bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stop the Smudge: A Novel Solution to Loss of Vision During Laparoscopic Colorectal Surgery
Authors: Ozgur Ilker , Liska David , Valente Michael A. , Steele Scott R. , Gorgun Emre 
Published: August 2022

Background:
An obscured vision of surgical field during laparoscopic surgery is inconvenient. Several temporary methods were described as solutions to loss of vision, and common practice is scope removal, cleaning, and heating. A lately developed and introduced device claims continuous clear vision during laparoscopic surgery. This study aims to present our initial experience with the device during laparoscopic colorectal surgery.

Materials and Methods:
We have included medical records of all patients scheduled for laparoscopic colorectal surgery with the device between March and August 2021 at Cleveland Clinic. Patient demographics, surgery type and time, the number of loss of vision events were recorded.

Results:
Fifteen patients underwent laparoscopic colorectal surgery during the study period. The median age was 42 (range: 25 to 86) years, and 10 (66%) were female. The median surgery time was 127 (range: 67 to 240) minutes, and the median loss of vision event number was 3 (1 to 6) per surgery. There was no need for laparoscope removal during any of the surgeries. All surgeries were completed without any intraoperative complications.

Conclusion:
The novel system, provides clear vision during laparoscopic colorectal surgery with no need of scope removal for loss of vision events. The system provides removal of particulate gathering on the tip of the scope.
Bergenin has neuroprotective effects in mice with ischemic stroke through antioxidative stress and anti-inflammation via regulating Sirt1/FOXO3a/NF-κB signaling
Authors: Zhang Xuemei , Zhang Fang , Yao Fenfen , Wang Peng , Xiong Qun , Neng Penghui 
Published: September 2022

Objective
Bergenin (BGN) is a C-glycoside of 4-O-methylgallic acid with anti-inflammatory, antioxidant, and tissue-repairing abilities. Here, we probed the roles and mechanisms of BGN in ischemic stroke-mediated cerebral injury.

Methods
The middle cerebral artery occlusion (MCAO) model was established in mice, which were injected intraperitoneally with varying concentrations of BGN (10, 20, and 40 mg/kg). The modified neurological severity score (mNSS) and the water maze experiment were adopted to evaluate mice’s neural functions (movement and memory). The brain edema was assessed by the dry and wet method. TdT-mediated dUTP nick end labeling (TUNEL)-labeled apoptotic neurons and Iba1-labeled microglia in the cortex were measured by immunohistochemistry (IHC). Quantitative reverse transcription-PCR and ELISA were implemented to determine the expression of inflammatory cytokines (TNFα, IL-1β, and IL-6), neurotrophic factors (BDNF and VEGF), and oxidative stress factors (SOD and MDA) in brain tissues. The profiles of Sirt1, FOXO3a, Nrf2, NF-κB, and STAT6 in brain tissues were checked by western blot.

Results
BGN significantly improved MCAO mice’s cognitive, learning, and motor functions, reduced brain edema, hampered the production of inflammatory factors and oxidative stress mediators, and suppressed neuronal apoptosis. Additionally, BGN dampened the expression of proinflammatory cytokines and upregulated neurotrophic factors and oxidative stress factors in ischemic brain tissues of MCAO mice. Meanwhile, BGN reduced the expression of inflammatory cytokines and oxidative stressors in oxygen-glucose deprivation/reoxygenation-induced BV2 microglia. Further mechanistic studies revealed that BGN concentration dependently elevated the profiles of Sirt1, FOXO3a, STAT6, and Nrf2, and abated the NF-κB phosphorylation.

Conclusion
BGN protects against ischemic stroke in mice by boosting the Sirt1/FOXO3a pathway, suggesting its potential as a therapeutic agent for ischemic stroke.
Development and testing of a polygenic risk score for breast cancer aggressiveness
Authors: Shieh Yiwey , Roger Jacquelyn , Yau Christina , Wolf Denise M. , Hirst Gillian L. , Swigart Lamorna Brown , Huntsman Scott , Hu Donglei , Nierenberg Jovia L. , Middha Pooja , Heise Rachel S. , Shi Yushu , Kachuri Linda , Zhu Qianqian , Yao Song , Ambrosone Christine B. , Kwan Marilyn L. , Caan Bette J. , Witte John S. , Kushi Lawrence H. , van ‘T Veer Laura , Esserman Laura J. , Ziv Elad 
Published: September 2022

AbstractAggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a novel PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature. Using 2,363 breast cancers with tumor gene expression data and single nucleotide polymorphism (SNP) genotypes, we examined the associations between ROR-P and known breast cancer susceptibility SNPs using linear regression models. We constructed PRSs based on varying p-value thresholds and selected the optimal PRS based on model r2in 10-fold cross-validation. We then used Cox proportional hazards regression to test the ROR-P PRS’s association with breast cancer-specific survival in two independent cohorts totaling 10,196 breast cancers and 785 events. In meta-analysis of these cohorts, higher ROR-P PRS was associated with worse survival, HR per SD = 1.13 (95% CI 1.05-1.21, p=0.001). The ROR-P PRS had a similar magnitude of effect on survival as a comparator PRS for estrogen receptor (ER)-negative versus positive cancer risk (PRSER-/ER+).Furthermore, its effect was minimally attenuated when adjusted for PRSER-/ER+, suggesting that the ROR-P PRS provides additional prognostic information beyond ER status. In summary, we used a novel approach based on integrated analysis of germline SNP and tumor gene expression data to construct a PRS associated with aggressive tumor biology and worse survival. These findings could potentially enhance risk stratification for breast cancer screening and prevention.
A Joint Compartmental Model for The Co-infection of SARS-CoV-2 and Influenza
Authors: Zafarnejad Reyhaneh , Griffin Paul M. , Ventresca Mario 
Published: September 2022

AbstractCo-infection of COVID-19 and other respiratory pathogens, including influenza virus family, has been of importance since the beginning of the recent pandemic. As the upcoming flu season arrives in countries with ongoing COVID-19 epidemic, the need for preventive policy actions becomes more critical. We present a joint compartmental SEIRS-SIRS model for the co-circulation of SARS-CoV-2 and influenza and discuss the characteristics of the model, such as the basic reproduction number (R0) and cases of death and recovery. We implemented the model using 2020 to early 2021 data derived from global healthcare organizations and studied the impact of interventions and policy actions such as vaccination, quarantine, and public education. The VENSIM simulation of the model resulted in R0 = 7.5, which is higher than what was reported for the COVID-19 pandemic. Vaccination against COVID-19 dramatically slowed its spread and the co-infection of both diseases significantly, while other types of interventions had a limited impact on the co-dynamics of the diseases given our assumptions. These findings can help provide guidance as to which preventive policies would be most effective at the time of concurrent epidemics, and contributes to the literature as a novel model to simulate and analyze the co-circulation of respiratory pathogens in a compartmental setting that can further be used to study the co-infection of COVID-19 or similar respiratory infections with other diseases.
Social health and change in cognitive capability among older adults: findings from four European longitudinal studies
Authors: Maddock Jane , Gallo Federico , Wolters Frank J , Stafford Jean , Marseglia Anna , Dekhtyar Serhiy , Lenart-Bugla Marta , Verspoor Eline , Perry Marieke , Samtani Suraj , Vernooij-Dassen Myrra , Wolf-Ostermann Karin , Melis Rene , Brodaty Henry , Ikram Mohammad Arfan , Welmer Anna-Karin , Davis Daniel , Ploubidis George B , Richards Marcus , Patalay Praveetha 
Published: September 2022

AbstractIntroductionIn this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies.MethodsWe applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline.ResultsPooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (≥6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous.ConclusionOverall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any interventions.
Persistence of Pulmonary Hypertension in Patients undergoing Ventricular Assist Devices and Orthotopic Heart Transplantation
Authors: Rajaratnam Arun , El-Swais Ameen , McTiernan Charles , Thoma Floyd W. , Baghal Moaaz O. , Raffensperger Kristen , Chang Chung-Chou H. , Hickey Gavin W. , Shah Faraaz A. , Ghouleh Imad Al 
Published: September 2022

AbstractBackgroundPulmonary hypertension (PH) is common in advanced heart failure which exhibits short-term improvement after left ventricular assist device (VAD) implantation or orthotopic heart transplantation (OHT), but long-term effects remain unknown. This study evaluated PH persistence after VAD as destination therapy (VAD-DT), bridge to transplant (VAD-BTT), or OHT-alone.MethodsA retrospective review of patients who underwent VAD-DT (n=164), VAD-BTT (n=111), or OHT-alone (n= 138) at a single tertiary-care center. Right heart catheterization (RHC) data was collected pre-, post-intervention (VAD and/or OHT), and 1-year from final intervention (latest-RHC) to evaluate the longitudinal hemodynamic course of right ventricular (RV) function and PH. PH (Group-II and Group-I) definitions were adapted from expert guidelines.ResultsAll groups showed significant improvements in mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO), and pulmonary vascular resistance (PVR) at each RHC with greatest improvement at post-intervention RHC (Post-VAD or Post-OHT). PH proportion reduced from 98% to 26% in VAD-BTT, 92% to 49% VAD-DT, and 76% to 28% from pre-intervention to latest-RHC. At latest-RHC mPAP remained elevated in all groups despite normalization of PAWP and PVR. VAD-supported patients exhibited suppressed pulmonary artery pulsatility index (PaPi< 3.7) with improvement only post-transplant at latest-RHC alongside improved right atrial pressures (RAP). Furthermore, post-transplant with PH at latest-RHC (n=60) exhibited lower survival (HR: 2.1 [95%CI: 1.3-3.4], p<0.001).ConclusionDespite an overall significant improvement in pulmonary pressures and PH proportion, a notable subset of patients exhibited residual RV derangements and PH persistence post-intervention. This post-intervention PH impacted post-transplant survival.Condensed AbstractThis study evaluates the longitudinal hemodynamic course of right ventricular (RV) function associated with heart-failure-related Pulmonary Hypertension (PH) and the impact of advanced interventions such as ventricular assist device and/or orthotopic heart transplant on PH persistence. Patients undergoing advanced interventions exhibit differences in PH prevalence which are dependent on the intervention received. Our results highlight despite an overall improvement in pulmonary pressures and PH, a notable number of patients exhibit RV dysfunction consistent with persistent PH. Furthermore, the persistence of PH after successful cardiac transplantation in a subset of patients continues to impact mortality in the long-term.
Alcohol Intake Differentiates AD and LATE: A Telltale Lifestyle from Two Large-Scale Datasets
Authors: Wu Xinxing , Peng Chong , Nelson Peter T. , Cheng Qiang 
Published: September 2022

AbstractAlzheimer’s disease (AD), as a progressive brain disease, affects cognition, memory, and behavior. Similarly, limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined common neurodegenerative disease that mimics the clinical symptoms of AD. At present, the risk factors implicated in LATE and those distinguishing LATE from AD are largely unknown. We leveraged an integrated feature selection-based algorithmic approach, to identify important factors differentiating subjects with LATE and/or AD from Control on significantly imbalanced data. We analyzed two datasets ROSMAP and NACC and discovered that alcohol consumption was a top lifestyle and environmental factor linked with LATE and AD and their associations were differential. In particular, we identified a specific subpopulation consisting of APOE e4 carriers. We found that, for this subpopulation, light-to-moderate alcohol intake was a protective factor against both AD and LATE, but its protective role against AD appeared stronger than LATE. The codes for our algorithms are available at https://github.com/xinxingwu-uk/PFV.
Folate receptor targeted nanoparticles containing niraparib and doxorubicin for treatment of high grade serous ovarian cancer
Authors: Wang Lucy , Evans James C. , Ahmed Lubabah , Allen Christine 
Published: September 2022

AbstractCombination chemotherapy is an established approach used to manage toxicities while eliciting an enhanced therapeutic response. Delivery of combinations of drugs in specific molar ratios has been considered a means to achieve synergistic effects resulting in improvements in efficacy while minimizing dose related adverse drug reactions.The benefits of this approach have been realized with the FDA approval of Vyxeos®, the first liposome formulation to deliver a synergistic drug combination leading to improved overall survival against standard of care. In the current study, we demonstrate the synergistic potential of the PARP inhibitor niraparib and doxorubicin for the treatment of ovarian cancer. Through in vitro screening in a panel of ovarian cancer cell lines, we find that niraparib and doxorubicin demonstrate consistent synergy/additivity at the majority of evaluated molar ratio combinations.Further to these findings, we report formulation of a nanoparticle encapsulating our identified synergistic combination. We describe a rational design process to achieve highly stable liposomes that are targeted with folate to folate-receptor-alpha, which is known to be overexpressed on the surface of ovarian cancer cells. With this approach, we aim to achieve targeted delivery of niraparib and doxorubicin at a pre-determined synergistic molar ratio via increased receptor-mediated endocytosis.Graphical Abstract
Digital system augmented by artificial intelligence to interpret bone marrow samples for hematological disease diagnosis
Authors: Bermejo-Peláez David , Charro Sandra Rueda , Roa María García , Trelles-Martínez Roberto , Bobes-Fernández Alejandro , Soto Marta Hidalgo , García-Vicente Roberto , Morales María Luz , Rodríguez-García Alba , Ortiz-Ruiz Alejandra , Sánchez Alberto Blanco , Urbina Adriana Mousa , Álamo Elisa , Lin Lin , Dacal Elena , Cuadrado Daniel , Postigo María , Vladimirov Alexander , Garcia-Villena Jaime , Santos Andrés , Ledesma-Carbayo Maria Jesús , Díaz Rosa Ayala , Martínez-López Joaquín , Linares María , Luengo-Oroz Miguel 
Published: September 2022

AbstractAnalysis of bone marrow aspirates (BMA) is an essential step in the diagnosis of hematological disorders. This analysis is usually performed based on visual examination of the samples under a conventional optical microscope, which involves a labor-intensive process, limited by clinical experience and subject to high observer variability. In this work, we present a comprehensive digital system that enables BMA analysis for cell type counting and differentiation in an efficient and objective manner. This system not only provides an accessible and simple method to digitize, store and analyze BMA samples remotely, but is also supported by an artificial intelligence (AI) pipeline that accelerates the differential cell counting (DCC) process and reduces inter-observer variability. It has been designed to integrate AI algorithms with the daily clinical routine and can be used in any regular hospital workflow.
Structural basis for antagonism of the ubiquitin ligase BIRC6 by SMAC
Authors: Dietz Larissa , Ellison Cara J. , Riechmann Carlos , Cassidy C. Keith , Felfoldi F. Daniel , Pinto-Fernández Adán , Kessler Benedikt M. , Elliott Paul R. 
Published: September 2022

ABSTRACTApoptosis, a form of genetically programmed cell death, can be triggered by either internal or external signals ultimately activating caspases, a family of proteases1. Certain members of the inhibitors of apoptosis (IAP) family are sentinel proteins preventing untimely cell death by inhibiting caspases. IAPs are in turn regulated by antagonists including second mitochondria-derived activator of caspase (SMAC). Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP, possesses dual E2/E3 ubiquitin ligase activity and is implicated in apoptosis via caspase inhibition2–7. How this is achieved remains unknown. Here we show BIRC6 directly restricts activated caspase-3, and ubiquitinates activated caspases-3, −7 and −9 working exclusively with the non-canonical E1, UBA6. Importantly, we show SMAC supresses both mechanisms. Cryo-electron microscopy (cryo-EM) structures of BIRC6 alone and in complex with SMAC reveal BIRC6 exists as an anti-parallel dimer with a substrate-binding module juxtaposed to the catalytic domain at each end, and we identify multiple highly conserved unannotated domains important for architecture and function. Through our structural, biochemical and biophysical findings, we discover SMAC engages BIRC6 at multiple sites resulting in a sub-nanomolar affinity enabling SMAC to competitively displace caspases, thus antagonising BIRC6-mediated caspase inhibition.
Asymmetric horseshoe-like assembly of peroxisomal Yeast Oxalyl-CoA synthetase
Authors: Bürgi Jérôme , Lill Pascal , Giannopoulou Evdokia-Anastasia , Jeffries Cy M. , Chojnowski Grzegorz , Raunser Stefan , Gatsogiannis Christos , Wilmanns Matthias 
Published: September 2022

ABSTRACTOxalyl-CoA synthetase from Saccharomyces cerevisiae is one of the most abundant peroxisomal protein in yeast and hence has become a model to study peroxisomal translocation. It contains a C-terminal Peroxisome Targeting Signal 1, which however is partly dispensable, suggesting additional receptor bindings sites. To unravel any additional features that may contribute to its capacity to be recognized as peroxisomal target, we determined its assembly and overall architecture by an integrated structural biology approach, including X-ray crystallography, single particle cryo-electron microscopy and small angle X-ray scattering. Surprisingly, it assembles into mixture of concentration-dependent dimers, tetramers and hexamers by dimer self-association. Hexameric particles form an unprecedented asymmetric horseshoe-like arrangement, which considerably differs from symmetric hexameric assembly found in many other protein structures. A single mutation within the self-association interface is sufficient to abolish any higher-level oligomerization, resulting in homogenous dimeric assembly. The small C-terminal domain of yeast Oxalyl-CoA synthetase is connected by a partly flexible hinge with the large N-terminal domain, which provides the sole basis for oligomeric assembly. Our data provide a basis to mechanistically study peroxisomal translocation of this target.
A Bayesian approach to estimate the probability of resistance to bedaquiline in the presence of a genomic variant
Authors: Anlay Degefaye Zelalem , Rivière Emmanuel , Trang Tu Pham Hien , Abrams Steven , Van Rie Annelies 
Published: August 2022

ABSTRACTBackgroundBedaquiline is a core drug for treatment of rifampicin-resistant tuberculosis. Few genomic variants have been statistically associated with bedaquiline resistance. Alternative approaches for determining the genotypic-phenotypic association are needed to guide clinical care.MethodsUsing published phenotype data for variants inRv0678, atpE, pepQandRv1979cgenes in 756Mycobacterium tuberculosisisolates and survey data of the opinion of 33 experts, we applied Bayesian methods to estimate the posterior probability of bedaquiline resistance and corresponding 95% credible intervals.ResultsExperts agreed on the role ofRv0678, andatpE, were uncertain about the role ofpepQandRv1979cvariants and overestimated the probability of bedaquiline resistance for most variant types, resulting in lower posterior probabilities compared to prior estimates. The posterior median probability of bedaquiline resistance was low for synonymous mutations inatpE(0.1%) andRv0678(3.3%), high for missense mutations inatpE(60.8%) and nonsense mutations inRv0678(55.1%), relatively low for missense (31.5%) mutations and frameshift (30.0%) inRv0678and low for missense mutations inpepQ(2.6%) andRv1979c(2.9%), but 95% credible intervals were wide.ConclusionsBayesian probability estimates of bedaquiline resistance given the presence of a specific mutation could be useful for clinical decision-making as it presents interpretable probabilities compared to standard odds ratios. For a newly emerging variant, the probability of resistance for the variant type and gene can still be used to guide clinical decision-making. Future studies should investigate the feasibility of using Bayesian probabilities for bedaquiline resistance in clinical practice.