bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly nanoparticle albumin-bound paclitaxel and paclitaxel for relapsed small cell lung cancer
Authors: Oi Hajime , Matsuda Toshiaki , Kimura Tomoki , Morise Masahiro , Yamano Yasuhiko , Yokoyama Toshiki , Kataoka Kensuke , Kondoh Yasuhiro 
Published: February 2022

Abstract
In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.
We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.
The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.
Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX.
Utility of Follow-up Cervical Length Screening in Low-Risk Women With a Cervical Length of 26 to 29 mm
Authors: Boelig Rupsa C. , Kripalu Varsha , Chen Sarah L. , Cruz Yuri , Roman Amanda , Berghella Vincenzo 
Published: February 2022

(Abstracted from Am J Obstet Gynecol 2021;225:179.e1–179.e6)
Preterm birth (PTB) is one of the main causes of neonatal morbidity and mortality worldwide. Neonatal outcomes associated with PTB include respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and cardiovascular abnormalities.
Linguistic Aspects of Stuttering
Authors: Brundage Shelley B. , Bernstein Ratner Nan 
Published: February 2022

Purpose:
Although commonly defined as a speech disorder, stuttering interacts with the language production system in important ways. Our purpose is to summarize research findings on linguistic variables that influence stuttering assessment and treatment.

Method and Results:
Numerous topics are summarized. First, we review research that has examined linguistic features that increase stuttering frequency and influence where it occurs. Second, we tackle the question of whether or not persons who stutter exhibit subtle language differences or deficits. Next, we explore language factors that appear to influence recovery from early stuttering in children. The final topic discusses the unique challenges inherent in differentially diagnosing stuttering in bilingual children. Clinical implications for each topic are discussed.

Discussion:
The article concludes with a discussion of the unique differences in the integration of language and speech demands by people who stutter, when compared with people who are typically fluent, and their clinical ramifications.
Tropical land use alters functional diversity of soil food webs and leads to monopolization of the detrital energy channel
Authors: Zhou Zheng , Krashevska Valentyna , Widyastuti Rahayu , Scheu Stefan , Potapov Anton 
Published: February 2022

AbstractAgricultural expansion is among the main threats to biodiversity and functions of tropical ecosystems. Conversion of rainforest into plantations erodes biodiversity with little-explored consequences for food-web structure and energetics of belowground communities, and associated ecosystem functions and services. We used a unique combination of approaches in stable isotope analysis and food web energetics to analyze in a comprehensive way consequences of the conversion of rainforest into plantations on the structure of and channeling of energy through soil animal food webs in Sumatra, Indonesia. Across the 23 animal groups studied, the channeling of energy shifted towards freshly-fixed plant carbon in plantations, indicating fast energy channeling as opposed to slow energy channeling in rainforests. Earthworms as major detritivores stayed unchanged in their trophic niche and monopolized the detrital pathway in plantations. Functional diversity metrics of soil food webs reflected the reduced amount of litter, tree density and species richness in plantations, providing guidelines how to improve the complexity of the structure of and channeling of energy through soil food webs. Our results highlight the strong restructuring of soil food webs with the conversion of rainforest into plantations threatening soil functioning and ecosystem stability in the long term.
A single cell atlas of the cycling murine ovary
Authors: Morris ME , Meinsohn MC , Chauvin M , Saatcioglu HD , Kashiwagi A. , Sicher NA. , Nguyen NMP , Yuan S , Stavely Rhian , Hyun M , Donahoe PK , Sabatini B , Pépin D 
Published: February 2022

AbstractThe estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate the hormonal and ovulatory functions of the ovary. Folliculogenesis and follicle progression require the orchestrated response of a variety of cell types to allow the maturation of the follicle and its sequela, ovulation, corpus luteum (CL) formation, and ovulatory wound repair. Little is known about the cell state dynamics of the ovary during the estrous cycle, and the paracrine factors that help coordinate this process. Herein we used single-cell RNA sequencing to evaluate the transcriptome of > 34,000 cells of the adult mouse ovary and describe the transcriptional changes that occur across the normal estrous cycle and other reproductive states to build a comprehensive dynamic atlas of murine ovarian cell types and states.
Orchestration of Chlorophyll and Carotenoid Biosynthesis by ORANGE Family Proteins in Plant
Authors: Sun Tianhu , Wang Peng , Lu Shan , Yuan Hui , Yang Yong , Fish Tara , Thannhauser Theodore , Liu Jiping , Mazourek Michael , Grimm Bernhard , Li Li 
Published: February 2022

AbstractChlorophyll and carotenoid are essential photosynthetic pigments. Plants must spatiotemporally coordinate the needs of chlorophyll and carotenoid for optimal photosynthesis and plant fitness in response to diverse environmental and developmental cues. However, how these two biosynthesis pathways are orchestrated remains largely unknown. Here, we report that the highly conserved ORANGE (OR) family proteins are the common regulators of both pathways via posttranslationally regulating the first committed enzyme in each pathway. We demonstrate that OR family proteins physically interact with magnesium chelatase subunit I (CHLI) in addition to phytoene synthase (PSY) and concurrently regulate CHLI and PSY protein stability and activity. We show that loss of OR genes hinders both chlorophyll and carotenoid biosynthesis, limits light-harvesting complex assembly, and impairs thylakoid grana stacking in chloroplast. OR overexpression safeguards photosynthetic pigment biosynthesis and enhances thermotolerance in both Arabidopsis and tomato plants. Our findings establish a conserved mechanism of green plant to coordinate chlorophyll and carotenoid biosynthesis and provide a potential genetic target to generate climate-resilient crops.
Somatic mutations reveal hypermutable brains and are associated with neuropsychiatric disorders
Authors: Bae Taejeong , Fasching Liana , Wang Yifan , Shin Joo Heon , Suvakov Milovan , Jang Yeongjun , Norton Scott , Dias Caroline , Mariani Jessica , Jourdon Alexandre , Wu Feinan , Panda Arijit , Roberts Rosalinda C. , Huttner Anita , Kleinman Joel E. , Hyde Thomas M. , Straub Richard E. , Walsh Christopher A. ,   Brain Somatic Mosaicism Network, Urban Alexander , Leckman James F. , Weinberger Daniel R. , Vaccarino Flora M. , Abyzov Alexej 
Published: February 2022

AbstractSomatic mutations have causative roles in many diseases and contribute to neuropsychiatric disorders. Here, we analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic single nucleotide and structural mutations after whole genome sequencing to a depth of over 200X. Typically, brains had 20 to 60 detectable single nucleotide mutations that likely arose in early development; however, about 5% of brains harbored hundreds and up to 2000 somatic mutations. Hypermutability was associated with age and putative damaging mutations in genes previously implicated in cancer and likely reflectsin vivoclonal expansions. Somatic duplications of likely early developmental origin were present in 1 out of 20 normal and diseased brains, reflecting background mutagenesis. Brains of individuals with autism were enriched in somatic deletions and in point mutations that create putative transcription factor binding motifs in enhancers that are active in the developing brain. The most affected motifs corresponded to MEIS transcription factors, suggesting a potential link between their involvement in gene regulation and autism.
Machine Learning Generalizability Across Healthcare Settings: Insights from multi-site COVID-19 screening
Authors: Yang Jenny , Soltan Andrew A. S. , Clifton David A. 
Published: February 2022

AbstractAs patient health information is highly regulated due to privacy concerns, the majority of machine learning (ML)-based healthcare studies are unable to test on external patient cohorts, resulting in a gap between locally reported model performance and cross-site generalizability. Different approaches have been introduced for developing models across multiple clinical sites, however no studies have compared methods for translating ready-made models for adoption in new settings. We introduce three methods to do this – (1) applying a ready-made model “as-is”; (2) readjusting the decision threshold on the output of a ready-made model using site-specific data; and (3) finetuning a ready-made model using site-specific data via transfer learning. Using a case study of COVID-19 diagnosis across four NHS Hospital Trusts, we show that all methods achieve clinically-effective performances (NPV >0.959), with transfer learning achieving the best results (mean AUROCs between 0.870-0.925). Our models demonstrate that site-specific customization improves predictive performance when compared to other ready-made approaches.
Cov2MS: an automated matrix-independent assay for mass spectrometric detection and measurement of SARS-CoV-2 nucleocapsid protein in infectious patients
Authors: Van Puyvelde Bart , Van Uytfanghe Katleen , Van Oudenhove Laurence , Gabriels Ralf , Van Royen Tessa , Matthys Arne , Razavi Morteza , Yip Richard , Pearson Terry , van Hulle Marijn , Claereboudt Jan , Wyndham Kevin , Jones Don , Saelens Xavier , Martens Geert A. , Stove Christophe , Deforce Dieter , Martens Lennart , Vissers Johannes P.C. , Anderson N. Leigh , Dhaenens Maarten 
Published: February 2022

AbstractINTRODUCTIONThe pandemic readiness toolbox needs to be extended, providing diagnostic tools that target different biomolecules, using orthogonal experimental setups and fit-for-purpose specification of detection. Here we build on a previous Cov-MS effort that used liquid chromatography-mass spectrometry (LC-MS) and describe a method that allows accurate, high throughput measurement of SARS-CoV-2 nucleocapsid (N) protein.MATERIALS and METHODSWe used Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA) technology to enrich and quantify proteotypic peptides of the N protein from trypsin-digested samples from COVID-19 patients.RESULTSThe Cov2MS assay was shown to be compatible with a variety of sample matrices including nasopharyngeal swabs, saliva and blood plasma and increased the sensitivity into the attomole range, up to a 1000-fold increase compared to direct detection in matrix. In addition, a strong positive correlation was observed between the SISCAPA antigen assay and qPCR detection beyond a quantification cycle (Cq) of 30-31, the level where no live virus can be cultured from patients. The automatable “addition only” sample preparation, digestion protocol, peptide enrichment and subsequent reduced dependency upon LC allow analysis of up to 500 samples per day per MS instrument. Importantly, peptide enrichment allowed detection of N protein in a pooled sample containing a single PCR positive sample mixed with 31 PCR negative samples, without loss in sensitivity. MS can easily be multiplexed and we also propose target peptides for Influenza A and B virus detection.CONCLUSIONSThe Cov2MS assay described is agnostic with respect to the sample matrix or pooling strategy used for increasing throughput and can be easily multiplexed. Additionally, the assay eliminates interferences due to protein-protein interactions including those caused by anti-virus antibodies. The assay can be adapted to test for many different pathogens and could provide a tool enabling longitudinal epidemiological monitoring of large numbers of pathogens within a population, applied as an early warning system.
COVID Testing in the Workplace: Return to Work Testing in an Occupational Cohort
Authors: Sikka Robby , Wyllie Anne L. , Premsrirut Prem , Berke Ethan M. 
Published: February 2022

AbstractBackgroundThe Omicron SARS-CoV-2 variant resulted in significant community-based transmission. Numerous occupational settings have employed surveillance testing strategies to minimize occupational exposure and return workers safely to work following isolation.MethodsFrom an occupational COVID-19 testing program, we obtained longitudinal (February 2021-January 2022) saliva-based RT-qPCR results and starting December 27th, 2021, daily on-site molecular over-the-counter (OTC) nasal swab-based isothermal nucleic acid amplification test (molecular OTC; Cue Health COVID-19 test) results. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30 on each day post detection from suspected and confirmed Omicron infections (n=37), compared results to molecular OTC testing, and measured workplace and household transmission. We evaluated return-to-work timing using a post-isolation, two-test threshold of Ct >30, or two negative molecular OTC tests over a 24 hour period, or a single PCR test >30 plus negative molecular OTC test.ResultsFrom the paired testing cohort, 37 (48%) individuals tested positive; all 37 were vaccinated. All individuals tested positive ≤1 day after a previous negative test, and 19 (51.3%) remained PCR-positive with Ct values <30 at day 5. While 3 (8.1%) remained PCR-positive with a Ct value <30 on day 10, no individuals remained PCR-positive on day 12. The average time to PCR clearance/return-to-work was 7.94 days (median=9.5 days). Time to clearance for those boosted (n=8; 7.75 days) and those not yet boosted (8.04 days) did not differ (p=0.49). Peak viral load measured by PCR was 1.97 days from the initial positive test. There were no cases of transmission after returning to work.ConclusionsA large percentage of individuals remain contagious at day 5 post first positive test based on serial PCR testing and can continue until day 12. Early discontinuation of isolation can utilize a two test framework separated by 24 hours. Rapid onsite tests may be useful.
Viruses previously identified in Brazil as belonging to HIV-1 circulating recombinant form (CRF) 72_BF1 represent two closely related CRFs, one of which, designated CRF122_BF1, is also circulating in Spain
Authors: Cañada-García Javier E. , Delgado Elena , Gil Horacio , Benito Sonia , Sánchez Mónica , Ocampo Antonio , Cabrera Jorge Julio , Miralles Celia , García-Bodas Elena , Mariño Ana , Ordóñez Patricia , Gude María José , Ezpeleta Carmen , Thomson Michael M 
Published: February 2022

AbstractCirculating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Those derived from recombination between subtype B and subsubtype F1, with 18 reported, most of them of South American origin, are among the most diverse. Here we identify a HIV-1 BF1 recombinant cluster that is expanding in Spain, transmitted mainly via heterosexual contact, which, analyzed in near full-length genomes in 4 viruses, exhibited a coincident BF1 mosaic structure, with 12 breakpoints, that fully coincided with that of two viruses from Brazil (10BR_MG003 and 10BR_MG005), previously classified as CRF72_BF1. The three remaining Brazilian viruses previously identified as CRF72_BF1 (10BR_MG002, 10BR_MG004, and 10BR_MG008), exhibited mosaic structures highly similar, but not identical, to that of the Spanish viruses and to 10BR_MG003 and 10BR_MG005, with discrepant subtypes in two short genome segments, located in pol and gp120env. Based on these results, we propose that the 5 viruses from Brazil previously identified as CRF72_BF1 actually belong to two closely related CRFs, one comprising 10BR_MG002, 10BR_MG004, and 10BR_MG008, which keep their CRF72_BF1 designation, and the other, designated CRF122_BF1, comprising 10BR_MG003, 10BR_MG005 and the viruses of the identified Spanish cluster. Three other BF1 recombinant genomes, 2 from Brazil and 1 from Italy, previously identified as unique recombinant forms, were classified as CRF72_BF1. CRF122_BF1, but not CRF72_BF1, was associated with protease L89M substitution, reported to contribute to antiretroviral drug resistance. Phylodynamic analyses estimate the emergence of CRF122_BF1 in Brazil around 1987. Given their close phylogenetic relationship and similar structures, the grouping of CRF72_BF1 and CRF122_BF1 in a CRF family is proposed.
Enhancing the Discriminatory Power of ADHD and Autism Spectrum Disorder Polygenic Scores in Clinical and Non-Clinical Samples
Authors: Li James J. , He Quanfa , Wang Zihang , Lu Qiongshi 
Published: February 2022

AbstractObjectivePolygenic scores (PGS) are widely used in psychiatric genetic associations studies due to their impressive power to predict focal outcomes. However, they lack in discriminatory power, in part due to the high degree of genetic overlap between psychiatric disorders. The lack of prediction specificity limits the clinical utility of psychiatric PGS, particularly for diagnostic applications. The goal of the study was to enhance the discriminatory power of psychiatric PGS for two highly comorbid and genetically correlated neurodevelopmental disorders in ADHD and autism spectrum disorder (ASD).MethodsGenomic structural equation modeling (GenomicSEM) was used to generate novel PGS for ADHD and ASD by accounting for the genetic overlap between these disorders (and eight others) to achieve greater discriminatory power in non-focal outcome predictions. PGS associations were tested in two large independent samples – the Philadelphia Neurodevelopmental Cohort (N=4,789) and the Simons Foundation Powering Autism Research for Knowledge (SPARK) ASD and sibling controls (N=5,045) cohort.ResultsPGS from GenomicSEM achieved superior discriminatory power in terms of showing significantly attenuated associations with non-focal outcomes relative to traditionally computed PGS for these disorders. Additionally, genetic correlations between GenomicSEM PGS for ASD and ADHD were significantly attenuated in cross-trait associations with other psychiatric disorders and outcomes.ConclusionsPsychiatric PGS associations are likely inflated by the high degree of genetic overlap between the psychiatric disorders. Methods such as GenomicSEM can be used to refine PGS signals to be more disorder-specific, thereby enhancing their discriminatory power for future diagnostic applications.
Sun exposure behavior and knowledge on photoprotection of children and adolescents living in tropical regions
Authors: de Paula Corrêa Marcelo , Martins Fabrina Bolzan , Campos Yamamoto Ana Letícia , Paiva Natana Batista , Silva Luiz Felipe , Sant’Anna Silva Reynaldo José , Melo Mayara Motta , de Carvalho Ribeiro Clarissa Santos 
Published: February 2022

AbstractBackgroundExcessive and continuous exposure to ultraviolet radiation (UVR) can cause skin cancer (SC), photoaging, and cataracts. Photoprotection (PhP) is the most important tool in preventing against these harmful effects. Elementary and high school students should be targeted in PhP campaigns because the solar radiation that youngers receive increases the risk of SC in adulthood. However, PhP policies are scarce in developing countries.ObjectivesTo evaluate the use and knowledge of PhP with youngsters living in tropical regions.Methods2,844 students aged from 4 to 20 years-old were interviewed about their knowledge on sun exposure and PhP habits. Age, sex, family income and skin phototype were statistically related to the proposed questions.ResultsBrazilian youngsters do not have the habit of wearing long-sleeved clothing (<15% in summer), nor sunglasses (0.0%), and hats (2.1%). More than 40% had no knowledge about UVI while another 30% misinterpret what it is. Less than half of all students wear sunscreen when out in the sun. Despite this low PhP use-rate, more than 90% know that UVR causes SC. Income was the factor that showed the greatest number of significant relationships respect to PhP.ConclusionsChildren and adolescents showed little knowledge about the sun exposure effects and lack PhP use. The lack of educational programs predisposes these youngsters to an increased chance of SC in the future. These results suggest that PhP campaigns should be part of school curricula from elementary school onwards.
Glycomic Analysis Identifies Pre-Vaccination Markers of Response to Influenza Vaccine, Implicating the Complement Pathway
Authors: Qin Rui , Meng Guanmin , Pushalkar Smruti , Carlock Michael A. , Ross Ted M. , Vogel Christine , Mahal Lara K. 
Published: February 2022

ABSTRACTResponse to vaccination can vary significantly from person to person. A key to improving vaccine design and vaccination strategy is to understand the mechanism behind this variation. The role of glycosylation, a critical modulator of immunity, is unknown in determining vaccine responses. To gain insight into the association between glycosylation and vaccine-induced antibody levels we profiled the pre- and post-vaccination serum protein glycomes of 160 Caucasian adults receiving the FLUZONE™ influenza vaccine during the 2019-2020 influenza season. Using lectin microarrays, we observed that pre-vaccination levels of Lewis A antigen (Lea) are significantly higher in people who did not mount significant antibody responses, when compared to responders. Glycoproteomic analysis showed that Lea-bearing proteins are enriched in complement activation pathways, suggesting a potential role of glycosylation in tuning the activities of complement proteins, which may be implicated in mounting vaccine responses. We also observed post-vaccination increases in sialyl Lewis X antigen (sLex) and decreases in high mannose glycans among high responders, which were not observed in non-responders. This data suggests that the immune system may actively modulate glycosylation as part of its effort to establish effective protection post-vaccination.