bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRASG12C mutation‐induced TOPK overexpression contributes to tumour progression in non‐small cell lung cancer
Authors: Cai Chang , Yao Shuo , Zou Yanmei , Lu Hui , Chen Xiuqiong , Wang Yali , Zheng Kun , Zhu Feng , Wang Yihua , Xiong Hua , Zhu Junfei 
Published: May 2023

AbstractKRAS mutation is the most frequent type of genetic mutation in non‐small cell lung cancer (NSCLC), especially in lung adenocarcinoma. However, KRAS mutation can affect many biological processes and the mechanisms underlying KRAS mutation‐mediate carcinogenesis in NSCLC have not been fully understood. In this research, we found that KRASG12C mutation was associated with the upregulation of T‐LAK cell‐originated protein kinase (TOPK), which is a well‐known serine/threonine MAPK‐like protein kinase implicated in tumorigenesis. The overexpression of TOPK significantly promoted the malignant phenotype of A549 cells, and TOPK silencing impaired the malignant phenotype with KRASG12C mutation. Moreover, we demonstrated that TOPK level was regulated by MAPK/ERK signalling and the transcription factor Elk1. TOPK was also found to promote the activation of NF‐κB signalling in A549 cells with KRASG12C mutation via facilitating the phosphorylation of TAK1. In the in vivo tumorigenesis model, the administration of TOPK inhibitor OTS514 enhanced the anticancer effect of 5‐FU, and the combinatory use of OTS514 and KRASG12C inhibitor AMG510 showed synergistic anti‐tumour effect. These results suggest that KRAS‐TOPK axis contributes to the progression of NSCLC and targeting this axis could synergize with anticancer effect of the existing chemotherapeutics.
Introducing value‐based healthcare perspectives into hospital performance assessment: A scoping review
Authors: He Wenbo , Li Meixuan , Cao Liujiao , Liu Rui , You Jiuhong , Jing Fangyuan , Zhang Jiawen , Zhang Wei , Feng Mengling 
Published: May 2023

AbstractObjectiveValue‐based healthcare (VBHC) puts patient outcomes at the center of the healthcare process while optimizing the use of hospital resources across multiple stakeholders. This scoping review was conducted to summarize how VBHC had been represented in theory and in practice, how it had been applied to assess hospital performance, and how well it had been ultimately implemented.MethodsFor this review, we followed the PRISMA‐ScR protocol and searched five major online databases for articles published between January 2006 and July 2022. We included original articles that used the concept of VBHC to conduct performance assessments of healthcare organizations. We extracted and analyzed key concepts and information on the dimensions of VBHC, specific strategies and methods for using VBHC in performance assessment, and the effectiveness of the assessment.ResultsWe identified 48 eligible studies from 7866 articles. Nineteen nonempirical studies focused on the development of a VBHC performance assessment indicator system, and 29 empirical studies reported on the ways and points of introducing VBHC into performance assessment and its effectiveness. Ultimately, we summarized the key dimensions, processes, and effects of performance assessment after introducing VBHC.ConclusionCurrent healthcare performance assessment has begun to focus on implementing VBHC as an integrated strategy, and future work should further clarify the reliability of metrics and their association with evaluation outcomes and consider the effective integration of clinical outcomes and patient‐reported outcomes.
IRS Private Letter Rulings: Initial Evidence on Determinants and Consequences
Authors: Devos Elizabeth , Devos Erik , Farber David B. , Li He , Rahman Shofiqur 
Published: May 2023

AbstractThis study examines the determinants of firms' requests for Private Letter Rulings (PLRs) from the US Internal Revenue Service (IRS) and their impact on firms' cash holdings. Our results show that PLR requests tend to be made by firms with more active tax planning, more acquisitions, higher analyst following, higher leverage, and less in‐house tax expertise. We also show that firms with IRS audit red flags are less likely to request a PLR. We use a difference‐in‐difference approach to assess changes in cash holdings following PLR requests and report a decrease in cash holdings for PLR firms, consistent with the notion that PLRs act to reduce tax uncertainty. Our study provides the first empirical evidence about the determinants of PLR requests and complements prior work on tax uncertainty and cash holdings (Hanlon, Maydew and Saavedra, 2017).
High intramuscular adipose tissue content was a favorable prognostic factor in patients with advanced gastric cancer treated with nivolumab monotherapy
Authors: Tanaka Toshimitsu , Miwa Keisuke , Shimotsuura Yasutaka , Nagasu Sachiko , Shigyou Hirona , Hirota Keisuke , Koya Shunji , Akagi Yoshito , Kawaguchi Takumi 
Published: May 2023

AbstractBackgroundNivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab.MethodsWe enrolled patients with AGC treated with nivolumab (n = 58, 67 years old, men/women 40/18). The subjects were classified into long‐term or short‐term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis.ResultsIn decision tree analysis, immune‐related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717 days (95% confidence interval [CI], 223 to not reached) in profile 1, 245 days (95% CI, 126 to 252) in profile 2, and 132 days (95% CI, 69 to 163) in profile 3.ConclusionImmune‐related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.
Social participation and tooth loss, vision, and hearing impairments among older Brazilian adults
Authors: Bernabé Eduardo , de Oliveira Cesar , de Oliveira Duarte Yeda Aparecida , Bof de Andrade Fabiola , Sabbah Wael 
Published: May 2023

AbstractBackgroundVision and hearing impairments can reduce participation in social activities. Given the prominent role of the mouth in face‐to‐face interactions, this study evaluated the associations of tooth loss, vision, and hearing impairments with social participation among older adults.MethodsThis analysis included 1947 participants, aged 60+ years, who participated in three waves (2006, 2010, and 2015) of the Health, Wellbeing and Aging Study (SABE) in Brazil. Social participation was measured by the number of formal and informal social activities (requiring face‐to‐face interaction) participants were regularly involved in. Teeth were counted during clinical examinations and categorized as 0, 1–19, and 20+ teeth. Reports on vision and hearing impairments were classified into three categories (good, regular, and poor). The associations of each impairment with the 9‐year change in the social participation score were tested in negative binomial mixed‐effects models adjusting for time‐variant and time‐invariant covariates.ResultsEach impairment was associated with the baseline social participation score and the annual rate of change in the social participation score. Participants with 1–19 (incidence rate ratio: 0.96, 95% CI: 0.91–1.01) and no teeth (0.92, 95% CI: 0.87–0.97), those with regular (0.98, 95% CI: 0.95–1.01) and poor vision (0.86, 95% CI: 0.81–0.90), and those with regular (0.94, 95% CI: 0.91–0.98) and poor hearing (0.91, 95% CI: 0.87–0.95) had lower baseline social participation scores than those with 20+ teeth, good vision, and good hearing, respectively. Furthermore, participants with 1–19 (0.996, 95% CI: 0.990–1.002) and no teeth (0.994, 95% CI: 0.987–0.999), those with regular (0.996, 95% CI: 0.992–0.999) and poor vision (0.997, 95% CI: 0.991–1.003), and those with regular (0.997, 95% CI: 0.992–1.001) and poor hearing (0.995, 95% CI: 0.990–0.999) had greater annual declines in the social participation score than those with 20+ teeth, good vision and good hearing, respectively.ConclusionThis 9‐year longitudinal study shows that tooth loss, vision, and hearing impairments are associated with reduced social participation among older adults.
Omega‐3 as an adjuvant in the treatment eating and psychological symptoms in patients with anorexia nervosa: a systematic review and meta‐analyses
Authors: Candido Ana Claudia Rodrigues , Ferraz Sarah Dagostin , Uggioni Maria Laura Rodrigues , Zanevan Ivan Rosso , Colonetti Laura , Grande Antônio José , Colonetti Tamy , Rosa Maria Inês da 
Published: May 2023

AbstractBackgroundThis study was carried out to assess the effects of omega‐3 supplementation as an adjunct treatment for eating and psychological symptoms in patients with anorexia nervosa.MethodsWe conducted a systematic review of the literature using the terms ‘anorexia nervosa’ AND ‘Fatty Acids, Omega‐3’. Five randomised controlled trials with a total of 144 participants, published between 2003 and 2022, were included.ResultsThe effects of supplementation of omega‐3 on anxiety were standardised mean difference (SMD) 0.79, 95% confidence interval (CI) −0.08 to 1.66; p = 0.08; I² = 3%; two studies, 33 participants; moderate quality of evidence. For depression, the supplementation of omega‐3 was SMD: 0.22, 95% CI: −0.50 to 0.93; p = 0.18; I² = 45%; two studies, 33 participants; moderate quality of evidence. For obsessive‐compulsive disorder, the supplementation of omega‐3 was SMD: −0.22, 95% CI: −0.70 to 2.25; p = 0.36; I² = 0%; three studies, 32 participants; low quality of evidence.ConclusionThis research showed that regardless of dose, time or, if associated with other components, the use of omega‐3 supplementations as an adjuvant treatment showed no evidence of effect in eating and psychological symptoms in patients with anorexia nervosa.
Cell type‐specific proteomics uncovers a RAF15‐SnRK2.6/OST1 kinase cascade in guard cells
Authors: Wang Hongliang , Wang Yubei , Sang Tian , Lin Zhen , Li Rongxia , Ren Weiwei , Shen Xin , Zhao Bing , Wang Xiao , Zhang Xuebin , Zhou Shaoqun , Dai Shaojun , Hu Honghong , Song Chun‐Peng , Wang Pengcheng 
Published: May 2023

ABSTRACTMulticellular organisms such as plants contain various cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances our understanding of organization and function at the organismal level. Guard cells (GCs) are specialized epidermal cells that regulate the movement of the stomata and gaseous exchange, and provide a model genetic system for analyzing cell fate, signaling, and function. Several proteomics analyses of GC are available, but these are limited in depth. Here we used enzymatic isolation and flow cytometry to enrich GC and mesophyll cell protoplasts and perform in‐depth proteomics in these two major cell types in Arabidopsis leaves. We identified approximately 3,000 proteins not previously found in the GC proteome and more than 600 proteins that may be specific to GC. The depth of our proteomics enabled us to uncover a guard cell‐specific kinase cascade whereby Raf15 and Snf1‐related kinase2.6 (SnRK2.6)/OST1(open stomata 1) mediate abscisic acid (ABA)‐induced stomatal closure. RAF15 directly phosphorylated SnRK2.6/OST1 at the conserved Ser175 residue in its activation loop and was sufficient to reactivate the inactive form of SnRK2.6/OST1. ABA‐triggered SnRK2.6/OST1 activation and stomatal closure was impaired in raf15 mutants. We also showed enrichment of enzymes and flavone metabolism in GC, and consistent, dramatic accumulation of flavone metabolites. Our study answers the long‐standing question of how ABA activates SnRK2.6/OST1 in GCs and represents a resource potentially providing further insights into the molecular basis of GC and mesophyll cell development, metabolism, structure, and function.
Training of the lateral pterygoid muscle in the treatment of temporomandibular joint disc displacement with reduction: A randomised clinical trial
Authors: Olbort Christin , Pfanne Falk , Schwahn Christian , Bernhardt Olaf 
Published: May 2023

AbstractBackgroundDisc displacement with reduction (DDwR) therapy should be performed only when pain or discomfort is presented. Data on treatment options for painful DDwR are very limited.ObjectiveThe aim was to investigate whether isometric training of the lateral pterygoid muscle (LPM) is equivalent to stabilisation appliance therapy with regard to the treatment of painful DDwR. The training program is based on the science of Janda.MethodsThis was a prospective, randomised study with a comparative treatment group. Sixty patients (≥18 years) with DDwR and pain were randomly assigned to two groups: (1) muscle training and (2) stabilisation appliance. The following variables were recorded at baseline examination and after 2, 4 and 6 months: changes in orofacial pain, clicking sounds of the temporomandibular joint (TMJ), force degrees for the lateral movement of the mandible and interincisal opening distance. p values of <.05 were considered statistically significant but 95% confidence intervals were also presented.ResultsA decrease in orofacial pain intensity was seen in both groups (p < .0001). Registered TMJ clicking disappeared after 6 months of treatment in 37% (n = 11) of the patients in the training group and in 27% (n = 8) of the appliance group (p = .0009 and p = .0047). Muscle training showed 27 improvements in Janda force degrees at the end of the study (p < .0001).ConclusionMuscle training and appliance therapy improved mouth opening and reduced pain intensity in both patient groups. Muscle training might be a promising option in the treatment of patients suffering from painful DDwR.
The prevalence of breastfeeding aversion response in Australia: A national cross‐sectional survey
Authors: Morns Melissa A. , Burns Elaine , McIntyre Erica , Steel Amie E. 
Published: May 2023

AbstractSome women who breastfeed will experience complex ongoing difficulties, such as breastfeeding aversion response (BAR). This recently named breastfeeding challenge is defined as feelings of aversion while breastfeeding for the entire time that the child is latched. This study provides the first prevalence data for the experience of BAR in Australian breastfeeding women. A national online survey investigated the breastfeeding experience of Australian women including data on (1) participant demographics, (2) breastfeeding experience with up to four children, (3) breastfeeding challenges and prevalence of BAR, and (4) the value of available breastfeeding support. This study found that of the Australian breastfeeding women who participated (n = 5511), just over one in five self‐identified as having experienced a BAR (n = 1227, 22.6%). Most reported experiencing some breastfeeding challenges, with only 4.5% (n = 247) having had no breastfeeding complications. Importantly, despite these difficulties, 86.9% of the total women in this study rated their overall breastfeeding experience as good (n = 2052, 37.6%), or very good (n = 2690, 49.3%), and 82.5% of those who experience BAR as good (n = 471, 38.7%) or very good (n = 533, 43.8%). BAR reporting was decreased in higher education and income groups. Women who are breastfeeding for the first time are more likely to encounter difficulties with breastfeeding such as BAR. Complications with breastfeeding are pervasive, but women who can overcome breastfeeding issues often report a positive overall breastfeeding experience.
Ectomycorrhizal diversity, taxon‐specific traits and root N uptake in temperate beech forests
Authors: Khokon Anis Mahmud , Janz Dennis , Polle Andrea 
Published: May 2023

Summary
Roots of forest trees are colonized by a diverse spectrum of ectomycorrhizal (EM) fungal species differing in their nitrogen (N) acquisition abilities. Here, we hypothesized that root N gain is the result of EM fungal diversity or related to taxon‐specific traits for N uptake.
To test our hypotheses, we traced 15N enrichment in fine roots, coarse roots and taxon‐specific ectomycorrhizas in temperate beech forests in two regions and three seasons, feeding 1 mM NH4NO3 labelled with either 15NH4+ or 15NO3−.
We morphotyped > 45 000 vital root tips and identified 51 of 53 detected EM species by sequencing. EM root tips exhibited strong, fungal taxon‐specific variation in 15N enrichment with higher NH4+ than NO3− enrichment. The translocation of N into the upper parts of the root system increased with increasing EM fungal diversity. Across the growth season, influential EM species predicting root N gain were not identified, probably due to high temporal dynamics of the species composition of EM assemblages.
Our results support that root N acquisition is related to EM fungal community‐level traits and highlight the importance of EM diversity for tree N nutrition.
Biological properties, genetic structure and molecular variability of brome mosaic virus population
Authors: Trzmiel Katarzyna , Zarzyńska‐Nowak Aleksandra , Hasiów‐Jaroszewska Beata 
Published: May 2023

AbstractBrome mosaic virus (BMV) is a member of the Bromovirus genus in the Bromoviridae family. Due to its genetic and biochemical features, BMV is considered as one of the most important plant viruses in molecular plant pathology. Although BMV is widely used in many laboratories as a convenient model for molecular studies, knowledge regarding its biology, pathogenicity, virulence and genetic differentiation within natural populations is rather limited. In this study, the complete genome sequence of 16 BMV isolates originating from different hosts was obtained. Recombination, selection pressure and phylogenetic analyses were carried out using newly obtained BMV sequences and 10 others described to date. The nucleotide and amino acid sequence identities of the 26 BMV sequences were relatively high and ranged from 96.4% to 99.4% for nucleotide sequences and from 95.7% to 99.6% for amino acid sequences. Further analysis revealed that both selection and recombination are shaping the population structure of BMV. The presence of six possible recombination sites within open reading frames and one within the 3′ untranslated region of RNA2 was identified. Selection pressure analysis indicated that most codons were subjected to purifying selection; however, 14 codons were found to be under positive selection pressure. The results presented here expand the current knowledge regarding BMV diversity and the evolutionary forces shaping BMV population structure.
HCPro affects heterologous virus infection through salicylic acid and auxin pathways
Authors: Zeng Mengyuan , Jiao Bolei , Liu Sucen , Yang Yufan , Peng Qiding , Huang Wanying , Xi Dehui 
Published: May 2023

AbstractMixed infection by plant viruses is common in nature, but how a key viral protein of one virus affects the infection by heterologous viruses is not yet fully understood. The helper component proteinase (HCPro) is a widely studied RNA silencing suppressor encoded by viruses of the family Potyviridae. Here, we investigated the defence response of Nicotiana tabacum plants overexpressing HCPro of chilli veinal mottle virus (HCPro‐OX) to tobacco mosaic virus and cucumber mosaic virus infection. We monitored the physiological and molecular changes of HCPro‐OX plants in response to virus infection. The results showed that HCPro‐OX plants under virus infection exhibited higher susceptibility at the early stage but stronger tolerance at the later stage compared to wild‐type plants. The tolerance to heterologous virus infection of HCPro‐OX plants corresponded to a lower level of reactive oxygen species accumulation and higher activities of several antioxidant enzymes. Reverse transcription‐quantitative PCR assays showed that the expression of genes related to salicylic acid (SA) pathways was significantly upregulated, but the expression of genes related to the auxin pathways was downregulated at the late stage of virus infection in HCPro‐OX plants compared to wild‐type plants. By contrast, the situation in the early stage of virus infection was reversed. In addition, pretreatment with SA, the auxin naphthylacetic acid (NAA) and their respective inhibitors 1‐aminobenzotriazole (ABT) and naphthalam (NPA) further confirmed the antagonistic effects of SA and NAA in the response of HCPro‐OX plants to heterologous virus infection. Thus, our results demonstrate that HCPro affects heterologous virus infection through SA and auxin pathways.
A job trial subsidy for youth: Cheap labour or a screening device?
Authors: Krekó Judit , Munkácsy Balázs , Csillag Márton , Scharle Ágota 
Published: May 2023

AbstractThis paper evaluates a 90‐day hiring subsidy designed for young jobseekers aged below 25, introduced in Hungary in 2015 as part of the Youth Guarantee programme. The subsidy covers the total wage cost with no obligation to retain the new hire when the subsidy expires. The analysis is based on linked administrative data on registered unemployment, cognitive skills measured around age 15, healthcare, and social security records. The causal impact of the subsidy on subsequent employment is identified in comparison to participants of a uniquely large public works programme, using propensity score matching with exceptionally rich controls. The estimates indicate significant positive effects: participants spent 14–20 days more in employment within 6 months after the programme ended in the whole sample. The impact is weaker on the 12‐month horizon. We find that the subsidy works well as a screening device: the programme has the highest impact on youths who have very low levels of schooling (8 years of primary school or less), but scored high on cognitive skills tests. One potential explanation is that employers tend to retain those with better cognitive skills, irrespective of their formal qualifications. We also find some indication that the subsidy is (mis)used by some employers to hire short term, seasonal workers.
Evaluating the inventory impact of utilizing low titer platelets in regional hospitals
Authors: Blake John T. , Clarke Gwenn , Bodnar Melanie , Stepien Jennifer 
Published: May 2023

AbstractBackgroundAs a result of constrained supply, it is sometimes necessary to provide patients with ABO‐mismatched platelets. Such practices increase the risk of acute hemolytic transfusion reaction (AHTR). Providing patients with platelets suspended in O plasma having low‐titer Anti‐A and Anti‐B antibodies (LtABO) could reduce the incidence of AHTR. However, natural scarcity limits the number of such units that can be produced. In this paper we present a study to evaluate strategies for deploying LtABO at regional hospitals in Canada.Study Design and MethodsRegional hospitals often experience demand for platelets on an irregular basis. They are, however, required to stock some number of platelets (typically one A‐unit and one O‐unit) for emergencies; outdates are common, with discard rates sometimes >>50%. A simulation study was completed to determine the impact of replacing a (1A, 1O) inventory with 2 or 3 units of LtABO at regional hospitals.ResultsA significant decreases in wastage and shortage can be expected by replacing a (1A, 1O) inventory policy with 2 units of LtABO. In tested cases, a 2‐unit LtABO dominated a (1A, 1O) policy, resulting in statistically fewer outdates and instances of shortage. Holding 3 units of LtABO, increases product availability, but results in an increase in outdates when compared to a (1A, 1O) policy.ConclusionProviding LtABO platelets to smaller, regional hospitals will lower wastage rates and improve patient access to care, when compared to existing (1A, 1O) inventory policies.