bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elastin‐like polypeptide delivery of anti‐inflammatory peptides to the brain following ischemic stroke
Authors: Howell John Aaron , Gaouette Nicholas , Lopez Mariper , Burke Stephen P. , Perkins Eddie , Bidwell Gene L. 
Published: July 2023

AbstractInflammatory processes are activated following ischemic stroke that lead to increased tissue damage for weeks following the ischemic insult, but there are no approved therapies that target this inflammation‐induced secondary injury. Here, we report that SynB1‐ELP‐p50i, a novel protein inhibitor of the nuclear factor kappa B (NF‐κB) inflammatory cascade bound to the drug carrier elastin‐like polypeptide (ELP), decreases NF‐κB induced inflammatory cytokine production in cultured macrophages, crosses the plasma membrane and accumulates in the cytoplasm of both neurons and microglia in vitro, and accumulates at the infarct site where the blood–brain barrier (BBB) is compromised following middle cerebral artery occlusion (MCAO) in rats. Additionally, SynB1‐ELP‐p50i treatment reduces infarct volume by 11.86% compared to saline‐treated controls 24 h following MCAO. Longitudinally, SynB1‐ELP‐p50i treatment improves survival for 14 days following stroke with no effects of toxicity or peripheral organ dysfunction. These results show high potential for ELP‐delivered biologics for therapy of ischemic stroke and other central nervous system disorders and further support targeting inflammation in ischemic stroke.
Controversies and strengths of robot-assisted mastectomy
Authors: Kim Joo Heung , Toesca Antonio , Pozzi Giada , Gazzetta Guglielmo , Marrazzo Emilia , Park Hyung Seok 
Published: July 2023

Nipple-sparing mastectomy (NSM) is used to improve cosmetic outcomes while maintaining oncological safety in patients with early breast cancer; however, NSM requires a higher level of skill and workload than mastectomy and is associated with long, visible scars. Robotic surgical systems reduce surgeon workload and facilitate precise surgery. Considering the increasing support of robot-assisted NSM (RNSM), this paper aims to discuss the current controversies based on the research findings reported thus far.
There are four concerns regarding RNSM; increased cost, oncological outcomes, the level of experience and skill, and standardization. It should be noted that RNSM is not a surgery performed on all patients but rather a procedure performed on selected patients who meet specific indications. A large-scale randomized clinical trial comparing robotic and conventional NSM has recently begun in Korea; therefore, it is necessary to wait for these results for more insight into oncological outcomes. Although the level of experience and skill required for robotic mastectomy may not be easily achieved by all surgeons, the learning curve for RNSM appears manageable and can be overcome with appropriate training and practice. Training programs and standardization efforts will help improve the overall quality of RNSM.
There are some advantages to RNSM. The robotic system provides improved precision and accuracy, helping remove breast tissue more effectively. RNSM has advantages such as smaller scars, less blood loss, and a lower rate of surgical complications. Patients who undergo RNSM report better quality of life.
Molecular characteristics and prognosis of breast cancer patients with different level of HER2 positivity after adjuvant and neoadjuvant chemotherapy
Authors: Tuluhong Dilihumaer , Li Xinfang , Gao Hongyu , Zhu Yueyun , Li Qiurong , Wang Shaohua 
Published: July 2023

Purpose
HER2-low breast cancer (BC) has renewed interests of researchers worldwide. Here, we aimed to investigate the clinicopathological characteristics of patients with HER2-low, HER2-0 and HER2 ultra-low BC and make conclusion.

Methods
We collected cases of patients who were diagnosed as BC at Jingling General hospital. Immunohistochemistry was used to redefine HER2 scores. Kaplan–Meier methods and Cox proportional hazards regression analysis were used to compare survival.

Results
We found that HER2-low BC was more frequent in hormone receptor (HR)–positive BC patients and was associated with fewer T3-T4, lower breast conserving surgery rate and higher adjuvant chemotherapy rate. HER2-low BC patients had better overall survival (OS) compared to HER2-0 BC in premenopausal and stage II BC. Furthermore, HER2-0 BC patients had lower Ki-67 expression levels compared to HER2-ultra low and HER2-low BC in HR–negative BC. HER2-0 BC patients also had worse OS rate compared to those with HER2-ultra low BC in HR–positive BC. Finally, HER2-0 BC patients showed a higher pathological response rate compared to those with HER2-low BC after neoadjuvant chemotherapy.

Conclusions
These findings suggest that HER2-low BC has distinct biology and clinical features compared to HER2-0 BC, and more investigation is needed to understand the biology of HER2-ultra low BC.
Outcomes of the distal rectal cancer treatment depending on the type of sphincter-sparing surgery
Authors: Gordiichuk Prokip , Gordiichuk Mykola 
Published: July 2023

Introduction:
The increase in mid-ampullary and lower ampullary rectal cancer with disappointing treatment results requires ongoing discussion, research, and improvement of the complex treatment.

Materials and methods:
We analyzed the results of complex treatment in 442 patients with stages II–III mid-ampullary and lower ampullary rectal cancer that underwent three types of sphincter-sparing surgeries, including low anterior resection (LAR), intersphincteric resection (ISR), and abdomino-anal resection of the rectum (AAR) at the second stage of complex treatment.

Results:
There was a significant difference between groups in terms of surgery type selection based on the distance from the tumor to the dentate line. When the tumor was located at a distance of 30 mm or less from the dentate line, LAR was performed in 16.4% of cases, whereas ISR and AAR were used in 96.58 and 58.09% of cases, respectively, which is statistically significant (P<0.001). Preventive stoma was used in 78.87% of LAR, 5.9% of ISR, and 6.62% of AAR, which had a significant difference (P<0.001). In the structure of postoperative complications, a group of typical complications (ІІІ–IV) was identified for the types of operations performed. Their frequency when performing LAR was 18.2%, ISR – 7.7%, and AAR – 8.1%, which was statistically significant (P=0.003). The frequency of local recurrences, depending on the type of surgery was not statistically significant (P>0.05), but had a direct correlation with the recurrence-free survival curves. Relapse-free and overall (3 years and 5 years) survival depending on the type of sphincter-preserving surgery did not have a significant difference according to the log-rank test.

Conclusion:
The more types of surgical intervention surgeons have at their disposal, the more rational it is to select the one that will ensure the best treatment results.
Dynamic properties and the roton mode attenuation in liquid
3
He:
ab initio
study within the self-consistent method of moments
Authors: Filinov A. V. , Ara J. , Tkachenko I. M. 
Published: July 2023

The dynamic structure factor and the eigenmodes of density fluctuations in liquid
3
He are studied using a novel non-perturbative approach. This new version of the self-consistent method of moments invokes up to nine sum rules and other exact relations, the two-parameter Shannon information entropy maximization procedure, and the
ab initio
path integral Monte Carlo simulations which provide necessary reliable input information on the system static properties. Detailed analysis is performed of the collective excitations dispersion relations, the modes’ decrements and the static structure factor of
3
He at the saturated vapour pressure. The results are compared to available experimental data by Albergamo
et al.
(Albergamo
et al.
2007
Phys. Rev. Lett.
99
, 205301. (
doi:10.1103/PhysRevLett.99.205301
)) and Fåk
et al.
(Fåk
et al.
1994
J. Low Temp. Phys.
97
, 445–487. (
doi:10.1007/BF00754303
)). The theory reveals a clear signature of the roton-like feature in the particle-hole segment of the excitation spectrum with a significant reduction of the roton decrement in the wavenumber range

1.3

Å

−
1

≤
q
≤
2.2

Å

−
1

. The observed roton mode remains a well-defined collective mode even in the particle-hole band, where it is strongly damped. The existence of the roton-like mode in the bulk liquid
3
He is confirmed like in other quantum fluids. The phonon branch of the spectrum is in a reasonable agreement with the same experimental data.

This article is part of the theme issue ‘Dynamic and transient processes in warm dense matter’.
Preclinical and Human Phase 1 Studies of Aerosolized Hydroxychloroquine: Implications for Antiviral COVID-19 Therapy
Authors: Bentur Ohad S. , Hutt Richard , Brassil Donna , Kriegegr Ana C. , Bäckman Per , Charous B. Lauren , Boushey Homer , Gonda Igor , Coller Barry S. , MacArthur Robert B. 
Published: July 2023

AbstractBased on early reports of the efficacy of hydroxychloroquine sulfate (HCQS) to inhibit SARS-CoV-2 viral replication in vitro, and since severe pulmonary involvement is the major cause of COVID-19 mortality, we assessed the safety and efficacy of aerosolized HCQS (aHCQS) therapy in animals and humans. In a Phase 1 study of aHCQS in healthy volunteers, doses up to 50 mg were well tolerated and estimated epithelial lining fluid concentrations immediately after inhalation (>2,000 μM) exceeded the in vitro concentrations needed for suppression of viral replication (≥119 μM). A study in rats comparing HCQS solution administered orally (13.3 mg/kg) and by intratracheal installation (IT 0.18 mg/kg, <5% of oral dose) demonstrated that at 2 minutes, IT administration was associated with 5X higher mean hydroxychloroquine (HCQ) concentrations in the lung (IT: 49.5 ± 6.5 µg HCQ/g tissue, oral: 9.9 ± 3.4; p<0.01). A subsequent study of IT and intranasal HCQS in the Syrian hamster model of SARS-CoV-2 infection, however, failed to show clinical benefit. We conclude that aHCQS alone is unlikely to be effective for COVID-19, but based on our aHCQS pharmacokinetics and current viral entry data, adding oral HCQS to aHCQS, along with a transmembrane protease inhibitor, may improve efficacy.
Longitudinal multi-omics study reveals common etiology underlying association between plasma proteome and BMI trajectories in adolescent and young adult twins
Authors: Drouard Gabin , Hagenbeek Fiona A. , Whipp Alyce , Pool René , Hottenga Jouke Jan , Jansen Rick , Hubers Nikki , Afonin Aleksei ,   BIOS Consortium,   BBMRI-NL Metabolomics Consortium, Willemsen Gonneke , de Geus Eco J. C. , Ripatti Samuli , Pirinen Matti , Kanninen Katja M. , Boomsma Dorret I. , van Dongen Jenny , Kaprio Jaakko 
Published: July 2023

AbstractBackgroundThe influence of genetics and environment on the association of the plasma proteome with body mass index (BMI) and changes in BMI remain underexplored, and the links to other omics in these associations remain to be investigated. We characterized protein-BMI trajectory associations in adolescents and adults and how these connect to other omics layers.MethodsOur study included two cohorts of longitudinally followed twins: FinnTwin12 (N=651) and the Netherlands Twin Register (NTR) (N=665). Follow-up comprised four BMI measurements over approximately 6 (NTR: 23-27 years old) to 10 years (FinnTwin12: 12-22 years old), with omics data collected at the last BMI measurement. BMI changes were calculated using latent growth curve models. Mixed-effects models were used to quantify the associations between the abundance of 439 plasma proteins with BMI at blood sampling and changes in BMI. The sources of genetic and environmental variation underlying the protein abundances were quantified using twin models, as were the associations of proteins with BMI and BMI changes. In NTR, we investigated the association of gene expression of genes encoding proteins identified in FinnTwin12 with BMI and changes in BMI. We linked identified proteins and their coding genes to plasma metabolites and polygenic risk scores (PRS) using mixed-effect models and correlation networks.ResultsWe identified 66 and 14 proteins associated with BMI at blood sampling and changes in BMI, respectively. The average heritability of these proteins was 35%. Of the 66 BMI-protein associations, 43 and 12 showed genetic and environmental correlations, respectively, including 8 proteins showing both. Similarly, we observed 6 and 4 genetic and environmental correlations between changes in BMI and protein abundance, respectively.S100A8gene expression was associated with BMI at blood sampling, and thePRG4andCFIgenes were associated with BMI changes. Proteins showed strong connections with many metabolites and PRSs, but we observed no multi-omics connections among gene expression and other omics layers.ConclusionsAssociations between the proteome and BMI trajectories are characterized by shared genetic, environmental, and metabolic etiologies. We observed few gene-protein pairs associated with BMI or changes in BMI at the proteome and transcriptome levels.
Community Antibiotic Prescribing in Patients with COVID-19 Across Three Pandemic Waves: A Population-Based Cohort Study
Authors: Ciaccio Laura , Donnan Peter T , Parcell Benjamin J , Marwick Charis A 
Published: July 2023

AbstractBackgroundReported changes in antibiotic prescribing during the COVID-19 pandemic have focused on hospital prescribing or community population trends. Community antibiotic prescribing for individuals with COVID-19 are less well described.MethodsData covering a complete geographic population (∼800,000) were utilised. SARS-CoV-2 virus test results from February 1, 2020-March 31, 2022 were included. Anonymised data were linked to prescription data +/-28 days of the test, GP data for high-risk comorbidities, and demographic data. Multivariate binary logistic regression examined associations between patient factors and the odds of antibiotic prescription.ResultsData included 768,206 tests for 184,954 individuals, identifying 16,240 COVID-19 episodes involving 16,025 individuals. There were 3,263 antibiotic prescriptions +/-28 days for 2,385 patients. 35.6% of patients had a prescription only before the test date, 52.5% of patients after, and 11.9% before and after. Antibiotic prescribing reduced over time: 20.4% of episodes in wave one, 17.7% in wave two, and 12.0% in wave three. In multivariate logistic regression, being female (OR 1.31, 95% CI 1.19,1.45), older (OR 3.02, 95% CI 2.50, 3.68 75+ vs <25 years), having a high-risk comorbidity (OR 1.45, 95% CI 1.31, 1.61), a hospital admission +/-28 days of an episode (OR 1.58, 95% CI 1.42, 1.77), and health board region (OR 1.14, 95% CI 1.03, 1.25, board B versus A) increased the odds of receiving an antibiotic.ConclusionCommunity antibiotic prescriptions in COVID-19 episodes were uncommon in this population and likelihood was associated with patient factors. The reduction over pandemic waves may represent increased knowledge regarding COVID-19 treatment and/or evolving symptomatology.
Network analysis of the whole body kinematics in Parkinson diseases following levodopa intake
Authors: Romano Antonella , Liparoti Marianna , Minino Roberta , Polverino Arianna , Cipriano Lorenzo , Ciaramella Francesco , Carotenuto Anna , Tafuri Domenico , Sorrentino Giuseppe , Sorrentino Pierpaolo , Lopez Emahnuel Troisi 
Published: July 2023

AbstractBackgroundThree-dimensional motion analysis represents a quantitative and objective approach to assess spatio-temporal and kinematic changes in Parkinson’s disease (PD). However, these parameters, focusing on a specific body segment, provide only segmental information, discarding the complex whole-body patterns underlying the motor impairment. We aimed to assess how levodopa intake affects the whole body, large-scale kinematic network in PD.MethodsBorrowing from network theory, we used the kinectome framework by calculating the Pearson’s correlation coefficients between the time series acceleration of 21 bone markers. Then, we performed a topological analysis to evaluate the large-scale interactions between body elements. Finally, we performed a multilinear regression analysis in order to verify whether the kinectome’s topological features could predict the clinical variation before and after levodopa intake.ResultsPD patients showed lower nodal strength (i.e., lower synchronization) in the upper body in the medio-lateral acceleration while in on-state with respect to the off state (p-head=0.048; p-C7=0.032; p-T10=0.006). On the contrary, PD patients in on state displayed higher nodal strength (i.e., higher synchronization) of both elbows (right, p=0.002; left, p=0.005), wrists (right, p=0.003; left, p=0.002) and knees (right, p=0.003; left, p=0.039) in the antero-posterior acceleration. Furthermore, the predictive analysis revealed that the nodal strength variations of the arms, following levodopa intake, significantly predicted the clinical variations assessed through the UPDRS-III (R2=0.65; p=0.025).ConclusionsPD patients in the on-state showed less rigidity during walking, proportional to the UPDRS-III variation. More importantly, we showed that levodopa induces an improvement of the whole body, large-scale kinematic pattern.
Clinical Profile, Comorbidities, and Outcome of the Unvaccinated and Hospitalized for COVID-19 in Northern Brazil: Retrospective Cohort
Authors: Lúcia da Silva Ferreira Ana , Sardinha Daniele Melo , Cristina Viana de Moraes Daiane , Raimunda Rodrigues de Oliveira Maria , Carolina Frazão Viana Mayara , Cristina Oliveira Andrade Natasha , de Nazaré Soares Tamires , José de Paula Souza e Guimarães Ricardo , Nepomuceno Gondim Costa Lima Luana , Valéria Batista Lima Karla 
Published: July 2023

AbstractOver the course of the pandemic, COVID-19 affected health, the economy and quality of life in Brazil. The worst years for the country were the first and second. There were delays in vaccine purchases for political reasons at the time. The northern region of the country had a higher mortality rate compared to other regions, associated with local vulnerabilities and fragility of surveillance due to geographic and population characteristics. This study aims to investigate the clinical profile, comorbidities, and outcome of unvaccinated people hospitalized for COVID-19 in the state of Pará in 2022. Retrospective cohort epidemiological study, with data from the national epidemiological surveillance of acute and severe respiratory syndromes. Cases reported in 2022 with vaccinated yes or no field and completed doses were included. Only closed cases cure or death were included. We performed a chi-square test on categorical variables and a Mann-Whitney test on numerical variables. We compared vaccinated VS non-vaccinated; we performed the Odds Ratio in the significant variables. We used the SPSS 20.0 software. The study worked with 2,634 cases of COVID-19 hospitalized in the study period, confirmed by RT-PCR (851/32.30%) and (1,784/67.70%) rapid antigen test. The lethality was (778/29.53%), and those vaccinated with two doses were (1,473/55.90%) and those unvaccinated with no dose (1,162/44.10%). Death represents p-<0.001 (HR 1.306 - CI 1.124/1.517) higher risk of the event occurring in the unvaccinated cases, followed by male sex p-0.004 (HR 1.188 - CI 1.058/1.334).. The first cohort in Brazil and in the north of the country to evaluate the clinical profile, comorbidities, and outcome of COVID-19 in hospitalized patients in this Amazon region, which is a region characterized by local vulnerability factors unique to the other regions of Brazil, showed that the unvaccinated were males, younger, with fewer comorbidities, and that they were associated the deaths.
Defining overlooked structures reveals new associations between cortex and cognition in aging and Alzheimer’s disease
Authors: Maboudian Samira A. , Willbrand Ethan H. , Jagust William J. , Weiner Kevin S. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2023

AbstractRecent work suggests that indentations of the cerebral cortex, or sulci, may be uniquely vulnerable to atrophy in aging and Alzheimer’s disease (AD) and that posteromedial cortex (PMC) is particularly vulnerable to atrophy and pathology accumulation. However, these studies did not consider small, shallow, and variable tertiary sulci that are located in association cortices and are often associated with human-specific aspects of cognition. Here, we first manually defined 4,362 PMC sulci in 432 hemispheres in 216 participants. Tertiary sulci showed more age- and AD-related thinning than non-tertiary sulci, with the strongest effects for two newly uncovered tertiary sulci. A model-based approach relating sulcal morphology to cognition identified that a subset of these sulci were most associated with memory and executive function scores in older adults. These findings support the retrogenesis hypothesis linking brain development and aging, and provide new neuroanatomical targets for future studies of aging and AD.
Design, construction and optimization of formaldehyde growth biosensors with broad application in Biotechnology
Authors: Schann Karin , Bakker Jenny , Boinot Maximilian , Kuschel Pauline , He Hai , Nattermann Maren , Erb Tobias , Bar-Even Arren , Wenk Sebastian 
Published: July 2023

AbstractFormaldehyde is a key metabolite in natural and synthetic one-carbon metabolism as well as an important environmental toxin with high toxicity at low concentrations. To engineer efficient formaldehyde producing enzymes and to detect formaldehyde in industrial or environmental samples, it is important to establish highly sensitive, easy to use and affordable formaldehyde detection methods. Here, we transformed the workhorse bacteriumEscherichia coliinto biosensors that can detect a broad range of formaldehyde concentrations. Based on natural and promiscuous formaldehyde assimilation enzymes, we designed and engineered three differentE. colistrains that depend on formaldehyde assimilation for cellular growth. After in depth characterization of these biosensors, we show that the formaldehyde sensitivity can be improved through adaptive laboratory evolution or modification of metabolic branch points. The metabolic engineering strategy presented in this work allowed the creation ofE. colibiosensors that can detect formaldehyde in a concentration range from ∼30 μM to ∼13 mM. Using the most sensitive strain, we benchmarked thein vivoactivities of different, widely used NAD-dependent methanol dehydrogenases, the rate-limiting enzyme in synthetic methylotrophy. We also show that the strains can grow upon external addition of formaldehyde indicating their potential use for applications beyond enzyme engineering. The formaldehyde biosensors developed in this study are fully genomic and can be used as plug and play devices for screening large enzyme libraries. Thus, they have the potential to greatly advance enzyme engineering and might even be used for environmental monitoring or analysis of industrial probes.Highlights-Conversion ofE. coliinto three different formaldehyde growth biosensors-Biosensors are fully genomic and grow robustly when formaldehyde is present-Biosensors can detect formaldehyde concentrations ranging from ∼30 μM to ∼13 mM-Benchmarking of biotechnological relevant methanol dehydrogenases reveals potential of biosensors for enzyme engineering-Biosensors grow upon direct addition of formaldehyde indicating potential use in environmental or industrial settings