bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine release syndrome after treatment with immune checkpoint inhibitors: an observational cohort study of 2672 patients from Karolinska University Hospital in Sweden
Authors: Hamida Osama , Karlsson Frans , Lundqvist Andreas , Gerling Marco , Liu Lisa L. 
Published: March 2024

AbstractImmune checkpoint inhibitors (ICIs) are linked to diverse immune-related adverse events (irAEs). Rare irAEs surface first in clinical practice. Here, we systematically studied the rare irAE, cytokine-release syndrome (CRS), in a cohort of 2672 patients treated with ICIs at Karolinska University Hospital in Stockholm, Sweden. We find that the risk of ICI-induced CRS – defined as fever, negative microbiological findings and absence of other probable causes within 30 days after ICI treatment – is approximately 1%, higher than previously reported. ICI-induced CRS was often mild and ICI rechallenge was generally safe. Two out of 28 patients experienced high-grade CRS, and one was fatal. While C-reactive protein and procalcitonin were not discriminative of fatal CRS, our data suggest that the quick Sequential Organ Failure Assessment (qSOFA) score might identify high-risk patients. These data provide a framework for CRS risk assessment and motivate multicenter studies to improve early CRS diagnosis.HighlightsCytokine release syndrome following immune checkpoint inhibition is rare and often mild.Risk assessment using quick Sequential Organ Failure Assessment, but not serum CRP, can potentially detect severe cytokine release syndrome and improve treatment decisions.Rechallenge with immune checkpoint inhibitors after mild cytokine release syndrome is generally well tolerated.
Perceived and endocrine acute and chronic stress indicators in fibromyalgia syndrome
Authors: Beiner Eva , Hermes Michelle , Reichert Julian , Kleinke Kristian , Vock Stephanie , Löffler Annette , Ader Leonie , Sirazitdinov Andrei , Keil Sebastian , Schmidt Tim , Schick Anita , Löffler Martin , Hopp Micheal , Ruckes Christian , Hesser Jürgen , Reininghaus Ulrich , Flor Herta , Eich Wolfgang , Friederich Hans-Christoph , Tesarz Jonas ,   PerPAIN consortium
Published: March 2024

AbstractIntroductionFibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue and tenderness and closely associated with high levels of stress. FMS is therefore often considered a stress-related disease.MethodsA comparative study was conducted with 99 individuals diagnosed with FMS and a control group of 50 pain-free individuals. Stress indicators were classified into three categories: perceived stress assessed using the Perceived Stress Scale, and daily average salivary cortisol and hair cortisol concentrations as indicators of acute and chronic stress levels related to the hypothalamic-pituitary-adrenal axis. Analysis of variance and covariance were used to identify group differences and the influence of covariates age, sex, and body mass index. Correlational analyses further elucidated the relationship between stress indicators and clinical symptoms.ResultsParticipants with FMS reported significantly higher perceived stress levels than controls (p< .001, ηp2= .3), which were positively correlated with symptom burden (r= .64,p< .001). In contrast, there were no significant differences in the endocrinological stress indicators salivary and hair cortisol between the groups (p> .05), nor were these indicators associated with clinical symptoms.ConclusionThe study highlights the central role of perceived stress in FMS, whereas endocrinological indicators did not differentiate FMS from controls. This finding calls for a nuanced approach to clinical assessment and therapeutic interventions tailored to patients with FMS, emphasizing the management of perceived stressors.
Colorectal cancer screening based on predicted risk: a pilot randomized controlled trial
Authors: Plys Ekaterina , Bulliard Jean-Luc , Chaouch Aziz , Durand Marie-Anne , van Duuren Luuk A. , Braendle Karen , Auer Reto , Froehlich Florian , Vogelaar Iris Lansdorp , Corley Douglas A. , Selby Kevin 
Published: March 2024

AbstractBackground & AimsColorectal cancer (CRC) screening relies primarily on colonoscopy and fecal immunochemical testing (FIT). Aligning utilization of these options with individual CRC risk (i.e. personalized screening) may maximize benefit with lower risks, individual burdens, and societal costs. We studied the effect of communicating personalized CRC risk and corresponding screening recommendations on appropriate screening uptake in an organized screening setting.MethodsPilot randomized controlled trial among residents aged 50-69 years old not yet invited for screening in Vaud, Switzerland. The intervention was a mailed brochure communicating individual 15-year CRC risk and corresponding screening recommendation. The control group received a brochure comparing FIT and colonoscopy. The primary outcome was self-reported risk-appropriate screening (FIT if <3% risk, FIT or colonoscopy if ≥3% and <6%, colonoscopy if ≥6%), assessed by a mailed questionnaire at 6 months. A secondary outcome was overall screening uptake.ResultsOf 5396 invitations, 1059 people responded (19%), of whom 258 were randomized to intervention and 257 to control materials (average 15-year risk 1.4% (SD 0.5), age 52.2 years (SD 2.2), 51% women). Risk-appropriate screening completion was 37% in the intervention group and 23% in the control group (absolute difference 14%, 95%CI 6%-22%, p<0.001). Overall screening uptake was 50% in the intervention and 49% in the control group (absolute difference 1%, 95CI −7%−10%, p=0.758).ConclusionsIn a population not known to be at elevated CRC risk, brochures providing personalized CRC risk and screening recommendations improved risk-appropriate screening without impacting overall screening uptake. This approach could be helpful for aligning screening methods, risks, and benefits with cancer risk.Trial registration:Clinicaltrials.govNCT05357508.What You Need to KnowBackgroundColorectal cancer can be effectively prevented by screening using colonoscopy or fecal immunochemical test (FIT). Optimizing use of colonoscopy resources is crucial to reduce screening burden for patients and society.FindingsAfter reading our intervention brochure, participants were 14% more likely to choose the screening test appropriate to their risk level. This result did not impact overall screening participation.Implications for patient careRisk-based screening recommendations for FIT or colonoscopy could be a means of better allocating colonoscopy resources in countries relying heavily on colonoscopy for screening, thus decreasing the burden of CRC screening for low-risk participants.
Scoping review of factors associated with stem cell mobilisation and collection in allogeneic stem cell donors
Authors: Peck Rachel C , Knapp-Wilson Amber , Burley Kate , Dorée Carolyn , Griffin James , Mumford Andrew D , Stanworth Simon , Sharplin Kirsty 
Published: March 2024

ABSTRACTBackgroundThere is a large inter-individual variation in CD34+ cell yield after G-CSF mobilisation and collection from peripheral blood in healthy allogenic haematopoietic stem cell donors. Donor characteristics including gender and age, baseline and pre-collection blood results, mobilisation factors and collection factors have been associated with CD34+ cell concentration in the blood after G-CSF mobilisation and/or CD34+ cell yield after collection. Since the literature reporting these associations is heterogeneous, we here clarify the determinants of CD34+ cell concentration and yield through a scoping literature review.Materials and MethodsMEDLINE, Embase, PubMed and Stem Cell Evidence were searched for studies published between 2000 and 2023. The inclusion criteria were studies of allogeneic donors undergoing G-CSF mobilisation and peripheral blood stem cell collection (PBSC). Eligible studies assessed an outcome of mobilisation or collection efficacy, indicated by the blood CD34+ cell concentration after 4 or 5 days of G-CSF treatment and/or CD34+cell yield in the first PBSC collection after mobilisation. Included studies assessed associations between these outcomes and donor factors (such as age, gender, weight, ethnicity), mobilisation factors (G-CSF scheduling or dose), collection factors (venous access, processed blood volume) and laboratory factors (such as blood cell counts at baseline and after mobilisation).ResultsThe 51 eligible studies evaluated between 23 and 20,884 donors. 43 studies were retrospective, 32 assessed blood CD34+ cell concentration after mobilisation and 37 assessed CD34+ cell yield. In studies that recorded both outcomes, blood CD34+ cell concentration always predicted CD34+ cell yield. The most frequently assessed factor was donor age for which most studies reported that younger donors had a higher blood CD34+ cell concentration and CD34+ cell yield. Non-European ancestry was associated with both higher blood CD34+ cell concentration and yield although this finding was inconsistent.ConclusionsThere remains poor consensus about the best predictors of blood CD34+ cell concentration and yield that requires further prospective study, particularly of the role of donor ancestry. The current focus on donor gender as a major predictor may require re-evaluation.
Domain-specific LLM Development and Evaluation – A Case-study for Prostate Cancer
Authors: Tariq Amara , Luo Man , Urooj Aisha , Das Avisha , Jeong Jiwoong , Trivedi Shubham , Patel Bhavik , Banerjee Imon 
Published: March 2024

AbstractIn this work, we present our strategy for developing domain-specific large language models which cover the vocabulary of the target domain and train on reliable sources of clinical information. Prostate cancer was chosen as a use-case for this study. We collected more than 1.8 million clinical notes and radiology and pathology reports for 15341 patients treated for prostate cancer in Mayo Clinic across three sites and outpatient clinics. In addition to domain-specific training data, we built domain-specific tokenizers and devised knowledge-guided training strategies for LLM development. During the self-supervised training, LLM was forced to predict domain-specific information by marking clinical terms using UMLS parser. We evaluated the model for downstream tasks of clinical information prediction and question answering using quantitative and user evaluation study to measure the accuracy, reliability and information completeness. We compared the domain-specific model against similarly sized general purpose model GPT-2 and a three-times larger domain specialized model. i.e., BioGPT. Our model outperformed GPT-2 on both tasks by a wide margin. Our model was also able to outperform BioGPT on clinical information prediction tasks and showed some advantages over BioGPT in question-answering tasks.
Generation of densely labeled oligonucleotides for the detection of small genomic elements
Authors: Steinek Clemens , Ortiz Miguel Guirao , Stumberger Gabriela , Tölke Annika J. , Hörl David , Carell Thomas , Harz Hartmann , Leonhardt Heinrich 
Published: March 2024

SUMMARYThe genome contains numerous regulatory elements that may undergo complex interactions and contribute to the establishment, maintenance, and change of cellular identity. Three-dimensional genome organization can be explored with fluorescence in situ hybridization (FISH) at the single-cell level, but the detection of small genomic loci remains challenging. Here, we provide a rapid and simple protocol for the generation of bright FISH probes suited for the detection of small genomic elements. We systematically optimized probe design and synthesis, screened polymerases for their ability to incorporate dye-labeled nucleotides and streamlined purification conditions to yield nanoscopy-compatible oligonucleotides with dyes in variable arrays (NOVA-probes). With these probes, we detect genomic loci ranging from genome-wide repetitive regions down to non-repetitive loci below the kilobase scale. In conclusion, we introduce a simple workflow to generate densely labeled oligonucleotide pools that facilitate detection and nanoscopic measurements of small genomic elements in single cells.
Measuring integrin force loading rates using a two-step DNA tension sensor
Authors: Combs J. Dale , Foote Alexander K. , Ogasawara Hiroaki , Velusamy Arventh , Rashid Sk Aysha , Mancuso Joseph Nicholas , Salaita Khalid 
Published: March 2024

ABSTRACTCells apply forces to extracellular matrix (ECM) ligands through transmembrane integrin receptors: an interaction which is intimately involved in cell motility, wound healing, cancer invasion and metastasis. These small (pN) forces exerted by cells have been studied by molecular tension fluorescence microscopy (MTFM), which utilizes a force-induced conformational change of a probe to detect mechanical events. MTFM has revealed the force magnitude for integrins receptors in a variety of cell models including primary cells. However, force dynamics and specifically the force loading rate (LR) have important implications in receptor signaling and adhesion formation and remain poorly characterized. Here, we develop a LR probe which is comprised of an engineered DNA structures that undergoes two mechanical transitions at distinct force thresholds: a low force threshold at 4.7 pN corresponding to hairpin unfolding and a high force threshold at 56 pN triggered through duplex shearing. These transitions yield distinct fluorescence signatures observed through single-molecule fluorescence microscopy in live-cells. Automated analysis of tens of thousands of events from 8 cells showed that the bond lifetime of integrins that engage their ligands and transmit a force >4.7 pN decays exponentially with a τ of 45.6 sec. A small subset of these events (<10%) mature in magnitude to >56pN with a median loading rate of 1.3 pNs-1with these mechanical ramp events localizing at the periphery of the cell-substrate junction. Importantly, the LR probe design is modular and can be adapted to measure force ramp rates for a broad range of mechanoreceptors and cell models, thus aiding in the study of mechanotransduction.TOC
asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers
Authors: Stadler Mara , Lukauskas Saulius , Bartke Till , Müller Christian L. 
Published: March 2024

AbstractChromatin, the nucleoprotein complex consisting of DNA and histone proteins, plays a crucial role in regulating gene expression by controlling access to DNA. Chromatin modifications are key players in this regulation, as they help to orchestrate DNA transcription, replication, and repair. These modifications recruit epigenetic “reader” proteins, which mediate downstream events. Most modifications occur in distinctive combinations within a nucleosome, suggesting that epigenetic information can be encoded in combinatorial chromatin modifications. A detailed understanding of how multiple modifications cooperate in recruiting such proteins has, however, remained largely elusive. Here, we integrate nucleosome affinity purification data with high-throughput quantitative proteomics and hierarchical interaction modeling to estimate combinatorial effects of chromatin modifications on protein recruitment. This is facilitated by the computational workflowasteRIawhich combines hierarchical interaction modeling, stability-based model selection, and replicate-consistency checks fora stableestimation ofRobustInteractions among chromatin modifications.asteRIaidentifies several epigenetic reader candidates responding to specificinteractionsbetween chromatin modifications. For the polycomb protein CBX8, we independently validate our results using genome-wide ChIP-Seq and bisulphite datasets. We provide the first quantitative framework for identifying cooperative effects of chromatin modifications on protein binding.
A prenatal window for enhancing spatial resolution of cortical barrel maps
Authors: Aníbal-Martínez Mar , Puche-Aroca Lorenzo , Pumo Gabriele , Madrigal M. Pilar , Rodríguez-Malmierca Luis M. , Martini Francisco J. , Rijli Filippo M. , López-Bendito Guillermina 
Published: March 2024

ABSTRACTPrecise mapping of peripheral inputs onto cortical areas is required for appropriate sensory processing. In the mouse primary somatosensory cortex, mystacial whiskers are represented in large barrels, while upper lip whiskers are in smaller, less defined barrels. Barrel size and definition of these two functionally distinct barrel maps are believed to be determined by the type of whisker input and peripheral receptor density. However, spontaneous activity and transcriptional programs at prenatal developmental stages can influence somatosensory map development independently of sensory experience. Thus, the mechanisms defining distinct barrel field territories, including their size and definition, remain poorly understood. Here, we show that prenatal ablation of mystacial whiskers remap somatosensory cortical territories resulting in enhancement of the functional and anatomical definition of upper lip whisker barrels. These changes do not result from alterations in receptor type but rather stem from thalamic upper lip input-receiving neurons adopting a mystacial-like transcriptional profile. Our results unveil a regulated prenatal mechanism within the thalamus that maps available somatosensory input to ensure sufficient cortical barrel size and functional spatial resolution for sensory processing, irrespective of peripheral receptor type and density.
Evolution of temperature preference behaviour among drosophilids
Authors: Kafle Tane , Grub Manuel , Sakagiannis Panagiotis , Nawrot Martin Paul , Arguello Roman 
Published: March 2024

AbstractSmall-bodied ectotherms are acutely vulnerable to temperature changes, but diverse thermotactic behaviours have contributed to their ability to inhabit broad climatic niches. Understanding how - and how quickly - these behaviours evolve are outstanding biological questions that are also relevant to conservation. Among insects,Drosophila melanogasteris a preeminent ectothermic model for temperate sensing and thermotaxis. However, little is known about how its temperature-related behaviours have evolved in comparison to its closely related species. We have thermo-profiled over 2400 larvae from eight closely related species ofDrosophilafrom different thermal habitats. Consistent with local adaptation, we found substantial variation in temperature preference and fine-scale navigational behaviours amongst these species. Agent-based modelling of the larval thermotaxis circuit suggests that it is the balance between cool and warm avoidance circuits, rather than changes in temperature sensitivity, that drive differences in temperature preference. Our findings highlight the recurrent evolution of temperature-related behaviours in an experimentally tractable cross-species system.
Impact of extracellular current flow on action potential propagation in myelinated axons
Authors: Abdollahi Nooshin , Prescott Steven A 
Published: March 2024

ABSTRACTMyelinated axons conduct action potentials, or spikes, in a saltatory manner. Inward current caused by a spike occurring at one node of Ranvier spreads axially to the next node, which regenerates the spike when depolarized enough for voltage-gated sodium channels to activate, and so on. The rate at which this process progresses dictates the velocity at which the spike is conducted, and depends on several factors including axial resistivity and axon diameter that directly affect axial current. Here we show through computational simulations in modified double-cable axon models that conduction velocity also depends on extracellular factors whose effects can be explained by their indirect influence on axial current. Specifically, we show that a conventional double-cable model, with its outside layer connected to ground, transmits less axial current than a model whose outside layer is less absorptive. A more resistive barrier exists when an axon is packed tightly between other myelinated fibers, for example. We show that realistically resistive boundary conditions can significantly increase the velocity and energy efficiency of spike propagation, while also protecting against propagation failure. Certain factors like myelin thickness may be less important than typically thought if extracellular conditions are more resistive than normally considered. We also show how realistically resistive boundary conditions affect ephaptic interactions. Overall, these results highlight the unappreciated importance of extracellular conditions for axon function.SIGNIFICANCE STATEMENTAxons transmit spikes over long distances. Transmission is sped up and made more efficient by myelination, which allows spikes to jump between nodes of Ranvier without activating the intervening (internodal) membrane. Conduction velocity depends on the current transmitted axially from one node to the next. Axial current is known to depend on a variety of features intrinsic to myelinated fibers (e.g. axon diameter, myelin thickness) but we show here, through detailed biophysical simulations, how extracellular conditions (e.g. axon packing density) are also important. The effects ultimately boil down to the variety of paths current can follow, and the amount of current taking alternative paths rather than flowing directly from one node to the next.
Antecedents to service quality in the National Parks of Ecuador: leadership, talent management, work climate and training
Authors: Rivas Carolina , Tarí Juan José , Pereira-Moliner Jorge 
Published: March 2024

PurposeThis paper analyzes how quality management in Ecuador’s national parks is explained through the quality practices contained in Deming’s quality principles from the point of view of employees.Design/methodology/approachQuantitative research was conducted with the participation of 254 employees from all national parks in Ecuador who rated the quality management practices (leadership, talent management, work climate and training) in their respective parks.FindingsThe results show that leadership, talent management, work climate and training significantly explain the service quality in the national parks. This study contributes to the adaptation of Deming’s quality principles to national parks via individual and joint analysis of the relationship between leadership, talent management, work climate and training with service quality in order to highlight which practices are the most important to service quality.Originality/valueThe paper provides a comprehensive overview of the key factors that influence service quality in the National Parks of Ecuador. Its multidisciplinary approach and exhaustive research make this work an invaluable tool for understanding and improving the preservation of natural resources and the tourism experience in these protected areas.