bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells
Authors: Valente Michael , Collinet Nils , Vu Manh Thien-Phong , Popoff Dimitri , Rahmani Khalissa , Naciri Karima , Bessou Gilles , Rua Rejane , Gil Laurine , Mionnet Cyrille , Milpied Pierre , Tomasello Elena , Dalod Marc 
Published: March 2023

AbstractPlasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN− pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.
Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial
Authors: Cascone Tina , Leung Cheuk H. , Weissferdt Annikka , Pataer Apar , Carter Brett W. , Godoy Myrna C. B. , Feldman Hope , William William N. , Xi Yuanxin , Basu Sreyashi , Sun Jing Jing , Yadav Shalini S. , Rojas Alvarez Frank R. , Lee Younghee , Mishra Aditya K. , Chen Lili , Pradhan Monika , Guo Haiping , Sinjab Ansam , Zhou Nicolas , Negrao Marcelo V. , Le Xiuning , Gay Carl M. , Tsao Anne S. , Byers Lauren Averett , Altan Mehmet , Glisson Bonnie S. , Fossella Frank V. , Elamin Yasir Y. , Blumenschein George , Zhang Jianjun , Skoulidis Ferdinandos , Wu Jia , Mehran Reza J. , Rice David C. , Walsh Garrett L. , Hofstetter Wayne L. , Rajaram Ravi , Antonoff Mara B. , Fujimoto Junya , Solis Luisa M. , Parra Edwin R. , Haymaker Cara , Wistuba Ignacio I. , Swisher Stephen G. , Vaporciyan Ara A. , Lin Heather Y. , Wang Jing , Gibbons Don L. , Jack Lee J. , Ajami Nadim J. , Wargo Jennifer A. , Allison James P. , Sharma Padmanee , Kadara Humam , Heymach John V. , Sepesi Boris 
Published: March 2023

AbstractNeoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129.)
Genetic association analysis of 77,539 genomes reveals rare disease etiologies
Authors: Greene Daniel ,   Genomics England Research Consortium, Pirri Daniela , Frudd Karen , Sackey Ege , Al-Owain Mohammed , Giese Arnaud P. J. , Ramzan Khushnooda , Riaz Sehar , Yamanaka Itaru , Boeckx Nele , Thys Chantal , Gelb Bruce D. , Brennan Paul , Hartill Verity , Harvengt Julie , Kosho Tomoki , Mansour Sahar , Masuno Mitsuo , Ohata Takako , Stewart Helen , Taibah Khalid , Turner Claire L. S. , Imtiaz Faiqa , Riazuddin Saima , Morisaki Takayuki , Ostergaard Pia , Loeys Bart L. , Morisaki Hiroko , Ahmed Zubair M. , Birdsey Graeme M. , Freson Kathleen , Mumford Andrew , Turro Ernest 
Published: March 2023

AbstractThe genetic etiologies of more than half of rare diseases remain unknown. Standardized genome sequencing and phenotyping of large patient cohorts provide an opportunity for discovering the unknown etiologies, but this depends on efficient and powerful analytical methods. We built a compact database, the ‘Rareservoir’, containing the rare variant genotypes and phenotypes of 77,539 participants sequenced by the 100,000 Genomes Project. We then used the Bayesian genetic association method BeviMed to infer associations between genes and each of 269 rare disease classes assigned by clinicians to the participants. We identified 241 known and 19 previously unidentified associations. We validated associations with ERG, PMEPA1 and GPR156 by searching for pedigrees in other cohorts and using bioinformatic and experimental approaches. We provide evidence that (1) loss-of-function variants in the Erythroblast Transformation Specific (ETS)-family transcription factor encoding gene ERG lead to primary lymphoedema, (2) truncating variants in the last exon of transforming growth factor-β regulator PMEPA1 result in Loeys–Dietz syndrome and (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment. The Rareservoir provides a lightweight, flexible and portable system for synthesizing the genetic and phenotypic data required to study rare disease cohorts with tens of thousands of participants.
A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer
Authors: Assaf Zoe June F. , Zou Wei , Fine Alexander D. , Socinski Mark A. , Young Amanda , Lipson Doron , Freidin Jonathan F. , Kennedy Mark , Polisecki Eliana , Nishio Makoto , Fabrizio David , Oxnard Geoffrey R. , Cummings Craig , Rode Anja , Reck Martin , Patil Namrata S. , Lee Mark , Shames David S. , Schulze Katja 
Published: March 2023

AbstractOne of the great challenges in therapeutic oncology is determining who might achieve survival benefits from a particular therapy. Studies on longitudinal circulating tumor DNA (ctDNA) dynamics for the prediction of survival have generally been small or nonrandomized. We assessed ctDNA across 5 time points in 466 non-small-cell lung cancer (NSCLC) patients from the randomized phase 3 IMpower150 study comparing chemotherapy-immune checkpoint inhibitor (chemo-ICI) combinations and used machine learning to jointly model multiple ctDNA metrics to predict overall survival (OS). ctDNA assessments through cycle 3 day 1 of treatment enabled risk stratification of patients with stable disease (hazard ratio (HR) = 3.2 (2.0–5.3), P < 0.001; median 7.1 versus 22.3 months for high- versus low-intermediate risk) and with partial response (HR = 3.3 (1.7–6.4), P < 0.001; median 8.8 versus 28.6 months). The model also identified high-risk patients in an external validation cohort from the randomized phase 3 OAK study of ICI versus chemo in NSCLC (OS HR = 3.73 (1.83–7.60), P = 0.00012). Simulations of clinical trial scenarios employing our ctDNA model suggested that early ctDNA testing outperforms early radiographic imaging for predicting trial outcomes. Overall, measuring ctDNA dynamics during treatment can improve patient risk stratification and may allow early differentiation between competing therapies during clinical trials.
Impact of hypothermia alert device (BEMPU) on improvement of duration of Kangaroo Mother Care (KMC) provided at home: parallel-group randomized control trial
Authors: Nimbalkar Somashekhar Marutirao , Patel Viral Thakorbhai , Patel Dipen Vasudev , Phatak Ajay Gajanan 
Published: March 2023

AbstractThe objective of the study was to determine if using the hypothermia-detecting bracelet (named BEMPU) improves the duration of Kangaroo Mother Care (KMC) at home by one hour. This parallel-group randomized controlled trial was conducted at a step-down nursery of a teaching hospital. Neonates between 1000 and 2000 g were randomized to BEMPU and control groups at the time of discharge. BEMPU was applied at the wrist of each newborn in the BEMPU (intervention) group. Parents were advised to keep the BEMPU in place till 4 weeks post-discharge. The BEMPU generates a beep sound as an alarm when a newborn's temperature drops below 36.5 °C. Parents in both groups were trained to provide KMC at home. Parents in the BEMPU group received the "KMC chart" and "BEMPU beep chart," while the control group received the "KMC chart" only. In the "KMC chart," parents entered information about KMC hours on a real-time basis, and in the "BEMPU beep chart," they entered information about alarm beeps from BEMPU on a real-time basis till 4 weeks post-discharge. Independent samples t-test was used to compare mean KMC hours between the two groups. A total of 128 neonates participated in the study (64 in BEMPU and 64 in Control groups). The mean(SD) gestational age for the BEMPU group was 34.04(2.84) weeks vs 34.75(2.70) weeks for the control group. In BEMPU group, mean(SD) daily time spent doing KMC was significantly higher in 1st week [4.78(2.93) vs. 3.22(2.44) h, p = 0.003], in 2nd week [4.52(3.43) vs. 2.84(2.95) h, p = 0.008], in 3rd week [4.23(3.71) vs. 2.30(2.70) h, p = 0.003], in 4th week [3.72(3.30) vs. 1.95(2.65) h, p = 0.003] as compared to control group. BEMPU improved the daily duration of KMC hours at home compared to the control group over four weeks. Clinical Trial Registration: This trial is registered at Clinical Trials Registry India with registration number: CTRI/2018/08/015154 and accessible at http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=27600&EncHid=&modid=&compid=%27,%2727600det%27 Registered on 01/08/2018.
On the forecastability of food insecurity
Authors: Foini Pietro , Tizzoni Michele , Martini Giulia , Paolotti Daniela , Omodei Elisa 
Published: March 2023

AbstractFood insecurity, defined as the lack of physical or economic access to safe, nutritious and sufficient food, remains one of the main challenges included in the 2030 Agenda for Sustainable Development. Near real-time data on the food insecurity situation collected by international organizations such as the World Food Programme can be crucial to monitor and forecast time trends of insufficient food consumption levels in countries at risk. Here, using food consumption observations in combination with secondary data on conflict, extreme weather events and economic shocks, we build a forecasting model based on gradient boosted regression trees to create predictions on the evolution of insufficient food consumption trends up to 30 days in to the future in 6 countries (Burkina Faso, Cameroon, Mali, Nigeria, Syria and Yemen). Results show that the number of available historical observations is a key element for the forecasting model performance. Among the 6 countries studied in this work, for those with the longest food insecurity time series, that is Syria and Yemen, the proposed forecasting model allows to forecast the prevalence of people with insufficient food consumption up to 30 days into the future with higher accuracy than a naive approach based on the last measured prevalence only. The framework developed in this work could provide decision makers with a tool to assess how the food insecurity situation will evolve in the near future in countries at risk. Results clearly point to the added value of continuous near real-time data collection at sub-national level.
A pangenome approach-based loop-mediated isothermal amplification assay for the specific and early detection of Bordetella pertussis
Authors: Juscamayta-López Eduardo , Valdivia Faviola , Soto María Pía , Nureña Brenda , Horna Helen 
Published: March 2023

AbstractDespite widespread vaccination, Bordetella pertussis continues to cause pertussis infections worldwide, leaving infants at the highest risk of severe illness and death, while people around them are likely the main sources of infection and rapidly spread the disease. Rapid and less complex molecular testing for the specific and timely diagnosis of pertussis remains a challenge that could help to prevent the disease from worsening and prevent its transmission. We aimed to develop and validate a colorimetric loop-mediated isothermal amplification (LAMP) assay using a new target uvrD_2 informed by the pangenome for the specific and early detection of B. pertussis. Compared to that of multitarget quantitative polymerase chain reaction (multitarget qPCR) using a large clinical DNA specimen (n = 600), the diagnostic sensitivity and specificity of the uvrD_2 LAMP assay were 100.0% and 98.6%, respectively, with a 99.7% degree of agreement between the two assays. The novel colorimetric uvrD_2 LAMP assay is highly sensitive and specific for detecting B. pertussis DNA in nasopharyngeal swabs and showed similar diagnostic accuracy to complex and high-cost multitarget qPCR, but it is faster, simpler, and inexpensive, which makes it very helpful for the reliable and timely diagnosis of pertussis in primary health care and resource-limited settings.
Identification of potential LncRNAs as papillary thyroid carcinoma biomarkers based on integrated bioinformatics analysis using TCGA and RNA sequencing data
Authors: Feng Jia-Lin , Zheng Wen-Jie , Xu Le , Zhou Qin-Yi , Chen Jun 
Published: March 2023

AbstractThe roles and mechanisms of long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remain elusive. We obtained RNA sequencing (RNA-seq) data of surgical PTC specimens from patients with thyroid cancer (THCA; n = 20) and identified differentially expressed genes (DEGs) between cancer and cancer-adjacent tissue samples. We identified 2309 DEGs (1372 significantly upregulated and 937 significantly downregulated). We performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment, and protein–protein interaction network analyses and screened for hub lncRNAs. Using the same methods, we analyzed the RNA-seq data from THCA dataset in The Cancer Genome Atlas (TCGA) database to identify differentially expressed lncRNAs. We identified 15 key differentially expressed lncRNAs and pathways that were closely related to PTC. Subsequently, by intersecting the differentially expressed lncRNAs with hub lncRNAs, we identified LINC02407 as the key lncRNA. Assessment of the associated clinical characteristics and prognostic correlations revealed a close correlation between LINC02407 expression and N stage of patients. Furthermore, receiver operating characteristic curve analysis showed that LINC02407 could better distinguish between cancerous and cancer-adjacent tissues in THCA patients. In conclusion, our findings suggest that LINC02407 is a potential biomarker for PTC diagnosis and the prediction of lymph node metastasis.
Ecological niche overlap in the Arctic vegetation influenced by seabirds
Authors: Zwolicki Adrian , Zmudczyńska-Skarbek Katarzyna , Weydmann-Zwolicka Agata , Stempniewicz Lech 
Published: March 2023

AbstractIn the High Arctic, nutrients are the most limiting resources, so terrestrial vegetation is of low complexity and grows slowly. However, locally, large seabird colonies increase soil fertility by deposition of faeces, supporting the development of rich and fast-growing plant communities. Here, we assessed how seabird colonies affected ecological niche segregation of plants, across the fertilisation gradient. Study sites were located near five little auk colonies, distributed longitudinally across the Svalbard archipelago. We described vascular plant composition and identified 13 environmental variables, based on which, we calculated and tested the niche overlap (NO) between the 18 most frequent species. Based on the hierarchical classification of the NO matrix, we distinguished typical High Arctic Vegetation (HAV), and Bird-Cliff Vegetation (BCV). The BCV was characterised by higher average NO and soilδ15N compared to HAV. The highest NO values across the fertilisation gradient were found on the border between the distinguished communities and were positively correlated with species diversity. We suggest that in the High Arctic, seabirds-delivered nutrients lead to the development of separate plant communities through the mechanism of avoiding inter-species competition, while simultaneous high species diversity and NO are related to high facilitation between plants on the border between the communities.
Food taboo practices and associated factors among pregnant women in Ethiopia: a systematic review and meta-analysis
Authors: Debela Berhanu Gidisa , Sisay Daniel , Hareru Habtamu Endashaw , Ewune Helen Ali , Tesfa Anene , Shewaye Daniel Alayu , Ewunie Temesgen Muche 
Published: March 2023

AbstractFood taboos have a negative impact on pregnant women and their fetuses by preventing them from consuming vital foods. Previous research found that pregnant women avoided certain foods during their pregnancy for a variety of reasons. This review aimed to determine the pooled prevalence of food taboo practices and associated factors in Ethiopia. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, we searched the literature using PubMed/MEDLINE, AJOL (African Journal Online), HINARI, Science Direct, Google Scholar, and Google electronic databases. The random-effects model was used to estimate the pooled prevalence of food taboo and its determinants at a 95% confidence interval with their respective odds ratios. The pooled food taboo practice among Ethiopian pregnant women was 34.22% (95% CI 25.47–42.96), and after adjustment for publication bias with the trim-and-fill analysis, the pooled food taboo practice of pregnant women was changed to 21.31% (95% CI: 10.85–31.67%). Having less than a secondary education level (OR = 3.57; 95% CI 1.43–8.89), having no ANC follow-up (OR = 4.35; 95% CI 1.12–16.94), and being a rural resident (OR = 3.08; 95% CI 1.14–8.28) were the significant factors. Dairy products, some fruits, green leafy vegetables, meat, and honey are among the taboo foods. The most frequently stated reasons for this taboo practice were: fear of producing a big fetus, which is difficult during delivery; attachment to the fetus's body or head; and fear of fetal abnormality.
Long-term prognostic value of Murray law-based quantitative flow ratio in jailed left circumflex coronary artery after left main crossover stenting
Authors: Li Lieyou , Feng Zhihai , Zhang Lin , Chen Huang , Zheng Hong , Lin Huizhong , Jiang Qiong , Lin Yunlin , Chen Lianglong , Fan Lin 
Published: March 2023

AbstractWe aimed to evaluate the impact of new Murray law-based QFR of jailed left circumflex coronary artery (LCx) on long-term clinical outcomes after left main coronary artery (LM) simple crossover stenting. 164 patients who underwent LM-to-left anterior descending coronary artery simple crossover stenting and had appropriate angiographic view of LCx for QFR computation were enrolled. The primary clinical outcome was the 5-year target lesion failure (TLF), defined as a composite of cardiac death, a target vessel myocardial infarction or target lesion repeat revascularization. The mean QFR of the LCx after LM stent implantation was 0.88 ± 0.09, and 29 patients (17.7%) had a low QFR (< 0.80), which was significantly associated with a higher 5-year rate of TLF when compared with the high QFR group (27.6% vs. 6.7%; HR: 4.235; 95% CI 1.21–14.95; p = 0.0015). The 5-year LCx ostium-related TLR rate in the low QFR group was also higher (17.2% vs. 3.0% in the high QFR group; HR: 6.07, 95% CI 1.63–22.59, p = 0.002). In a multivariate Cox regression analysis, a low QFR in the LCx after LM stenting was an independent predictor of the 5-year TLF rate (HR: 3.21, 95% CI 1.21–8.53; p = 0.019). ROC analysis showed that QFR a negative predictive value (NPV) of 89.6% ([AUC] 0.73, 95% CI 0.58–0.88, p < 0.05), the cutoff point is 0.85. The patients with a low QFR (< 0.80) in jailed LCX after LM simple crossover stenting had worse 5-year outcomes than those with a high QFR. Conversely, a QFR ≥ 0.85 of jailed LCx could serve as a good predictor of low risk of adverse outcome in LCx ostium. The QFR computation of the jailed LCx may be helpful to determine whether an additional procedure is required for the jailed side branch.
Whole genome characterization and diagnostics of prunus necrotic ringspot virus (PNRSV) infecting apricot in India
Authors: Noorani Md Salik , Baig Mirza Sarwar , Khan Jawaid Ahmad , Pravej Alam 
Published: March 2023

AbstractPrunus necrotic ringspot virus (PNRSV) is a pathogen that infects Prunus species worldwide, causing major economic losses. Using one and two-step RT-PCR and multiplex RT-PCR, the whole genome of the PNRSV-infecting apricot was obtained and described in this study. Computational approaches were used to investigate the participation of several regulatory motifs and domains of the Replicase1, Replicase2, MP, and CP. A single degenerated reverse and three forward oligo primers were used to amplify PNRSV’s tripartite genome. The size of RNA1 was 3.332 kb, RNA2 was 2.591 kb, and RNA3 was 1.952 kb, according to the sequencing analysis. The Sequence Demarcation Tool analysis determined a percentage pair-wise identity ranging between 91 and 99% for RNA1 and 2, and 87–98% for RNA3. Interestingly, the phylogenetic analysis revealed that closely related RNA1, RNA2, and RNA3 sequences of PNRSV strains from various geographical regions of the world are classified into distinct clades or groups. This is the first report on the characterization of the whole genome of PNRSV from India, which provides the cornerstone for further studies on the molecular evolution of this virus. This study will assist in molecular diagnostics and management of the diseases caused by PNRSV.
Heterostrain and temperature-tuned twist between graphene/h-BN bilayers
Authors: Yang Xing , Zhang Bin 
Published: March 2023

AbstractTwo-dimensional materials stacked atomically at small twist angles enable the modification of electronic states, motivating twistronics. Here, we demonstrate that heterostrain can rotate the graphene flake on monolayer h-BN within a few degrees (− 4° to 4°), and the twist angle stabilizes at specific values with applied constant strains, while the temperature effect is negligible in 100–900 K. The band gaps of bilayers can be modulated from ~ 0 to 37 meV at proper heterostrain and twist angles. Further analysis shows that the heterostrain modulates the interlayer energy landscape by regulating Moiré pattern evolution. The energy variation is correlated with the dynamic instability of different stacking modes of bilayers, and arises from the fluctuation of interlayer repulsive interaction associated with p-orbit electrons. Our results provide a mechanical strategy to manipulate twist angles of graphene/h-BN bilayers, and may facilitate the design of rotatable electronic nanodevices.