bluuebunny/crossref_metadata_2025_split huggingface dataset:
CodonBERT: Large Language Models for mRNA design and optimization
Authors: Li Sizhen , Moayedpour Saeed , Li Ruijiang , Bailey Michael , Riahi Saleh , Kogler-Anele Lorenzo , Miladi Milad , Miner Jacob , Zheng Dinghai , Wang Jun , Balsubramani Akshay , Tran Khang , Zacharia Minnie , Wu Monica , Gu Xiaobo , Clinton Ryan , Asquith Carla , Skaleski Joseph , Boeglin Lianne , Chivukula Sudha , Dias Anusha , Montoya Fernando Ulloa , Agarwal Vikram , Bar-Joseph Ziv , Jager Sven 
Published: September 2023

AbstractmRNA based vaccines and therapeutics are gaining popularity and usage across a wide range of conditions. One of the critical issues when designing such mRNAs is sequence optimization. Even small proteins or peptides can be encoded by an enormously large number of mRNAs. The actual mRNA sequence can have a large impact on several properties including expression, stability, immunogenicity, and more. To enable the selection of an optimal sequence, we developed CodonBERT, a large language model (LLM) for mRNAs. Unlike prior models, CodonBERT uses codons as inputs which enables it to learn better representations. CodonBERT was trained using more than 10 million mRNA sequences from a diverse set of organisms. The resulting model captures important biological concepts. CodonBERT can also be extended to perform prediction tasks for various mRNA properties. CodonBERT outperforms previous mRNA prediction methods including on a new flu vaccine dataset.
Passivating blunt-ended helices to control monodispersity and multi-subunit assembly of DNA origami structures
Authors: Berengut Jonathan F. , Berg Willi R. , Rizzuto Felix J. , Lee Lawrence K. 
Published: September 2023

AbstractDNA origami facilitates the synthesis of bespoke nanoscale structures suitable for a wide range of applications. Effective design requires prevention of uncontrolled aggregation, while still permitting directed assembly of multi-subunit superstructures. Uncontrolled aggregation can be caused by base-stacking interactions between arrays of blunt-ended helices on different structures, which are routinely passivated by incorporating disordered regions as either scaffold loops or poly-nucleotide brushes (usually poly-thymine) at the end of DNA helices. Such disordered regions are ubiquitous in DNA origami structures yet their exact design requirements in different chemical environments are ill defined. In this study, we systematically examine the use of scaffold loops and poly-nucleotide brushes for passivation and for controlling multi-subunit assembly. We assess the dependence of length and sequence for preventing aggregation amidst a titration of MgCl2concentrations and the suitability of each strategy for enabling controlled multi-subunit assembly. We then introduce a novel strategy where double-stranded DNA helices run orthogonal to arrays of blunt-ended DNA helices forming a steric shield that prevents base stacking. The results define the limitations of each method and important design considerations for achieving monodispersity. For example, poly-thymine brushes are most effective for achieving monodispersity in the broadest conditions whereas scaffold loops can facilitate directed multi-subunit assembly. Finally, orthogonal DNA helices remove the need for disordered regions altogether, prevent aggregation in a broad range of MgCl2concentrations and facilitate directed multi-subunit assembly. This study expands the design tools available and enables a more informed approach for achieving control of monodispersity and multi-subunit assembly in DNA origami structures.
Spatial molecular profiling of mixed invasive ductal-lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations
Authors: Shah Osama Shiraz , Nasrazadani Azadeh , Foldi Julia , Atkinson Jennifer M. , Kleer Celina G , McAuliffe Priscilla F. , Johnston Tyler J , Stallaert Wayne , da Silva Edaise M , Selenica Pier , Dopeso Higinio , Pareja Fresia , Mandelker Diana , Weigelt Britta , Reis-Filho Jorge S. , Bhargava Rohit , Lucas Peter C. , Lee Adrian V. , Oesterreich Steffi 
Published: September 2023

AbstractMixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially-resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity (e.g., MDLC with TNBC/basal ductal and ER+/luminal lobular regions), distinct enrichment of senescence/dormancy and oncogenic (ER and MYC) signatures, genetic and epigeneticCDH1inactivation in lobular, but not ductal regions, and single-cell ductal and lobular sub-populations with unique oncogenic signatures further highlighting intra-regional heterogeneity. Altogether, we demonstrated that the intra-tumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma.SignificanceMDLC displays both ductal and lobular tumor regions. Our multi-omic profiling approach revealed that these morphologically distinct tumor regions harbor distinct intrinsic subtypes and oncogenic features that may cause prognostic uncertainty and therapeutic dilemma. Thus histopathological/molecular profiling of individual tumor regions may guide clinical decision making and benefit patients with MDLC, particularly in the advanced setting where there is increased reliance on next generation sequencing.
Evaluating Risk Progression in Mental Health Chatbots Using Escalating Prompts
Authors: Heston Thomas F. 
Published: September 2023

ABSTRACTThe safety of large language models (LLMs) as mental health chatbots is not fully established. This study evaluated the risk escalation responses of publicly available ChatGPT conversational agents when presented with prompts of increasing depression severity and suicidality. The average referral point to a human was at the midpoint of escalating prompts. However, most agents only definitively recommended professional help at the highest level of risk. Few agents included crisis resources like suicide hotlines. The results suggest current LLMs may fail to escalate mental health risk scenarios appropriately. More rigorous testing and oversight are needed before deployment in mental healthcare settings.
A Decade’s Experience Performing Forensic Medical and Psychologic Evaluations for Pediatric Asylum Seekers in the United States
Authors: Plesons Marina , Hullfish Haley , Joshi Priyashma , Symes Stephen , Saxena Anjali 
Published: September 2023

AbstractBackgroundThe number of children seeking asylum in the US has increased substantially in recent years. To add to the limited evidence base related to children seeking asylum in the US, this paper describes the sociodemographic characteristics, nature of human rights violations, and guardianship status of the children served by the Human Rights Clinic of Miami from 2010-2021.MethodsA retrospective study was conducted on affidavits for pediatric patients seeking forensic medical and psychological evaluation at the Human Rights Clinic of Miami from 2010 to 2021. We determined trends among sociodemographic characteristics and the nature of human rights violations among these patients and used logistic regression to determine factors associated with having a guardian present at the evaluation.ResultsOf the total 64 pediatric patients who received a forensic medical and psychological evaluation, over half were male (56%) and two-thirds were aged 15-17. Honduras was the most common country of origin (53%). Physical violence was the most reported human rights abuse (72%) followed by gang violence (53%), sexual violence (22%), and political violence (3%). The majority of children (87%) reported being detained at the border upon entry into the USA. Only 31% of pediatric patients had a guardian present during the evaluation, with guardianship significantly less likely for older patients (p <0.05).ConclusionsThese findings identified specific challenges unique to the pediatric population, including lack of guardianship among older children. Future efforts may include the development of formal pediatric-specific guidelines for conducting evaluations of children seeking asylum.
A brief report on the of mycobacterial proteins regulated by the loss of PtkA in Mtb-H37Ra
Authors: Jaiswal Swati , Srivasatava Kishore K 
Published: September 2023

AbstractKinase-phosphatase signaling plays an important role in cellular signaling pathways. The genome ofMycobacterium tuberculosis, (the causative agent of tuberculosis), is embossed with several kinases and phosphatases. Recently identified protein tyrosine kinase (PtkA) is a novel tyrosine kinase that phosphorylates protein tyrosine phosphatase A (PtpA) and regulates its secretion in the cytosol. PtkA is considered as a regulatory protein. In this study, the mycobacterial proteins regulated due to theptkAgene deletion in Mtb-H37Ra have been studied and highlighted using two-dimensional (2D) gel electrophoresis coupled with MALDI TOF MS/MS analysis. We have identified 13 differentially expressed proteins that play an important role in mycobacterial intracellular survival and pathogenesis.
VAMP2/Munc18-1 domain 3a interaction controls the nanoscale reorganization underpinning vesicular priming
Authors: Jiang Anmin , Gormal Rachel S. , Kasula Ravikiran , Blum Ailisa , Salla-Martret Mercè , Chai Ye Jin , Wallis Tristan P. , Brouillet Julie Z. , Padmanabhan Pranesh , Weeratunga Saroja , Livingstone Emma K. , Mollazade Mahdie , Joensuu Merja , Martínez-Mármol Ramón , Collins Brett M. , Meunier Frédéric A. 
Published: September 2023

SummarySNARE-mediated secretory vesicle (SV) exocytosis underpins neuronal communication. Munc18-1 orchestrates SNARE complex formation by controlling the opening of syntaxin-1A. How the SV-plasma membrane interface becomes fusion-competent at the nanoscale level is poorly understood. Here, we propose that the interaction of Munc18-1 with VAMP2 during vesicular docking triggers nanoscale re-organization which renders the SV-plasma membrane interface fusion-competent. We identified and mutated key residues in Munc18-1 domain 3a (A297 and T304) hypothesised to impair its interaction with VAMP2. Munc18-1A297H, and to a lesser extent Munc18-1T304H, constrained SVs on the plasma membrane and reduced stimulated secretion, under re-expression conditions in Munc18-1/2 double knockout neurosecretory cells. Moreover, the de-clustering of Munc18-1 in response to activity was lost for both mutants. The interaction of VAMP2 with the Munc18-1 domain 3a therefore controls the re-organization of the nanoscale environment of the docked SV-plasma membrane interface, fostering syntaxin-1A opening and Munc18-1 release to ensure that SNARE assembly only occurs within the confinement of docked vesicles.
The Origin And Speciation Of Orchids
Authors: Perez-Escobar Oscar A. , Bogarín Diego , Przelomska Natalia A.S. , Ackerman James D. , Balbuena Juan A. , Bellot Sidonie , Bühlmann Roland P. , Cabrera Betsaida , Cano Jose Aguilar , Charitonidou Martha , Chomicki Guillaume , Clements Mark A. , Cribb Phillip , Fernández Melania , Flanagan Nicola S. , Gravendeel Barbara , Hágsater Eric , Halley John M. , Hu Ai-Qun , Jaramillo Carlos , Mauad Anna Victoria , Maurin Olivier , Müntz Robert , Leitch Ilia J. , Li Lan , Negrao Raquel , Oses Lizbeth , Phillips Charlotte , Rincon Milton , Salazar-Chavez Gerardo , Simpson Lalita , Smidt Eric , Solano-Gomez Rodolfo , Parra-Sánchez Edicson , Tremblay Raymond L. , van den Berg Cassio , Villanueva Boris Stefan , Zuluaga Alejandro , Chase Mark W. , Fay Michael F. , Condamine Fabien L. , Forest Felix , Nargar Katharina , Renner Susanne S. , Baker William J. , Antonelli Alexandre 
Published: September 2023

Summary⍰ Orchids constitute one of the most spectacular radiations of flowering plants. However, their geographical origin, historical spread across the globe, and hotspots of speciation remain uncertain due to the lack of a broad phylogenomic framework.⍰ We present a new Orchidaceae phylogeny based on high-throughput and Sanger sequencing datasets, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and ∼7% (1,921) of the currently 29,524 accepted species. We then use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distribution data through the World Checklist of Vascular Plants.⍰ Orchid’s most recent common ancestor is traced back to the Late Cretaceous in Laurasia. The modern Southeast Asian range of subfamily Apostasioideae is interpreted as relictual, matching the history of numerous clades that went extinct at higher latitudes following the global climate cooled during the Oligocene. Despite their ancient origins, modern orchid species’ diversity mainly originated over the last 5 Ma, with the fastest speciation rates found in south-eastern Central America.⍰ Our results substantially alter our understanding of the geographic origin of orchids, previously proposed as Australian, and further pinpoint the role of Central American as a region of recent and explosive speciation.
Knockout of the longevity gene Klotho perturbs aging- and Alzheimer’s disease-linked brain microRNAs and tRNA fragments
Authors: Dubnov Serafima , Yayon Nadav , Yakov Or , Bennett David A. , Seshadri Sudha , Mufson Elliott , Tzur Yonat , Bennet Estelle R. , Greenberg David , Kuro-o Makoto , Paldor Iddo , Abraham Carmela R. , Soreq Hermona 
Published: September 2023

Introductory paragraphOverexpression of the longevity gene Klotho prolongs, while its knockout shortens lifespan and impairs cognition via altered fibroblast growth factor signaling that perturbs myelination and synapse formation; however, comprehensive analysis of Klotho’s knockout consequences on mammalian brain transcriptomics is lacking. Here, we report the altered levels under Klotho knockout of 1059 long RNAs, 27 microRNAs (miRs) and 6 tRNA fragments (tRFs), reflecting effects upon aging and cognition. Perturbed transcripts included key neuronal and glial pathway regulators that are notably changed in murine models of aging and Alzheimer’s Disease (AD) and in corresponding human post-mortem brain tissue. To seek cell type distributions of the affected short RNAs, we isolated and FACS-sorted neurons and microglia from live human brain tissue, yielding detailed cell type-specific short RNA-seq datasets. Together, our findings revealed multiple Klotho deficiency-perturbed aging- and neurodegeneration-related long and short RNA transcripts in both neurons and glia from murine and human brain.
Enhanced Omicron subvariant cross-neutralization efficacy of a monovalent SARS-CoV-2 BA.4/5 mRNA vaccine encoding a noncleaved, nonfusogenic spike antigen
Authors: Seo Han Young , Jung Haewon , Woo Hawon , Jung Hae-Gwang , Cho Hee , Bak Yeonju , Lee Se-Young , Son Yu-Min , Yoon Gone , Hwang Seo-Yeon , Park Inho , Shin Jeon-Soo , Oh Jong-Won 
Published: September 2023

AbstractThe rapid emergence of diverse SARS-CoV-2 variants, notably the Omicron variant, poses challenges to vaccine development. Here, we present a noncleaved, nonfusogenic spike (S) protein eliciting robust B- and T-cell immune responses against Omicron BA.5. The antigen incorporates the R685S and R815A mutations, effectively preventing the shedding of the S1 subunit and eliminating fusogenic activity of the resulting S antigen, termed S(SA). Through reverse genetic analysis, we found that the noncleaved form S protein with the R685S mutation enhances ACE2-dependent viral entry in vitro compared to the wild-type S protein, without increasing the virulence of the mutant virus in mice. The mRNA vaccine encoding the Omicron BA.4/5 S(SA) antigen conferred protective immunity in mice following two doses of 1 μg Ψ-UTP- or UTP-incorporated mRNA vaccines. Despite a roughly 6-fold reduction in neutralizing potency, both mRNA vaccines exhibited broad neutralizing efficacy against Omicron subvariants, including the XBB lineage variants XBB.1.5 and XBB.1.16.
Influence of open-source virtual-reality based gaze training on navigation performance in Retinitis pigmentosa patients in a crossover randomized controlled trial
Authors: Neugebauer Alexander , Sipatchin Alexandra , Stingl Katarina , Ivanov Iliya , Wahl Siegfried 
Published: September 2023

AbstractMotivationPeople living with tunnel vision caused by Retinitis pigmentosa (RP) oftentimes face challenges navigating and avoiding obstacles due to a severely decreased Visual Field. Previous studies have shown that gaze training – guided tasks to encourage specific gaze behavior – help improve visual performance in patients with limited Visual Field. We propose a Virtual-Reality based, at-home gaze training – to the best of our knowledge the first of its kind – to increase effective eye movements and navigation performance of RP patients in a real-world obstacle course.MethodsA group of RP patients (n=8) participated in a study consisting of two 4-week-phases, both carried out by the same patient group in randomized order: In the ‘training phase’, participants carried out a Virtual-Reality gaze training for 30 minutes per day; In the ‘control phase’, no training occurred. Before and after each phase, participants were tasked to move through a randomized real-world obstacle course. Navigation performance in the obstacle course as well as eye-tracking data during the trials were evaluated. The study is registered at the German Clinical Trials Register (DRKS) with the ID DRKS00032628.ResultsOn average, the time required to move through the obstacle course decreased by 17.0% after the training phase (p <0.001), the number of collisions decreased by 50.0% (p <0.001) and the average visual area observed by participants increased by 4.41% (p <0.001). In comparison, after the control phase, the time required to move through the obstacle course was found to have decreased by 5.9% (p= 0.003), collisions decreased by 10.4% (p= 0.609) and the observed visual area increased by 2.06% (p= 0.0835).ConclusionThe performance increase over the training phase significantly surpasses the natural learning effect found in the control phase, suggesting that Virtual-Reality based gaze training can improve real-world navigation performance and effective gaze movements of patients with RP. The training is available as work-in-progress open-source software.
Parental Perceptions of Early Childhood Research with In-Home Monitoring: A Qualitative Study
Authors: Smith Gabriella B. , Jones Mickayla D. , Akel Mary J. , Barrera Leonardo , Heffernan Marie , Seed Patrick C. , Macy Michelle L. , Fisher Stephanie A. , Mithal Leena B. 
Published: September 2023

AbstractBackgroundDespite growing interest in novel approaches to measure home environmental effects on the developing child (the exposome), parental perceptions remain poorly understood. Parents’ perspectives are important for building trust, assessing feasibility, and increasing participation in research that includes home monitoring technologies. We aimed to explore parents’ perceptions regarding these topics.MethodsA diverse group of new and expecting mothers participated in semi-structured interviews. A single interviewer conducted all sessions and introduced a hypothetical longitudinal observational early childhood home-based research study including novel home monitoring approaches: 1) wearable devices, 2) audio monitoring, and 3) environmental sampling. Interviews were audio-recorded, transcribed, and coded. A constant comparative approach identified themes from transcripts.ResultsTwenty-four interviews were completed. Emerging themes included 1) Positive Perceptions; 2) Incentives; 3) Transparency and Purpose; 4) Privacy and Safety Concerns; and 5) Logistics and Feasibility. Perceptions were similar across racial, ethnic, and socioeconomic groups. Overall perceptions were positive with several central motivators for hypothetical participation. Participants desired additional information related to feasibility and the purpose of studies. Many had concerns related to wearable device safety and data privacy; a trusting relationship with the research team was a priority.ConclusionMany participants had positive sentiments regarding longitudinal observational studies involving pregnancy and infancy with various incentives, yet they expressed concerns about safety, privacy, feasibility, and transparency. These findings can inform future perinatal and early childhood research study design, particularly those that novel home monitoring approaches, to ensure protocols and communication are transparent, inclusive, and appealing to parents.
Flow-mediated dilatation: learning curve study with a novice operator
Authors: Dhar Arko S. , Fisk Marie , McEniery Carmel M. , Cseh Domonkos 
Published: September 2023

AbstractIntroductionBrachial artery flow-mediated dilatation (FMD) is commonly measured to assess endothelial function in experimental and clinical research studies. However, attaining reproducible results can be challenging, especially among inexperienced operators. Until now, no detailed learning curve study of novice operators has been published.MethodsWe assessed the learning curve of FMD measurement in one novice operator. Following a one-week basic training period, the operator performed duplicate measurements on 6-8 individuals per week, for six weeks. The operator followed the recommendations of the most recent FMD measurement guideline. Duplex ultrasound was used for the simultaneous and continuous measurement of brachial artery diameter and local blood flow velocity. Following a 1-minute recording of baseline diameter (D), FMD was measured after a 5-minute period of occlusion of the proximal forearm vessels. Inter-session coefficient of variation (CV) values for D and FMD were calculated for each week.ResultsThe majority of participants did not have any cardiovascular disease history. The number of volunteers assessed each week were the following: 8, 7, 7, 6, 7, 7 individuals, from week 1 to week 6. CV values for both D and FMD exhibited a decreasing trend over the training period, ending at 1.73% for D and 14.24% for FMD at week 6. The CV values at week 6 were within the range outlined in the most recent FMD guideline for proficiency.ConclusionsWithin a reasonable timeframe, and with careful adherence to measurement guidelines, the attainment of sound reproducibility in FMD measurements by a novice operator is feasible.