bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effectiveness of telemedicine in the prevention of type 2 diabetes: a systematic review and meta-analysis of interventions
Authors: Suhlrie Laura , Ayyagari Raga , Mba Camille , Olsson Kjell , Torres-Aparcana Harold , James Steven , Vounzoulaki Elpida , Ibsen Daniel B. 
Published: May 2024

ABSTRACTObjectiveTo evaluate the effectiveness of telemedicine-delivered diet and/or exercise interventions to prevent type 2 diabetes (T2D) in people at risk.MethodsEmbase (via Ovid), Medline (via Ovid), Web of Science, CINAHL, Scopus and SciELO were searched from January 2010-December 2020 for intervention studies using a diet and/or exercise intervention delivered through telemedicine for T2D prevention in people at risk. Parallel randomised controlled trials were meta-analyzed and other intervention designs narratively synthesised.ResultsWe identified 11,645 studies via database searches, of which 226 were full text screened, and 52 interventions included; 32 were included in the meta-analysis and 20 in the narrative synthesis. Telemedicine interventions reduced body weight (mean difference (MD): -1.66 kg, 95% confidence interval (CI) -2.48,-0.90, I2=81%, nstudies=17), body mass index (MD -0.71 kg/m2, 95% CI -1.06,-0.37, I2=70%, nstudies=11), waist circumference (MD -2.82 cm, 95% CI -5.16,-2.35, I2=84%, nstudies=7) and HbA1c (MD -0.07%, 95% CI -0.14,0.00, I2=71%, nstudies=11). No significant effects were found for other clinical outcomes. The narrative synthesis supported the results.ConclusionsOur study highlights the potential for telemedicine-delivered interventions in preventing T2D in people at risk.
Overexpression of miR-3168 impairs angiogenesis in Pulmonary Arterial Hypertension: Insights from circulating miRNA analysis
Authors: Lago-Docampo Mauro , Iglesias-López Ainhoa , Vilariño Carlos , Baloira Adolfo , Barberá Joan Albert , Blanco Isabel , Valverde Diana 
Published: May 2024

AbstractBackgroundPulmonary Arterial Hypertension (PAH) is a rare disease where the thickening of the precapillary pulmonary arteries ends up inducing right heart failure. Nowadays, obtaining an early diagnosis is challenging and typically delayed until undergoing right-heart catheterization.MethodsWe performed small RNA sequencing (microRNA-seq) in the plasma of idiopathic PAH patients and controls, that we validated by qPCR. We then interrogated the role of miR-3168 in HUVECs by performing western-blot, flow cytometry and tube formation assays.ResultsWe found 29 differentially expressed microRNAs and validate 7 of them let-(7a-5p, let-7b-5p, let-7c-5p, let-7f-5p, miR-9-5p, miR-31-5p, miR-3168) in a nationwide cohort of 120 patients and 110 controls. We then used classification models to analyze their potential as PAH predictor. In the first half of our cohort, we obtained a model with an AUC of 0.888. Although, this value lowered to 0.738 after using this model in the whole cohort of patients. Additionally, we validated the effect of miR-3168, a novel upregulated miRNA in PAH patients which targetsBMPR2,and impairs angiogenesis, as assessed by the tube formation assay.ConclusionWe identified novel downregulated and upregulated microRNAs in idiopathic PAH patients, developed a 3-microRNA signature for diagnosis, and validatedin vitrothat miR-3168 targetsBMPR2,thereby impairing angiogenesis.
Biomarkers Correspond with Echocardiographic Phenotypes in Heart Failure with Preserved Ejection Fraction: A Secondary Analysis of the RELAX Trial
Authors: Hyson Peter R. , Kao David P. 
Published: May 2024

AbstractBackgroundLittle is known about the relationship between structural phenotypes in in heart failure with preserved ejection fraction (HFpEF) and cardiac biomarkers. We used cluster analysis to identify cardiac structural phenotypes and their relationships to biomarkers in HFpEF.Methods and resultsLatent class analysis (LCA) was applied to echocardiographic data including left atrial enlargement (LAE), diastolic dysfunction (DD), E/e’, EF≤55%, and right ventricular dysfunction from 216 patients enrolled in the RELAX trial. Three structural phenotypes were identified. Phenotype A had the most grade II DD. Phenotype B had the most grade III DD, worst LAE, elevated E/e’ and right ventricular dysfunction. Phenotype C had the least DD and moderate LAE. Phenotypes B and C had prevalent atrial fibrillation (AF). Phenotype B patients had increased carboxy-terminal telopeptide of collagen type I (CITP), cystatin-c (CYSTC), endothelin-1 (ET1), NT-proBNP, and high-sensitivity troponin I (TNI). Type A had the next highest CITP and CYSTC levels while Type C had next highest NT-proBNP.ConclusionsStructural HFpEF phenotypes demonstrated different characteristics including cardiac biomarkers. These findings may help explain phenotype-specific differences in natural history and prognosis, and they may represent phenotype-specific pathophysiology that could be amenable to targeted therapy.
Strategies for motion- and respiration-robust estimation of fMRI intrinsic neural timescales
Authors: Goldberg Andrew , Rosario Isabella , Power Jonathan , Horga Guillermo , Wengler Kenneth 
Published: May 2024

ABSTRACTIntrinsic neural timescale (INT) is a resting-state fMRI (rs-fMRI) measure that reflects the time window of neural integration within a brain region. Despite the potential relevance of INT to cognition, brain organization, and neuropsychiatric illness, the influences of physiological artifacts on INT have not been systematically considered. Two artifacts, head motion and respiration, pose serious issues in rs-fMRI studies. Here, we described their impact on INT estimation and tested the ability of two denoising strategies for mitigating these artifacts, high-motion frame censoring and global signal regression (GSR). We used a subset of the HCP Young Adult dataset with runs annotated for breathing patterns (Lynch et al., 2020) and at least one “clean” (reference) run that had minimal head motion and no respiration artifacts; other runs from the same participants (n = 46) were labeled as “non-clean.” We found that non-clean runs exhibited brain-wide increases in INT compared to their respective clean runs and the magnitude of error in INT between non-clean and clean runs correlated with the amount of head motion. Importantly, effect sizes were comparable to INT effects reported in the clinical literature. GSR and high-motion frame censoring improved the similarity between INT maps from non-clean runs and their respective clean run. Using a pseudo-random frame-censoring approach, there was a relationship between the amount of censored frames and both the mean INT and mean error, suggesting that frame censoring itself biases INT estimation. A group-level correction procedure reduced this bias and improved similarity between non-clean runs and their respective clean run. Based on our findings, we offer recommendations for rs-fMRI INT studies, which include implementing GSR and high-motion frame censoring with Lomb-Scargle interpolation of censored data, and performing group-level correction of the bias introduced by frame censoring.
Thalamocortical interactions reflecting the intensity of flicker light-induced visual hallucinatory phenomena
Authors: Amaya Ioanna A. , Nierhaus Till , Schmidt Timo T. 
Published: May 2024

AbstractThe thalamus has a critical role in the orchestration of cortical activity. Aberrant thalamocortical connectivity occurs together with visual hallucinations in various pathologies and drug-induced states, highlighting the need to better understand how thalamocortical interactions may contribute to hallucinatory phenomena. However, concurring symptoms and physiological changes that occur during psychopathologies and pharmacological interventions make it difficult to distil the specific neural correlates of hallucinatory experiences. Flicker light stimulation (FLS) at 10 Hz reliably and selectively induces transient visual hallucinations in healthy participants. Arrhythmic flicker elicits fewer hallucinatory effects while delivering equal amounts of visual stimulation, together facilitating a well-controlled experimental setup to investigate the neural correlates of visual hallucinations driven by flicker rhythmicity. In this study, we implemented rhythmic and arrhythmic FLS during fMRI scanning to test the elicited changes in cortical activation and thalamocortical functional connectivity. We found that rhythmic FLS elicited stronger activation in higher-order visual cortices compared to arrhythmic control. Consistently, we found that rhythmic flicker selectively increased connectivity between ventroanterior thalamic nuclei and higher-order visual cortices compared to arrhythmic control, which was also found be positively associated with the subjective intensity of visual hallucinatory effects. As these thalamic and cortical areas do not receive primary visual inputs, it suggests that the thalamocortical connectivity changes relate to a higher-order function of the thalamus, such as in the coordination of cortical activity. In sum, we present novel evidence for the role of specific thalamocortical interactions with ventroanterior nuclei within visual hallucinatory experiences. Importantly, this can inform future clinical research into the mechanistic underpinnings of pathologic hallucinations.
Evolutionary convergence of sensory circuits in the pallium of amniotes
Authors: Rueda-Alaña Eneritz , Senovilla-Ganzo Rodrigo , Grillo Marco , Vázquez Enrique , Marco-Salas Sergio , Gallego-Flores Tatiana , Ftara Artemis , Escobar Laura , Benguría Alberto , Quintas-Gorozarri Ana , Dopazo Ana , Rábano Miriam , dM Vivanco María , Aransay Ana María , Garrigos Daniel , Toval Ángel , Ferrán José Luis , Nilsson Mats , Encinas Juan Manuel , De Pitta Maurizio , García-Moreno Fernando 
Published: May 2024

AbstractThe amniote pallium contains sensory circuits structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. Our study employs birthdating analysis, single-cell RNA and spatial transcriptomics, and mathematical modeling to compare the development and evolution of known pallial circuits across birds (chick), lizards (gecko) and mammals (mouse). We reveal that neurons within these circuits’ stations are generated at varying developmental times and brain regions across species, and found an early developmental divergence in the transcriptomic progression of glutamatergic neurons. Together, we show divergent developmental and evolutionary trajectories in the pallial cell types of sauropsids and mammals. Our research highlights significant differences in circuit construction rules among species and pallial regions. Interestingly, despite these developmental distinctions, the sensory circuits in birds and mammals appear functionally similar, which suggest the convergence of high-order sensory processing across amniote lineages.
Action potential propagation speed compensates for traveling distance in the human retina
Authors: Bucci Annalisa , Büttner Marc , Domdei Niklas , Rosselli Federica Bianca , Znidaric Matej , Diggelmann Roland , De Gennaro Martina , Cowan Cameron S. , Harmening Wolf , Hierlemann Andreas , Roska Botond , Franke Felix 
Published: May 2024

AbstractNeural information processing requires accurately timed action potentials arriving from presynaptic neurons at the postsynaptic neuron. However, axons of ganglion cells in the human retina feature low axonal conduction speeds and vastly different lengths, which poses a challenge to the brain for constructing a temporally coherent image over the visual field. Combining results from microelectrode array recordings, human behavioral measurements, transmission electron microscopy, and mathematical modelling of the retinal nerve fiber layer, we demonstrate that axonal propagation speeds compensate for variations in axonal length across the human retina including the fovea. The human brain synchronizes the arrival times of action potentials at the optic disc by increasing the diameters of longer axons, which increases their propagation speeds.
Ventral pallidal GABAergic neurons drive consumption in male, but not female rats
Authors: Scott Alexandra , Paulson Anika , Prill Collin , Kermoade Klaiten , Newell Bailey , Richard Jocelyn M. 
Published: May 2024

ABSTRACTFood intake is controlled by multiple converging signals: hormonal signals that provide information about energy homeostasis, but also hedonic and motivational aspects of food and food cues that can drive non-homeostatic or “hedonic “feeding. The ventral pallidum (VP) is a brain region implicated in the hedonic and motivational impact of food and foods cues, as well as consumption of rewards. Disinhibition of VP neurons has been shown to generate intense hyperphagia, or overconsumption. While VP gamma-Aminobutyric acidergic (GABA) neurons have been implicated in cue-elicited reward seeking and motivation, the role of these neurons in the hyperphagia resulting from VP activation remains unclear. Here, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate or inhibit VP GABA neurons in sated male and female rats during chow and sucrose consumption. We found that activation of VP GABA neurons increases consumption of chow and sucrose in male rats, but not female rats. We also found that, while inhibition of VP GABA neurons tended to decrease sucrose consumption, this effect was not statistically significant. Together, these findings suggest that activation of VP GABA neurons can stimulate consumption of routine or highly palatable rewards selectively in male rats.
Reversal of Obesity by Enhancing Slow-wave Sleep via a Prokineticin Receptor Neural Circuit
Authors: Han Yong , Xia Guobin , Harris Lauren , Liu Panpan , Guan Dongyin , Wu Qi 
Published: May 2024

AbstractObese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealedProkr2in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2RLPOneurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2RLPO→PBN circuit or the postsynaptic PROKR2PBNneurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2PBNneurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.
Representation of navigational affordances and ego-motion in the occipital place area
Authors: Kamps Frederik S. , Chen Emily M. , Kanwisher Nancy , Saxe Rebecca 
Published: May 2024

AbstractHumans effortlessly use vision to plan and guide navigation through the local environment, or “scene”. A network of three cortical regions responds selectively to visual scene information, including the occipital (OPA), parahippocampal (PPA), and medial place areas (MPA) – but how this network supports visually-guided navigation is unclear. Recent evidence suggests that one region in particular, the OPA, supports visual representations for navigation, while PPA and MPA support other aspects of scene processing. However, most previous studies tested only static scene images, which lack the dynamic experience of navigating through scenes. We used dynamic movie stimuli to test whether OPA, PPA, and MPA represent two critical kinds of navigationally-relevant information: navigational affordances (e.g., can I walk to the left, right, or both?) and ego-motion (e.g., am I walking forward or backward? turning left or right?). We found that OPA is sensitive to both affordances and ego-motion, as well as the conflict between these cues – e.g., turning toward versus away from an open doorway. These effects were significantly weaker or absent in PPA and MPA. Responses in OPA were also dissociable from those in early visual cortex, consistent with the idea that OPA responses are not merely explained by lower-level visual features. OPA responses to affordances and ego-motion were stronger in the contralateral than ipsilateral visual field, suggesting that OPA encodes navigationally relevant information within an egocentric reference frame. Taken together, these results support the hypothesis that OPA contains visual representations that are useful for planning and guiding navigation through scenes.
Bacterial Receptors but Not Anti-Phage Defence Mechanisms Determine Host Range for a Pair ofPseudomonas aeruginosaLytic Phages
Authors: Müller Dea M. , Pourtois Julie D. , Kim Minyoung Kevin , Targ Bobby , Burgener Elizabeth B. , Milla Carlos , McBride Robert , Antani Jyot D. , Turner Paul E. , Koff Jonathan L. , Bollyky Paul L. 
Published: May 2024

AbstractLytic bacteriophages (phage), viral predators of bacteria, offer a promising solution for treating bacterial infections. However, the narrow host range of phages limits the broad utility of individual phages, making the determinants of phage host range a subject of great interest. Here, we perform a genome-wide association study (GWAS) to identify bacterial genes associated with resistance or susceptibility to two lytic phages, OMKO1 and LPS-5, recently used in a clinical trial for patients with cystic fibrosis (pwCF). We analyzed 80Pseudomonas aeruginosaclinical isolates collected from pwCF. For OMKO1, genes crucial for infection were associated with biofilm formation, exopolysaccharide synthesis, metabolism, porins, and flagellum assembly. We validate a critical role for flagellum genes in transposon mutagenesis experiments and functional assays. For LPS-5, genes associated with DNA repair, metabolism, and lipopolysaccharide biosynthesis are crucial for infection. We confirme the critical role for LPS/O-antigen in susceptibility to LPS-5. Interestingly, the presence of bacterial genes encoding bacterial defence mechanisms is not predictive of phage susceptibility. Instead, the relative abundance of several known defence elements is associated with the number of temperate phages within bacterial genomes. Together, our findings highlight the central role of receptors in determining phage host range, providing valuable insights for the development of phage-based therapies against bacterial infections.
Heterogeneous local structures of the microtubule lattice revealed by cryo-ET and non-averaging analysis
Authors: Liu Hanjin , Yamaguchi Hiroshi , Kikkawa Masahide , Shima Tomohiro 
Published: May 2024

SummaryMicrotubule cytoskeletons play pivotal roles in various cellular processes, including cell division and locomotion, by dynamically changing their length and distribution in cells through tubulin polymerization/depolymerization. Recent structural studies have revealed the polymorphic lattice structure of microtubules closely correlate with the microtubule dynamics, but the studies were limited to averaged structures. To reveal the transient and localized structures, such as GTP-cap, we developed several non-averaging methods for cryogenic electron tomography to precisely measure the longitudinal spacing and helical twisting of individual microtubule lattices at the tubulin subunit level. Our analysis revealed that polymerizing and depolymerizing ends share a similar structure with regards to lattice spacing. The most distinctive property specific to the polymerizing plus end was left-handed twisting in the inter-dimer interface, suggesting that the twisting might accelerate fast polymerization at the plus ends. Our analysis uncovered the heterogeneity of native microtubules and will be indispensable for the study of microtubules dynamics under physiological contexts or during specific cellular events.
Evidence that minocycline treatment confounds the interpretation of neurofilament as a biomarker
Authors: Gentile Juliana E , Heiss Christina , Corridon Taylor L , Mortberg Meredith A , Fruhwürth Stefanie , Guzman Kenia , Grötschel Lana , Chan Kwan , Herring Neil C , Janicki Timothy , Nhass Rajaa , Sarathy Janani Manavala , Erickson Brian , Kunz Ryan , Erickson Alison , Braun Craig , Henry Katherine T , Bry Lynn , Arnold Steven E , Minikel Eric Vallabh , Zetterberg Henrik , Vallabh Sonia M 
Published: May 2024

AbstractNeurofilament light (NfL) concentration in cerebrospinal fluid (CSF) and blood serves as an important biomarker in neurology drug development. Changes in NfL are generally assumed to reflect changes in neuronal damage, while little is known about the clearance of NfL from biofluids. We observed an NfL increase of 3.5-fold in plasma and 5.7-fold in CSF in an asymptomatic individual at risk for genetic prion disease following 6 weeks’ treatment with oral minocycline for a dermatologic indication. Other biomarkers remained normal, and proteomic analysis of CSF revealed that the spike was exquisitely specific to neurofilaments. NfL dropped nearly to normal levels 5 weeks after minocycline cessation, and the individual remained free of disease 2 years later. Plasma NfL in dermatology patients was not elevated above normal controls. Dramatically high plasma NfL (>500 pg/mL) was variably observed in some hospitalized individuals receiving minocycline. In mice, treatment with minocycline resulted in variable increases of 1.3- to 4.0-fold in plasma NfL, with complete washout 2 weeks after cessation. In neuron-microglia co-cultures, minocycline increased NfL concentration in conditioned media by 3.0-fold without any visually obvious impact on neuronal health. We hypothesize that minocycline does not cause or exacerbate neuronal damage, but instead impacts the clearance of NfL from biofluids, a potential confounder for interpretation of this biomarker.