bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia
Authors: Lu Shanshan , Li Yiwei , Shen Qiang , Zhang Wanli , Gu Xiaofan , Ma Mingliang , Li Yiming , Zhang Liuqiang , Liu Xuan , Zhang Xiongwen 
Published: May 2021

AbstractBackgroundCancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti‐inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.MethodsThe in vitro cell models of C2C12 myotube atrophy and 3T3‐L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour‐bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.ResultsCarnosol and its analogues [dimethyl‐carnosol (DCS) and dimethyl‐carnosol‐D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3‐L1 adipocytes in vitro. Interestingly, CS and its analogues exhibited stronger inhibitive effects on muscle atrophy induced by tumour necrosis factor‐α (TNF‐α) (CS, P < 0.001; DCS, P < 0.001; DCSD, P < 0.001) in C2C12 myoblasts than on muscle atrophy induced by IL‐6 (CS, P < 0.05; DCS, P = 0.08; DCSD, P < 0.05). In a C26 tumour‐bearing mice model, administration of CS or its analogue DCSD significantly prevented body weight loss without affecting tumour size. At the end of the experiment, the body weight of mice treated with CS and DCSD was significantly increased by 11.09% (P < 0.01) and 11.38% (P < 0.01) compared with that of the C26 model group. CS and DCSD also improved the weight loss of epididymal adipose tissue in C26 model mice by 176.6% (P < 0.01) and 48.2% (P < 0.05) increase, respectively. CS and DCSD treatment partly preserved gastrocnemius myofibres cross‐sectional area. CS treatment decreased the serum level of TNF‐α (−95.02%, P < 0.01) but not IL‐6 in C26 tumour‐bearing mice. Inhibition on NF‐κB and activation of Akt signalling pathway were involved in the ameliorating effects of CS and its analogues on muscle wasting both in vitro and in vivo. CS and its analogues also alleviated adipose tissue loss by inhibiting NF‐κB and AMPK signalling pathways both in vitro and in vivo.ConclusionsCS and its analogues exhibited anticachexia effects mainly by inhibiting TNF‐α/NF‐κB pathway and decreasing muscle and adipose tissue loss. CS and its analogues might be promising drug candidates for the treatment of cancer cachexia.
Mild anemia as a single independent predictor of mortality in patients with COVID‐19
Authors: Tremblay Douglas , Rapp Joseph L. , Alpert Naomi , Lieberman‐Cribbin Wil , Mascarenhas John , Taioli Emanuela , Ghaffari Saghi 
Published: May 2021

AbstractThe coronavirus disease 2019 (COVID‐19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented international health crisis. COVID‐19 clinical presentations cover a wide range from asymptomatic to severe illness and death. Given the limited therapeutic resources and unexpected clinical features of the disease, readily accessible predictive biomarkers are urgently needed to improve patient care and management. We asked the degree to which anemia may influence the outcome of patients with COVID‐19. To this end, we identified 3777 patients who were positively diagnosed with COVID‐19 between March 1 and April 1 2020 in New York City. We evaluated 2,562 patients with available red blood cell, hemoglobin, and related laboratory values. Multivariable cox proportional hazards regression showed that anemia was a significant independent predictor of mortality (hazard ratio (HR): 1.26, 95% Confidence Interval [CI]: 1.06‐1.51), independent of age, sex, and comorbidities. There was a direct correlation between the degree of anemia and the risk of mortality when hemoglobin was treated as a continuous variable (HRadj 1.05; [CI]: 1.01‐1.09). The hemoglobin level that was maximally predictive of mortality, was 11.5 g/dL in males and 11.8 g/dL in females. These findings identify a routinely measured biomarker that is predictive of disease outcomes and will aid in refining clinical care algorithms and optimize resource allocation. Mechanisms of impacts of anemia on COVID‐19 outcome are likely to be multiple in nature and require further investigation.
Effects of mesenchymal stromal cell-derived extracellular vesicles in acute respiratory distress syndrome (ARDS): Current understanding and future perspectives
Authors: Su Yue , Guo Haiyan , Liu Qinghua 
Published: May 2021

AbstractAcute respiratory distress syndrome (ARDS) is a devastating and life-threatening syndrome that results in high morbidity and mortality. Current pharmacologic treatments and mechanical ventilation have limited value in targeting the underlying pathophysiology of ARDS. Mesenchymal stromal cells (MSCs) have shown potent therapeutic advantages in experimental and clinical trials through direct cell-to-cell interaction and paracrine signaling. However, safety concerns and the indeterminate effects of MSCs have resulted in the investigation of MSC-derived extracellular vesicles (MSC-EVs) due to their low immunogenicity and tumorigenicity. Over the past decades, soluble proteins, microRNAs, and organelles packaged in EVs have been identified as efficacious molecules to orchestrate nearby immune responses, which attenuate acute lung injury by facilitating pulmonary epithelium repair, reducing acute inflammation, and restoring pulmonary vascular leakage. Even though MSC-EVs possess similar bio-functional effects to their parental cells, there remains existing barriers to employing this alternative from bench to bedside. Here, we summarize the current established research in respect of molecular mechanisms of MSC-EV effects in ARDS and highlight the future challenges of MSC-EVs for clinical application.
Intratumoral and Peritumoral Radiomics Based on Functional Parametric Maps from Breast DCE‐MRI for Prediction of HER‐2 and Ki‐67 Status
Authors: Li Chunli , Song Lirong , Yin Jiandong 
Published: May 2021

BackgroundRadiomics has been applied to breast magnetic resonance imaging (MRI) for gene status prediction. However, the features of peritumoral regions were not thoroughly investigated.PurposeTo evaluate the use of intratumoral and peritumoral regions from functional parametric maps based on breast dynamic contrast‐enhanced MRI (DCE‐MRI) for prediction of HER‐2 and Ki‐67 status.Study TypeRetrospective.PopulationA total of 351 female patients (average age, 51 years) with pathologically confirmed breast cancer were assigned to the training (n = 243) and validation (n = 108) cohorts.Field Strength/Sequence3.0T, T1 gradient echo.AssessmentRadiomic features were extracted from intratumoral and peritumoral regions on six functional parametric maps calculated using time‐intensity curves of DCE‐MRI. The intraclass correlation coefficients (ICCs) were used to determine the reproducibility of feature extraction. Based on the intratumoral, peritumoral, and combined intra‐ and peritumoral regions, three radiomics signatures (RSs) were built using the least absolute shrinkage and selection operator (LASSO) logistic regression model, respectively.Statistical TestsWilcoxon rank‐sum test, minimum redundancy maximum relevance, LASSO, receiver operating characteristic curve (ROC) analysis, and DeLong test.ResultsThe intratumoral and peritumoral RSs for prediction of HER‐2 and Ki‐67 status achieved areas under the ROC (AUCs) of 0.683 (95% confidence interval [CI], 0.574–0.793) and 0.690 (95% CI, 0.577–0.804), and 0.714 (95% CI, 0.616–0.812) and 0.692 (95% CI, 0.590–0.794) in the validation cohort, respectively. The combined RSs yielded AUCs of 0.713 (95% CI, 0.604–0.823) and 0.749 (95% CI, 0.656–0.841), respectively. There were no significant differences in prediction performance among intratumoral, peritumoral, and combined RSs. Most (69.7%) of the features had good agreement (ICCs >0.8).Data ConclusionRadiomic features of intratumoral and peritumoral regions on functional parametric maps based on breast DCE‐MRI had the potential to identify HER‐2 and Ki‐67 status.Level of Evidence: 3Technical Efficacy Stage: 2
Elucidation of the structure of supramolecular polymorphs in peptide nanofibres using Raman spectroscopy
Authors: Sloan‐Dennison Sian , Lampel Ayala , Raßlenberg Eileen , Ulijn Rein V. , Smith Ewen , Faulds Karen , Graham Duncan 
Published: May 2021

AbstractPeptide fibre formation via molecular self‐assembly is a key step in a range of cellular processes and increasingly considered as an approach to produce supramolecular biomaterials. We previously demonstrated the self‐assembly of the tripeptide lysine‐dityrosine (KYY) as a substrate for the formation of proton‐conducting melanin‐like materials. Point based Raman scattering is one of several techniques which were used to characterise the secondary structure of the KYY nanofibre but as is often the case with this type of fibre, the spectra are rather complex and in addition there were variations in intensity between samples making interpretation difficult. Using Raman mapping we show that, as a drop of KYY in solution dries, it self‐assembles into two different fibre forms and the simpler spectra obtained for each are easier to interpret. The tyrosine amide marker bands, 852 and 828 cm−1, are present in both forms with similar intensities indicating the formation of a similar secondary structure in both forms with some stacking of the tyrosine rings. However, the tyrosine marker bands at 1614 and 1661 cm−1 vary considerably in intensity between the two forms. It is concluded that both forms consist of stacked polypeptide units joined by hydrogen bonds to form structures similar to β‐sheet structures in longer peptides. There are other clear differences such the large intensity difference in the lysine side chain band at 1330 cm−1 and the relative intensities of the bands at 982 and 1034 cm−1. These differences are attributed to changes in the conformation of tyrosine side chains causing different electron withdrawing effects on the ring.
Perfusion Patterns of Peripheral Pulmonary Granulomatous Lesions Using Contrast‐Enhanced Ultrasound (CEUS) and Their Correlation with Immunohistochemically Detected Vascularization Patterns
Authors: Safai Zadeh Ehsan , Keber Corinna U. , Dietrich Christoph F. , Westhoff Christina C. , Günter Christina , Beutel Björn , Alhyari Amjad , Trenker Corinna , Görg Christian 
Published: May 2021

PurposeTo describe the perfusion patterns of peripheral pulmonary granulomatous lesions (PPGLs) by contrast‐enhanced ultrasound (CEUS) and their correlation with vascularization patterns (VPs) represented by immunohistochemical (CD34) endothelial staining.Patients and methodsFrom January 2007 until September 2020, 10 consecutive patients with histologically confirmed PPGLs were investigated by CEUS. The time to enhancement, classified as early pulmonary‐arterial (PA) pattern of enhancement versus delayed bronchial‐arterial (BA) pattern of enhancement, the extent of enhancement, classified as marked or reduced, the homogeneity of enhancement, classified as homogeneous or inhomogeneous, and the decrease of enhancement, classified as rapid washout (<120 seconds) or a late washout (≥120 seconds), were analyzed retrospectively. Furthermore, the tissue samples from the study patients and as a control group, 10 samples of normal lung tissue obtained by autopsy, and 10 samples of lung tissue with acute pneumonia obtained by autopsy were immunohistochemically stained with CD34 antibody. The presence of avascular areas (AAs) and the VPs were evaluated in all tissue samples.ResultsOn CEUS, all PPGLs showed a reduced inhomogeneous BA pattern of enhancement and a rapid washout (<120 seconds). On CD34 staining, all PPGLs showed central AAs in granulomas and a chaotic VP similar to angiogenesis in lung tumors. The lung tissue in control groups revealed on CD34 staining a regular alveolar VP.ConclusionThe PPGLs on CEUS show an identical perfusion pattern similar to those of malignant lesions. Furthermore, for the first time, neoangiogenesis was demonstrated as a histopathological correlate to BA pattern of enhancement on CEUS.
T‐cell mediated responses against alpha‐foetoprotein in hepatocellular carcinoma: Relationship with hepatitis C virus infection, tumour phenotype and patients’ survival
Authors: Pinato David J. , Fessas Petros , Gibbin Antonello , Occhino Giuseppa , Boccato Elisa , Smirne Carlo , Minisini Rosalba , Pirisi Mario 
Published: May 2021

AbstractBackgroundAlpha‐foetoprotein (AFP) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). However, T‐cell response (TR) to AFP is suppressed in HCC due to immune evasion. It is unknown whether HCV infection may pre‐condition TR against AFP, or whether TR may influence the clinical course of HCC.MethodsWe prospectively enrolled 18 HCV+ treatment‐naïve patients with cirrhosis (CC), 18 HCV+ HCC cases and 17 HCV‐ HCC cases. TR was quantified by ELISPOT using assays specific to interleukin (IL) 2, IL10 and granulocyte‐monocyte colony stimulating factor (GM‐CSF) on ex‐vivo peripheral blood mononuclear cells (PBMC) stimulated in vitro with AFP peptides. Cytokine ratios were compared between groups and with clinicopathological features of HCC, including overall survival (OS).ResultsThe proportion of AFP‐specific responses was not different across the studied groups for any of the assayed cytokines. AFP‐specific IL‐2 responses were increased in larger (P = .02), multifocal tumours (P = .01) and correlated with advanced disease (P = .01). TRs did not correlate with other clinicopathological factors and did not predict for OS.ConclusionTumour stage but not HCV infection is related to the emergence of anti‐AFP TRs. These data enable formulation of a rationale for the further development of anti‐AFP immunotherapy in HCC, facilitating optimal patient selection for future studies.
Coupled dynamics of iron, manganese, and phosphorus in brackish coastal sediments populated by cable bacteria
Authors: Hermans Martijn , Astudillo Pascual Marina , Behrends Thilo , Lenstra Wytze K. , Conley Daniel J. , Slomp Caroline P. 
Published: May 2021

AbstractCoastal waters worldwide suffer from increased eutrophication and seasonal bottom water hypoxia. Here, we assess the dynamics of iron (Fe), manganese (Mn), and phosphorus (P) in sediments of the eutrophic, brackish Gulf of Finland populated by cable bacteria. At sites where bottom waters are oxic in spring, surface enrichments of Fe and Mn oxides and high abundances of cable bacteria were observed in sediments upon sampling in early summer. At one site, Fe and P were enriched in a thin layer (~ 3 mm) just below the sediment–water interface. X‐ray absorption near edge structure and micro X‐ray fluorescence analyses indicate that two‐thirds of the P in this layer was associated with poorly crystalline Fe oxides, with an additional contribution of Mn(II) phosphates. The Fe enriched layer was directly overlain by a Mn oxide‐rich surface layer (~ 2 mm). The Fe oxide layer was likely of diagenetic origin, formed through dissolution of Fe monosulfides and carbonates, potentially induced by cable bacteria in the preceding months when bottom waters were oxic. Most of the Mn oxides were likely deposited from the water column as part of a cycle of repeated deposition and remobilization. Further research is required to confirm whether cable bacteria activity in spring indeed promotes the formation of distinct layers enriched in Fe, Mn, and P minerals in Gulf of Finland sediments. The temporal variations in biogeochemical cycling in this seasonally hypoxic coastal system, potentially controlled by cable bacteria activity, have little impact on permanent sedimentary Fe, Mn, and P burial.
Detecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning
Authors: Mirelman Anat , Ben Or Frank Mor , Melamed Michal , Granovsky Lena , Nieuwboer Alice , Rochester Lynn , Del Din Silvia , Avanzino Laura , Pelosin Elisa , Bloem Bastiaan R. , Della Croce Ugo , Cereatti Andrea , Bonato Paolo , Camicioli Richard , Ellis Theresa , Hamilton Jamie L. , Hass Chris J. , Almeida Quincy J. , Inbal Maidan , Thaler Avner , Shirvan Julia , Cedarbaum Jesse M. , Giladi Nir , Hausdorff Jeffrey M. 
Published: May 2021

ABSTRACTBackgroundIt is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD).ObjectiveTo identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage.MethodsCross‐sectional wearable‐sensor records were collected in 332 patients with PD (Hoehn and Yahr scale I−III) and 100 age‐matched healthy controls. Sensors were adhered to the participant's lower back, bilateral ankles, and wrists. Study participants walked in a ~15‐meter corridor for 1 minute under two walking conditions: (1) preferred, usual walking speed and (2) walking while engaging in a cognitive task (dual‐task). A subgroup (n = 303, 67% PD) also performed the Timed Up and Go test. Multiple machine‐learning feature selection and classification algorithms were applied to discriminate between controls and PD and between the different PD severity stages.ResultsHigh discriminatory values were found between motor disease stages with mean sensitivity in the range 72%–83%, specificity 69%–80%, and area under the curve (AUC) 0.76–0.90. Measures from upper‐limb sensors best discriminated controls from early PD, turning measures obtained from the trunk sensor were prominent in mid‐stage PD, and stride timing and regularity were discriminative in more advanced stages.ConclusionsApplying machine‐learning to multiple, wearable‐derived features reveals that different measures of gait and mobility are associated with and discriminate distinct stages of PD. These disparate feature sets can augment the objective monitoring of disease progression and may be useful for cohort selection and power analyses in clinical trials of PD. © 2021 International Parkinson and Movement Disorder Society
Efficacy and safety of probiotics and prebiotics in liver transplantation: A systematic review and meta‐analysis
Authors: Ma Ming , Wang Xiaodong , Li Junjie , Jiang Wentao 
Published: May 2021

AbstractProbiotics were used for liver transplantation (LT) patients to reduce postoperative infection, but clinical trials examining the combined use of prebiotics and probiotics are limited. This meta‐analysis aimed to compare the safety and efficacy of combined use of prebiotics and probiotics in patients undergoing LT. PubMed, Cochrane, and Embase databases were reviewed for the combined use of prebiotics and probiotics in patients undergoing LT. The weighted mean difference (WMD), risk ratio (RR), and 95% CI were calculated. A total of 6 related studies comprising 345 patients were included. Most prebiotics and probiotics were given for 7.14 days. The overall infection rate (RR = 0.29; 95% CI, 0.14.0.60; P value for heterogeneity [PH] = .066; test for heterogeneity [I2] = 51.7%) and the incidence of urinary tract infection (RR = 0.14; 95% CI, 0.04–0.47, PH = .724; I2 = 0%) were lower in the probiotics group when compared with those in the control group. Furthermore, probiotics significantly reduced the hospital length of stay (WMD = −1.37; 95% CI, −1.92 to 0.82; PH = .506; I2 = 0%) and the duration of antimicrobial therapy (WMD = −4.31; 95% CI, −5.41 to 3.22; PH = .019; I2 = 69.8%) in patients undergoing LT. These findings suggested that the combined use of prebiotics and probiotics (Lactobacillus and Bifidobacterium) was effective in lowering the incidence of bacterial infections and shortening the hospital length of stay and duration of antibiotic therapy in patients undergoing LT, when compared with conventional nutrition.
Back pain associated with centrally administered parenteral nutrition
Authors: Swartz Sheila , Dummann Kacy , Guell Caitlin , Lubinsky Mark , Kozeniecki Michelle 
Published: May 2021

AbstractParenteral nutrition (PN) is well recognized for its ability to provide nutrition to patients without the ability to digest enterally; however, PN must also be seen as a medication with associated adverse drug events similar to any other pharmacological agent that is administered to patients. Here we present a case report of localized lower back pain with central PN infusion. The initial areas of concern were the intravenous lipid emulsion, peripherally inserted central catheter placement, osmolarity of the formula, and the additives. The patient's back pain was ultimately felt to be an adverse reaction to the multivitamin component of the infusion based on an elimination trial of the PN components.
Mixed‐method research protocol: Development and evaluation of a nursing intervention in patients discharged from the intensive care unit
Authors: Cuzco Cecilia , Castro Rebollo Pedro , Marín Pérez Raquel , Núñez Delgado Ana Isabel , Romero García Marta , Martínez Momblan M. Antonia , Estrada Reventós Dolors , Martínez Estalella Gemma , Delgado‐Hito Pilar 
Published: May 2021

AbstractAim(a) To understand patients’ lived experience at intensive care unit (ICU) discharge and (b) to evaluate the impact of a nursing empowerment intervention (NEI) on patients’ anxiety and depression levels at ICU discharge.DesignA mixed‐methods approach will be applied.MethodsIn the qualitative phase, the hermeneutic phenomenological method will be used. Participants will be patients from three university hospitals who will be selected by purposive sampling. Data will be gathered through in‐depth interviews and analysed using content analysis. The qualitative data obtained will be employed to develop the nursing intervention. Subsequently, a multicenter, parallel‐group, experimental pre‐test/post‐test design with a control group will be used to measure the effectiveness of the nursing empowerment intervention in the quantitative phase by means of the Hospital Anxiety and Depression Scale (HADS). Simple random probabilistic sampling will include 172 patients in this phase.