bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINE-1 repression in Epstein–Barr virus-associated gastric cancer through viral–host genome interaction
Authors: Zhang Mengyu , Sun Weikang , You Xiaoxin , Xu Dongge , Wang Lingling , Yang Jingping , Li Erguang , He Susu 
Published: March 2023

AbstractLong INterspersed Element 1 (LINE-1 or L1) acts as a major remodeling force in genome regulation and evolution. Accumulating evidence shows that virus infection impacts L1 expression, potentially impacting host antiviral response and diseases. The underlying regulation mechanism is unclear. Epstein–Barr virus (EBV), a double-stranded DNA virus linked to B-cell and epithelial malignancies, is known to have viral–host genome interaction, resulting in transcriptional rewiring in EBV-associated gastric cancer (EBVaGC). By analyzing publicly available datasets from the Gene Expression Omnibus (GEO), we found that EBVaGC has L1 transcriptional repression compared with EBV-negative gastric cancer (EBVnGC). More specifically, retrotransposition-associated young and full-length L1s (FL-L1s) were among the most repressed L1s. Epigenetic alterations, especially increased H3K9me3, were observed on FL-L1s. H3K9me3 deposition was potentially attributed to increased TASOR expression, a key component of the human silencing hub (HUSH) complex for H3K9 trimethylation. The 4C- and HiC-seq data indicated that the viral DNA interacted in the proximity of the TASOR enhancer, strengthening the loop formation between the TASOR enhancer and its promoter. These results indicated that EBV infection is associated with increased H3K9me3 deposition, leading to L1 repression. This study uncovers a regulation mechanism of L1 expression by chromatin topology remodeling associated with viral–host genome interaction in EBVaGC.
Nutrition and food security in Nepal: a narrative review of policies
Authors: Adhikari Nabin , Adhikari Mukesh , Shrestha Namuna , Pradhananga Priza , Poudel Bikram , Dhungel Saurya , Joshi Prakash Chandra , Ide Nicole , Sharma Guna Nidhi , Shrestha Archana 
Published: March 2023

Abstract
In the past few decades, the Nepali government has endorsed several nutritional policies, strategies, and guidelines. Given the lack of a comprehensive review of such policy documents, this review aims to describe the nutrition and food security policies and understand the existing policy gaps in Nepal. Findings from this study can be used to develop policies and programs to address Nepal's current and future nutritional needs. Policies relevant to nutrition and food security were identified by searching government websites and directly approaching relevant government ministries. Thematic analysis was conducted using framework methods under 8 predetermined themes: nutrition intervention, food security, food system, capacity building of human resources, nutrition education, nutrition governance, research, and monitoring and evaluation. The contents of each document reviewed were manually extracted in a spreadsheet stratified by the themes, and the findings were summarized for the respective themes. A total of 30 policy documents were reviewed. Most policies have focused on undernutrition; only a few have addressed overnutrition and diet-related noncommunicable diseases. Food security through a sustainable food system has been considered a key policy area in Nepal. Other areas in the food and nutrition policy landscape are capacity building for human resources, behavior change practices, nutrition governance, monitoring, and evaluation. Policy gaps have been identified in the quality and sustainability of nutrition programs; access to health care services; competent human resources for nutrition; intersectoral coordination and commitment; and support for monitoring, evaluation, and research activities. Most policies have tried to address a wide range of components of food and nutrition security; however, strategies focused on overnutrition and diet-related noncommunicable diseases are lacking. Several gaps are identified in this policy review; the findings can guide the policymakers to address these gaps via further policy development.
Examining the Early Distribution of the Artemisinin-Resistant Plasmodium falciparum kelch13 R561H Mutation in Areas of Higher Transmission in Rwanda
Authors: Kirby Rebecca , Giesbrecht David , Karema Corine , Watson Oliver , Lewis Savannah , Munyaneza Tharcisse , Butera Jean De Dieu , Juliano Jonathan J , Bailey Jeffrey A , Mazarati Jean-Baptiste 
Published: March 2023

Abstract

Background
Artemisinin resistance mutations in Plasmodium falciparum kelch13 (Pfk13) have begun to emerge in Africa, with Pfk13-R561H being the first reported in Rwanda in 2014, but limited sampling left questions about its early distribution and origin.

Methods
We genotyped P. falciparum positive dried blood spot (DBS) samples from a nationally representative 2014–2015 Rwanda Demographic Health Surveys (DHS) HIV study. DBS were subsampled from DHS sampling clusters with &gt;15% P. falciparum prevalence, as determined by rapid testing or microscopy done during the DHS study (n clusters = 67, n samples = 1873).

Results
We detected 476 parasitemias among 1873 residual blood spots from a 2014–2015 Rwanda Demographic Health Survey. We sequenced 351 samples: 341/351 were wild-type (97.03% weighted), and 4 samples (1.34% weighted) harbored R561H that were significantly spatially clustered. Other nonsynonymous mutations found were V555A (3), C532W (1), and G533A (1).

Conclusions
Our study better defines the early distribution of R561H in Rwanda. Previous studies only observed the mutation in Masaka as of 2014, but our study indicates its presence in higher-transmission regions in the southeast of the country at that time.
Predicting Hyperglycemia Among Patients Receiving Alpelisib Plus Fulvestrant for Metastatic Breast Cancer
Authors: Ge Xuan , Behrendt Carolyn E , Yost Susan E , Patel Niki , Samoa Raynald , Stewart Daphne , Sedrak Mina , Lavasani Sayeh , Waisman James , Yuan Yuan , Mortimer Joanne 
Published: March 2023

AbstractBackgroundHyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.Patients and MethodsWe retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method.ResultsThe study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects’ risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28).ConclusionWhile receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.
Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study
Authors: Lemij Annelieke A , Liefers Gerrit Jan , Derks Marloes G M , Bastiaannet Esther , Fiocco Marta , Lans Titia E , van der Pol Carmen C , Vulink Annelie J E , van Gerven Leander , Guicherit Onno R , Linthorst-Niers Eugenie M H , Merkus Jos W S , van Dalen Thijs , Portielje Johanneke E A , de Glas Nienke A 
Published: March 2023

Abstract

Background
A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline.

Methods
Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed.

Results
A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline −11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes.

Discussion
Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.
Target Landscape of Conserved Plant MicroRNAs and the Complexities of Their Ancient MicroRNA-Binding Sites
Authors: Wong Gigi Y , Millar Anthony A 
Published: March 2023

AbstractIn plants, microRNA (miRNA)—target interactions (MTIs) require high complementarity, a feature from which bioinformatic programs have predicted numerous and diverse targets for any given miRNA, promoting the idea of complex miRNA networks. Opposing this is a hypothesis of constrained miRNA specificity, in which functional MTIs are restricted to the few targets whose required expression output is compatible with the expression of the miRNA. To explore these opposing views, the bioinformatic pipeline Targets Ranked Using Experimental Evidence was applied to strongly conserved miRNAs to identity their high-evidence (HE) targets across species. For each miRNA family, HE targets predominantly consisted of homologs from one conserved target gene family (primary family). These primary families corresponded to the known canonical miRNA–target families, validating the approach. Very few additional HE target families were identified (secondary family), and if so, they were likely functionally related to the primary family. Many primary target families contained highly conserved nucleotide sequences flanking their miRNA-binding sites that were enriched in HE homologs across species. A number of these flanking sequences are predicted to form conserved RNA secondary structures that preferentially base pair with the miRNA-binding site, implying that these sites are highly structured. Our findings support a target landscape view that is dominated by the conserved primary target families, with a minority of either secondary target families or non-conserved targets. This is consistent with the constrained hypothesis of functional miRNA specificity, which potentially in part is being facilitated by features beyond complementarity.
Diversity of woodland strawberry inflorescences arises from heterochrony regulated by TERMINAL FLOWER 1 and FLOWERING LOCUS T
Authors: Lembinen Sergei , Cieslak Mikolaj , Zhang Teng , Mackenzie Kathryn , Elomaa Paula , Prusinkiewicz Przemyslaw , Hytönen Timo 
Published: March 2023

Abstract
A vast variety of inflorescence architectures have evolved in angiosperms. Here, we analyze the diversity and development of the woodland strawberry (Fragaria vesca) inflorescence. Contrary to historical classifications, we show that it is a closed thyrse: a compound inflorescence with determinate primary monopodial axis and lateral sympodial branches, thus combining features of racemes and cymes. We demonstrate that this architecture is generated by 2 types of inflorescence meristems differing in their geometry. We further show that woodland strawberry homologs of TERMINAL FLOWER 1 (FvTFL1) and FLOWERING LOCUS T (FvFT1) regulate the development of both the racemose and cymose components of the thyrse. Loss of functional FvTFL1 reduces the number of lateral branches of the main axis and iterations in the lateral branches but does not affect their cymose pattern. These changes can be enhanced or compensated by altering FvFT1 expression. We complement our experimental findings with a computational model that captures inflorescence development using a small set of rules. The model highlights the distinct regulation of the fate of the primary and higher-order meristems, and explains the phenotypic diversity among inflorescences in terms of heterochrony resulting from the opposite action of FvTFL1 and FvFT1 within the thyrse framework. Our results represent a detailed analysis of thyrse architecture development at the meristematic and molecular levels.
INDETERMINATE1 autonomously regulates phosphate homeostasis upstream of the miR399-ZmPHO2signaling module in maize
Authors: Wang Xufeng , Yuan Dan , Liu Yanchun , Liang Yameng , He Juan , Yang Xiaoyu , Hang Runlai , Jia Hong , Mo Beixin , Tian Feng , Chen Xuemei , Liu Lin 
Published: March 2023

AbstractThe macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.
Plasma membrane-associated calcium signaling regulates arsenate tolerance in Arabidopsis
Authors: Liu Yisong , Zhang Yanting , Wang Zhangqing , Guo Shiyuan , Fang Yanjun , Zhang Zhenqian , Gao Huiling , Ren Huimin , Wang Cun 
Published: March 2023

AbstractArsenate [As(V)] is a metalloid with heavy metal properties and is widespread in many environments. Dietary intake of food derived from arsenate-contaminated plants constitutes a major fraction of the potentially health-threatening human exposure to arsenic. However, the mechanisms underlying how plants respond to arsenate stress and regulate the function of relevant transporters are poorly understood. Here, we observed that As(V) stress induces a significant Ca2+ signal in Arabidopsis (Arabidopsis thaliana) roots. We then identified a calcium-dependent protein kinase, CALCIUM-DEPENDENT PROTEIN KINASE 23 (CPK23), that interacts with the plasma membrane As(V)/Pi transporter PHOSPHATE TRANSPORTER 1;1 (PHT1;1) in vitro and in vivo. cpk23 mutants displayed a sensitive phenotype under As(V) stress, while transgenic Arabidopsis plants with constitutively active CPK23 showed a tolerant phenotype. Furthermore, CPK23 phosphorylated the C-terminal domain of PHT1;1, primarily at Ser514 and Ser520. Multiple experiments on PHT1;1 variants demonstrated that PHT1;1S514 phosphorylation is essential for PHT1;1 function and localization under As(V) stress. In summary, we revealed that plasma-membrane-associated calcium signaling regulates As(V) tolerance. These results provide insight for crop bioengineering to specifically address arsenate pollution in soils.
Calcium-binding protein OsANN1 regulates rice blast disease resistance by inactivating jasmonic acid signaling
Authors: Zhao Qiqi , Liu Rui , Zhou Qinzheng , Ye Jie , Meng Fanwei , Liu Jun , Yang Chao 
Published: March 2023

Abstract
Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most devastating diseases in rice (Oryza sativa L.). Plant annexins are calcium- and lipid-binding proteins that have multiple functions; however, the biological roles of annexins in plant disease resistance remain unknown. Here, we report a rice annexin gene, OsANN1 (Rice annexin 1), that was induced by M. oryzae infection and negatively regulated blast disease resistance in rice. By yeast 2-hybrid screening, we found that OsANN1 interacted with a cytochrome P450 monooxygenase, HAN1 (“HAN” termed “chilling” in Chinese), which has been reported to catalyze the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile. Pathogen inoculation assays revealed that HAN1 was also a negative regulator in rice blast resistance. Genetic evidence showed that OsANN1 acts upstream of HAN1. OsANN1 stabilizes HAN1 in planta, resulting in the inactivation of the endogenous biologically active JA-Ile. Taken together, our study unravels a mechanism where an OsANN1–HAN1 module impairs blast disease resistance via inactivating biologically active JA-Ile and JA signaling in rice.
Deplatforming did not decrease Parler users’ activity on fringe social media
Authors: Horta Ribeiro Manoel , Hosseinmardi Homa , West Robert , Watts Duncan J 
Published: March 2023

Abstract
Online platforms have banned (“deplatformed”) influencers, communities, and even entire websites to reduce content deemed harmful. Deplatformed users often migrate to alternative platforms, which raises concerns about the effectiveness of deplatforming. Here, we study the deplatforming of Parler, a fringe social media platform, between 2021 January 11 and 2021 February 25, in the aftermath of the US Capitol riot. Using two large panels that capture longitudinal user-level activity across mainstream and fringe social media content (N = 112, 705, adjusted to be representative of US desktop and mobile users), we find that other fringe social media, such as Gab and Rumble, prospered after Parler’s deplatforming. Further, the overall activity on fringe social media increased while Parler was offline. Using a difference-in-differences analysis (N = 996), we then identify the causal effect of deplatforming on active Parler users, finding that deplatforming increased the probability of daily activity across other fringe social media in early 2021 by 10.9 percentage points (pp) (95% CI [5.9 pp, 15.9 pp]) on desktop devices, and by 15.9 pp (95% CI [10.2 pp, 21.7 pp]) on mobile devices, without decreasing activity on fringe social media in general (including Parler). Our results indicate that the isolated deplatforming of a major fringe platform was ineffective at reducing overall user activity on fringe social media.
E-learning and practical performance in musculoskeletal ultrasound: a multicentre randomized study
Authors: Carstensen Stine Maya Dreier , Just Søren Andreas , Velander Marie , Konge Lars , Hubel Martin Slusarczyk , Rajeeth Savarimuthu Thiusius , Pfeiffer Jensen Mogens , Østergaard Mikkel , Terslev Lene 
Published: March 2023

Abstract

Objectives
To examine the effect of pre-course e-learning on residents’ practical performance in musculoskeletal ultrasound (MSUS).

Methods
This was a multicentre, randomized controlled study following the Consolidated Standards of Reporting Trials (CONSORT) statement. Residents with no or little MSUS experience were randomized to either an e-learning group or a traditional group. One week before a 2-day face-to-face MSUS course, the e-learning group received access to an interactive platform consisting of online lectures, assignments, and practical instruction videos aligned with the content of the course. The traditional group only received standard pre-course information (program, venue, and time). All participants performed a pre- and post-course practical MSUS examination and were assessed by two individual raters, blinded to the group allocation, using the validated Objective Structured Assessment of Ultrasound Skills (OSAUS) tool.

Results
Twenty-eight participants completed the study. There were no statistically significant differences in the pre- or post-course practical MSUS performance between the e-learning group and the traditional group; the mean pre-course OSAUS score (s.d.) in the -learning group was 5.4 (3.7) compared with 5.2 (2.4) in the traditional group (P = 0.8), whereas the post-course OSAUS score in the e-learning group was 11.1 (2.8) compared with 10.9 (2.4) in the traditional group (P = 0.8). There was a significant difference between the mean pre- and post-course scores (5.74 points, P &lt; 0.001). The OSAUS assessment tool demonstrated good inter-rater reliability (intra-class correlation = 0.84).

Conclusion
We found no significant impact of pre-course e-learning on novices’ acquisition of practical MSUS skills. Hands-on training is of the utmost importance and improves MSUS performance significantly. The OSAUS assessment tool is an applicable tool with high interrater reliability.

Trial registration
https://clinicaltrials.gov/ NCT04959162.