bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Platysma Prominence: A Randomized Phase 2 Dose-Ranging Study
Authors: Rohrich Rod J. , Bertucci Vince , Dayan Steven , Jones Derek , Solish Nowell , Rivers Jason K. , Weiss Robert A. , Muhn Channy Y. , Harutunian Christy , Park Grace S. , Shimoga Sandhya , Lee Elisabeth , Tong Warren 
Published: April 2024

Background:
With aging, repetitive contraction of the platysma leads to an increase in platysma prominence (PP), characterized by the accentuation of vertical neck bands and blunting of the jawline contour.

Methods:
This multicenter, double-blind, phase 2 study evaluated onabotulinumtoxinA treatment in adults with moderate to severe PP. Participants were randomized to receive 1 treatment of onabotulinumtoxinA low dose (LD), onabotulinumtoxinA high dose (HD), or placebo, and were followed up for 4 months. Efficacy end points were achievement of a 1 grade or greater improvement on both the left and right sides at day 14 at maximum contraction as assessed by the investigator (primary) or by participants (secondary) using validated scales. Safety was evaluated throughout.

Results:
Participants in the modified intent-to-treat population (n = 164) had a mean age of 50 years; 95.1% were women and 93.9% were White. The primary end point was met for both onabotulinumtoxinA groups, with investigator-assessed 1 grade or greater improvement in 77.8% (LD) and 88.2% (HD) versus 12.0% (placebo) of participants on day 14 (P < 0.0001 versus placebo). Based on participant self-assessment, 75.9% (LD) and 88.2% (HD) versus 18.0% (placebo) achieved 1 grade or greater improvement on day 14 (P < 0.0001 versus placebo). Most treatment-related adverse events were procedure-related, transient, and mild in severity. The most frequent onabotulinumtoxinA-related adverse event was neck muscle weakness, reported in the HD group.

Conclusion:
OnabotulinumtoxinA was effective in improving the appearance of PP based on both investigators’ and participants’ ratings. Treatment was well tolerated.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, I.
Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol
Authors: Piemonti Lorenzo , Melzi Raffella , Aleotti Francesca , Capretti Giovanni , Nano Rita , Mercalli Alessia , Magistretti Paola , Caldara Rossana , Pecorelli Nicolò , Catarinella Davide , Gremizzi Chiara , Gavazzi Francesca , De Cobelli Francesco , Poretti Dario , Falconi Massimo , Zerbi Alessandro , Balzano Gianpaolo 
Published: April 2024

Background.
Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis.

Methods.
This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes.

Results.
Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms.

Conclusions.
These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.
Joint Gray and White Matter Networks Predict Mindfulness and Mind Wandering Traits: A Data Fusion Machine Learning Approach
Authors: Chang Minah , Sorella Sara , Crescentini Cristiano , Grecucci Alessandro 
Published: April 2024

AbstractMind wandering is a ubiquitous part of our normal cognition and daily lives, with people reporting that their mind wanders during 25-50% of their waking hours. Studies suggest that mind wandering shares an inverse relationship with mindfulness skills. Our aim was to expand this evidence directly by investigating the mediating effect among mindfulness, mind wandering, and brain features. The main goal of our study in particular was to find out which morphometric brain features are associated with mindfulness and mind wandering, and to investigate how mindfulness mediates deliberate and spontaneous mind wandering in terms of these associated brain components. GM and WM MRI scans of 76 individuals and self-reported questionnaires were included in the analysis. We predicted that specific gray matter (GM) and white matter (WM) networks would also influence deliberate and spontaneous mind wandering tendencies with mindfulness as a mediator. We found that GM and WM networks including structures that have been consistently linked to mindfulness, such as the cingulate, the insula, the basal ganglia and fronto-parietal attentive regions, exert direct effects on mindfulness, and deliberate and spontaneous mind wandering. We also found an indirect mediating effect of the FFMQ facetacting with awarenesson spontaneous mind wandering in terms of increased and decreased GM volume concentrations. This study elicited the link between mind wandering and mindfulness and expands our knowledge on the neural bases of these two psychological constructs.
Spatio-temporal transformers for decoding neural movement control
Authors: Candelori Benedetta , Bardella Giampiero , Spinelli Indro , Ramawat Surabhi , Pani Pierpaolo , Ferraina Stefano , Scardapane Simone 
Published: April 2024

AbstractDeep learning tools applied to high-resolution neurophysiological data have significantly progressed, offering enhanced decoding, real-time processing, and readability for practical applications. However, the design of artificial neural networks to analyze neural activity remains a challenge, requiring a delicate balance between efficiency in low-data regimes and the interpretability of the results. To this end, we introduce a novel specialized transformer architecture to analyze single-neuron spiking activity. We test our model on multi electrodes recordings from the dorsal premotor cortex (PMd) of non-human primates while performing a motor inhibition task. The proposed architecture provides a very early prediction of the correct movement direction - no later than 230ms after the Go signal presentation across animals - and can accurately forecast whether the movement will be generated or withheld before a Stop signal, unattended, is actually presented. We also analyze the internal dynamics of the model by computing the predicted correlations between time steps and between neurons at successive layers of the architecture. We find that their evolution mirrors previous theoretical analyses. Overall, our framework provides a comprehensive use case for the practical implementation of deep learning tools in motor control research.
Axon demyelination and degeneration in a zebrafishspastizinmodel of hereditary spastic paraplegia
Authors: Garg Vranda , Heyer Luisa , Ruhwedel Torben , André Selina , Kracht Gudrun , Scholz Patricia , Ischebeck Till , Werner Hauke B. , Dullin Christian , Engelmann Jacob , Möbius Wiebke , Dosch Roland , Göpfert Martin C. , Geurten Bart R.H. 
Published: April 2024

AbstractHereditary spastic paraplegias (HSPs) are a diverse set of neurological disorders characterized by progressive spasticity and weakness in the lower limbs caused by damage to the axons of the corticospinal tract. More than 88 genetic mutations have been associated with HSP, yet the mechanisms underlying these disorders are little understood. We studied the pathogenesis of one form of HSP known as spastic paraplegia 15 (SPG15). This disorder is caused by mutations in theZFYVE26gene, which codes for a protein called SPASTIZIN. We show that, in zebrafish, the significant reduction of Spastizin caused degeneration of Mauthner (M)-cells. M-cell degeneration is associated with axon demyelination in the spinal cord and impaired locomotion in thespastizinmutants. Our findings reveal that the mutation not only compromises axonal integrity but also affects the structural molecules of the myelin sheath, laying the foundation for degeneration and advancing our understanding of the intricate mechanisms underlying HSPs.
Prevalence of non-tuberculous mycobacteria among people presumed to have tuberculosis, positive for acid-fast bacilli in Mali
Authors: Cisse Aissata Boubakar , Dean Anna S. , Van Deun Armand , Keysers Jelle , De Rijke Willem-Bram , Gumusboga Mourad , Samake Hawa , Arama Seydou , Diarra Bassirou , Djilla Ibrahim , Coulibaly Fatoumata N. , Simpara Hawa , Berthe Mamadou , Ouattara Khadidia , Toloba Yacouba , Guindo Ibrehima , de Jong Bouke , Rigouts Leen 
Published: April 2024

AbstractBackgroundNon-tuberculosis mycobacteria (NTMs) are environmental agents that can cause opportunistic pulmonary disease in humans and animals which is often misdiagnosed as tuberculosis (TB). In this study, we describe the cases of NTMs identified during the first national anti-TB drug-resistance survey conducted in Mali, and associated risk factors.MethodsSputum was collected from people presenting for pulmonary TB diagnosis, from April to December 2019, regardless of age. Microscopy-positive patients were enrolled and were tested by GeneXpert MTB/RIF. Cases that tested negative for theMycobacterium tuberculosiscomplex (MTBc) were tested for presence of mycobacteria by amplification of the IS6110and 16SrRNA genes through double quantitative real-time PCR, followed by nested PCR and Sanger sequencing of the IS6110-negative samples for NTM species identification.ResultsA total of 1,418 sputum smear-positive patients were enrolled, including 1,199 new cases, 211 previously treated cases and 8 whose previous treatment history was unknown. Based on the results of GeneXpert MTB/RIF and in-house PCR methods, 1331 (93.9%) patients were positive for MTBc, 48 (3.4%) for NTMs and for 39 (2.7%) no species identification was possible. Advanced age (65 and over) (OR 8.8, p=0.001) and previous TB treatment (OR 3.4 and p=0.016) were the risk factors statistically associated with NTM detection.M. avium complex(MAC) was the predominant NTM species, detected in 20 cases.ConclusionDetection of NTMs in people presumed to have TB is an ongoing challenge, confounding correct TB diagnosis. Concomitant use of microscopy and GeneXpert testing among at-risk individuals could lessen confusion.
Exploring Factors Influencing Adherence to HIV Medication among patients using Community Pharmacies and Public Hospital: A Qualitative Study
Authors: Olaleye Odunayo Betty , Ilesanmi Olayinka Stephen 
Published: April 2024

AbstractIntroductionHIV/AIDS is a major global health emergency as it is estimated that close to 40 million people live with HIV/AIDS, among which the majority are adults. Despite the availability of ARVs at community, secondary, and tertiary health facilities in Nigeria, adherence rates remain low. This study conducted in Ibadan, Nigeria, investigated factors influencing adherence to antiretroviral therapy (ART) among HIV patients.MethodsThe research employed a cross-sectional approach, utilizing qualitative techniques, including in-depth interviews (IDI) with patients and key informant interviews (KII) with healthcare providers and pharmacists. The target population consisted of HIV patients receiving ART at the Community Pharmacies and Public Hospital University in Ibadan. Data saturation determined sample sizes for the interviews.ResultsIn the in-depth interviews, two primary themes emerged from the findings: “Socio-economic factors influencing adherence” and “Factors related to the process of care.” Socio-economic factors encompassed issues such as transportation costs, societal pressure, food costs, advice from third parties, and religious reasons. These factors were further categorized into economic reasons and societal pressure/misinformation, shedding light on patients’ challenges and choices. Factors related to the process of care included the cost of medication, side effects, drug-drug interactions, the quantity and duration of drug use, and discontinuation after feeling better.Key informant interviews with healthcare providers and pharmacists revealed insights into compliance by gender, financial constraints, and treatment-related factors such as side effects, drug interactions, and medication volume. Socio Cultural and religious factors, including advice from third parties, stigmatization, disclosure of status to partners, social support, and religious beliefs, played significant roles in influencing patients’ adherence.ConclusionThese findings shed light on the complex interplay of factors affecting ART adherence and highlight the importance of considering economic, social, and medical aspects when designing interventions to improve adherence in HIV care. The study’s findings hold implications for healthcare programs and interventions aimed at enhancing the quality of care and support for HIV patients, particularly in resource-limited settings like Southwestern Nigeria.
Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations
Authors: Selvavinayagam Sivaprakasam T. , Sankar Sathish , Yong Yean K. , Murugesan Amudhan , Suvaithenamudhan Suvaiyarasan , Hemashree Kannan , Rajeshkumar Manivannan , Kumaresan Anandhazhvar , Pandey Ramendra P. , Shanmugam Saravanan , Arthydevi Parthiban , Kumar Masilamani S. , Gopalan Natarajan , Kannan Meganathan , Cheedarla Narayanaiah , Tan Hong Y. , Zhang Ying , Larsson Marie , Balakrishnan Pachamuthu , Velu Vijayakumar , Byrareddy Siddappa N. , Shankar Esaki M. , Raju Sivadoss 
Published: April 2024

ABSTRACTIn December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.
How many microbial species are there in human tumor and normal tissues?
Authors: Ma Zhanshan (Sam) 
Published: April 2024

AbstractThe study of tissue microbiomes is a recent endeavor in human microbiome research, particularly in the area of blood microbiomes. This is primarily due to their low biomass, which presents inadvertent operational contamination as a significant experimental obstacle. The critical role of the tissue microbiomes in cancer development has brought this topic to the forefront of cancer research. However, a fundamental question regarding the potential biodiversity, as stated in the title, has not been addressed to our knowledge. In this study, we estimate the potential microbial diversity or “dark” biodiversity in human tumor and normal tissues using the Diversify-Area Relationship (DAR) method (Ma 2018, 2019) based on large datasets from TCGA (The Cancer Genome Atlas) database (Pooreet al. 2021). We found that the total species richness (number), typical species equivalents (number), and dominant species equivalents (number) of tumor tissues are approximately 1948, 36, and 22, respectively. Among the total species richness, the proportions of archaea, bacteria, and viruses are about 3%-5%, 78%-79%, and 17%-18%, respectively. Moreover, the tissue species richness is approximately 12.5% of skin microbiomes, and 25% of gut microbiomes. We also found that tumor growth does not significantly influence the global or pan-tumor scale diversity, which means that the previous numbers also represent the potential microbial diversity of human tissues, including blood. On a local or single cancer-type scale, tumors may influence the potential diversity in approximately 5% of cases. We hypothesize that, globally, local diversity variations would offset each other.Lay SummaryThis study focused on microbiomes - the tiny microbes that live in our tissues, especially blood. Studying them is challenging due to their low biomass and risk of contamination. Microbiomes may play a key role in cancer, but their diversity within tissues remains unclear. Using diversity-area relationship modeling with data from “The Cancer Genome Atlas” database, we estimated the potential microbial diversity of human tumor and normal tissues. We found approximately 1,948 microbial species in tumors, comprising archaea (5%), bacteria (78%) and viruses (17%). However, dominant or common microbial species number only about two to three dozen. Tissue microbe diversity was 12.5% of that found in skin microbiomes and 25% of gut microbiomes. Tumor growth did not significantly impact overall diversity. Therefore, the previous diversity numbers also represent the microbiome diversity of general human tissues and blood. However, some cancer types may affect it locally. While local diversity changes can occur, globally these variations between tissues likely balance out.
Localised Astrocyte Ca2+ Activity Regulates Neurovascular Coupling Responses to Active Sensing
Authors: Stelzner Jakob Akbar , Krogsgaard Aske , Kulkoviene Gabriele , Sperling Leonora , Lind Barbara Lykke 
Published: April 2024

AbstractNeurovascular coupling (NVC) ensures sufficient and targeted blood flow during increased neuronal activity. Astrocytic participation in NVC has long been debated, likely due to the intricacy of the intracellular Ca2+ fluxes and the diversity of their regulatory capacities. As astrocyte signaling changes with brain states, we focused on their involvement in voluntary sensing in freely behaving mice. We used 2-photon microscopy to record cellular and vascular activity in the whisker barrel cortex of awake head-fixed animals. The NVC initiated by volitional whisking in the resting mouse was compared to the whisking preceding locomotion and experimenter-evoked whisker deflections. We developed an analysis method to detect early, subcellular astrocytic activity and found it corresponded with neuronal and vascular responses under all three conditions. After the depletion of noradrenaline (NA), the early astrocytic Ca2+ response to volitional whisking was only moderately reduced and primarily in astrocytic processes closest to the blood vessels. Meanwhile, the dilation of 1storder capillaries was also reduced. Together, these findings demonstrate significant disruptions in the focal regulation of cerebral blood flow, potentially limiting the sustenance of activated neurons. This disruption appeared to translate into behavioral aberrations, as NA-depleted mice exhibited an extended period of exploratory whisking prior to locomotion. Remarkably, NA-depletion did not alter cellular or blood flow responses to locomotion or experimenter-evoked whisking. Our study confirms an astrocytic contribution to NVC, which is relevant during volitional sensing. It also suggests that self-directed sensory processing depends on an appropriate NVC response, which itself depends on NA and astrocyte activity.
Lipid Nanoparticle-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects
Authors: Omo-Lamai Serena , Wang Yufei , Patel Manthan N. , Essien Eno-Obong , Shen Mengwen , Majumdar Aparajeeta , Espy Carolann , Wu Jichuan , Channer Breana , Tobin Michael , Murali Shruthi , Papp Tyler E. , Maheshwari Rhea , Wang Liuqian , Chase Liam S. , Zamora Marco E. , Arral Mariah L. , Marcos-Contreras Oscar A. , Myerson Jacob W. , Hunter Christopher A. , Tsourkas Andrew , Muzykantov Vladimir , Brodsky Igor , Shin Sunny , Whitehead Kathryn A. , Gaskill Peter , Discher Dennis , Parhiz Hamideh , Brenner Jacob S. 
Published: April 2024

AbstractLipid nanoparticles (LNPs) have emerged as the dominant platform for RNA delivery, based on their success in the COVID-19 vaccines and late-stage clinical studies in other indications. However, we and others have shown that LNPs induce severe inflammation, and massively aggravate pre-existing inflammation. Here, using structure-function screening of lipids and analyses of signaling pathways, we elucidate the mechanisms of LNP-associated inflammation and demonstrate solutions. We show that LNPs’ hallmark feature, endosomal escape, which is necessary for RNA expression, also directly triggers inflammation by causing endosomal membrane damage. Large, irreparable, endosomal holes are recognized by cytosolic proteins called galectins, which bind to sugars on the inner endosomal membrane and then regulate downstream inflammation. We find that inhibition of galectins abrogates LNP-associated inflammation, bothin vitroandin vivo. We show that rapidly biodegradable ionizable lipids can preferentially create endosomal holes that are smaller in size and reparable by the endosomal sorting complex required for transport (ESCRT) pathway. Ionizable lipids producing such ESCRT-recruiting endosomal holes can produce high expression from cargo mRNA with minimal inflammation. Finally, we show that both routes to non-inflammatory LNPs, either galectin inhibition or ESCRT-recruiting ionizable lipids, are compatible with therapeutic mRNAs that ameliorate inflammation in disease models. LNPs without galectin inhibition or biodegradable ionizable lipids lead to severe exacerbation of inflammation in these models. In summary, endosomal escape induces endosomal membrane damage that can lead to inflammation. However, the inflammation can be controlled by inhibiting galectins (large hole detectors) or by using biodegradable lipids, which create smaller holes that are reparable by the ESCRT pathway. These strategies should lead to generally safer LNPs that can be used to treat inflammatory diseases.