bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgeon-Scientists Going Extinct
Authors: Pfister Matthias , Li Zhihao , Huwyler Florian , Tibbitt Mark W. , Puhan Milo A. , Clavien Pierre-Alain ,   the Research Sustainability Group
Published: August 2024

Objective:
To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies.

Background:
Surgeons who conduct research in addition to patient care are referred to as “surgeon-scientists.” While their value to society remains undisputed, their numbers and associated impact have been plunging. While reasons have been well identified along with proposals for countermeasures, their application has largely failed.

Methods:
We conducted a systematic review covering all aspects of surgeon-scientists together with a global online survey among 141 young academic surgeons. Using gap analysis, we determined implementation gaps for proposed measures. Then, we developed a comprehensive rescue package.

Results:
A surgeon-scientist must actively and continuously engage in both patient care and research. Competence in either field must be established through protected training and criteria of excellence, particularly reflecting contribution to innovation. The decline of surgeon-scientists has reached an unprecedented magnitude. Leadership turning hospitals into “profit factories” is one reason, a flawed selection process not exclusively based on excellence is another. Most importantly, the appreciation for the academic mission has vanished. Along with fundamentally addressing these root causes, surgeon-scientists’ path to excellence must be streamlined, and their continuous devotion to innovation cherished.

Conclusions:
The journey of the surgeon-scientist is at a crossroads. As a society, we either adapt and shift our priorities again towards innovation or capitulate to greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere.
Rewilding psychology
Authors: Baggs Edward , Sanches de Oliveira Guilherme 
Published: August 2024

Some commentators have recently argued that scientific psychology is overly reliant on artificial laboratory-based activities and that it undervalues field-based investigations. However, it remains unclear how a field-based programme of psychological research might be organized in a scalable way. We examine and compare two existing field-based approaches: Roger Barker’s behaviour settings programme and Edwin Hutchins’s distributed cognition programme. Both programmes prioritize observational work, and both reject the individual as the unit of analysis in favour of a community-scale unit. However, whereas the behaviour settings programme is concerned with structural properties of community life, distributed cognition is concerned more narrowly with the functional analysis of expert team performance. We discuss how these programmes can inform a future community-scale approach to studying psychology in the wild. We conclude that the two programmes are proof of concept of the possibility of a scientific psychology that rejects methodological individualism.
This article is part of the theme issue ‘People, places, things and communities: expanding behaviour settings theory in the twenty-first century’.
Navigating the normativity of behaviour settings: an observational case study
Authors: Di Rienzo Giulia , Myin Erik , van Dijk Ludger 
Published: August 2024

Traditionally, sensitivity to situational norms is understood as deriving from internal cognitive states that represent the rules for appropriate conduct. On an alternative view, norms are ‘out there’, in the practices and situations themselves, without being duplicated in the head. However, what does normativity look like when it is performed by people engaging with a concrete situation? A ‘behaviour setting’ offers a window onto these dynamics. This article presents an observational case study of normative coordination within a behaviour setting. Immersed in a scientific laboratory setting, the observations show how the normative demands of the overall behaviour setting can give shape to various places of action, or ‘synomorphs’, which invite the participants’ activities. Responding to the different needs of each synomorph, in turn, maintains the behaviour setting. What connects these two reciprocal timescales of activity are the situationally sensitive activities of the participants. We end with several examples that bring such sensitivity to the interdependence of the norms of a behaviour setting to the fore.
This article is part of the theme issue ‘People, places, things, and communities: expanding behaviour settings theory in the twenty-first century’.
Individualized Hybrid Electroconvulsive Therapy (i-HECT) Shows Rapid Anti-Depressant Effect and Improved Cognition in Young Patients with Depression
Authors: Zhang Jing-ya , Zeng Lun , Li Jia , Chen Mian-mian , Xu Shu-xian , Tan Baijian , Xie Xin-hui 
Published: August 2024

AbstractBackgroundFor young patients with depression, electroconvulsive therapy (ECT) is highly effective but causes acute cognitive side effects. We designed a new i-HECT therapy combines ECT with low-charge electrotherapy (LCE) and individual symptom monitoring to reduce cognitive impairments.Methodsi-HECT comprised two treatments: ECT and LCE. ECT utilized an energy set of 1.5 times the seizure threshold (ST), while LCE was set at 0.5 ST. The initial session employed ECT. Subsequent sessions involved ECT or LCE, depending on whether meeting the ECT-LCE transition criteria (MADRS total score < 22 or ≥ 50% reduction), assessed after each session.ResultsThe intention-to-treat analysis revealed an 80.4% response rate and a 58.7% remission rate (Hedges’ g = 3.29). Notably, both subjective and objective cognitive functions significantly improved post-i-HECT treatments and during the 3-month follow-up periods.ConclusionThe i-HECT protocol may provide a rapid antidepressant treatment option with cognitive benefits for young depression patients.HighlightsDesigned a novel but simple ECT protocol, i-HECT, for young depression patients.The trial employed Simon’s optimal two-stage design with a high power of 0.95.The i-HECT rapidly improved both depression symptoms and cognitive functions.
Genetic estimates and genome-wide association studies of antibody response in Tanzanian dairy cattle
Authors: Hernandez-Castro Luis E , Cook Elizabeth Anne Jessie , Matika Oswald , Mengele Isaac Joseph , Motto Shabani Kiyabo , Bwatota Shedrack Festo , Zirra-Shallangwa Bibiana , Pong-Wong Ricardo , Prendergast James , Mrode Raphael , Toye Philip G. , Komwihangilo Daniel Mushumbusi , Lyatuu Eliamoni , Karani Benedict E. , Nangekhe Getrude , Mwai Okeyo Ally , Shirima Gabriel Mkilema , de Clare Bronsvoort Barend Mark 
Published: August 2024

AbstractIdentifying the genetic determinants of host defence against infectious pathogens is central to enhancing disease resilience and therapeutic efficacy in livestock. Here we have taken a genome-wide association approach to identify genetic variants associated with the presence of serological markers for important infectious diseases affecting dairy cattle in smallholder farms. Assessing 668,911 single-nucleotide polymorphisms in 1977 crossbreed cattle sampled from six regions of Tanzania, we identified high levels of interregional admixture and European introgression which may increase infectious disease susceptibility relative to indigenous breeds. Heritability estimates ranged from 0.03 (SE ± 0.06) to 0.44 (SE ± 0.07) depending on the pathogen assayed. Preliminary genome scans revealed several loci associated with seropositivity to the viral diseases Rift Valley fever and bovine viral diarrhoea, the protozoan parasitesNeospora caninumandToxoplasma gondii, and the bacterial pathogensBrucella sp, Leptospira hardjoandCoxiella burnetti. The associated loci mapped to genes involved in immune defence, tumour suppression, neurological processes, and cell exocytosis. We discuss future work to clarify the cellular pathways contributing to general and taxon-specific infection responses and to advance selective breeding and therapeutic target designs.
Role of SCAL1 in Modulating Oxidative Stress, Cancer Stemness, Apoptotic Resistance in Tumorigenic Differentiation of Cigarette Smoke-Exposed BEAS-2B Cells
Authors: Sengupta Debmalya , Banerjee Souradeep , Sengupta Mainak 
Published: August 2024

AbstractThe smoke and cancer-associated lncRNA 1 (SCAL1) is an emergent biomarker in lung cancer. However, the precise role of SCAL1 as a mediator of tobacco smoke-induced lung carcinogenesis remains unclear. BEAS-2B cells were cultured and exposed to 20% cigarette smoke extract (CSE), followed by quantification of SCAL1. We evaluated the impact of SCAL1 on cell viability, ROS mitigation, cancer stemness, tumorigenic differentiation, cellular invasiveness, and apoptosis for different CSE incubation time points through SCAL1 expressional modulation using SCAL1-specific siRNAs and scrambled controls. We observed an upregulation of SCAL1 in cells exposed to CSE for 2, 4, and 6 hours, with the highest expression observed at 6 hours (p<0.001). Exposure of BEAS-2B cells to CSE showed the formation of focal adhesions and stress fibers resembling tunneling nanotubes. Intracellular ROS levels significantly increased upon CSE exposure compared to control cells (p<0.05). We found increased levels of anti-apoptotic and cancer stem (CSC) cell markers like BCL2, ALDH1A1, CD133, CD44, and TCTP and decreased levels of TP53 in CSE-exposed cells. Knockdown of SCAL1 using siRNA transfection reversed these effects at all time points. Additionally, we observed a significant decrease in the number of spheroid colonies in siSCAL1 (+) cells compared to siSCAL1 (-) cells (p<0.01) exposed to CSE. SCAL1 is pivotal in mediating cellular responses to cigarette smoke, leading to tumorigenic differentiation of BEAS-2B cells. Understanding the mechanisms could provide valuable insights into lung cancer pathogenesis and therapeutic approaches.
LongReadSum: A fast and flexible quality control and signal summarization tool for long-read sequencing data
Authors: Perdomo Jonathan Elliot , Ahsan Mian Umair , Liu Qian , Fang Li , Wang Kai 
Published: August 2024

AbstractWhile several well-established quality control (QC) tools are available for short reads sequencing data, there is a general paucity of computational tools that provide long read metrics in a fast and comprehensive manner across all major sequencing platforms (such as PacBio, Oxford Nanopore, Illumina Complete Long Read) and data formats (such as ONT POD5, FAST5, basecall summary files and PacBio unaligned BAM). Additionally, none of the current tools provide support for summarizing Oxford Nanopore basecall signal or comprehensive base modification (methylation) information from genomic data. Furthermore, nowadays a single PromethION flowcell on the Oxford Nanopore platform can generate terabytes of signal data, which cannot be handled by existing tools designed for small-scale flowcells. To address these challenges, here we present LongReadSum, a multi-threaded C++ tool which provides fast and comprehensive QC reports on all major aspects of sequencing data (such as read, base, base quality, alignment, and base modification metrics) and produce basecalling signal intensity information from the Oxford Nanopore platform. We demonstrate use cases to analyze cDNA sequencing, direct mRNA sequencing, reduced representation methylation sequencing (RRMS) through adaptive sequencing, as well as whole genome sequencing (WGS) data using diverse long-read platforms.
A Dual-Fluorescence Assay for Gene Delivery Vehicle Screening in Macrophages with an Inflammation-Inducible Reporter Construct
Authors: Ivy Allie , Bess Shelby N , Agrawal Shilpi , Kochar Varun , Muldoon Timothy J , Nelson Christopher E. 
Published: August 2024

AbstractMacrophages are a promising target for therapeutics in various applications such as regenerative medicine and immunotherapy for cancer. Due to their plastic nature, macrophages can switch from a non-activated state to activated with the smallest environmental change. For macrophages to be effective in their respective applications, screening for phenotypic changes is necessary to elucidate the cell response to different delivery vehicles, vaccines, small molecules, and other stimuli. We created a sensitive and dynamic high-throughput screening method for macrophages based on the activation of NF-κB. For this reporter, we placed an mCherry fluorescence gene under the control of an inflammatory promoter, which recruits NF-κB response elements to promote expression during the inflammatory response in macrophages. We characterized the inflammatory reporter based on key markers of an inflammatory response in macrophages including TNF-α cytokine release and immunostaining for inflammatory and non-inflammatory cell surface markers. With the inflammatory reporter, we also were able to create an LPS dose curve to determine the dynamic range of the reporter and determine the sensitivity of the reporter to stimulus through timepoint analysis of stimulus vs. non-stimulus treated reporter cells. We then used the reporter cell line to determine both delivery efficiency and inflammatory response to different viral and non-viral gene delivery vehicles. Thie screening technique developed here provides a dynamic, high-throughput screening technique for determining inflammatory response by mouse macrophages to specific stimuli and provides insight into the inflammatory response of mouse macrophages to different viral and non-viral gene delivery methods.
PeakClimber: A software tool for the accurate quantification of complex multianalyte HPLC chromatograms using the exponential Gaussian function
Authors: Derrick Joshua T. , Deme Pragney , Haughey Norman , Farber Steven A. , Ludington William B. 
Published: August 2024

AbstractHigh-performance liquid chromatography (HPLC) is a common medium-throughput technique to quantify the components of often complex mixtures like those typically obtained from biological tissue extracts. However, analysis of HPLC data from complex multianalyte samples is hampered by a lack of tools to accurately determine the precise analyte quantities on a level of precision equivalent to mass-spectrometry approaches. To address this problem, we developed a tool we call PeakClimber, that uses a sum of exponential Gaussian functions to accurately deconvolve overlapping, multianalyte peaks in HPLC traces. Here we analytically show that HPLC peaks are well-fit by an exponential Gaussian function, that PeakClimber more accurately quantifies known peak areas than standard industry software for both HPLC and mass spectrometry applications, and that PeakClimber accurately quantifies differences in triglyceride abundances between colonized and germ-free fruit flies.
Spike-to-excite: photosensitive seizures in biologically-realistic spiking neural networks
Authors: Taylor Luke , Fasol Melissa Claire Maaike 
Published: August 2024

AbstractPhotosensitive Epilepsy (PE) is a neurological disorder characterized by seizures triggered by harmful visual stimuli, such as flashing lights and high-contrast patterns. The mechanisms underlying PE remain poorly understood, and to date, no computational model has captured the phenomena associated with this condition. Biologically detailed spiking networks trained for efficient prediction of natural scenes have been shown to capture V1-like characteristics. Here, we show that these models display seizure-like activity in response to harmful stimuli while retaining healthy responses to non-provocative stimuli when post-synaptic inhibitory connections are weakened. Notably, our adapted model resembles the motion tuning and contrast gain responses of excitatory V1 neurons in mice with optogenetically reduced inhibitory activity. We offer testable predictions underlying the pathophysiology of PE by exploring how reduced inhibition leads to seizure-like activity. Finally, we show that artificially injecting pulsating input current into the model units prevents seizure-like activity and restores baseline function. In summary, we present a model of PE that offers new insights to understand and treat this condition.
Parcellation of the primate prefrontal cortex by cognitive control operations
Authors: Wang Xuanyu , Hähnke Daniel , Nieder Andreas , Jacob Simon N. 
Published: August 2024

AbstractModular organization, the division of the cerebral cortex into functionally distinct subregions, is well established in the primate sensorimotor cortex, but debated in the cognitive association cortex, including the lateral prefrontal cortex (PFC). So far, single-unit recordings have not confirmed the prefrontal rostro-caudal gradients observed in neuroimaging and neuroanatomical experiments. To bridge these microscale and macroscale perspectives, we obtained microelectrode recordings with twice the spatial coverage of conventional studies from the PFC of monkeys engaged in a working memory task. Neighboring electrodes shared task-related neural dynamics that were stable across recording sessions and formed spatially continuous, mesoscale clusters with distinct local and long-range fronto-parietal connectivity. Spiking activity was cluster-specific and related to either the encoding, maintenance or decoding of working memory content. Our findings support parcellation of the PFC by cognitive control operations rather than by processed information, indicating that modularity is a fundamental architectural principle across the primate cortex.
Cryptic host phenotypic heterogeneity drives diversification of bacteriophage λ
Authors: De La Fuente Caesar A. , Lahoud Nehme , Meyer Justin R. 
Published: August 2024

AbstractBacteriophages, the most abundant and genetically diverse life forms, seemingly defy fundamental ecological theory by exhibiting greater diversity than their numerous bacterial prey. This paradox raises questions about the mechanisms underlying parasite diversity. To investigate this, we took advantage of a surprising experimental result: when bacteriophage λ is continually supplied a single host, λ repeatedly evolves multiple genotypes within the same flask that vary in their receptor use. Measurements of negative frequency-dependent selection between receptor specialists revealed that diversifying selection drove their evolution and maintenance. However, the source of environmental heterogeneity necessary to generate this type of selection was unclear, as only a single isogenic host was provided and replenished every eight hours. Our experiments showed that selection for different specialist phages oscillated over the 8-hour incubation period, mirroring oscillations in gene expression of λ’s two receptors (Escherichia coliouter membrane proteins LamB and OmpF). These receptor expression changes were attributed to both cell-to-cell variation in receptor expression and rapid bacterial evolution, which we documented using phenotypic resistance assays and population genome sequencing. Our findings suggest that cryptic phenotypic variation in hosts, arising from non-genetic phenotypic heterogeneity and rapid evolution, may play a key role in driving viral diversity.
Manipulation of the microRNA172 -AP2L2interaction provides precise control of wheat and triticale plant height
Authors: Zhang Chaozhong , Hegarty Joshua , Padilla Mariana , Tricoli David M. , Dubcovsky Jorge , Debernardi Juan M. 
Published: August 2024

AbstractTheREDUCED HEIGHT(RHT) dwarfing allelesRht-B1bandRht-D1bwere essential in the “Green Revolution” to optimize wheat plant height and increase grain yield. However, those alleles reduce coleoptile length limiting sowing depth, which triggered the search for alternative dwarfing genes. In this study, we engineered the interaction between miR172 andAP2L2genes to fine-tune wheat and triticale plant height without affecting coleoptile and first-leaf length.
Novel Perceval Sizing Technique: Single Center Experience
Authors: Margaryan Rafik , Concistre Giovanni , Bianchi Giacomo , Solinas Marco 
Published: August 2024

AbstractObjectiveAim of this study was to compare old (manufacturer recommended) and new (institution based) sizing techniques for sutureless valve.MaterialsA 226 consecutively operated patients underwent aortic valve replacement with Perceval sutureless valve (Corcym) and had CT scan with contrast enhancement were included to this study. The final decision of appropriate size is based on intra-operative obturator sizing. Briefly, we have measured on the CT scans the annular ring surface and perimeter in order to estimate the prosthesis size. New sizing technique uses only white obturator of Perceval and it should passe trough the annulus with slight friction, which practically under-sizes with respect to manufacturer’s recommendations.ResultsThe operative mortality was 1 (0.4424779%). There were no prosthesis migration neither annular rupture in any group. The mean follow up was lower in new group (3.3 ± 2.0 vs 9.7 ± 1.6, p < 0.01). At the discharge the patients who have used the new sizing technique had less gradient on the prosthetic valve (13.4 ± 5.0 vs 15.2 ± 5.5, p = 0.02). The new sizing was less prone to degeneration at the follow-up which would require intervention (13.4 ± 5.0 vs 15.2 ± 5.5, p = 0.02). Oversizing of 22.6% had significant role on valve gradient increase and structural degeneration (p< 0.05).ConclusionsNew sizing technique is safe and reproducible. It seem to deliver better immediate and long term benefits for Perceval sutureless valve, less postoperative gradient, less probability or structural degeneration.
Decoding critical targets and signaling pathways in EBV-mediated diseases using large language models
Authors: Yu Jingwen , Wang Yaohao , Wang Haidong , Wei Zhi , Pei Yonggang 
Published: August 2024

AbstractEpstein-Barr virus (EBV), a member of the gamma-herpesvirus, is the first identified human oncovirus and is associated with various malignancies. Understanding the intricate interactions between EBV antigens and cellular pathways is crucial to unravel the molecular mechanisms in EBV-mediated diseases. However, fully elucidating EBV-host interactions and the associated pathogenesis remains a significant challenge. In this study, we utilized LLMs to screen 36,105 EBV-relevant scientific publications, presenting a descriptive overview of the interactions between EBV antigens and host cellular pathways through comprehensive interaction networks. We described the critical roles of EBV antigens by constructing functional subsets of host proteins targeted by EBV antigens and illustrated the interactions using protein- protein interaction (PPI) networks. Furthermore, we developed an antigen-pathway network that highlights the connections with EBV-associated diseases, including DLBCL, BL, NPC, gastric cancer (GC), and post-transplant lymphoproliferative disorders (PTLD). Utilizing our dataset and public dataset, we validated the efficacy of using BLLF3-targeted TLR2-associated factors as marker genes for DLBCL. Next, we confirmed the co-expression of calcium pathway factors induced by LMP1 over- expression in BL. Finally, based on shared results suggesting that LMP1 actively regulates the glycolysis pathway, we identified and validated the correlation and co- expression of LMP1-induced PARP1, HIF1A, HOXB3, and key transcription-related factors, revealing the complete picture of LMP1’s influence on the glycolysis pathway. Our study presents a comprehensive functional encyclopedia of the interactions between EBV antigens and host signaling pathways across various EBV-associated disease contexts, providing valuable insights for the development of therapeutic strategies.