bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-motif model illuminates DICER cleavage preferences
Authors: Le Cong Truc , Nguyen Trung Duc , Nguyen Tuan Anh 
Published: January 2024

Abstract
In humans, DICER is a key regulator of gene expression through its production of miRNAs and siRNAs by processing miRNA precursors (pre-miRNAs), short-hairpin RNAs (shRNAs), and long double-stranded RNAs (dsRNAs). To advance our understanding of this process, we employed high-throughput dicing assays using various shRNA variants and both wild-type and mutant DICER. Our analysis revealed that DICER predominantly cleaves shRNAs at two positions, specifically at 21 (DC21) and 22 (DC22) nucleotides from their 5′-end. Our investigation identified two different motifs, mWCU and YCR, that determine whether DICER cleaves at DC21 or DC22, depending on their locations in shRNAs/pre-miRNAs. These motifs can work together or independently to determine the cleavage sites of DICER. Furthermore, our findings indicate that dsRNA-binding domain (dsRBD) of DICER enhances its cleavage, and mWCU strengthens the interaction between dsRBD and RNA, leading to an even greater enhancement of the cleavage. Conversely, YCR functions independently of dsRBD. Our study proposes a two-motif model that sheds light on the intricate regulatory mechanisms involved in gene expression by elucidating how DICER recognizes its substrates, providing valuable insights into this critical biological process.
Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial
Authors: Hendrick Jennifer , Ma Jennie Z , Haughey Heather M , Coleman Rachael , Nayak Uma , Kadl Alexandra , Sturek Jeffrey M , Jackson Patrick , Young Mary K , Allen Judith E , Petri William A 
Published: January 2024

Abstract

Background
We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions.

Methods
Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk test (6MWT) at the 1-year visit.

Results
Of those survivors who consented to 1-year visits (n = 16), subjects who had originally received dupilumab were less likely than those who received placebo to have an abnormal DLCO or 6MWT (Fisher exact P = .011; adjusted P = .058). As a secondary endpoint, we saw that 16% of subjects in the dupilumab group died by 1 year compared to 38% in the placebo group, though this was not statistically significant (log-rank P = .12). We did not find significant differences in neurocognitive testing, symptoms, or chest computed tomography between treatment groups but observed a larger reduction in eotaxin levels in those who received dupilumab.

Conclusions
In this observational study, subjects who received dupilumab during acute COVID-19 hospitalization were less likely to have a reduced DLCO or 6MWT, with a nonsignificant trend toward reduced mortality at 1 year compared to placebo.
Long-term Neutralizing Antibody Levels Against Measles and Rubella Viruses Among Adults With 3 Doses of Measles-Mumps-Rubella Vaccine
Authors: Alonge Oluwakemi D , Marin Mona , Hickman Carole J , Sowers Sun B , Chen Min-hsin , Hao Lijuan , Mercader Sara , El-Badry Elina , McClure David L , Icenogle Joseph P , Sugerman David E , Crooke Stephen N , Nguyen Huong Q 
Published: January 2024

Abstract

Background
A third dose of measles-mumps-rubella vaccine (MMR) may be administered for various reasons, but data on long-term immunity are limited. We assessed neutralizing antibody levels against measles and rubella among adults up to 11 years after receipt of a third MMR dose.

Methods
In this longitudinal study, healthy adults who received a third MMR dose as young adults (ages 18–28 years) were recalled around 5 years and 9–11 years after the third dose. Measles and rubella antibody levels were assessed by plaque-reduction and immunocolorimetric neutralization assays, respectively. Antibody concentrations &lt;120 mIU/mL and &lt;10 U/mL were considered potentially susceptible to measles and rubella, respectively. Geometric mean concentrations (GMCs) and 95% confidence intervals (CIs) over time were estimated from generalized estimating equation models.

Results
Approximately 5 and 9–11 years after receipt of the third dose, 405 and 304 adults were assessed, respectively. Measles GMC was 428 mIU/mL (95% CI, 392–468 mIU/mL) 5 years postvaccination, declining to 381 mIU/mL (95% CI, 339–428 mIU/mL) 11 years postvaccination. At the last follow-up visit (9–11 years postvaccination), 10% of participants were potentially susceptible to measles infection. Rubella GMCs were stable throughout the follow-up period (63 U/mL to 65 U/mL); none of the participants was susceptible to rubella at the last follow-up visit.

Conclusions
Eleven years after receiving a third MMR dose, measles and rubella neutralizing antibody levels remained high in adults. However, on the basis of waning antibody levels, some adults may become susceptible to measles infection over time despite receipt of 3 vaccine doses.
Artifactual Orthologs and the Need for Diligent Data Exploration in Complex Phylogenomic Datasets: A Museomic Case Study from the Andean Flora
Authors: Frost Laura A , Bedoya Ana M , Lagomarsino Laura P 
Published: January 2024

Abstract
The Andes mountains of western South America are a globally important biodiversity hotspot, yet there is a paucity of resolved phylogenies for plant clades from this region. Filling an important gap in our understanding of the World’s richest flora, we present the first phylogeny of Freziera (Pentaphylacaceae), an Andean-centered, cloud forest radiation. Our dataset was obtained via hybrid-enriched target sequence capture of Angiosperms353 universal loci for 50 of the ca. 75 spp., obtained almost entirely from herbarium specimens. We identify high phylogenomic complexity in Freziera, including the presence of data artifacts. Via by-eye observation of gene trees, detailed examination of warnings from recently improved assembly pipelines, and gene tree filtering, we identified that artifactual orthologs (i.e., the presence of only one copy of a multicopy gene due to differential assembly) were an important source of gene tree heterogeneity that had a negative impact on phylogenetic inference and support. These artifactual orthologs may be common in plant phylogenomic datasets, where multiple instances of genome duplication are common. After accounting for artifactual orthologs as source of gene tree error, we identified a significant, but nonspecific signal of introgression using Patterson’s D and f4 statistics. Despite phylogenomic complexity, we were able to resolve Freziera into 9 well-supported subclades whose evolution has been shaped by multiple evolutionary processes, including incomplete lineage sorting, historical gene flow, and gene duplication. Our results highlight the complexities of plant phylogenomics, which are heightened in Andean radiations, and show the impact of filtering data processing artifacts and standard filtering approaches on phylogenetic inference.
The evolving landscape of antibody-drug conjugates in ovarian cancer: new drugs for a new era
Authors: García-Illescas David , Mazzeo Roberta , García-Durán Carmen , Oaknin Ana 
Published: January 2024

Purpose of review
This review addresses the emerging role of antibody-drug conjugates (ADCs) in the treatment of ovarian cancer, a field marked by a high need for more effective and targeted therapies. Given the recent advancements in ADC technology and the ongoing challenges in treating ovarian cancer, particularly in late-stage and recurrent cases, this review is both timely and relevant. It synthesizes current research findings and clinical trial data, highlighting the potential of ADCs to revolutionize ovarian cancer treatment.

Recent findings
The review covers key themes including the mechanism of action of ADCs, their specificity in targeting ovarian cancer cells, recent clinical trial outcomes, advancements in ADC design for improved efficacy and reduced toxicity, and strategies to overcome drug resistance in ovarian cancer. It also addresses the heterogeneity of ovarian cancer and the implications for personalized ADC therapies.

Summary
The review underscores the potential of ADCs to significantly impact clinical practice, offering a more effective and personalized treatment approach for ovarian cancer patients. The review suggests a paradigm shift in the treatment of this malignancy, emphasizing the need for further research and development in this area.
A case report of a large Splenic epidermoid cyst treated with partial splenectomy
Authors: Chaouch Mohamed Ali , Hadj Taieb Ahmed , Ben Jabra Sadok , Noomen Mohamed , Zayeti Mohamed , Mili Emna , Gafsi Besma , Noomen Faouzi 
Published: January 2024

Introduction and importance:
Splenic epidermoid cysts are rare primary congenital cysts composed of an epithelial lining that represent a small proportion of nonparasitic splenic cysts. Despite their infrequency, there is a lack of uniform diagnostic and treatment guidelines for these cysts, emphasizing the need for further research and standardized reporting.

Case presentation:
A 45-year-old female presented with left upper quadrant abdominal pain, characterized by a pressing sensation. Physical examination revealed a palpable mass in the upper left quadrant. Laboratory test results were normal. Abdominal ultrasonography and CT tomography confirmed a large splenic unilocular cyst consistent with an epidermoid cyst. Surgical intervention involved aspiration of the cystic fluid, partial splenectomy, and pathological examination. The patient’s postoperative recovery was uneventful.

Clinical discussion:
The origin of splenic epidermoid cysts remains unclear, with theories suggesting entrapment of mesothelial cells during embryonic development. The clinical presentation varies with cyst size, often causing abdominal pain and a palpable mass. Diagnostic modalities include ultrasonography and CT scans. Surgical intervention is recommended for symptomatic or suspicious cysts to prevent complications. The chosen approach depends on cyst characteristics and patient factors. This case highlights the challenges and considerations in managing splenic epidermoid the cysts and emphasizes the need for individualized treatment approaches.

Conclusion:
This case contributes to the understanding of splenic epidermoid cysts and demonstrates a successful subtotal splenectomy as a treatment approach. Further research and standardized guidelines are essential to improve the management of these rare lesions and to provide better insights into their etiology and optimal treatment strategies.
Water and foodborne bacterial pathogens isolated from hospitalized children are extensively resistance against commonly used Penicillin-type antibiotics in developing countries
Authors: Awuor Silas Onyango , Omwenga Eric O. , Mariita Richard M. , Musila Jonathan M. , Mbeke Alexander , Musyoka Thommas M. 
Published: January 2024

Diarrheal diseases pose a significant risk to children under the age of five, ranking as the second leading cause of death within this demographic. This threat is exacerbated by the emergence of multidrug-resistant enteric bacteria, contributing to the ongoing global health crisis. This study aims to identify prevalent bacteria responsible for diarrhea and evaluate their susceptibility to antibiotics in children under five receiving medical attention at a model Kenyan hospital; Muhoroni County Hospital. Varied approaches comprising biochemical analyses, microbial monitoring and susceptibility testing were conducted using conventional antibiotics on carefully collected patients’ samples to assess respective trends. Enteric bacterial pathogens were identified in 43 out of 196 samples (21.9%), with Escherichia coli constituting 25 out of 43 (58.1%), Shigella spp. accounting for 11 out of 43 (25.6%), and Salmonella spp. making up 7 out of 43 (16.3%). All isolated E. coli, Shigella spp., and Salmonella spp. demonstrated susceptibility to Ceftriaxone. Notably, 14 out of 25 (56%), E. coli isolates and 13 out of 25 (52%) E. coli isolates, 11 out of 11 (100%) and 10 out of 11(91%) Shigella spp. isolates, and finally 6 out of 7 (86%) and 5 out of 7(71%) Salmonella spp. showed resistance to Amoxicillin and Ampicillin respectively, commonly prescribed drugs for children under five years. The findings underscore the prevalence of enteric bacterial pathogens contributing to diarrhea in children under five, emphasizing the urgent need for targeted interventions. Furthermore, the observed resistance to commonly prescribed antibiotics highlights the imperative for ongoing surveillance and development of alternative treatment strategies to address the evolving landscape of antimicrobial resistance in pediatric healthcare.
Investigative needle core biopsies for multi-omics in Glioblastoma
Authors: Yu Kenny K.H. , Basu Sreyashi , Baquer Gerard , Ahn Ryuhjin , Gantchev Jennifer , Jindal Sonali , Regan Michael S. , Abou-Mrad Zaki , Prabhu Michael C. , Williams Marc J. , D’Souza Alicia D. , Malinowski Seth W. , Hopland Kelsey , Elhanati Yuval , Stopka Sylwia A. , Stortchevoi Alexei , He Zhong , Sun Jingjing , Chen Yulong , Espejo Alexsandra B. , Chow Kin Hoe , Yerrum Smitha , Kao Pei-Lun , Kerrigan Brittany Parker , Norberg Lisa , Nielsen Douglas ,   The GBM TeamLab, Puduvalli Vinay K. , Huse Jason , Beroukhim Rameen , Kim Yon Son Betty , Goswami Sangeeta , Boire Adrienne , Frisken Sarah , Cima Michael J. , Holdhoff Matthias , Lucas Calixto-Hope G. , Bettegowda Chetan , Levine Stuart S. , Bale Tejus A. , Brennan Cameron , Reardon David A. , Lang Frederick F. , Antonio Chiocca E. , Ligon Keith L. , White Forest M. , Sharma Padmanee , Tabar Viviane , Agar Nathalie Y. R. 
Published: December 2023

AbstractGlioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies – tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses (‘Multi-omics”) has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient’s disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.One sentence summaryIntegrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma
Impact of changes in Achilles tendon thickening on cardiovascular events in patients with familial hypercholesterolemia
Authors: Tada Hayato , Kojima Nobuko , Takeji Yasuaki , Nohara Atsushi , Kawashiri Masa-aki , Takamura Masayuki 
Published: December 2023

AbstractBackgroundAchilles tendon thickening (ATT) can be ameliorated by lowering low-density lipoprotein (LDL) levels in patients with familial hypercholesterolemia (FH). The Japan Atherosclerosis Society (JAS) defines ATT as ≥8.0 mm in males and ≥7.5 mm in females. We aimed to determine the clinical impact of changes in ATT on the development of major adverse cardiovascular events (MACE).MethodsPatients with clinically diagnosed heterozygous FH (HeFH) (N = 1273; 614 males, 659 females) with ATT data from X-ray were assessed. Patients were divided into four groups: patients without ATT from baseline until follow-up (group 1), patients without ATT at baseline but developed ATT at follow-up (group 2), patients with ATT at baseline but regressed at follow-up (group 3), and patients with ATT from baseline until follow-up (group 4). Cox proportional hazard models were used to assess the factors associated with MACE, including cardiovascular death and any coronary events.ResultsOn follow-up (median: 10.9 years), 142 MACEs were observed, and the median ATT regressed from 7.8 to 7.6 mm. Changes in ATT were significantly associated with the occurrence of MACE in all groups, when compared to group 1 (hazard ratio [HR]: 2.73; 95% confidence interval [CI]: 1.33–4.13 [p < 0.001], HR: 2.18, 95% CI: 1.08–3.28, [p < 0.001], HR: 6.34, 95% CI: 3.10–9.58, [p < 0.001], in groups 2, 3, and 4, respectively).ConclusionsAssessing ATT has diagnostic value and allows for risk stratification among patients with HeFH.
Raptor-informed feathered drone reveals tail-twist functions in avian turning manoeuvres
Authors: Phan Hoang-Vu , Floreano Dario 
Published: December 2023

AbstractBanked turn is a common flight manoeuvre observed in birds and aircraft. To initiate the turn, whereas traditional aircraft rely on the wing ailerons, most birds use a variety of asymmetric wing morphing control techniques, validated in engineered replicas, to roll their bodies and thus redirect the lift vector to the direction of the turn. Nevertheless, when searching for prey, soaring raptors execute steady banked turns without exhibiting observable wing movements apart from tail twisting around the body axis. Despite the role as a vertical stabilizer in traditional aircraft, the reasons why birds twist the tails in banked turn are still not well understood. Here, we use an avian-inspired feathered drone to find that the tail located in proximal arrangement behind the wings enters wing-induced asymmetric flow region during twisting and generates asymmetric lift that results in both roll and yaw moments sufficient to coordinate banked turns. Moreover, twisting the tail induces a nose-up pitch moment that increases the angle of attack of the wings, thereby generating more lift that compensates for losses caused by the banking motion. Flight experiments confirm the effectiveness of tail twist to control not only steady low-speed banked turns but also high-speed sharp turns by means of coordinated tail twist and pitch with asymmetric wing shape morphing. These findings contribute to the understanding of avian flight behaviours that are difficult to study in controlled laboratory settings, and provide effective control strategies for agile drones with morphing aerial surfaces.One sentence summaryRaptor-informed feathered drone reveals that twisting the tail located at the trailing edges of the wings generates aerodynamic control forces caused by wing-induced asymmetric flow to let birds execute both steady banked turns and high-speed sharp turns.
The packaging signal ofXanthomonasintegrative filamentous phages
Authors: Yeh Ting-Yu , Feehley Patrick J. , Feehley Michael C. , Ooi Vivian Y. , Wu Pei-Chen , Hsieh Frederick , Chiu Serena S. , Su Yung-Ching , Lewis Maxwell S. , Contreras Gregory P. 
Published: December 2023

ABSTRACTUnlike Ff, the packaging signal (PS) and the mechanism of integrative filamentous phage assembly remain largely unknown. Here we revived twoInoviridaeprophage sequences, ϕLf2 and ϕLf-UK, as infectious virions lysogenize black rot pathogenXanthomonas campestris pv. campestris. ϕLf2 and ϕLf-UK genomes consist of 6,363 and 6,062 nucleotides and share 85.8% and 98.7% identity with ϕLf, respectively. To explore their assembly, we first identified 20-26– nucleotide long PS sequences of 10Xanthomonasphages. These PS consist of a DNA hairpin with the consensus GGX(A/-)CCG(C/T)G sequence in the stem and C/T nucleotides in the loop, both of which are conserved and essential for PS activity. In contrast to Ff, the 5’ to 3‘ orientation of PS sequence is not conserved or critical for their competence. This is the first report to offer insights into the structure and function of integrative phage PS, revealing the diversity of filamentous phage encapsidation.
A highly contiguous hexaploid wheat genome assembly facilitates analysis of 1RS translocation and mining of a new adult plant resistance locus to yellow rust disease
Authors: Li Guangwei , Ren Yan , Yang Yuxin , Chen Shulin , Zheng Jizhou , Zhang Xiaoqing , Chen Mengen , Sun Xiaonan , Lv Chunlei , Li Xiaode , Li Yujia , Dong Chunhao , Tang Jianwei , Huang Zhenpu , Peng Yanyan , Gu Dengbin , Wang Zhiyong , Zheng Hongyuan , Shi Cuilan , Kang Guozhang , Zheng Tiancun , Chen Feng , Wang Daowen , Zhang Kunpu , Yin Guihong 
Published: December 2023

AbstractHigh-quality genome information is essential for efficiently deciphering and improving crop traits. Here we report a highly contiguous hexaploid genome assembly for the key wheat breeding parent Zhou8425B, an elite 1BL/1RS translocation line with durable adult plant resistance (APR) against rust diseases. By using HiFi and Hi-C sequencing reads, a 14.75 Gb genome assembly, with contig N50 and scaffold N50 values reaching 70.94 and 735.11 Mb, respectively, was developed. Comparison with 16 previously sequenced common wheat cultivars revealed unique chromosomal structural features in Zhou8425B. Notably, the 1RS translocation in Zhou8425B was apparently longer and carried more genes encoding AP2/ERF-ERF and B3 transcription factors relative to its counterpart in several genome sequenced 1BL/1RS varieties and rye lines. Aided by Zhou8425B genome assembly, a new APR locus (i.e.,YrZH3B) against yellow rust (YR) disease was finely mapped to a 1 - 2 Mb interval on chromosome 3BS. Analysis with 212 Zhou8425B derivative varieties showed that pyramiding ofYrZH3Bwith two other APR loci (YrZH22andYrZH84) significantly decreased YR severity and enhanced grain yield, with triple combination (YrZH3B/YrZH22/YrZH84) having the highest effects. Our data demonstrate the high value of Zhou8425B assembly in studying wheat genome and agronomically important genes.