

Conclusions

The results confirmed the importance and benefits of timely identification of children with an intellectual disability and the positive role that screening might play in this.
Upregulation of ATG9b by propranolol promotes autophagic cell death of hepatic stellate cells to improve liver fibrosis
Authors: Wang Sining , Ding Qian , Xiu Aiyuan , Xia Yifu , Wang Guangchuan , Zhang Chunqing
Published: November 2023

Proranolol has long been recommended to prevent variceal bleeding in patients with cirrhosis. However, the mechanisms of propranolol in liver fibrosis have not yet been thoroughly elucidated. Autophagic cell death (ACD) of activated hepatic stellate cells (HSCs) is important in the alleviation of liver fibrosis. Our study aims to assess the mechanisms of propranolol regulating HSC ACD and liver fibrosis. ACD of HSCs was investigated using lentivirus transfection. The molecular mechanism was determined using a PCR profiler array. The role of autophagy‐related protein 9b (ATG9b) in HSC ACD was detected using co‐immunoprecipitation and co‐localization of immunofluorescence. Changes in the signalling pathway were detected by the Phospho Explorer antibody microarray. Propranolol induces ACD and apoptosis in HSCs. ATG9b upregulation was detected in propranolol‐treated HSCs. ATG9b upregulation promoted ACD of HSCs and alleviated liver fibrosis in vivo. ATG9b enhanced the P62 recruitment to ATG5‐ATG12‐LC3 compartments and increased the co‐localization of P62 with ubiquitinated proteins. The PI3K/AKT/mTOR pathway is responsible for ATG9b‐induced ACD in activated HSCs, whereas the p38/JNK pathway is involved in apoptosis. This study provides evidence for ATG9b as a new target gene and propranolol as an agent to alleviate liver fibrosis by regulating ACD of activated HSCs.
Post‐transcriptional regulation of grain weight and shape by the RBP‐A‐J‐K complex in rice
Authors: Ren Ding , Liu Hui , Sun Xuejun , Zhang Fan , Jiang Ling , Wang Ying , Jiang Ning , Yan Peiwen , Cui Jinhao , Yang Jinshui , Li Zhikang , Lu Pingli , Luo Xiaojin
Published: November 2023

RNA‐binding proteins (RBPs) are components of the post‐transcriptional regulatory system, but their regulatory effects on complex traits remain unknown. Using an integrated strategy involving map‐based cloning, functional characterizations, and transcriptomic and population genomic analyses, we revealed that RBP‐K (LOC_Os08g23120), RBP‐A (LOC_Os11g41890), and RBP‐J (LOC_Os10g33230) encode proteins that form an RBP‐A‐J‐K complex that negatively regulates rice yield‐related traits. Examinations of the RBP‐A‐J‐K complex indicated RBP‐K functions as a relatively non‐specific RBP chaperone that enables RBP‐A and RBP‐J to function normally. Additionally, RBP‐J most likely affects GA pathways, resulting in considerable increases in grain and panicle lengths, but decreases in grain width and thickness. In contrast, RBP‐A negatively regulates the expression of genes most likely involved in auxin‐regulated pathways controlling cell wall elongation and carbohydrate transport, with substantial effects on the rice grain filling process as well as grain length and weight. Evolutionarily, RBP‐K is relatively ancient and highly conserved, whereas RBP‐J and RBP‐A are more diverse. Thus, the RBP‐A‐J‐K complex may represent a typical functional model for many RBPs and protein complexes that function at transcriptional and post‐transcriptional levels in plants and animals for increased functional consistency, efficiency, and versatility, as well as increased evolutionary potential. Our results clearly demonstrate the importance of RBP‐mediated post‐transcriptional regulation for the diversity of complex traits. Furthermore, rice grain yield and quality may be enhanced by introducing various complete or partial loss‐of‐function mutations to specific RBP genes using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated protein 9 technology and by exploiting desirable natural tri‐genic allelic combinations at the loci encoding the components of the RBP‐A‐J‐K complex through marker‐assisted selection.
Concordance of verbal memory and language fMRI lateralization in people with epilepsy
Authors: Kokkinos Vasileios , Seimenis Ioannis
Published: November 2023

Background and Purpose

This work investigates verbal memory functional MRI (fMRI) versus language fMRI in terms of lateralization, and assesses the validity of performing word recognition during the functional scan.

Methods

Thirty patients with a diagnosis of epilepsy underwent verbal memory, visuospatial memory, and language fMRI. We used word encoding, word recognition, image encoding, and image recognition memory tasks, and semantic description, reading comprehension, and listening comprehension language tasks. We used three common lateralization metrics: network spatial distribution, maximum statistical value, and laterality index (LI).

Results

Lateralization of signal spatial distribution resulted in poor similarity between verbal memory and language fMRI tasks. Signal maximum lateralization showed significant (>.8) but not perfect (1) similarity. Word encoding LI showed significant correlation only with listening comprehension LI (p = .016). Word recognition LI was significantly correlated with expressive language semantic description LI (p = .024) and receptive language reading and listening comprehension LIs (p = .015 and p = .019, respectively). There was no correlation between LIs of the visuospatial tasks and LIs of the language tasks.

Conclusions

Our results support the association between language and verbal memory lateralization, optimally determined by LI quantification, and the introduction of quantitative means for language fMRI interpretation in clinical settings where verbal memory lateralization is imperative.
Associations between metabolic hyperferritinaemia, fibrosis‐promoting alleles and clinical outcomes in steatotic liver disease
Authors: Suresh Deepika , Li Ashley , Miller Matthew J. , Wijarnpreecha Karn , Chen Vincent L.
Published: November 2023

Background & Aims

Ferritin has been investigated as a biomarker for liver fibrosis and iron in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). However, whether metabolic hyperferritinaemia predicts progression of liver disease remains unknown. In this study, we sought to understand associations between hyperferritinaemia and (1) adverse clinical outcomes and (2) common genetic variants related to iron metabolism and liver fibrosis.

Methods

This was a retrospective analysis of adults with MASLD seen at the University of Michigan Health System, where MASLD was defined by hepatic steatosis on imaging, biopsy or vibration‐controlled transient elastography, plus metabolic risk factors in the absence of chronic liver diseases other than hemochromatosis. The primary predictor was serum ferritin level, which was dichotomized based on a cut‐off of 300 or 450 mcg/L for women or men. Primary outcomes included (1) incident cirrhosis, liver‐related events, congestive heart failure (CHF), and mortality and (2) distribution of common genetic variants associated with hepatic fibrosis and hereditary hemochromatosis.

Results

Of 7333 patients with MASLD, 1468 (20%) had elevated ferritin. In multivariate analysis, ferritinaemia was associated with increased mortality (HR 1.68 [1.35–2.09], p < .001) and incident liver‐related events (HR 1.92 [1.11–3.32], p = .019). Furthermore, elevated ferritin was associated with carriage of cirrhosis‐promoting alleles including PNPLA3‐rs738409‐G allele (p = .0068) and TM6SF2‐rs58542926‐T allele (p = 0.0083) but not with common HFE mutations.

Conclusions

In MASLD patients, metabolic hyperferritinaemia was associated with increased mortality and higher incidence of liver‐related events, and cirrhosis‐promoting alleles but not with iron overload‐promoting HFE mutations.
Population genomics of the muskox' resilience in the near absence of genetic variation
Authors: Pečnerová Patrícia , Lord Edana , Garcia‐Erill Genís , Hanghøj Kristian , Rasmussen Malthe Sebro , Meisner Jonas , Liu Xiaodong , van der Valk Tom , Santander Cindy G. , Quinn Liam , Lin Long , Liu Shanlin , Carøe Christian , Dalerum Fredrik , Götherström Anders , Måsviken Johannes , Vartanyan Sergey , Raundrup Katrine , Al‐Chaer Amal , Rasmussen Linett , Hvilsom Christina , Heide‐Jørgensen Mads Peter , Sinding Mikkel‐Holger S. , Aastrup Peter , Van Coeverden de Groot Peter J. , Schmidt Niels Martin , Albrechtsen Anders , Dalén Love , Heller Rasmus , Moltke Ida , Siegismund Hans Redlef
Published: November 2023

Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present‐day individuals representing the current native range of both muskox subspecies, the white‐faced and the barren‐ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000‐year‐old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post‐glacial re‐colonizations. In particular, the white‐faced muskox has the lowest genome‐wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long‐term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.
Connecting the dots towards precision orthodontics
Authors: Kapila Sunil , Vora Siddharth R , Rengasamy Venugopalan Shankar , Elnagar Mohammed H. , Akyalcin Sercan
Published: November 2023

Precision orthodontics entails the use of personalized clinical, biological, social and environmental knowledge of each patient for deep individualized clinical phenotyping and diagnosis combined with the delivery of care using advanced customized devices, technologies and biologics. From its historical origins as a mechanotherapy and materials driven profession, the most recent advances in orthodontics in the past three decades have been propelled by technological innovations including volumetric and surface 3D imaging and printing, advances in software that facilitate the derivation of diagnostic details, enhanced personalization of treatment plans and fabrication of custom appliances. Still, the use of these diagnostic and therapeutic technologies is largely phenotype driven, focusing mainly on facial/skeletal morphology and tooth positions. Future advances in orthodontics will involve comprehensive understanding of an individual's biology through omics, a field of biology that involves large‐scale rapid analyses of DNA, mRNA, proteins and other biological regulators from a cell, tissue or organism. Such understanding will define individual biological attributes that will impact diagnosis, treatment decisions, risk assessment and prognostics of therapy. Equally important are the advances in artificial intelligence (AI) and machine learning, and its applications in orthodontics. AI is already being used to perform validation of approaches for diagnostic purposes such as landmark identification, cephalometric tracings, diagnosis of pathologies and facial phenotyping from radiographs and/or photographs. Other areas for future discoveries and utilization of AI will include clinical decision support, precision orthodontics, payer decisions and risk prediction. The synergies between deep 3D phenotyping and advances in materials, omics and AI will propel the technological and omics era towards achieving the goal of delivering optimized and predictable precision orthodontics.
Natural variation in the promoter of FLOWERING LOCUS T‐LIKE 2 in pumpkin (Cucurbita moschata Duch.) is associated with flowering time under short‐day conditions
Authors: Zhao Hang , Tian Zhiyu , Song Guoyi , Xiang Shuanglu , Wang Yi , He Yan , Lv Xiaoran , Wang Jie , Yang Zhongzhou , Liu Yongsheng , Wang Dongliang , Li Wei
Published: November 2023

Late flowering is a serious bottleneck in pumpkin (Cucurbita moschata Duch.) agriculture production. Although key genes governing flowering time have been reported in many species, the regulatory network of flowering in pumpkin remains largely obscure, thereby impeding the resolution of industry‐wide challenges associated with delayed fruit ripening in pumpkin cultivation. Here, we report an early flowering pumpkin germplasm accession (LXX‐4). Using LXX‐4 and a late flowering germplasm accession (HYM‐9), we constructed an F2 segregation population. A significant difference in FLOWERING LOCUS T‐LIKE 2 (FTL2) expression level was identified to be the causal factor of the flowering time trait discrepancy in LXX‐4 and HYM‐9. Moreover, we have shown that a 21 bp InDel in the FTL2 promoter was the key reason for the waxing and waning of its transcript level. The 21 bp deletion excluded a repressor‐AGL19 and recruited activators‐BBX7, WRKY40 and SVP to the FTL2 promoter in LXX‐4. Together, our data add a useful element to our knowledge which could be used to simplify breeding efforts for early‐maturing pumpkin.
Emotional impacts of excursions on parents of children with medical complexity
Authors: Kosaka Makoto , Kotera Yasuhiro , Masunaga Hidehisa , Bhandari Divya , Miyatake Hirotomo , Nishikawa Yoshitaka , Komori Naomi , Ozaki Akihiko , Beniya Hiroyuki
Published: November 2023

Background

Parents of children with medical complexity (CMC) have extra child‐raising responsibilities because of the time commitments necessary for care, and their social participation is often compromised. Experiencing leisure excursions with such children may be a solution to some of these problems but the first‐hand experience of excursions in regard to their psychological impact on the caregivers of CMC remains to be appraised.

Methods

Semi‐structured interviews were conducted, via video conference, with eight informal and eight formal caregivers of CMC who attended an excursion to Tokyo Disney Land (TDL). We investigated the psychological changes that they had experienced through the excursion, performing inductive thematic analysis.

Results

Three themes were identified among parents and five were identified among medical professionals. Themes reported by the parents were: Increased trust in the public and society (Theme 1); confidence for other challenges (Theme 2), and connection with other parents in the non‐medical settings (Theme 3). Themes reported by medical professionals were: Expanding the initiative to other CMC (Theme 1); feeling bonded with other caregivers within the working group (Theme 2); information exchange across different working groups (Theme 3), positive responses from CMC (Theme 4); families' confidence to go out (Theme 5).

Conclusions

This study showed that the excursion to TDL led to positive psychological changes in both medical professionals and parents of CMC, enhancing trust, connection, and confidence. The promising results of this study suggest a need for further research about the impact of an excursion on caregivers of CMC.
The HPA and SAM axis mediate the impairment of creativity under stress
Authors: Guo Xiaoyu , Wang Yifan , Kan Yuecui , Wu Meilin , Ball Linden J. , Duan Haijun
Published: November 2023

With the ever‐changing social environment, individual creativity is facing a severe challenge induced by stress. However, little is known regarding the underlying mechanisms by which acute stress affects creative cognitive processing. The current research explored the impacts of the neuroendocrine response on creativity under stress and its underlying cognitive flexibility mechanisms. The enzyme‐linked immuno sorbent assay was employed to assess salivary cortisol, which acted as a marker of stress‐induced activation of the hypothalamic–pituitary–adrenal (HPA) axis. Eye blink rate (EBR) and pupil diameter were measured as respective indicators of dopamine and noradrenaline released by the activation of the sympathetic–adrenal–medullary (SAM) axis. The Wisconsin card task (WCST) measured cognitive flexibility, while the alternative uses task (AUT) and the remote association task (RAT) measured separately divergent and convergent thinking in creativity. Results showed higher cortisol increments following acute stress induction in the stress group than control group. Ocular results showed that the stress manipulation significantly increased EBR and pupil diameter compared to controls, reflecting increased SAM activity. Further analysis revealed that stress‐released cortisol impaired the originality component of the AUT, reducing cognitive flexibility as measured by perseverative errors on the WCST task. Serial mediation analyses showed that both EBR and pupil diameter were also associated with increased perseverative errors leading to poor originality on the AUT. These findings confirm that physiological arousal under stress can impair divergent thinking through the regulation of different neuroendocrine pathways, in which the deterioration of flexible switching plays an important mediating role.
Calibration‐free blood pressure estimation based on a convolutional neural network
Authors: Cho Jinwoo , Shin Hangsik , Choi Ahyoung
Published: November 2023

In this study, we conducted research on a deep learning‐based blood pressure (BP) estimation model suitable for wearable environments. To measure BP while wearing a wearable watch, it needs to be considered that computing power for signal processing is limited and the input signals are subject to noise interference. Therefore, we employed a convolutional neural network (CNN) as the BP estimation model and utilized time‐series electrocardiogram (ECG) and photoplethysmogram (PPG) signals, which are quantifiable in a wearable context. We generated periodic input signals and used differential and thresholding methods to decrease noise in the preprocessing step. We then applied a max‐pooling technique with filter sizes of 2 × 1 and 5 × 1 within a 3‐layer convolutional neural network to estimate BP. Our method was trained, validated, and tested using 2.4 million data samples from 49 patients in the intensive care unit. These samples, totaling 3.1 GB were obtained from the publicly accessible MIMIC database. As a result of a test with 480,000 data samples, the average root mean square error in BP estimation was 3.41, 5.80, and 2.78 mm Hg in the prediction of pulse pressure, systolic BP (SBP), and diastolic BP (DBP), respectively. The cumulative error percentage less than 5 mm Hg was 68% and 93% for SBP and DBP, respectively. In addition, the cumulative error percentage less than 15 mm Hg was 98% and 99% for SBP and DBP. Subsequently, we evaluated the impact of changes in input signal length (1 cycle vs. 30 s) and the introduction of noise on BP estimation results. The experimental results revealed that the length of the input signal did not significantly affect the performance of CNN‐based analysis. When estimating BP using noise‐added ECG signals, the mean absolute error (MAE) for SBP and DBP was 9.72 and 6.67 mm Hg, respectively. Meanwhile, when using noise‐added PPG signals, the MAE for SBP and DBP was 26.85 and 14.00 mm Hg, respectively. Therefore, this study confirmed that using ECG signals rather than PPG signals is advantageous for noise reduction in a wearable environment. Besides, short sampling frames without calibration can be effective as input signals. Furthermore, it demonstrated that using a model suitable for information extraction rather than a specialized deep learning model for sequential data can yield satisfactory results in BP estimation.