bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques
Authors: O’Connor Megan A. , Erasmus Jesse H. , Randall Samantha , Archer Jacob , Lewis Thomas B. , Brown Brieann , Fredericks Megan , Groenier Skyler , Iwayama Naoto , Ahrens Chul , Garrison William , Wangari Solomon , Guerriero Kathryn A. , Fuller Deborah H.
Published: December 2021

The ongoing COVID-19 vaccine rollout is critical for reducing SARS-CoV-2 infections, hospitalizations, and deaths worldwide. Unfortunately, massive disparities exist in getting vaccines to vulnerable populations, including people living with HIV. Preliminary studies indicate that COVID-19 mRNA vaccines are safe and immunogenic in people living with HIV that are virally suppressed with potent antiretroviral therapy but may be less efficacious in immunocompromised individuals. This raises the concern that COVID-19 vaccines may be less effective in resource poor settings with limited access to antiretroviral therapy. Here, we evaluated the immunogenicity of a single dose COVID-19 replicon RNA vaccine expressing Spike protein (A.1) from SARS-CoV-2 (repRNA-CoV2S) in immunocompromised, SIV infected and immune competent, naïve pigtail macaques. Moderate vaccine-specific cellular Th1 T-cell responses and binding and neutralizing antibodies were induced by repRNA-CoV2S in SIV infected animals and naïve animals. Furthermore, vaccine immunogenicity was elicited even among the animals with the highest SIV viral burden or lowest peripheral CD4 counts prior to immunization. This study provides evidence that a SARS-CoV-2 repRNA vaccine could be employed to induce strong immunity against COVID-19 in HIV infected and other immunocompromised individuals.
Case Report: Nasal Cavity Epithelial-Myoepithelial Carcinoma With High Fluoro-D-Glucose Uptake on Positron Emission Tomography/Computed Tomography
Authors: Dzuko Kamga Jacques , Leclere Jean-Christophe , Uguen Arnaud , Amrane Karim , Abgral Ronan
Published: December 2021

Epithelial-myoepithelial carcinoma (EMC) is a rare malignant neoplasm arising most frequently in the salivary glands and exceptionally in the nasal cavity. EMC accounts for ~1–2% of salivary gland tumors. Even if the nodal and distant metastasis rates are low, tumor staging remains indicated. Here, the authors present the 2-deoxy-2-[18F]fluoro-D-glucose PET-CT (18F-FDG-PET/CT) study of a very rare case of biopsy-proven EMC of the left nasal cavity. This 18F-FDG-PET/CT was performed to stage this tumor and guide the therapeutic strategy due to an atypical high-grade presentation in immunohistochemistry. To our knowledge, this is the first case reporting such high 18F-FDG avidity of EMC of the nasal cavity in PET/CT.
Prevalence and Mortality of Hypochloremia Among Patients Suffering From Coronary Artery Disease and Congestive Heart Failure: An Analysis of Patients in CIN-I and MIMIC-III Databases
Authors: Huang Haozhang , Liu Jin , Liang Yan , Bao Kunming , Qiao Linfang , Liu Jiulin , Li Qiang , Wang Bo , Chen Shiqun , Lai Wenguang , Chen Cong , Zhang Lingyu , Huang Xiaoyu , Huang Dehua , Chen Jiyan , Tan Ning , Liu Yong
Published: December 2021

Background: Hypochloremia is an independent predictor for mortality in patients with coronary artery disease (CAD) but whether the same correlation exists in CAD patients with congestive heart failure (CHF) is unclear.

Methods: This is an analysis of data stored in the databases of the CIN-I [a registry of Cardiorenal Improvement (NCT04407936) in China from January 2007 to December 2018] and Medical Information Mart for Intensive Care (MIMIC)-III. CAD patients with CHF were included. The outcome measures were 90-day all-cause mortality (ACM) and long-term ACM.

Results: Data from 8,243 CAD patients with CHF were analyzed. We found that 10.2% of the study population had hypochloremia (Cl− <98 mmol/L) in CIN-I (n = 4,762) and 20.1% had hypochloremia in MIMIC-III (n = 3,481). Patients suffering from hypochloremia were, in general, older and had a higher prevalence of comorbidities. After adjustment for confounders, hypochloremia remained a significant predictor of short-term mortality risk [90-day ACM: adjusted hazard ratio (aHR), 1.69; 95% CI, 1.27–2.25; P < 0.001 in CIN-I, and 1.36 (1.17–1.59); P < 0.001 in MIMIC-III]. Hypochloremia was also associated with long-term mortality [aHR, 1.26; 95% CI, 1.06–1.50; P = 0.009 in CIN-I, and 1.48 (1.32–1.66); P < 0.001 in MIMIC-III]. Prespecified subgroup analyses revealed an association of hypochloremia with long-term ACM to be attenuated slightly in the women of the two databases (P interaction < 0.05).

Conclusions: Hypochloremia is independently associated with higher short-term and long-term ACM. Further studies are needed to determine if early preventive measurements and active intervention of hypochloremia can reduce the mortality risk of CAD patients with CHF.
Retrospective Robot-Measured Upper Limb Kinematic Data From Stroke Patients Are Novel Biomarkers
Authors: Goffredo Michela , Pournajaf Sanaz , Proietti Stefania , Gison Annalisa , Posteraro Federico , Franceschini Marco
Published: December 2021

Background: The efficacy of upper-limb Robot-assisted Therapy (ulRT) in stroke subjects is well-established. The robot-measured kinematic data can assess the biomechanical changes induced by ulRT and the progress of patient over time. However, literature on the analysis of pre-treatment kinematic parameters as predictive biomarkers of upper limb recovery is limited.

Objective: The aim of this study was to calculate pre-treatment kinematic parameters from point-to-point reaching movements in different directions and to identify biomarkers of upper-limb motor recovery in subacute stroke subjects after ulRT.

Methods: An observational retrospective study was conducted on 66 subacute stroke subjects who underwent ulRT with an end-effector robot. Kinematic parameters were calculated from the robot-measured trajectories during movements in different directions. A Generalized Linear Model (GLM) was applied considering the post-treatment Upper Limb Motricity Index and the kinematic parameters (from demanding directions of movement) as dependent variables, and the pre-treatment kinematic parameters as independent variables.

Results: A subset of kinematic parameters significantly predicted the motor impairment after ulRT: the accuracy in adduction and internal rotation movements of the shoulder was the major predictor of post-treatment Upper Limb Motricity Index. The post-treatment kinematic parameters of the most demanding directions of movement significantly depended on the ability to execute elbow flexion-extension and abduction and external rotation movements of the shoulder at baseline.

Conclusions: The multidirectional analysis of robot-measured kinematic data predicts motor recovery in subacute stroke survivors and paves the way in identifying subjects who may benefit more from ulRT.
Promoter Hypomethylation of miR-124 Gene Is Associated With Major Depressive Disorder
Authors: Zeng Duan , He Shen , Zhao Nan , Hu Manji , Gao Jie , Yu Yimin , Huang Jingjing , Shen Yifeng , Li Huafang
Published: December 2021

Based on our previous studies and other evidence, miR-124 is an important biomarker and therapeutic target for major depressive disorder (MDD). The aim of this study was to clarify the role of miR-124 methylation in MDD and antidepressant effects from the perspective of epigenetics. MethylTarget™ was used to detect methylation levels of the three miR-124 precursor genes (MIR124-1, MIR124-2, and MIR124-3) in 33 pre- and post-treatment MDD patients and 33 healthy controls. A total of 11 cytosine-phosphate-guanine (CpG) islands in the three miR-124 precursor genes, including 222 CpG sites, were detected. All CpG islands were hypomethylated in MDD patients when compared to healthy controls and seven CpG regions were still identified with a statistically significant difference after Bonferroni correction. In addition, 137 of 222 CpG sites were found a statistical difference between MDD patients and controls, and 40 CpG sites were still statistically significant after Bonferroni correction. After performing the LASSO regression model, seven biomarkers with differential methylation among 40 CpG sites were identified. Mean methylation score was lower in MDD patients (z= −5.84,p= 5.16E-9). The AUC value reached 0.917 (95% CI: 0.854–0.981) to discriminate MDD and controls. No changes in methylation of the three miR-124 precursor genes were found in MDD patients following antidepressant treatment. The methylation of miR-124 could be a promising diagnostic biomarker for MDD.
The Role of Electrochemotherapy in the Cutaneous and Subcutaneous Metastases From Breast Cancer: Analysis of Predictive Factors to Treatment From an Italian Cohort of Patients
Authors: Russano Francesco , Del Fiore Paolo , Di Prata Claudia , Pasqual Andrea , Marconato Roberto , Campana Luca Giovanni , Spina Romina , Gianesini Carlo Maria , Collodetto Alessandra , Tropea Saveria , Dall’Olmo Luigi , Carraro Sabrina , Parisi Alessandro , Galuppo Sara , Scarzello Giovanni , De Terlizzi Francesca , Rastrelli Marco , Mocellin Simone
Published: December 2021

The treatment of cutaneous and subcutaneous localizations from breast cancer (BC) is still a therapeutic challenge. Electrochemotherapy (ECT) is one of the available options, and it is characterized by the association between the administration of a chemotherapic agent (Bleomycin) with the temporary raise of permeability of the cellular membrane induced by the local administration of electrical impulses (electroporation). ECT represents an effective therapy for loco-regional control of this disease. This study aimed to investigate the predictive factors of response in cutaneous and subcutaneous localizations from breast cancer treated with ECT. We decided to evaluate the response to this treatment in 55 patients who underwent ECT between January 2013 and March 2020 at our Institute. We performed a monocentric retrospective cohort study. ECT was administered following the ESOPE (European Standard Operative Procedure of Electrochemotherapy) guidelines, a set of criteria updated in 2018 by a panel of European experts on ECT who defined the indications for selecting the patients who can benefit from the ECT treatment and the ones for technically performing the procedure. The responses were evaluated with the RECIST criteria (Response Evaluation Criteria in Solid Tumor). We found after 12 weeks of treatment a complete response (CR) in 64% of our patients. From the analysis divided for subgroups of covariates is emerged that lower BMI, reduced body surface, and absence of previous radiation treatment could be predictive for a better complete response. This study suggests that the efficacy of the ECT treatment is related to the concurrent systemic therapies while administering ECT. The association between ECT and immunotherapy has offered better results than the association between ECT and chemotherapy (p-value = 0.0463). So, ECT is a valuable tool in the treatment of cutaneous and subcutaneous metastases from breast cancer and its efficacy in local control of these lesions improves when it is well planned in a therapeutic scenario.
Classification of Adverse Events Following Surgery in Patients With Diffuse Lower-Grade Gliomas
Authors: Gómez Vecchio Tomás , Corell Alba , Buvarp Dongni , Rydén Isabelle , Smits Anja , Jakola Asgeir S.
Published: December 2021

Background

Recently, the Therapy-Disability-Neurology (TDN) was introduced as a multidimensional reporting system to detect adverse events in neurosurgery. The aim of this study was to compare the novel TDN score with the Landriel–Ibanez classification (LIC) grade in a large cohort of patients with diffuse lower-grade glioma (dLGG). Since the TDN score lacks validation against patient-reported outcomes, we described health-related quality of life (HRQoL) change in relation to TDN scores in a subset of patients.

Methods

We screened adult patients with a surgically treated dLGG World Health Organization (WHO) grade 2 and 3 between 2010 and 2020. Up until 2017, it consists of a retrospective cohort (n = 158). From 2017 and onwards, HRQoL was registered using EuroQoL-5-dimension, three levels of response (EQ-5D 3L) questionnaire at baseline and 3 months follow-up, in a prospectively recruited cohort (n = 102). Both the LIC grade and TDN score were used to classify adverse events.

Results

In total, 231 patients were included. In 110/231 (47.6%) of the surgical procedures, a postoperative complication was registered. When comparing the TDN score to LIC grades, only a minor shift towards complications of higher order could be observed. EQ-5D 3L was reported for 45 patients. Patients with complications related to surgery had pre- to postoperative changes in EQ-5D 3L index values (n = 27; mean 0.03, 95% CI −0.06 to 0.11) that were comparable to patients without complications (n = 18; mean −0.06, 95% CI −0.21 to 0.08). In contrast, patients with new-onset neurological deficit had a deterioration in HRQoL at follow-up, with a mean change in the EQ-5D 3L index value of 0.11 (n = 13, 95% CI 0.0 to 0.22) compared to −0.06 (n = 32, 95% CI −0.15 to 0.03) for all other patients.

Conclusions

In patients with dLGG, TDN scores compared to the standard LIC tend to capture more adverse events of higher order. There was no clear relation between TDN severity and HRQoL. However, new-onset neurological deficit caused impairment in HRQoL. For the TDN score to better align with patient-reported outcomes, more emphasis on neurological deficit and function should be considered.
MRI Radiomics in Prostate Cancer: A Reliability Study
Authors: Urraro Fabrizio , Nardone Valerio , Reginelli Alfonso , Varelli Carlo , Angrisani Antonio , Patanè Vittorio , D’Ambrosio Luca , Roccatagliata Pietro , Russo Gaetano Maria , Gallo Luigi , De Chiara Marco , Altucci Lucia , Cappabianca Salvatore
Published: December 2021

Background

Radiomics can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols, as well as by the segmentation of the region of interest (ROI). Prostate cancer (PCa) represents a difficult playground for this technique, due to discrepancies in the identification of the cancer lesion and the heterogeneity of the acquisition protocols. The aim of this study was to investigate the reliability of radiomics in PCa magnetic resonance imaging (MRI).

Methods

A homogeneous cohort of patients with a PSA rise that underwent multiparametric MRI imaging of the prostate before biopsy was tested in this study. All the patients were acquired with the same MRI scanner, with a standardized protocol. The identification and the contouring of the region of interest (ROI) of an MRI suspicious cancer lesion were done by two radiologists with great experience in prostate cancer (>10 years). After the segmentation, the texture features were extracted with LIFEx. Texture features were then tested with intraclass coefficient correlation (ICC) analysis to analyze the reliability of the segmentation.

Results

Forty-four consecutive patients were included in the present analysis. In 26 patients (59.1%), the prostate biopsy confirmed the presence of prostate cancer, which was scored as Gleason 6 in 6 patients (13.6%), Gleason 3 + 4 in 8 patients (18.2%), and Gleason 4 + 3 in 12 patients (27.3%). The reliability analysis conversely showed poor reliability in the majority of the MRI acquisition (61% in T2, 89% in DWI50, 44% in DWI400, and 83% in DWI1,500), with ADC acquisition only showing better reliability (poor reliability in only 33% of the texture features).

Conclusions

The low ratio of reliability in a monoinstitutional homogeneous cohort represents a significant alarm bell for the application of MRI radiomics in the field of prostate cancer. More work is needed in a clinical setting to further study the potential of MRI radiomics in prostate cancer.
Integrative Bioinformatics Analysis Demonstrates the Prognostic Value of Chromatin Accessibility Biomarkers in Clear Cell Renal Cell Carcinoma
Authors: Meng Meng , Lan Tianjun , Tian Duanqing , Qin Zeman , Li Yu , Li Jinsong , Cao Haotian
Published: December 2021

Clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of renal cell carcinoma (RCC) and has a poor 5-year survival rate. In recent years, medical advancement has promoted the understanding of the histopathological and molecular characterization of ccRCC; however, the carcinogenesis and molecular mechanisms of ccRCC remain unclear. Chromatin accessibility is an essential determinant of cellular phenotype. This study aimed to explore the potential role of chromatin accessibility in the development and progression of ccRCC. By the combination of open-access genome-wide chromatin accessibility profiles and gene expression profiles in ccRCC, we obtained a total of 13,474 crucial peaks, corresponding to 5,120 crucial genes and 9,185 differentially expressed genes. Moreover, two potential function modules (P2 and G4) that contained 129 upregulated genes were identified via the weighted gene co-expression network analysis (WGCNA). Furthermore, we obtained five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT), and a prognostic model was established based on these genes through the least absolute shrinkage and selection operator-proportional hazards model (LASSO-Cox) analysis. This model can stratify the ccRCC samples into a high-risk and a low-risk group, from which the patients have distinct prognosis. Further analysis demonstrated a completely different immune cell infiltration pattern between these two risk groups. This study also suggested that mast cell resting is associated with the prognosis of ccRCC and could be a target of immunotherapy. Overall, this study indicated that chromatin accessibility plays an essential role in ccRCC. The five prognostic chromatin accessibility biomarkers and the prognostic immune cells can provide a new direction for the treatment of ccRCC.
Case Report: Early Onset Systemic Lupus Erythematosus Due to Hereditary C1q Deficiency Treated With Fresh Frozen Plasma
Authors: Zecevic Milica , Minic Aleksandra , Pasic Srdjan , Perovic Vladimir , Prohászka Zoltán
Published: December 2021

Background:Hereditary C1q deficiency is associated with early-onset autoimmunity causing SLE or SLE-like disease as well as increased risk for infections with encapsulated bacteria. It is a rare genetic condition inherited in an autosomal recessive manner, caused by mutations in C1q genes. Treatment and management of this rare disease are very complex and include prophylactic vaccination, antibiotics, and immunosuppressive drugs. There are two possible modalities for the replacement of the missing protein: regular fresh frozen plasma (FFP) administration and allogeneic hematopoietic stem cell transplant because the protein is derived from monocytes. Replacing C1q with FFP is being attempted in some patients with success in controlling the disease and in avoiding flare.

Case Report:We report a case of sixteen-month-old girl with ulcerations in her mouth, skin erythema, and elevated liver enzymes. ANAs were positive, antibodies against dsDNA were negative, but she had positive anti-Smith antibodies. Complement complements C3 and C4 levels were normal. Total complement activity, classical pathway (hemolytic test) was deficient and C1q antigen was below the detection limit supporting the presence of C1q deficiency. The girl has pathogenic homozygous nonsense mutation in C1qC gene, Arg69Ter (c205>T). The initial response to corticosteroid therapy was good. Regular fresh frozen plasma infusions keep her disease under control, and we were able to reduce the dose of corticosteroids.

Conclusion:Young patients with cutaneous lesions resembling SLE, early onset of autoimmunity, with normal C3, C4, elevated ANAs, and negative anti-dsDNA, C1q deficiency should be suspected and complement screening tests should be done. It is important to exclude secondary C1q deficiency. FFP in our patient seems to be well tolerated, without any side effects, able to control the disease.
Medullary Serotonergic Binding Deficits and Hippocampal Abnormalities in Sudden Infant Death Syndrome: One or Two Entities?
Authors: Haynes Robin L. , Kinney Hannah C. , Haas Elisabeth A. , Duncan Jhodie R. , Riehs Molly , Trachtenberg Felicia , Armstrong Dawna D. , Alexandrescu Sanda , Cryan Jane B. , Hefti Marco M. , Krous Henry F. , Goldstein Richard D. , Sleeper Lynn A.
Published: December 2021

Sudden infant death syndrome (SIDS) is understood as a syndrome that presents with the common phenotype of sudden death but involves heterogenous biological causes. Many pathological findings have been consistently reported in SIDS, notably in areas of the brain known to play a role in autonomic control and arousal. Our laboratory has reported abnormalities in SIDS cases in medullary serotonin (5-HT) receptor1Aand within the dentate gyrus of the hippocampus. Unknown, however, is whether the medullary and hippocampal abnormalities coexist in the same SIDS cases, supporting a biological relationship of one abnormality with the other. In this study, we begin with an analysis of medullary 5-HT1Abinding, as determined by receptor ligand autoradiography, in a combined cohort of published and unpublished SIDS (n= 86) and control (n= 22) cases. We report 5-HT1Abinding abnormalities consistent with previously reported data, including lower age-adjusted mean binding in SIDS and age vs. diagnosis interactions. Utilizing this combined cohort of cases, we identified 41 SIDS cases with overlapping medullary 5-HT1Abinding data and hippocampal assessment and statistically addressed the relationship between abnormalities at each site. Within this SIDS analytic cohort, we defined abnormal (low) medullary 5-HT1Abinding as within the lowest quartile of binding adjusted for age and we examined three specific hippocampal findings previously identified as significantly more prevalent in SIDS compared to controls (granular cell bilamination, clusters of immature cells in the subgranular layer, and single ectopic cells in the molecular layer of the dentate gyrus). Our data did not find a strong statistical relationship between low medullary 5-HT1Abinding and the presence of any of the hippocampal abnormalities examined. It did, however, identify a subset of SIDS (~25%) with both low medullary 5-HT1Abinding and hippocampal abnormalities. The subset of SIDS cases with both low medullary 5-HT1Abinding and single ectopic cells in the molecular layer was associated with prenatal smoking (p= 0.02), suggesting a role for the exposure in development of the two abnormalities. Overall, our data present novel information on the relationship between neuropathogical abnormalities in SIDS and support the heterogenous nature and overall complexity of SIDS pathogenesis.
Non-contact Sleep/Wake Monitoring Using Impulse-Radio Ultrawideband Radar in Neonates
Authors: Lee Won Hyuk , Kim Seung Hyun , Na Jae Yoon , Lim Young-Hyo , Cho Seok Hyun , Cho Sung Ho , Park Hyun-Kyung
Published: December 2021

Background: The gold standard for sleep monitoring, polysomnography (PSG), is too obtrusive and limited for practical use with tiny infants or in neonatal intensive care unit (NICU) settings. The ability of impulse-radio ultrawideband (IR-UWB) radar, a non-contact sensing technology, to assess vital signs and fine movement asymmetry in neonates was recently demonstrated. The purpose of this study was to investigate the possibility of quantitatively distinguishing and measuring sleep/wake states in neonates using IR-UWB radar and to compare its accuracy with behavioral observation-based sleep/wake analyses using video recordings.

Methods: One preterm and three term neonates in the NICU were enrolled, and voluntary movements and vital signs were measured by radar at ages ranging from 2 to 27 days. Data from a video camcorder, amplitude-integrated electroencephalography (aEEG), and actigraphy were simultaneously recorded for reference. Radar signals were processed using a sleep/wake decision algorithm integrated with breathing signals and movement features.

Results: The average recording time for the analysis was 13.0 (7.0–20.5) h across neonates. Compared with video analyses, the sleep/wake decision algorithm for neonates correctly classified 72.2% of sleep epochs and 80.6% of wake epochs and achieved a final Cohen's kappa coefficient of 0.49 (0.41–0.59) and an overall accuracy of 75.2%.

Conclusions: IR-UWB radar can provide considerable accuracy regarding sleep/wake decisions in neonates, and although current performance is not yet sufficient, this study demonstrated the feasibility of its possible use in the NICU for the first time. This unobtrusive, non-contact radar technology is a promising method for monitoring sleep/wake states with vital signs in neonates.
An Update on the Effects of Probiotics on Gastrointestinal Cancers
Authors: Davoodvandi Amirhossein , Fallahi Farzaneh , Tamtaji Omid Reza , Tajiknia Vida , Banikazemi Zarrin , Fathizadeh Hadis , Abbasi-Kolli Mohammad , Aschner Michael , Ghandali Maryam , Sahebkar Amirhossein , Taghizadeh Mohsen , Mirzaei Hamed
Published: December 2021

Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.
Comparison of Adverse Kidney Outcomes With Empagliflozin and Linagliptin Use in Patients With Type 2 Diabetic Patients in a Real-World Setting
Authors: Lee Yueh-Ting , Hsu Chien-Ning , Fu Chung-Ming , Wang Shih-Wei , Huang Chiang-Chi , Li Lung-Chih
Published: December 2021

Background: To compare the effects of empagliflozin and linagliptin use on kidney outcomes of type 2 diabetes mellitus (T2DM) patients in a real-world setting.

Methods: The study involved a propensity score-matched cohort comprising new users of empagliflozin or linagliptin with T2DM between January 1, 2013 and December 31, 2018 from a large healthcare delivery system in Taiwan. Clinical outcomes assessed: acute kidney injury (AKI), post-AKI dialysis, and mortality. Cox proportional hazard model was used to estimate the relative risk of empagliflozin or linagliptin use; a linear mixed model was used to compare the average change in estimated glomerular filtration rate (eGFR) over time.

Results: Of the 7,042 individuals, 67 of 3,521 (1.9%) in the empagliflozin group and 144 of 3,521 (4.1%) in the linagliptin group developed AKI during the 2 years follow-up. Patients in the empagliflozin group were at a 40% lower risk of developing AKI compared to those in the linagliptin group (adjusted hazard ratio [aHR], 0.60; 95% confidence interval [CI], 0.45–0.82, p = 0.001). Stratified analysis showed that empagliflozin users ≥65 years of age (aHR, 0.70; 95% CI, 0.43–1.13, p = 0.148), or with a baseline eGFR <60 ml/min/1.73 m2 (aHR, 0.97; 95% CI, 0.57–1.65, p = 0.899), or with a baseline glycohemoglobin ≦7% (aHR, 1.01; 95% CI, 0.51–2.00, p =0.973) experienced attenuated benefits with respect to AKI risk. A smaller decline in eGFR was observed in empagliflozin users compared to linagliptin users regardless of AKI occurrence (adjusted β = 1.51; 95% CI, 0.30–2.72 ml/min/1.73 m2, p = 0.014).

Conclusion: Empagliflozin users were at a lower risk of developing AKI and exhibited a smaller eGFR decline than linagliptin users. Thus, empagliflozin may be a safer alternative to linagliptin for T2DM patients.
A Novel Polysaccharide Isolated From Fresh Longan (Dimocarpus longan Lour.) Activates Macrophage via TLR2/4-Mediated PI3/AKT and MyD88/TRAF6 Pathways
Authors: Lan Haibo , Li Wu , Xu Jucai , Yang Yuzhe , Tan Zhaolun , Yang Ruili
Published: December 2021

A novel immunomodulatory polysaccharide (LP4) with a molecular weight 6.31 × 104 g/mol was purified from fresh longan pulp. It was composed of mannose, glucose, glucuronic acid, galactose, xylose, arabinose, galacturonic acid, fucose, and rhamnose in a molar percentage of 36:31:10:7:4:4:3:2:2, and mainly linked by (1→6)-β-Man, (1→4)-β-Glc and (1→6)-α-Glc. LP4 can obviously enhance the phagocytosis of macrophages and promote the proliferation of lymphocytes. After treating macrophages with LP4 (12.5–50 μg/ml), the production of IL-1β and TNF-α was significantly increased. These increases of cytokines were suppressed when the TLR2/TLR4 receptors were inhibited by anti-TLR2 and/or anti-TLR4 antibodies. Moreover, the mRNA expression of INOS, AKT, PI3K, TRAF6 and MyD88 was significantly suppressed by TLR2/TLR4 antibodies. These results indicated that LP4 induced macrophage activation mainly via the TLR2 and TLR4-induced PI3K/AKT and MyD88/TRAF6 pathways.
Levels of Adherence of an Exercise Referral Scheme in Primary Health Care: Effects on Clinical and Anthropometric Variables and Depressive Symptoms of Hypertensive Patients
Authors: Gallegos-Carrillo Katia , Garcia-Peña Carmen , Salgado-de-Snyder Nelly , Salmerón Jorge , Lobelo Felipe
Published: December 2021

Among the modifiable health behaviors, physical activity (PA) promotion has been one of the challenges in primary care, particularly how to translate the results of proven interventions and implement them in the real world. This study was aimed to compare whether two programs designed for hypertensive patients achieve changes in clinical and anthropometric variables, quality of life, and depressive symptoms; and if higher levels of adherence to one of the interventions using an exercise referral (ER) approach achieved better health outcomes. Pragmatic cluster randomized trials were carried out in four Primary Health Care Units (PHCUs). Physicians in the PHCUs identified hypertensive patients and assessed whether they were eligible to be part of this trial. Each center was randomized to a brief PA counseling (BC, n = 2) or an exercise referral (ER, n = 2) intervention to conducted PA programs among hypertensive patients aged 35–70 years, self-reported as physically inactive. Outcome variables included changes in blood pressure levels, triglycerides, HDL cholesterol, fasting glucose, body mass index, waist/hip ratio, abdominal obesity, and metabolic syndrome risk score, health-related quality of life, and depressive symptoms. Longitudinal multilevel analyses assessed the effects of the BC and ER programs and the level of adherence of the ER on clinical, anthropometric, and mental health variables, models were linear for continuous variables, and logistic for dichotomous variables. Differences were observed in triglycerides, BMI, metabolic risk scores variables, and depressive symptoms among ER and BC programs. In addition, differences in the ER group were observed according to the level of adherence in blood pressure levels, waist circumference and waist/hip ratio, depressive symptoms, and the mental health component of health-related quality of life. An ER program in comparison to a BC intervention is promoting changes in some specific health indicators of hypertensive patients, showing the usefulness of these PA programs in primary health care facilities.
Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses
Authors: Vornholz Lilian , Nienhaus Fabian , Gliem Michael , Alter Christina , Henning Carina , Lang Alexander , Ezzahoini Hakima , Wolff Georg , Clasen Lukas , Rassaf Tienush , Flögel Ulrich , Kelm Malte , Gerdes Norbert , Jander Sebastian , Bönner Florian
Published: December 2021

Patients with acute ischemic stroke (AIS) present an increased incidence of systemic inflammatory response syndrome and release of Troponin T coinciding with cardiac dysfunction. The nature of the cardiocirculatory alterations remains obscure as models to investigate systemic interferences of the brain-heart-axis following AIS are sparse. Thus, this study aims to investigate acute cardiocirculatory dysfunction and myocardial injury in mice after reperfused AIS. Ischemic stroke was induced in mice by transient right-sided middle cerebral artery occlusion (tMCAO). Cardiac effects were investigated by electrocardiograms, 3D-echocardiography, magnetic resonance imaging (MRI), invasive conductance catheter measurements, histology, flow-cytometry, and determination of high-sensitive Troponin T (hsTnT). Systemic hemodynamics were recorded and catecholamines and inflammatory markers in circulating blood and myocardial tissue were determined by immuno-assay and flow-cytometry. Twenty-four hours following tMCAO hsTnT was elevated 4-fold compared to controls and predicted long-term survival. In parallel, systolic left ventricular dysfunction occurred with impaired global longitudinal strain, lower blood pressure, reduced stroke volume, and severe bradycardia leading to reduced cardiac output. This was accompanied by a systemic inflammatory response characterized by granulocytosis, lymphopenia, and increased levels of serum-amyloid P and interleukin-6. Within myocardial tissue, MRI relaxometry indicated expansion of extracellular space, most likely due to inflammatory edema and a reduced fluid volume. Accordingly, we found an increased abundance of granulocytes, apoptotic cells, and upregulation of pro-inflammatory cytokines within myocardial tissue following tMCAO. Therefore, reperfused ischemic stroke leads to specific cardiocirculatory alterations that are characterized by acute heart failure with reduced stroke volume, bradycardia, and changes in cardiac tissue and accompanied by systemic and local inflammatory responses.
Caught in the Act: Live-Cell Imaging of Plant Meiosis
Authors: Prusicki Maria Ada , Balboni Martina , Sofroni Kostika , Hamamura Yuki , Schnittger Arp
Published: December 2021

Live-cell imaging is a powerful method to obtain insights into cellular processes, particularly with respect to their dynamics. This is especially true for meiosis, where chromosomes and other cellular components such as the cytoskeleton follow an elaborate choreography over a relatively short period of time. Making these dynamics visible expands understanding of the regulation of meiosis and its underlying molecular forces. However, the analysis of meiosis by live-cell imaging is challenging; specifically in plants, a temporally resolved understanding of chromosome segregation and recombination events is lacking. Recent advances in live-cell imaging now allow the analysis of meiotic events in plants in real time. These new microscopy methods rely on the generation of reporter lines for meiotic regulators and on the establishment of ex vivo culture and imaging conditions, which stabilize the specimen and keep it alive for several hours or even days. In this review, we combine an overview of the technical aspects of live-cell imaging in plants with a summary of outstanding questions that can now be addressed to promote live-cell imaging in Arabidopsis and other plant species and stimulate ideas on the topics that can be addressed in the context of plant meiotic recombination.
Unravelling Rubber Tree Growth by Integrating GWAS and Biological Network-Based Approaches
Authors: Francisco Felipe Roberto , Aono Alexandre Hild , da Silva Carla Cristina , Gonçalves Paulo S. , Scaloppi Junior Erivaldo J. , Le Guen Vincent , Fritsche-Neto Roberto , Souza Livia Moura , Souza Anete Pereira de
Published: December 2021

Hevea brasiliensis (rubber tree) is a large tree species of the Euphorbiaceae family with inestimable economic importance. Rubber tree breeding programs currently aim to improve growth and production, and the use of early genotype selection technologies can accelerate such processes, mainly with the incorporation of genomic tools, such as marker-assisted selection (MAS). However, few quantitative trait loci (QTLs) have been used successfully in MAS for complex characteristics. Recent research shows the efficiency of genome-wide association studies (GWAS) for locating QTL regions in different populations. In this way, the integration of GWAS, RNA-sequencing (RNA-Seq) methodologies, coexpression networks and enzyme networks can provide a better understanding of the molecular relationships involved in the definition of the phenotypes of interest, supplying research support for the development of appropriate genomic based strategies for breeding. In this context, this work presents the potential of using combined multiomics to decipher the mechanisms of genotype and phenotype associations involved in the growth of rubber trees. Using GWAS from a genotyping-by-sequencing (GBS) Hevea population, we were able to identify molecular markers in QTL regions with a main effect on rubber tree plant growth under constant water stress. The underlying genes were evaluated and incorporated into a gene coexpression network modelled with an assembled RNA-Seq-based transcriptome of the species, where novel gene relationships were estimated and evaluated through in silico methodologies, including an estimated enzymatic network. From all these analyses, we were able to estimate not only the main genes involved in defining the phenotype but also the interactions between a core of genes related to rubber tree growth at the transcriptional and translational levels. This work was the first to integrate multiomics analysis into the in-depth investigation of rubber tree plant growth, producing useful data for future genetic studies in the species and enhancing the efficiency of the species improvement programs.
From Classical Radiation to Modern Radiation: Past, Present, and Future of Radiation Mutation Breeding
Authors: Ma Liqiu , Kong Fuquan , Sun Kai , Wang Ting , Guo Tao
Published: December 2021

Radiation mutation breeding has been used for nearly 100 years and has successfully improved crops by increasing genetic variation. Global food production is facing a series of challenges, such as rapid population growth, environmental pollution and climate change. How to feed the world's enormous human population poses great challenges to breeders. Although advanced technologies, such as gene editing, have provided effective ways to breed varieties, by editing a single or multiple specific target genes, enhancing germplasm diversity through mutation is still indispensable in modern and classical radiation breeding because it is more likely to produce random mutations in the whole genome. In this short review, the current status of classical radiation, accelerated particle and space radiation mutation breeding is discussed, and the molecular mechanisms of radiation-induced mutation are demonstrated. This review also looks into the future development of radiation mutation breeding, hoping to deepen our understanding and provide new vitality for the further development of radiation mutation breeding.
Initial Experience of Self-Expanding Metal Ureteral Stent in Recurrent Ureteral Stricture After Ureteroplasty
Authors: Gao Xiaoshuai , Chen Jixiang , Jian Zhongyu , Wang Menghua , Wang Wei , Peng Liao , Liu Zhenghuan , Wei Xin
Published: December 2021

Background: The aim of this prospective study was to assess the safety and effectiveness of self-expanding metal ureteral stent (MUS) for the treatment of recurrent ureteral stricture after ureteroplasty.

Methods: We prospectively included 24 patients who underwent MUS implantation between February 2019 and August 2020. The inclusion criteria for the procedure were recurrent ureteral strictures after ureteroplasty. A paired T test was used to compare continuous variables before and after surgery.

Results: A total of 24 patients were finally included in this study. The stricture site was most common on the proximal ureter 19 (79.2%), followed by distal ureter 4 (16.7%) and middle ureter 1 (4.2%). The median length of ureteral stricture is 2.5 (range 1–18) cm. The median operative time was 51.5 min, and the median hospital stay time after surgery was 3 days. Post-operative complication included pain 1 (4.2%), urinary tract infection 2 (8.3%) and hematuria 2 (8.3%). After a median follow-up of 12 months, 19/24 (83.3%) patients were clinically and radiologically successful. We endoscopically adjusted or exchanged the failed stents. The volume of hydronephrosis (124.7 ± 132.5 vs. 66.4 ± 73.2 cm3, P = 0.015), blood creatinine level (104.5 ± 45.4 vs. 80.1 ± 23.2 μmol/L, P = 0.044) and urea nitrogen level (6.9 ± 2.4 vs. 4.8 ± 1.5 mmol/L, P = 0.003) decreased significantly after a median follow-up of 12 months.

Conclusions: MUS is a safe and effective way to manage recurrent ureteral strictures after ureteroplasty. This technique provides a new choice for the treatment of recurrent stricture.
Postoperative Outcomes Analysis After Pancreatic Duct Occlusion: A Safe Option to Treat the Pancreatic Stump After Pancreaticoduodenectomy in Low-Volume Centers
Authors: Giuliani Antonio , Avella Pasquale , Segreto Anna Lucia , Izzo Maria Lucia , Buondonno Antonio , Coluzzi Mariagrazia , Cappuccio Micaela , Brunese Maria Chiara , Vaschetti Roberto , Scacchi Andrea , Guerra Germano , Amato Bruno , Calise Fulvio , Rocca Aldo
Published: December 2021

Background: Surgical resection is the only possible choice of treatment in several pancreatic disorders that included periampullar neoplasms. The development of a postoperative pancreatic fistula (POPF) is the main complication. Despite three different surgical strategies that have been proposed–pancreatojejunostomy (PJ), pancreatogastrostomy (PG), and pancreatic duct occlusion (DO)–none of them has been clearly validated to be superior. The aim of this study was to analyse the postoperative outcomes after DO.

Methods: We retrospectively reviewed 56 consecutive patients who underwent Whipple's procedure from January 2007 to December 2014 in a tertiary Hepatobiliary Surgery and Liver Transplant Unit. After pancreatic resection in open surgery, we performed DO of the Wirsung duct with Cyanoacrylate glue independently from the stump characteristics. The mean follow-up was 24.5 months.

Results: In total, 29 (60.4%) were men and 19 were (39.6%) women with a mean age of 62.79 (SD ± 10.02) years. Surgical indications were in 95% of cases malignant diseases. The incidence of POPF after DO was 31 (64.5%): 10 (20.8%) patients had a Grade A fistula, 18 (37.5%) Grade B fistula, and 3 (6.2%) Grade C fistula. No statistical differences were demonstrated in the development of POPF according to pancreatic duct diameter groups (p = 0.2145). Nevertheless, the POPF rate was significantly higher in the soft pancreatic group (p = 0.0164). The mean operative time was 358.12 min (SD ± 77.03, range: 221–480 min). Hospital stay was significantly longer in patients who developed POPF (p < 0.001). According to the Clavien-Dindo (CD) classification, seven of 48 (14.58%) patients were classified as CD III–IV. At the last follow-up, 27 of the 31 (87%) patients were alive.

Conclusions: Duct occlusion could be proposed as a safe alternative to pancreatic anastomosis especially in low-/medium-volume centers in selected cases at higher risk of clinically relevant POPF.
Przedsiębiorczy „cwaniacy”? – przedsiębiorczość w Polsce i społeczna percepcja przedsiębiorców w trakcie pandemii COVID-19 oraz okresie bezpośrednio ją poprzedzającym
Authors: Staniszewski Robert
Published: December 2021

In this article, the author conducted an analysis of entrepreneurship in Poland and the social perception of entrepreneurs during the COVID-19 pandemic and the period immediately preceding it. In the analytical part, indicators on the most important rankings related to entrepreneurship were used, which take into account the position of Poland compared to other countries. The article also uses selected reports and studies on economic, financial and social issues, including the results of public opinion polls. The inspiration for writing the article was the statement of Jarosław Kaczyński, who being asked about the Polish Order and tax changes, stated that “Those who live … out of cunning, they can actually lose out on it…”.
ARTUR BATOSZEWICZ, KRZYSZTOF KSIĘŻOPOLSKI, ANDRZEJ ZYBAŁA (RED.) Polska… Unia Europejska… Świat… w pandemii COVID-19 – wybrane zagadnienia. Wnioski dla kształtowania i prowadzenia polityki publicznej
Authors: Ołdak Małgorzata
Published: December 2021

The COVID-19 pandemic is a traumatic experience that, unlike previous crises, affects all countries. A team of researchers from the Warsaw School of Economics undertook a preliminary study of its consequences. The author of the review introduces the assumptions of the monograph, its main goals and structure, and attempts to supplement the proposed research areas with further aspects that may be important from the point of view of political science.
Городские агломерации: проблемы и тенденции развития
Authors: Cherkasov Alexander
Published: December 2021

The subject of this research was the modern urban agglomerations and its aim was to find out the main tendencies of their development by way of the analyses of problems faced by urban agglomerations and their management mechanisms. The main method of the conducted research was the comparative legal method, as the study is based on comparing the experience of different countries in the sphere of urban governance. The author used sociological, systemic and structural-functional approaches as well. The author believes that the problems faced by urban agglomerations are caused by the activities of different administrative bodies at their territory, the lack of proper coordination in the face of pretty acute rivalry between them. The mentioned problems are also exacerbated by modern migration processes. The number of “native” inhabitants is being decreased in many cities, the middle class is largely moving to suburbs while poor people are moving to urban centers, the urban population is getting older. The article also contains the analyses of different attitudes towards organization of administrative structures at the territory of the modern agglomeration. Proponents of only one strong jurisdiction, functioning within the agglomeration and taking decisions obligatory for the whole area, were called “consolidationists. “Polycentrists” believe that the more various jurisdictions function within the agglomeration the better, because centralized and hierarchical administrative model is outdated and ineffective.