bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes of upper extremity nerve transfers in neuralgic amyotrophy
Authors: Solaja Ogi , Baergen Allison K. , Head Linden K. , Wolff Gerald K. , Boyd Kirsty U. 
Published: April 2023

SUMMARY:
Neuralgic amyotrophy (NA) is a disease affecting peripheral nerves. Historically, treatment has been conservative as the natural course of the disease was thought to be self-limiting. Recent work has demonstrated that as many as two-thirds of those affected suffer from persistent pain, fatigue, or weakness. At our centre, supercharge end-to-side (SETS) nerve transfers are commonly performed in patients with NA to optimize motor recovery while allowing for native axonal regrowth. We describe the technique and clinical outcomes of patients with NA affecting the anterior interosseous nerve (AIN) who were treated with SETS nerve transfer from extensor carpi radialis brevis (ECRB) to AIN. Ten patients (90% male, mean age 51.3 ± 9.7 years) underwent ECRB to AIN nerve transfer at a mean of 6.4 ± 1.4 months following onset of symptoms. Mean postoperative follow-up duration was 14.8 ± 3.2 months. Preoperatively, all patients demonstrated clinically significant weakness in the flexor pollicis longus (FPL), flexor digitorum profundus muscle to the index finger (FDP2), or both. FPL strength improved from a median Medical Research Council (MRC) grade of 1.5 to 4 (p = 0.011) and FDP2 strength improved from a median MRC of 1 to 5 (p = 0.016). A postoperative MRC grade of 4- or greater was achieved in 9 of 10 (90%) FPL and 10 of 10 (100%) FDP muscles. This is the first report of SETS nerve transfer for the treatment of NA. The outcomes of this work suggest that SETS nerve transfers may be an option to optimize the motor outcomes in patients with NA.
The Deep Fascia of the Head and Neck Revisited: Relationship with the Facial Nerve and Implications for Rhytidectomy
Authors: Minelli Lennert , van der Lei Berend , Mendelson Bryan C. 
Published: April 2023

Background:
The deep fascia is important in face-lift surgery, as it is relied on for protection of the facial nerve during surgical dissection. Lack of consistency with the term may be attributable to the term deep fascia having two different meanings. It is a specific type of connective tissue, classically thin, fibrous, and flat, whereas in the description of the layers of the face and neck, the deep fascia layer includes all the connective tissue deep to the superficial fascia layer. This cadaver study was undertaken to clarify the layered anatomy of the face and neck and its relationship with the facial nerve branches.

Methods:
Preliminary dissections and macrosectioning, followed by a conclusive series of standardized layered dissections, histologic analysis, and sheet plastination, were performed on 50 cadaver heads.

Results:
The deep fascia is thin in convex areas of the face and neck, and thicker in concave areas; it is interspersed with deep fat. The facial nerve branches, after emerging from the parotid gland, are embedded within the deep fascia, not deep to it. They transition from deep within the deep fascia at specific locations to course in the most superficial part of the deep fascia where they underlie their target superficial fascia muscles and are at risk from deep plane face-lift dissection.

Conclusions:
The deep fascia layer is a multilamellar fibrofatty layer of variable thickness, which includes the deep fat in which the facial nerve branches are embedded. In deep plane face-lift surgery, dissection must be performed in the most superficial level of this deep fascia layer.
EFFECTS OF BACTERIAL LIPOPOLYSACCHARIDE AND SHIGA TOXIN ON INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS
Authors: Martire-Greco Daiana , La Greca Alejandro , Castillo Montañez Luis , Biani Celeste , Lombardi Antonella , Birnberg-Weiss Federico , Norris Alessandra , Sacerdoti Flavia , Amaral María Marta , Rodrigues-Rodriguez Nahuel , Pittaluga Jose Ramón , Furmento Verónica Alejandra , Landoni Verónica Inés , Miriuka Santiago Gabriel , Luzzani Carlos , Fernández Gabriela Cristina 
Published: April 2023

ABSTRACT

Background: Mesenchymal stem cells (MSCs) can be activated by different bacterial toxins. Lipopolysaccharides and Shiga Toxin (Stx) are the main toxins necessary for hemolytic uremic syndrome development. The main etiological event in this disease is endothelial damage that causes glomerular destruction. Considering the repairing properties of MSC, we aimed to study the response of MSC derived from induced pluripotent stem cells (iPSC-MSC) to LPS and/or Stx and its effect on the restoration of injured endothelial cells. Methods: iPSC-MSC were treated with LPS and or/Stx for 24 h and secretion of cytokines, adhesion, and migration were measured in response to these toxins. In addition, conditioned media from treated iPSC-MSC were collected and used for proteomics analysis and evaluation of endothelial cell healing and tubulogenesis using human microvascular endothelial cells 1 as a source of endothelial cells. Results: The results obtained showed that LPS induced a proinflammatory profile on iPSC-MSC, whereas Stx effects were less evident, even though cells expressed the Gb3 receptor. Moreover, LPS induced on iPSC-MSC an increment in migration and adhesion to a gelatin substrate. Addition of conditioned media of iPSC-MSC treated with LPS + Stx, decreased the capacity of human microvascular endothelial cells 1 to close a wound, and did not favor tubulogenesis. Proteomic analysis of iPSC-MSC treated with LPS and/or Stx revealed specific protein secretion patterns that support the functional results described. Conclusions: iPSC-MSC activated by LPS acquired a proinflammatory profile that induces migration and adhesion to extracellular matrix proteins but the addition of Stx did not activate any repair program to ameliorate endothelial damage, indicating that the use of iPSC-MSC to regenerate endothelial injury caused by LPS and/or Stx in hemolytic uremic syndrome could not be the best option to consider to regenerate a tissue injury.
Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal
Authors: Santos Mónica , Sequeira João , Abreu Pedro , Guerreiro Rui , Santos Mariana , Ferreira João , Brum Marisa , Ladeira Filipa , Leitão Lia , Dias Rafael , Sá Maria José , Salgado Vasco , Capela Carlos , de Sá João 
Published: April 2023

ObjectivesCladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up.MethodsThis was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021.ResultsA total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1–3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening (P= 0.843, Mann-WhitneyUtest) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects.ConclusionOur study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.
A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults
Authors: Devinney Michael J. , Wong Megan K. , Wright Mary Cooter , Marcantonio Edward R. , Terrando Niccolò , Browndyke Jeffrey N. , Whitson Heather E. , Cohen Harvey J. , Nackley Andrea G. , Klein Marguerita E. , Ely E. Wesley , Mathew Joseph P. , Berger Miles ,   the MADCO-PC & INTUIT Study Groups
Published: April 2023

AbstractObjectiveAlthough animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.MethodsCognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).ResultsOf 207 patients (median age 68, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24-hours after surgery (median postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 1.15 [95% CI 1.09-1.22]; p<0.001)InterpretationPostoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay.
Daily rhythms, demographics and health: findings from a nationally representative survey
Authors: Ujma Péter P. , Horváth Csenge G. , Bódizs Róbert 
Published: April 2023

AbstractThe timing of daily activity in humans have been associated with various demographic and health-related factors, but the possibly complex patterns of confounding and interaction between these has not been systematically explored. We use data from Hungarostudy 2021, a nationally representative survey of 7000 Hungarians to assess the relationship between self- reported chronotype, social jetlag (using the Munich Chronotype Questionnaire), demographic variables and self-reported health and demographic variables, including ethnic and sexual minority membership. Supporting the validity of self-reports, participants with later chronotypes reported the lowest daytime sleepiness at a later clock time. We found that older age, female sex, a more eastward and southward geographical position, residence in a smaller settlement, less education and income, religiousness and cohabiting with small children were associated with an earlier chronotype. Younger age, higher education and income, and cohabiting with small children were associated with increased social jetlag. Of the 48 health-related variables surveyed, the relationship with both chronotype and social jetlag were mostly accounted for by age, sex, and socioeconomic effects, but we identified alcohol consumption, smoking, and physical activity as predictors of both social jetlag and chronotype, while a number of disorders were either positively or negatively associated with chronotype and social jetlag. Our findings from a large, nationally representative sample indicate that both biological and social factors influence chronotype and identified both demographic and health-related variables as risk factors for social jetlag. Our results, however, do not support a causal relationship between light exposure and mental health.
Development of Comorbidity Index for In-hospital Mortality for Patients Underwent Coronary Artery Revascularization
Authors: Li Renxi 
Published: April 2023

AbstractBackgroundFor myocardial revascularization, coronary artery bypass grafting (CAGB) and percutaneous coronary intervention (PCI) are two common modalities but with high in-hospital mortality. A comorbidity index is useful to predict mortality or can be used with other covariates to develop point-scoring systems. This study aimed to develop specific comorbidity indices for patients who underwent coronary artery revascularization.MethodsPatients who underwent CABG or PCI were identified in the National Inpatient Sample database between Q4 2015-2020. Patients of age<40 were excluded for congenital heart defects. Patients were randomly sampled into experimental (70%) and validation (30%) groups. Thirty-eight Elixhauser comorbidities were identified and included in multivariable regression to predict in-hospital mortality. Weight for each comorbidity was assigned and single indices, Li CABG Mortality Index (LCMI) and Li PCI Mortality Index (LPMI), were developed.ResultsMortality prediction by LCMI approached adequacy (c-statistic=0.691, 95% CI=0.682-0.701) and was comparable to multivariable regression with comorbidities (c-statistic=0.685, 95% CI=0.675-0.694). LCMI prediction performed significantly better than Elixhauser Comorbidity Index (ECI) (c-statistic=0.621, 95% CI=0.611-0.631) and can be further improved by adjusting age (c-statistic=0.721, 95% CI=0.712-0.730).LPMI moderately predicted in-hospital mortality (c-statistic=0.666, 95% CI=0.660-0.672) and performed significantly better than ECI (c-statistic=0.610, 95% CI=0.604-0.616). LPMI performed better than the all-comorbidity multivariable regression (c-statistic=0.658, 95% CI=0.652-0.663). After age adjustment, LPMI prediction was significantly increased and was approaching adequacy (c-statistic=0.695, 95% CI=0.690-0.701).ConclusionsLCMI and LPMI effectively predicted in-hospital mortality. These indices were validated and performed superior to ECI. The adjustment of age increased their predictive power to adequacy, implicating potential clinical application.
Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking
Authors: Liu Lihong , Casner Ryan G. , Guo Yicheng , Wang Qian , Iketani Sho , Chan Jasper Fuk-Woo , Yu Jian , Dadonaite Bernadeta , Nair Manoj S. , Mohri Hiroshi , Reddem Eswar R. , Yuan Shuofeng , Poon Vincent Kwok-Man , Chan Chris Chung-Sing , Yuen Kwok-Yung , Sheng Zizhang , Huang Yaoxing , Bloom Jesse D. , Shapiro Lawrence , Ho David D. 
Published: April 2023

SUMMARYSARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.
Network pharmacological analysis for the identification of the molecular mechanism ofLilium brownii(Baihe) against gastric cancer: 3-Demethylcolchicine targeting androgen receptor
Authors: An Zi-Yi , Zhang Wen-Hao , Hu Xiao-Gang , Yuan Le-Qi , Jin Wei-Lin 
Published: April 2023

AbstractLilium brownii(Baihe) contains several bioactive compounds with anti-cancer properties. This study aimed to predict the anticancer targets and related pathways of Baihe for the treatment of gastric cancer (GC) by using network pharmacology and to further explore its potential mechanism in GC. The active compounds and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The OMIM, CTD, and GeneCards databases provided information on GC-related targets. After the overlap, the targets of Baihe against GC were collected. The STRING network platform and Cytoscape software were used for protein–protein interaction (PPI) network and core target investigations. Network pharmacology predicted that the principal targets were retrieved from the Starbase database in connection with the GC overall survival. Molecular docking was also used to validate Baihe and the targets’ high affinity. Finally, the DAVID online tool was used for the overlapping target Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The TCMSP database showed that Baihe has seven bioactive components. Apoptosis and p53 signaling pathways were primarily enriched in overlapping genes according to KEGG analysis. Androgen receptor (AR) was identified as a major target by combining the PPI network, KEEG enrichment, and target gene prognostic analysis. Molecular docking results verified that the Baihe’s 3-demethylcolchicine has a high affinity for the GC target AR. Based on the results of network pharmacology analysis based on data mining and molecular docking methods, the multi-target drug Baihe may be a promising therapeutic candidate for GC, but further in vivo/ex vivo research is required.Graphical Abstract
A PCR-RFLP method for the detection of CRISPR-induced indels
Authors: Angelopoulou Lydia , Stylianopoulou Electra , Tegopoulos Konstantinos , Farmakioti Ioanna , Grigoriou Maria E. , Skavdis George 
Published: April 2023

ABSTRACTCRISPR-based technologies have revolutionised genome editing and are widely used for knocking out genes in cell lines and organisms. From a practical perspective, a critical factor that largely influences the successful outcome of CRISPR gene knockout experiments is the reliable and fast identification of fully mutated cells carrying exclusively null alleles of the target gene. Here we describe a novel strategy based on the well-documented reliability and simplicity of the classical PCR-Restriction Fragment Length Polymorphism (RFLP), which allows the assessment of the editing efficiency in pools of edited cells and the effective identification of cell clones that carry exclusively mutated alleles. This fast and cost-effective method, named PIM-RFLP (PCR Induced Mutagenesis-RFLP), is executed in two steps. In the first step, the editing target is amplified by a set of mutagenic primers that create a restriction enzyme degenerate cleavage site in the amplification product of the wild type allele. As a proof of principle, we chose the XcmI restriction site because it is especially suitable since it has the particularity of containing nine centrally placed non-specific nucleotides. This gives great flexibility in the mutagenic primers design and allows for efficient execution of the mutagenic PCR. In the second step, the evaluation of the editing efficiency in pools of edited cells or the identification of fully mutated single-cell derived clones is achieved following the standard procedure for any PCR-RFLP assay: digestion of the PCR products and analysis of the restriction fragments in an agarose gel.GRAPHICAL ABSTRACT
Dynamic oxygen-enhanced MRI of the lung at 3 T: feasibility, repeatability and reproducibility
Authors: Kim Mina , Naish Josephine H. , Needleman Sarah H. , Tibiletti Marta , Taylor Yohn , O’Connor James P. B. , Parker Geoff J. M. 
Published: April 2023

AbstractPurposeDynamic T1-weighted lung oxygen enhanced MRI (OE-MRI) is challenging at 3 T due to decreased longitudinal relaxivity of oxygen and increased magnetic susceptibility difference between air and tissue interfaces relative to 1.5 T, leading to poor signal quality. In this work, we evaluate the robustness of an alternative T2*-sensitised lung dynamic OE-MRI protocol in humans at 3 T.MethodsSimulations were performed to predict OE contrast behaviour and optimise the MRI protocol. Sixteen healthy subjects underwent dynamic free-breathing OE-MRI acquisitions using a dual echo RF-spoiled gradient echo acquisition at 3 T on two MRI scanners at different institutions. Non-linear registration and tissue density variation correction were applied. Percent signal enhancement (PSE) maps and ΔR2* were derived. Intra-class correlation coefficient (ICC) and Bland-Altman analyses were used to evaluate reproducibility of the OE indices across two sites and vendors as well as scan-rescan repeatability.ResultsSimulations and experimental data show negative contrast on oxygen inhalation due to substantial dominance of ΔR2* at TE longer than 0.2 ms when using our chosen flip angle and TR. Mean PSE values were TE dependent and mean ΔR2* was 0.14 ms-1± 0.03 ms-1, ICC values for intra-scanner (ICCintra) and inter-scanner (ICCinter) variability for OE indices were high (ICCintra> 0.74; ICCinter= 0.70) and 95% limits of agreement showed strong agreement of repeated measures.ConclusionOur results demonstrate excellent scan-rescan repeatability for the PSE indices and good reproducibility for ΔR2* across two sites and vendors, suggesting potential utility in multi-centre clinical studies.