bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Prognostic Value of Angiography-Derived Microcirculatory Resistance for Coronary Artery Bypass Grafting of Intermediate Coronary Stenosis
Authors: Yan Wenlong , Wang Yangyang , Hu Haoyu , Wang Wei , Li Zhenfu , Zheng Xin , Yang Sumin 
Published: November 2023

BACKGROUNDFor patients with intermediate coronary stenoses, the prognostic value of coronary artery bypass grafting (CABG) remains controversial. The prognostic impact of CABG may be different according to Murray law-based quantitative flow ratio (μQFR) and angiography-derived microcirculatory resistance (AMR) in patients with intermediate coronary stenoses.METHODS AND RESULTSClinical data of 1411 cases who were diagnosed with multivessel coronary artery disease and had coronary artery intermediate stenoses (50% to 70% by visual assessment) between January 2013 and January 2020 were collected. Patients were categorized into CABG and defer groups based on the decision to bypass intermediate stenoses. These patients were further divided into different subgroups based on μQFR and AMR. The primary outcome was the major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization and stroke. Multivariable analysis showed AMR (HR = 1.68, 95% CI 1.18-4.14, P = 0.008) was independent factor associated with MACCE in all patients. On receiver-operating characteristic (ROC) curve analysis, the estimated area under the curve was 0.75 (95% CI: 0.72-0.79) for MACCE. Using the maximum Youden’s index, the optimal cutoff value for AMR to predict MACCE was 2.50 mmHg*s/cm. In defer group, MACCE was significantly lower in patients with both μQFR > 0.80 and AMR < 2.50 mmHg*s/cm as compared with patients with μQFR > 0.80 (13.2% vs 22.0%, P = 0.031) or AMR < 2.50 mmHg*s/cm (13.2% vs 23.6%, P = 0.012) alone. Compared with patients with both normal μQFR and AMR, patients with both abnormal μQFR and AMR carried the highest risk for MACCE (HR = 3.46, 95% CI 2.10-5.71, P < 0.001). CABG was associated with a lower risk of MACCE compared with the deferral strategy when both μQFR and AMR were abnormal. In contrast, at normal μQFR and AMR, patients in both CABG and defer groups had similar MACCE outcomes.CONCLUSIONSIn patients with intermediate coronary stenoses, the prognostic value of treatment strategy differed according to μQFR and AMR, with a significant interaction. The combination of μQFR and AMR can help stratify risk and guide treatment strategies for patients with intermediate coronary stenoses.
Perceptual salience is insufficient for auditory streaming in eastern gray treefrogs (Hyla versicolor)
Authors: Kalra Lata , Altman Shoshana , Bee Mark A. 
Published: November 2023

AbstractAuditory streaming underlies a receiver’s ability to organize complex mixtures of auditory input into distinct perceptual “streams” that represent different sound sources in the environment. During auditory streaming, sounds produced by the same source are integrated through time into a single, coherent auditory stream that is perceptually segregated from other concurrent sounds. Based on human psychoacoustic studies, a prominent hypothesis regarding auditory streaming is thatanyperceptually salient acoustic difference between sounds can promote their segregation into distinct auditory streams. Here, we used the eastern gray treefrog,Hyla versicolor, to test this hypothesis in the context of vocal communication in a non-human animal. In this system, females choose their mate based on perceiving features of a male’s pulsatile advertisement calls in social environments (choruses) characterized by mixtures of overlapping vocalizations. We employed an experimental paradigm from human psychoacoustics to design interleaved pulsatile sequences (ABAB…) that mimicked key features of the species’ advertisement call, and in which alternating pulses differed in pulse rise time, which is a robust species recognition cue in eastern gray treefrogs. Using phonotaxis assays, we found no evidence that perceptually salient differences in pulse rise time promoted the segregation of interleaved pulse sequences into distinct auditory streams. These results suggest the hypothesis that any perceptually salient acoustic difference can be exploited as a cue for stream segregation is not supported in all species. We discuss these findings in the context of cues used for species recognition and auditory streaming.
Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythm and sleep
Authors: Sun Yuanqiang , Shui Ke , Li Qinyu , Liu Chenlu , Jin Wanting , Ni Jian-Quan , Lu Jian , Zhang Luoying 
Published: November 2023

AbstractThe circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene,Clock(Clk), rhythmically and substantially attenuate CLK protein translation inDrosophila, with pronounced suppression occurring during daylight hours. EliminatingClkuORFs results in elevated CLK protein levels during the day and a compressed circadian cycle, along with a broad shift in clock gene expression rhythms. Interestingly,ClkuORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments,ClkuORFs play a role in modulating sleep patterns in response to the varying day lengths of different seasons, inhibiting translation in a day-length contingent manner. Furthermore, theClkuORFs act as a master regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.
Multiparametric MRI detects multi-organ impairment in patients with chronic myeloid neoplasms with normal serum biomarkers
Authors: Reed Sophie , Diamond Charlie , Mahmood Samiya , Rymell Soubera , Smith Michael , Pansini Michele , Psaila Bethan , Mead Adam J. , Thomaides-Brears Helena , Chowdhury Onima 
Published: November 2023

AbstractAssessment of organ impairment in patients with chronic myeloid neoplasms is pivotal in selecting treatments and for accurate prognostication of patient outcomes. In order to determine the multi-organ health of patients with chronic myeloid neoplasms, we conducted a prospective, observational study utilising a novel MRI technology which quantitatively assesses the health of multiple organs in one scan. Organ impairment was significantly higher in the patient cohort compared to healthy controls, most notably with increased rates of kidney fibroinflammation 28% vs 0% (p-value = 0.002). MRI-defined kidney impairment was prevalent in patients with normal serum biomarkers of kidney disease, demonstrating the added value of MRI as a tool to identify occult organ impairment. This has wider implications for enhancing the assessment of organ health in patients with a variety of blood cancers at diagnosis and throughout treatment, guiding more personalised strategies and improving patient outcomes.
Fine-Tuning the Llama2 Large Language Model Using Books on the Diagnosis and Treatment of Musculoskeletal System in Physical Therapy
Authors: Kim Jun-hee 
Published: November 2023

ABSTRACTBackgroudGenerative language models (GLM) utilize machine learning algorithms to perform various tasks such as text generation, question response, and sentence completion by imitating the language that humans understand and use.PurposeThis study was to fine-tune the Llama2 language model using text data from books on the diagnosis and treatment of musculoskeletal system in physical therapy and compare it to the base model to determine its usability in medical fields.ResultsCompared to the base model, the fine-tuned model consistently generated answers specific to the musculoskeletal system diagnosis and treatment, demonstrating improved understanding of the specialized domain.ConclusionThe model fine-tuned for musculoskeletal diagnosis and treatment books provided more detailed information related to musculoskeletal topics, and the use of this fine-tuned model could be helpful in medical education and the acquisition of specialized knowledge.
Medial temporal lobe hyperconnectivity is key to Alzheimer’s disease: Insight from physiological aging to dementia
Authors: Chauveau Léa , Landeau Brigitte , Dautricourt Sophie , Turpin Anne-Laure , Delarue Marion , Hébert Oriane , de La Sayette Vincent , Chételat Gaël , de Flores Robin 
Published: November 2023

AbstractCuring Alzheimer’s disease (AD) remains hampered by an incomplete understanding of its pathophysiology and progression. Dysfunction within medial temporal lobe networks may provide key insights, as AD proteins seem to propagate specifically through the anterior-temporal (AT) and posterior-medial (PM) systems. Using monocentric longitudinal data from 267 participants spanning physiological aging to the full AD continuum, we found that advancing age was associated with decreased PM connectivity and increased AT connectivity over adult life. When specifically assessing AD-relevant connectivity changes, all AD-associated clinicopathological features, including elevated amyloid burden, AD-typical glucose hypometabolism, hippocampal atrophy, greater cognitive impairment and faster progression from MCI to AD-dementia, were consistently linked to AT hyperconnectivity in healthy to AD-demented older adults. Our comprehensive approach allowed us to reveal that excessive connectivity within the AT network is a pivotal mechanism catalysing pathological process and progression of AD. Such findings hold promise for early diagnosis and therapeutic strategies targeting these specific network alterations.
Hydroxyurea maintains working memory function in pediatric sickle cell disease
Authors: Lai Jesyin , Zou Ping , Dalboni da Rocha Josue L. , Heitzer Andrew M. , Patni Tushar , Li Yimei , Scoggins Matthew A. , Sharma Akshay , Wang Winfred C. , Helton Kathleen J. , Sitaram Ranganatha 
Published: November 2023

AbstractPediatric patients with sickle cell disease (SCD) have decreased oxygen-carrying capacity in the blood and reduced or restricted cerebral blood flow resulting in neurocognitive deficits and cerebral infarcts. The standard treatment for children with SCD is hydroxyurea; however, the treatment-related neurocognitive effects are unclear. A key area of impairment in SCD is working memory, which is implicated in other cognitive and academic skills. N-back tasks are commonly used to investigate neural correlates of working memory. We analyzed functional magnetic resonance imaging (fMRI) of patients with SCD while they performed n-back tasks by assessing the blood-oxygenation level-dependent (BOLD) signals during working memory processing. Twenty hydroxyurea-treated and 11 control pediatric patients with SCD (7–18 years old) performed 0-, 1-, and 2-back tasks at 2 time points, once before hydroxyurea treatment (baseline) and ∼1 year after treatment (follow-up). Neurocognitive measures (e.g., verbal comprehension, processing speed, full-scale intelligence quotient, etc.) were assessed at both time points. Although no significant changes in behavior performance of n-back tasks and neurocognitive measures were observed in the treated group, we observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2-> 0-back contrast. Through searchlight-pattern classifications in the treated and control groups to identify changes in brain activation between time points during the 2-back task, we found more brain areas, especially the posterior region, with changes in the pattern and magnitude of BOLD signals in the control group compared to the treated group. In the control group, increases in 2-back BOLD signals were observed in the right crus I cerebellum, right inferior parietal lobe, right inferior temporal lobe, right angular gyrus, left cuneus and left middle frontal gyrus at 1-year follow-up. Moreover, BOLD signals elevated as the working memory load increased from 0- to 1-back but did not increase further from 1- to 2-back in the right inferior temporal lobe, right angular gyrus, and right superior frontal gyrus. These observations may result from increased cognitive effort during working memory processing with no hydroxyurea treatment. In contrast, we found fewer changes in the pattern and magnitude of BOLD signals across time points in the treated group. Furthermore, BOLD signals in the left crus I cerebellum, right angular gyrus, left cuneus and right superior frontal gyrus of the treated group increased continuously with increasing working memory load from 0- to 2-back, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. Collectively, these findings suggest that hydroxyurea treatment helped maintain working memory function in SCD.
Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021/2022
Authors: Giacinti Jolene A. , Signore Anthony V. , Jones Megan E. B. , Bourque Laura , Lair Stéphane , Jardine Claire , Stevens Brian , Bollinger Trent , Goldsmith Dayna ,   British Columbia Wildlife AIV Surveillance Program (BC WASPs), Pybus Margo , Stasiak Iga , Davis Richard , Pople Neil , Nituch Larissa , Brook Rodney W. , Ojkic Davor , Massé Ariane , Dimitri-Masson Gabrielle , Parsons Glen J. , Baker Meghan , Yason Carmencita , Harms Jane , Jutha Naima , Neely Jon , Berhane Yohannes , Lung Oliver , French Shannon K. , Myers Lawrna , Provencher Jennifer F. , Avery-Gomm Stephanie , Robertson Gregory J. , Barychka Tatsiana , Gurney Kirsty E. B. , Wight Jordan , Rahman Ishraq , Hargan Kathryn , Lang Andrew S. , Brown Michael G. C. , Pekarik Cynthia , Thompson Trevor , McLaughlin Angela , Willie Megan , Wilson Laurie , Flemming Scott A. , Ross Megan V. , Leafloor Jim , Baldwin Frank , Sharp Chris , Lewis Hannah , Beaumont Matthieu , Hanson Al , Ronconi Robert A. , Reed Eric , Campbell Margaret , Saunders Michelle , Soos Catherine 
Published: November 2023

AbstractFollowing detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada in late 2021, avian influenza surveillance in wild birds was scaled-up across Canada. Herein, we present results of Canada’s Interagency Surveillance Program for Avian Influenza in wild birds during the first year (November 2021 – November 2022) following the incursions of HPAIV from Eurasia. Key objectives of the surveillance program were to (i) detect the presence, distribution and spread of HPAIV and other avian influenza viruses (AIVs), (ii) detect wild bird morbidity and mortality associated with HPAIV, (iii) identify the range of wild bird species infected by HPAIV, and (iv) characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across One Health partners.
E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled family members
Authors: Bugter Jeroen M. , van Kerkhof Peter , Janssen Eline , Tran Ngoc Minh Thi , Iglesias van Montfort Daniel , Jamieson Cara , Jordens Ingrid , Maurice Madelon M. 
Published: November 2023

AbstractThe transmembrane E3 ligases RNF43 and ZNRF3 perform key tumour suppressor roles by inducing endocytosis of members of the Frizzled (FZD) family, the primary receptors for WNT. Loss-of-function mutations inRNF43andZNRF3mediate FZD stabilisation and a WNT-hypersensitive growth state in various cancer types. Strikingly,RNF43andZNRF3mutations are differentially distributed across cancer types, raising questions about their functional redundance. Here, we compare the efficacy of RNF43 and ZNRF3 of targeting different FZDs for endocytosis. We find that RNF43 preferentially downregulates FZD1/FZD5/FZD7, while ZNRF3 displays preference towards FZD6/FZD10. We show that the RNF43 transmembrane domain (TMD) is a key molecular determinant for inducing FZD5 endocytosis. Furthermore, a TMD swap between RNF43 and ZNRF3 re-directs their preference for FZD member downregulation. We conclude that RNF43 and ZNRF3 preferentially downregulate specific FZDs by a TMD-dependent mechanism. In accordance, tissue-specific expression patterns of FZD homologues correlate with the incidence ofRNF43orZNRF3cancer mutations in those tissues. Consequently, our data point to druggable vulnerabilities of specific FZD receptors inRNF43-orZNRF3-mutant human cancers.
Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology
Authors: Wagner Paula M , Guido Mario E 
Published: November 2023

ABSTRACTThe circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase ε/δ (CK1ε/δ) with specific inhibitors (CHIR99022 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption afterPer2 knockdown expression in GBM-derived cells. CHIR99022-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition as compared with control cells. The combined treatment of CHIR99022 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone.Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects glioblastoma cell biology.
Millimeter-scale magnetic implants paired with a fully integrated wearable device for wireless biophysical and biochemical sensing
Authors: Wan Ji , Nie Zhongyi , Xu Jie , Zhang Zixuan , Yao Shenglian , Xiang Zehua , Lin Xiang , Lu Yuxing , Xu Chen , Zhao Pengcheng , Wang Yiran , Zhang Jingyan , Wang Yaozheng , Zhang Shaotong , Wang Jinzhuo , Man Weitao , Zhang Min , Han Mengdi 
Published: November 2023

AbstractImplantable sensors can directly interface with various organs for precise evaluation of health status. However, extracting signals from such sensors must rely on transcutaneous wires, integrated circuit chips, or cumbersome readout equipment, which increases the risks of infection, reduces the biocompatibility, or limits the portability. Here, we develop a set of millimeter-scale, chip-less and battery-less magnetic implants that can measure biophysical and biochemical signals wirelessly. In particular, the implants form two-way communications with a fully integrated wearable device, where the wearable device can induce a large-amplitude damped vibration of the magnetic implants and capture their subsequent motions in a wireless manner. Such damped vibrations reflect not only the biophysical conditions surrounding the implants movements, but also the concentration of a specific biochemical depending on the surface modification. Experiments in rat models demonstrate the capabilities in measuring cerebrospinal fluid (CSF) viscosity, intracranial pressure (ICP), and CSF glucose levels. This miniaturized system opens possibility for continuous, wireless monitoring of a wide range of biophysical and biochemical conditions within the living organism.
Zinc finger homeobox-3 (ZFHX3) orchestrates genome-wide daily gene expression in the suprachiasmatic nucleus
Authors: Bafna Akanksha , Banks Gareth , Vasilyev Vadim , Dallmann Robert , Hastings Michael H. , Nolan Patrick M. 
Published: November 2023

ABSTRACTThe mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological rhythms across the body. The SCN clockwork is a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn co-ordinates the expression of clock-controlled genes (CCGs) directing circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptomic and genomic levels are, however, poorly defined. Here, we used chromatin immunoprecipitation sequencing (ChIP-seq) to map the genomic localization of ZFHX3 binding sites in SCN chromatin. To test for function, we then conducted comprehensive RNA sequencing at six distinct times-of-day to compare the SCN transcriptional profiles of control and ZFHX3-conditional null mutants. We show that the genome-wide occupancy of ZFHX3 occurs predominantly around gene transcription start sites (TSS), co-localizing with known histone modifications, and preferentially partnering with clock transcription factors (CLOCK, BMAL1) to regulate clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, including changes in the levels of transcripts encoding elements of numerous neuropeptide neurotransmitter systems while attenuating the daily oscillation of the clock TFBmal1. Furthermore, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with an advanced in daily behavioural rhythms under 12h light-12h dark conditions. Together, these findings reveal the extensive genome-wide regulation mediated by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.