bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Medication Prescribing-Related Outcomes for Vulnerable Elderly In Transitions on High Risk Medications (IMPROVE-IT HRM): A Pilot Randomized Trial Protocol
Authors: Holbrook Anne , Perri Dan , Levine Mitch , Jarmain Sarah , Thabane Lehana , Tarride Jean-Eric , Dolovich Lisa , Hyland Sylvia , Forster Alan , Nieuwstraten Carmine 
Published: March 2023

ABSTRACTRationaleTransitions in, through, and out of hospital define the highest risk periods for patient safety. Hospitalized senior high-cost health care users taking high risk medications, are a large group of patients, usually highly complex with polypharmacy, and at high risk of serious adverse medication events. We will assess whether an expert Clinical Pharmacology Toxicology (CPT) medication management intervention during hospitalization with follow-up post-discharge and communication with circle of care, is feasible and can decrease drug therapy problems amongst this group.DesignPragmatic pilot randomized trial at SJHH with 1:1 patient-level concealed randomization with blinded outcome assessment and data analysis.ParticipantsAdults 65 years of age and older, admitted to Internal Medicine services for more than 2 days, who are high-cost users defined as at least one other hospitalization in the prior year, taking 5 or more chronic medications including at least one high risk medication.InterventionCPT consult service identifies medication target(s), completes consult, including priorities for improving prescribing negotiated with the patient, starts the care plan, ensures a detailed discharge medication reconciliation and circle-of-care communication, and sees the patient at least twice after hospital discharge via integrated virtual visits to consolidate the care plan in the community. Control group receives usual care as provided by admitting services.OutcomesInclude a) Feasibility Outcomes and b) Clinical Outcomes including the number of drug therapy problems improved, medication appropriateness and safety, the quality and coordination of transitions in care, quality of life, and health care utilization and costs by 3-month follow-up.ImpactIf results support feasibility of ramp-up and promising clinical outcomes, a follow-up definitive trial will be organized using a developing national platform and medication appropriateness network.RESEARCH QUESTIONOur detailed research question is ‘In a randomized pilot trial, can an expert Clinical Pharmacology team coordinate and improve medication management during the very high-risk transition period from hospitalization through post-hospital discharge follow-up for senior high-cost users of healthcare taking high risk medications, meeting key feasibility outcomes while improving patient-important outcomes and health care costs sufficiently to warrant a large subsequent trial?’
Reduction, removal or replacement of sodium nitrite in a model of cured and cooked meat: a joint evaluation of consequences on microbiological issues in food safety, colon ecosystem and colorectal carcinogenesis
Authors: Guéraud Françoise , Buisson Charline , Promeyrat Aurélie , Naud Nathalie , Fouché Edwin , Bézirard Valérie , Dupuy Jacques , Plaisancié Pascale , Héliès-Toussaint Cécile , Trouilh Lidwine , Martin Jean-Luc , Jeuge Sabine , Keuleyan Eléna , Petit Noémie , Aubry Laurent , Théodorou Vassilia , Frémaux Bastien , Olier Maïwenn , Caderni Giovanna , Kostka Tina , Nassy Gilles , Santé-Lhoutellier Véronique , Pierre Fabrice 
Published: March 2023

AbstractScopeEpidemiological and experimental evidence reported that processed meat consumption is associated with colorectal cancer (CRC) risk. Several studies suggest the involvement of nitrite or nitrate additivesvia N-nitroso-compound formation (NOCs).Methods and resultsCompared to the reference level (120 mg/kg of ham), the effects of sodium nitrite reduction (90 mg/kg of ham), removal and replacement were analysed on ham characteristics and in a CRC rat model. Sodium nitrite removal and reduction induced a similar decrease in CRC preneoplastic lesions, but only reduction led to (i) an inhibitory effect onListeria monocytogenesgrowth comparable to that obtained using the reference nitrite level of 120 mg/kg and (ii) an effective control of lipid peroxidation. Among the three alternatives tested, none led to a significant gain when compared to the 120 mg/kg ham reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions but the concomitant presence of nitrosyl iron in feces. Except vegetable stock, other alternatives were less efficient than sodium nitrite (≥ 90 mg/kg) in reducingL. monocytogenesgrowth.ConclusionNitrite reduction (90mg/kg) effectively reduced CRC risk through limiting NOC formation and lipid peroxidation, while mitigatingL. monocytogenesrisks from cooked hams. Going further in reduction should be possible if accompanied by antioxidants to limit lipid peroxidation and appropriate use-by dates.
Distance-dependent reconfiguration of hubs in Alzheimer’s disease: a cross-tissue functional network study
Authors: Zhang Xingxing , Li Yingjia , Guan Qing , Dong Debo , Zhang Jianfeng , Meng Xianghong , Chen Fuyong , Luo Yuejia , Zhang Haobo ,   Alzheimer’s Disease Neuroimaging Initiative
Published: March 2023

AbstractThe hubs of the intra-grey matter (GM) network were sensitive to anatomical distance and susceptible to neuropathological damage. However, few studies examined the hubs of cross-tissue distance-dependent networks and their changes in Alzheimer’s disease (AD). Using resting-state fMRI data of 30 AD patients and 37 normal older adults (NC), we constructed the cross-tissue networks based on functional connectivity (FC) between GM and white matter (WM) voxels. In the full-ranged and distance-dependent networks (characterized by gradually increased Euclidean distances between GM and WM voxels), their hubs were identified with weight degree metrics (frWD and ddWD). We compared these WD metrics between AD and NC; using the resultant abnormal WDs as the seeds, we performed seed-based FC analysis. With increasing distance, the GM hubs of distance-dependent networks moved from the medial to lateral cortices, and the WM hubs spread from the projection fibers to longitudinal fascicles. Abnormal ddWD metrics in AD were primarily located in the hubs of distance-dependent networks around 20-100mm. Decreased ddWDs were located in the left corona radiation (CR), which had decreased FCs with the executive network’s GM regions in AD. Increased ddWDs were located in the posterior thalamic radiation (PTR) and the temporal-parietal-occipital junction (TPO), and their FCs were larger in AD. Increased ddWDs were shown in the sagittal striatum, which had larger FCs with the salience network’s GM regions in AD. The reconfiguration of cross-tissue distance-dependent networks possibly reflected the disruption in the neural circuit of executive function and the compensatory changes in the neural circuits of visuospatial and social-emotional functions in AD.
Multiscale Computational Framework to Investigate Integrin Mechanosensing and Cell Adhesion
Authors: Montes Andre R. , Gutierrez Gabriela , Tepole Adrian Buganza , Mofrad Mohammad R.K. 
Published: March 2023

ABSTRACTIntegrin mechanosensing plays an instrumental role in cell behavior, phenotype, and fate by transmitting mechanical signals that trigger downstream molecular and cellular changes. For instance, force transfer along key amino acid residues can mediate cell adhesion. Disrupting key binding sites withinα5β1integrin’s binding partner, fibronectin (FN) diminishes adhesive strength. While past studies have shown the importance of these residues in cell adhesion, the relationship between the dynamics of these residues and how integrin distributes force across the cell surface remains less explored. Here, we present a multiscale mechanical model to investigate the mechanical coupling between integrin nanoscale dynamics and whole-cell adhesion mechanics. Our framework leverages molecular dynamics simulations to investigate residues withinα5β1-FN during stretching and the finite element method to visualize the whole-cell adhesion mechanics. The forces per integrin across the cell surface of the whole-cell model were consistent with past atomic force microscopy and Förster resonance energy transfer measurements from literature. The molecular dynamics simulations also confirmed past studies that implicate two key sites within FN that maintain cell adhesion: the synergy site and RGD motif. Our study contributed to our understanding of molecular mechanisms by which these sites collaborate to mediate whole-cell integrin adhesion dynamics. Specifically, we showed how FN unfolding, residue binding/unbinding, and molecular structure contribute toα5β1-FN’s nonlinear force-extension behavior during stretching. Our computational framework could be used to explain how the dynamics of key residues influence cell differentiation or how uniquely designed protein structures could dynamically limit the spread of metastatic cells.
Long-term citizen science data reveals environmental controls on tropical tree flowering at the regional scale
Authors: Anujan Krishna , Mardian Jacob , Luo Carina , Ramraj R ,   SeasonWatch Citizen Scientist Network, Tasic Hana , Akseer Nadia , Ramaswami Geetha 
Published: March 2023

AbstractTropical tree reproductive phenology is sensitive to changing climate, but inter-individual and interannual variability at the regional scale is poorly understood. While large-scale and long-term datasets of environmental variables are available, reproductive phenology needs to be measured in-site, limiting the spatiotemporal scales of the data. We leveraged a unique dataset assembled by SeasonWatch, a citizen-science phenology monitoring programme in India to assess the environmental correlates of flowering in three ubiquitous and economically important tree species - jackfruit, mango and tamarind - in the south-western Indian state of Kerala. We explored the possibility of predicting (i) the flowering status of a tree at any given time, knowing recent environmental conditions, (ii) the environmental conditions that predict the onset of flowering and (iii) explored spatiotemporal patterns in these predictors to aid future hypotheses for changing phenology patterns. We used 165006 phenology observations spread over 19591 individual trees over 9 years, environmental predictors for the fortnight preceding each observation derived from remotely sensed observations (ERA5-LAND) to model the environmental correlates of flowering using two statistical approaches - machine learning and generalised linear mixed models. We found strong influences of temperature and rainfall variables on phenophase presence - soil moisture and minimum temperature had high importance values under machine learning models of presence/absence and had strong effects in the onset of flowering. The effect of time-varying environmental factors, minimum temperature, soil moisture and solar radiation, were also modified by static predictors like elevation, aspect, and urbanisation. Taken together, our results show the pervasive influence of climate on tropical tree reproductive phenology and its variability among years and individuals. Our results become increasingly important in the face of large heterogenous change in the climate of this landscape and other tropical regions. We demonstrate the potential and limitations of citizen-science observations in making and testing predictions at scale for predictive climate science in tropical landscapes.OpenResearchStatementData are already published and publicly available, with those items properly cited in this submission. SeasonWatch data is publicly archived as Ramaswami (2022).
An intact oculomotor neural circuit in congenital blindness
Authors: Koba Cemal , Crimi Alessandro , Collignon Olivier , Ricciardi Emiliano , Hasson Uri 
Published: March 2023

ABSTRACTIn the past three decades, multiple studies revealed that congenital blindness is associated with functional and structural reorganization in early visual areas and its interaction with other neural systems. Among the most reproducible findings is the weaker connectivity between the visual and sensorimotor cortices, which in sighted individuals plays a role in eye-motor coordination. Here we demonstrate an important exception to this reorganization phenomena: we find that in congenitally blind individuals (as for normally sighted ones), spontaneous, non-controlled eye movements correlate with connectivity between visual and sensorimotor cortices. Furthermore, using time-lagged regression, we show that eye movements drive activity in the visual cortex, which subsequently drives sensorimotor activity. Remarkably, this phenomenon persists even though blind participants often exhibit unsynchronized eye movements and cannot sense or regulate their eye positions. These findings provide evidence of a preserved, “non-functional” connectivity in congenitally blind individuals and reveal a firm, hard-wired constraint on connectivity that remains immune to any reorganization phenomena produced by lack of visual experience and oculomotor control.
Cortical contributions to the perception of loudness and hyperacusis
Authors: McGill Matthew , Kremer Caroline , Stecyk Kamryn , Clayton Kameron , Skerleva Desislava , Hancock Kenneth , Kujawa Sharon G. , Polley Daniel B. 
Published: March 2023

ABSTRACTSound perception is closely linked to the spatiotemporal patterning of neural activity in the auditory cortex (ACtx). Inhibitory interneurons sculpt the patterns of excitatory ACtx pyramidal neuron activity, and thus play a central role in sculpting the perception of sound. Reduced inhibition from parvalbumin-expressing (PV) inhibitory interneurons and the associated increased gain of sound-evoked pyramidal neuron spike rates are well-established consequences of aging and sensorineural hearing loss. Here, we reasoned that changes in PV-mediated inhibition would directly impact the perception of loudness. We hypothesized that ACtx PV activity could function as a perceptual volume knob, where reduced or elevated PV activity would increase or decrease the perceived loudness of sound, respectively. To test these hypotheses, we developed a two-alternative forced-choice loudness classification task for head-fixed mice and demonstrated that noise-induced sensorineural hearing loss directly caused a ∼10 dB loudness hyperacusis that begins hours after noise-induced sensorineural hearing loss and persists for at least several weeks. Conversely, sounds were perceived as ∼10 dB softer during optogenetic activation of ACtx PV neurons without having any effect on the overall detectability of sound. These data suggest that ACtx PV neurons can bi-directionally control the perceived loudness of sound, presumably via the strength of their inhibition onto local pyramidal neurons. Further, these data identify cortical PV neurons as a target for hyperacusis therapies and demonstrate a direct link between acquired sensorineural hearing loss and loudness hyperacusis.
Transformations of sensory information in the brain reflect a changing definition of optimality
Authors: Manning Tyler S. , Alexander Emma , Cumming Bruce G. , DeAngelis Gregory C. , Huang Xin , Cooper Emily A. 
Published: March 2023

Neurons throughout the brain modulate their firing rate lawfully in response to changes in sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization: neurons aim to efficiently and robustly represent sensory information under resource limitations. Our understanding of how this optimization varies across the brain, however, is still in its infancy. Here, we show that neural responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation to optimizing for perceptual discrimination. Focusing on binocular disparity – the slight differences in how objects project to the two eyes – we re-analyze measurements from neurons characterizing tuning curves in macaque monkey brain regions V1, V2, and MT, and compare these to measurements of the natural visual statistics of binocular disparity. The changes in tuning curve characteristics are computationally consistent with a shift in optimization goals from maximizing the information encoded about naturally occurring binocular disparities to maximizing the ability to support fine disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective regions of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings support a key re-framing of optimal coding in regions of the brain that contain sensory information, emphasizing the need to consider not just information preservation and neural resources, but also relevance to behavior.SignificanceA major role of the brain is to transform information from the sensory organs into signals that can be used to guide behavior. Neural activity is noisy and can consume large amount of energy, so sensory neurons must optimize their information processing so as to limit energy consumption while maintaining key behaviorally-relevant information. In this report, we re-examine classically-defined brain areas in the visual processing hierarchy, and ask whether neurons in these areas vary lawfully in how they represent sensory information. Our results suggest that neurons in these brain areas shift from being an optimal conduit of sensory information to optimally supporting perceptual discrimination during natural tasks.
Pulmonary vein flow split effects in patient-specific simulations of left atrial flow
Authors: Durán E. , García-Villalba M. , Martinez-Legazpi P. , Gonzalo A. , McVeigh E. , Kahn A.M. , Bermejo J. , Flores O. , del Álamo J.C. 
Published: March 2023

AbstractDisruptions to left atrial (LA) blood flow, such as those caused by atrial fibrillation (AF), can lead to thrombosis in the left atrial appendage (LAA) and an increased risk of systemic embolism. LA hemodynamics are influenced by various factors, including LA anatomy and function, and pulmonary vein (PV) inflow conditions. In particular, the PV flow split can vary significantly among and within patients depending on multiple factors. In this study, we investigated how changes in PV flow split affect LA flow transport, focusing on blood stasis in the LAA, using a high-fidelity patient-specific computational fluid dynamics (CFD) model. We analyzed LA anatomies from eight patients with varying atrial function, including three with AF and either a LAA thrombus or a history of TIAs. Using four different flow splits (60/40% and 55/45% through right and left PVs, even flow rate, and same velocity through each PV), we found that flow patterns are sensitive to PV flow split variations, particularly in planes parallel to the mitral valve. Changes in PV flow split also had a significant impact on blood stasis and could contribute to increased risk for thrombosis inside the LAA, particularly in patients with AF and previous LAA thrombus or a history of TIAs. Our study highlights the importance of considering patient-specific PV flow split variations when assessing LA hemodynamics and identifying patients at increased risk for thrombosis and stroke.
Ocular following responses of the marmoset monkey are dependent on post-saccadic delay, spatiotemporal frequency and saccade direction
Authors: Ken Yip Hoi Ming , Allison-Walker Timothy John , Cloherty Shaun Liam , Hagan Maureen Ann , Chiang Price Nicholas Seow 
Published: March 2023

AbstractOcular following is a short-latency, reflexive eye movement that tracks wide-field visual motion. It has been studied extensively in humans and macaques and is an appealing behaviour for studying sensory-motor transformations in the brain due to its rapidity and rigidity. We explored ocular following in the marmoset, an emerging model in neuroscience because their lissencephalic brain allows direct access to most cortical areas for imaging and electrophysiological recordings. In three experiments, we tested ocular following responses in three adult marmosets. First, we varied the gap between saccade end and stimulus motion onset (post-saccadic delay), from 10 to 300 ms. As in other species, tracking had shorter onset latencies and higher eye speeds with shorter post-saccadic delays. Second, using sine-wave grating stimuli we explored the dependence of eye speed on spatiotemporal frequency. The highest eye speed was evoked at ∼16 Hz and ∼0.16 cycles per degree (cpd), however, the highest gain was elicited at ∼1.6 Hz and ∼1.2 cpd. The highest eye speed for each spatial frequency was observed at a different temporal frequency, but this interdependence was not consistent with complete speed tuning of the ocular following response. Finally, we found the highest eye speeds when saccade and stimulus motion directions were congruent, although latencies were unaffected by direction congruence. Our results showed comparable ocular following in marmosets, humans and macaques, despite over an order of magnitude variation in body and eye size across species. This characterization will help future studies examining the neural basis of sensory-motor transformations.New & NoteworthyPrevious ocular following studies focused on humans and macaques. We examined the properties of ocular following responses in marmosets in three experiments, in which post-saccadic delay, spatial-temporal frequency of stimuli and congruency of saccade and motion directions were manipulated. We have demonstrated short-latency ocular following in marmosets, and discuss the similarities across three species that vary markedly in eye and head size. Our findings will help future studies examining the neural mechanism of sensory-motor transformations.
Structure-function relationships underpin disulfide loop cleavage-dependent activation ofLegionella pneumophilalysophosholipase A PlaA
Authors: Hiller Miriam , Diwo Maurice , Wamp Sabrina , Gutsmann Thomas , Lang Christina , Blankenfeldt Wulf , Flieger Antje 
Published: March 2023

AbstractLegionella pneumophila,the causative agent of a life-threatening pneumonia, intracellularly replicates in a specialized compartment in lung macrophages, theLegionella-containing vacuole (LCV). Secreted proteins of the pathogen govern important steps in the intracellular life cycle including bacterial egress. Among these is the type II secreted PlaA which, together with PlaC and PlaD, belongs to the GDSL phospholipase family found inL. pneumophila. PlaA shows lysophospholipase A (LPLA) activity which increases after secretion and subsequent processing by the zinc metalloproteinase ProA at residue E266/L267 located within a disulfide loop. Activity of PlaA contributes to the destabilization of the LCV in the absence of the type IVB-secreted effector SdhA. We here present the 3D structure of PlaA which shows a typical α/β hydrolase fold and reveals that the uncleaved disulfide loop forms a lid structure covering the catalytic triad S30/D278/H282. This leads to reduction of both substrate access and membrane interaction before activation; however, the catalytic and membrane interaction site gets more accessible when the disulfide loop is processed. After structural modelling, a similar activation process is suggested for the GDSL hydrolase PlaC, but not for PlaD. Furthermore, the size of the PlaA substrate binding site indicated preference towards phospholipids comprising ~16 carbon fatty acid residues which was verified by lipid hydrolysis, suggesting a molecular ruler mechanism. Indeed, mutational analysis changed the substrate profile with respect to fatty acid chain length. In conclusion, our analysis revealed the structural basis for the regulated activation and substrate preference of PlaA.