bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of metastasis-associated in colon cancer 1 in retinoblastoma
Authors: Nair Rohini M , Prabhu Varsha , Manukonda Radhika , Mishra Dilip K , Kaliki Swathi , Vemuganti Geeta K 
Published: November 2020

Introduction:Metastasis-associated in colon cancer 1 (MACC1), one of the prognostic markers for colonic and other tumours was noted to be overexpressed in retinoblastoma (Rb) Y79 cancer stem cells. This prompted us to evaluate its expression in primary Rb tumour and serum samples with clinicopathologic correlation. The interacting partner, c-MET was also evaluated in primary tumour tissues to explore the activation of MACC1 signaling.Methodology:This study was done following institutional review board approval from participating institutes. Semiquantitative gene expression for MACC1 was evaluated using formalin-fixed paraffin-embedded sections and unfixed tumour samples from primary Rb cases ( n = 44). Immunolocalization for MACC1 was assessed in primary Rb tumours ( n = 22), bone marrow aspirates with metastasis ( n = 3), and c-MET expression was also assessed in Rb tumours ( n = 17). Serum MACC1 levels were analysed using enzyme-linked immunosorbent assay in samples collected from Rb patients undergoing enucleation ( n = 31), Rb patients with proven clinical metastasis ( n = 3), and compared to appropriate controls. Clinicopathologic correlation of MACC1 expression was analysed using the medical records with specific reference to histologic risk factors (HRF) for metastasis and differentiation.Results:High expression of MACC1 gene was noted in all the tumour samples ( n = 44), more so in cases with versus without HRF ( p < 0.0001). In cases with HRF, MACC1 and c-MET showed diffuse nuclear and cytoplasmic staining whereas it was predominantly cytoplasmic in cases without HRF. Mean immunoreactivity score of MACC1 and c-MET tissue immunolocalization revealed that cases with HRF showed significantly higher expression compared to cases without HRF ( p < 0.05). Unlike the findings in colonic tumours, serum levels of MACC1 were lower in patients compared to normal controls.Conclusion:Overexpression of MACC1 and c-MET in retinoblastoma tissues, specifically those with risk factors for metastasis, suggests its role in proliferation and possibly in invasion. However, the current data do not support it to be a clinical prognostic marker in retinoblastoma tumours. The inverse serum expression is an intriguing finding, which warrants further studies especially in retinoblastoma.
The right to revoke withdrawal notices from international organizations: The case of Brexit and the European Union
Authors: Naldi Gino , Magliveras Konstantinos 
Published: November 2020

Following the 2016 referendum, the UK notified its intention to withdraw from the European Union pursuant to Article 50 TEU. Given the political and legal consequences of a much-questioned referendum and the strong opinion of many parts of British society that the UK’s membership should not be terminated, the question arose whether such a notification could be revoked unilaterally. In the absence of any mention in Article 50, expert opinion was divided. International law – that is, the law of treaties and the law of international organizations – does not appear to provide a definite answer, while state practice is rather scarce. The constituent instruments of international and regional organizations containing withdrawal clauses are also silent, except for African organizations and development/investment organizations, which invariably allow Member States to rescind withdrawal notices. As regards the EU Treaties, before the Lisbon Treaty they did not contain a withdrawal clause. In the preliminary ruling given in Wightman v. Secretary of State for Exiting the European Union, which concerned whether an EU Member has the sovereign power under Article 50 to revoke unilaterally a withdrawal notice, the Court of Justice helped to clarify a critical question of EU Law but also of international law.
Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial
Authors: Sun Lingyun , Yan Yunzi , Chen Dongmei , Yang Yufei 
Published: November 2020

Aim: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. Method: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. Results: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_9 (coef. −0.64, P = .01). Conclusion: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.
Therapeutic Education and Physical Activity to Support Self-management of Cancer-related Fatigue in Hematologic Cancer Patients: Protocol of a Feasibility Randomized Controlled Trial
Authors: Denti Monica , Accogli Monia Allisen , Costi Stefania , Fugazzaro Stefania 
Published: November 2020

Introduction Hematologic malignancies account for nearly 8% of new cancer diagnosis in Italy. Cancer-related fatigue (CRF) is one of the most distressing symptoms reported by patients with cancer. As CRF has a multifactorial etiology, physical activity and therapeutic education may be beneficial for managing CRF, both during and after cancer treatment. However, there is a lack of evidence specific to hematologic malignancies. This paper describes the protocol of a feasibility study on Therapeutic Education and Physical Activity (TEPA) intervention to support self-management of CRF in patients with hematologic malignancies. Methods TEPA was addressed to newly diagnosed adult individuals with hematologic malignancy able to take part in a rehabilitation programme at the AUSL-IRCCS of Reggio Emilia. The protocol was developed in 2 phases. Phase I was an observational cohort study involving a convenience sample of 10 participants with the aim to evaluate the feasibility of the assessment schedule and to register longitudinal clinical data regarding CRF (FACIT-F), psychologic distress (NCCN Distress Thermometer), QoL (EORTC QLQ-C30), physical performance (TUG and 6MWT) and habitual level of physical activity during first months after diagnosis. Phase II (underway) is a feasibility randomized controlled trial (TEPA) involving a convenience sample of 40 participants and comparing 2 parallel active interventions (Therapeutic Education versus Therapeutic Education and Physical Activity) on top of usual care. The primary aim is to estimate the feasibility of TEPA, measured by the adherence rate to the intervention. Secondary aims are: to estimate the effect size of TEPA in terms of changes in CRF, psychological distress, QoL, physical performance and habitual level of physical activity (measured as in Phase I); to collect patient satisfaction, perception of usefulness of the TEPA intervention and data on long-term adherence to an active lifestyle. Data are collected in both phases at the time of diagnosis and then at 1-, 3- (completion of intervention) and 7-month follow-up. Discussion Data on feasibility and effect size of TEPA will be analyzed upon completion of Phase II, allowing us to design a large, adequately powered RCT to verify the effectiveness of this intervention on CRF management in patients with hematologic cancer. Trial registration: clinicaltrials.gov; Trial registration number: NCT03403075
Safety and Feasibility of Thoracoscopic Lung Resection for Non-Small-Cell Lung Cancer in Octogenarians
Authors: Lou Xiaoying , Sanders Andrew , Wagh Kaustubh , Binongo Jose N. , Sancheti Manu , Javidfar Jeffrey , Pickens Allan , Fernandez Felix , Force Seth , Khullar Onkar 
Published: November 2020

Objective Octogenarians comprise an increasing proportion of patients presenting with non-small-cell lung cancer (NSCLC). This study examines postoperative morbidity and mortality, and long-term survival in octogenarians undergoing thoracoscopic anatomic lung resection for NSCLC, compared with younger cohorts. Methods We conducted a retrospective review of our institutional Society of Thoracic Surgeons General Thoracic Surgery Database of all patients ≥60 years old undergoing elective lobectomy or segmentectomy for pathologic stage I, II, and IIIA NSCLC between 2009 and 2018. Results were compared between octogenarians ( n = 71) to 2 younger cohorts of 60- to 69-year-olds ( n = 359) and 70- to 79-year-olds ( n = 308). Long-term survival among octogenarians was graphically summarized using the Kaplan–Meier method. Cox regression analysis was used to identify preoperative risk factors for mortality. Results A greater proportion of octogenarians required intensive care unit admission and discharge to extended-care facilities; however, postoperative length of stay was similar between groups. Among postoperative complications, arrhythmia and renal failure were more likely in the older cohort. Compared to the youngest cohort, in-hospital and 30-day mortality were highest among octogenarians. Overall survival among octogenarians at 1, 3, and 5 years was 87.3%, 61.8%, and 50.5%, respectively. On multivariable Cox regression analysis of baseline demographic variables, presence of stroke (hazard ratio [HR] = 28.5, 95% confidence interval [CI]: 6.1 to 132.7, P < 0.001) and coronary artery disease (HR = 2.5, 95% CI: 1.2 to 5.3, P = 0.02) were significant predictors of overall mortality among octogenarians. Conclusions Thoracoscopic resection can be performed with favorable early postoperative outcomes among octogenarians. Long-term survival, although comparable to their healthy peers, is worse than those of younger cohorts. Further study into preoperative risk stratification and alternative therapies among octogenarians is needed.
Venous sinus stenting for the treatment of isolated pulsatile tinnitus: Results of a prospective trial
Authors: Patsalides Athos , Santillan Alejandro , Sundararajan Sri Hari , Michael Marissa , Suurna Maria , Alexiades George 
Published: November 2020

Objectives This prospective study evaluates the effectiveness and safety of venous sinus stenting for patients with isolated pulsatile tinnitus and lateral sinus stenosis. Methods Patients with isolated pulsatile tinnitus and lateral sinus stenosis with a minimum trans stenotic gradient of 4 mm Hg were treated with stenting. Pulsatile tinnitus before and after treatment was assessed with the Tinnitus Handicap Inventory (THI). Periprocedural adverse events, neurological complications, clinical and radiographic follow-up were also recorded. Results A total of 42 patients (41 females and 1 male) were included in the study (median age of 37.5 years). Thirty patients had post-stenotic fusiform and 12 had post-stenotic saccular venous sinus aneurysm. In addition to stenting, coils were used to treat the patients with saccular venous aneurysms. The median follow-up was 5 months (range 1 to 34 months). Most patients had complete (39/42) or near-complete (2/42) resolution of their pulsatile tinnitus post-procedure. There were no serious adverse events. Conclusion Stenting of the lateral venous sinus is a safe and effective treatment for patients with isolated pulsatile tinnitus due to venous sinus stenosis.
Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review
Authors: Yang Kaili , Li Jiarui , Sun Zhao , Zhao Lin , Bai Chunmei 
Published: November 2020

Background: A large proportion of patients eventually experience disease progression despite treatment with immune checkpoint inhibitors (ICIs), but subsequent treatment options are limited for this population. Retreatment with the same or different types of ICIs is a possible strategy, but the clinical efficacy and safety data are limited. This systematic review aims to evaluate the efficacy and safety of ICIs retreatment in patients with solid tumors after disease progression to previous ICIs. Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and major meeting libraries for prospective studies. The primary outcomes included the objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), and the incidence of grade ⩾3 immune-related adverse events (irAEs). Results: We identified 22 prospective studies including 1865 patients. For disease progression after CTLA-4 inhibitors, three studies evaluated anti-CTLA-4 retreatment. The ORR was 12–23%, the DCR was 48.4–67.7%, and the mOS was 12 months. The incidence of grade ⩾3 irAEs was 5.9–25%. Four studies evaluated anti-programmed cell death protein 1 (PD-1) retreatment. The ORR was 22–36%, the DCR was 40–64%, and the mOS was 13.4–20.6 months. The incidence of grade ⩾3 irAEs was <10%. For disease progression after PD-(L)1 inhibitors, 13 studies evaluated anti-PD-(L)1 retreatment. The ORR was 5–53%, the DCR was 38–83%, and the mOS was 13.9 months. The incidence of grade ⩾3 irAEs was 0–15% for patients retreated with single anti-PD-(L)1 agent, but was higher (0–64%) for those retreated with ICIs combined with other agents. Two studies evaluated anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) retreatment. The ORR was 0–22.4%, the DCR was 50–72%, and the mOS was 4–21 months. The incidence of grade ⩾3 irAEs was 26–61%. Conclusion: Retreatment with ICIs is feasible for cancer patients considering its encouraging efficacy and tolerable safety. Further prospective trials are needed to explore more promising strategies and identify suitable populations for retreatment.
Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin Administered via Continuous Subcutaneous Insulin Infusion Versus Subcutaneous Injection in Adults With Type 2 Diabetes and High-Dose Insulin Requirements
Authors: Ma Xiaosu , Benson Charles T. , Prescilla Randy , Zhang Shuyu , Linnebjerg Helle , LaBell Elizabeth S. , Morrow Linda A. , Jackson Jeffrey A. , Nguyen Alex , Ilag Liza L. , Johnson Jennal L. , Leishman Derek 
Published: November 2020

Introduction: Human regular U-500 insulin (U-500R) is approved for subcutaneous (SC) injection in patients with diabetes requiring >200 units/day of insulin. Here, pharmacokinetic and pharmacodynamic (PK/PD) profiles following U-500R administered by continuous subcutaneous insulin infusion (CSII) and SC injection in adults with type 2 diabetes (T2D) on high-dose insulin were studied. Methods: In this randomized, crossover, euglycemic clamp study, patients received a 100-unit bolus of U-500R via SC injection or CSII with basal infusion using a U-500R specific pump. PK parameters were estimated using non-compartmental methods. PD estimates were derived from the glucose infusion rate during the euglycemic clamp procedure. Results: When corrected for the basal infusion, the PK profiles for the 100-unit bolus of U-500R were similar for CSII and SC injection. Without correction for basal infusion, PK and PD profiles showed a greater insulin concentration and effect when U-500R was administered via CSII compared to SC injection, primarily due to basal insulin infusion for CSII. The ratio of geometric least squares AUC0-tlast means SC:CSII (90% CI) is 0.857 (0.729, 1.01) with correction (mean AUC0-tlast: 5230 pmol*L/h [SC injection] and 6070 pmol*L/h [CSII, with correction]) and 0.424 (0.361, 0.499) without correction (mean AUC0-tlast: 12300 pmol*L/h [CSII, without correction]). Median time-to-peak insulin concentration was six hours (range 0.5-8 hours) via SC injection and five hours (0.5-12 hours) via CSII. Conclusions: In adults with T2D on high-dose insulin, U-500R PK/PD parameters were similar for a 100-unit bolus when given by SC injection or CSII via a U-500R pump.
Self-Assessed Benefits of a Prostate Health Formulation on Nocturia in Healthy Males With Mild Lower Urinary Tract Symptoms: An Open Label Study
Authors: Hirsh Steven P , Pons Marianne , Joyal Steven V , Swick Andrew G 
Published: November 2020

Background Nocturia is the most bothersome lower urinary tract symptoms (LUTS) and can significantly reduce men's quality of life. It is often poorly managed with conventional treatments. Objective The purpose of this study was to evaluate the self-assessed benefits of a prostate health dietary combination formulation on mild LUTS, especially nocturia in healthy males. Methods In an open label clinical study, thirty healthy male subjects with mild LUTS took one daily capsule of the product for 60 days. The primary outcome was self-assessed severity of LUTS using the International Prostate Symptoms Score (IPSS) questionnaire at Day 1 (baseline), Day 30 and Day 60. Safety and compliance were also evaluated. Results At Day 60, IPSS significantly decreased from baseline by 16.3% (3.6 ± 2.1 vs. 4.3 ± 1.5, p < 0.05). Although the reduction in IPSS did not reach statistical significance at Day 30, it was mostly driven by a 30.7% decrease (p < 0.05) in the nocturia sub-score compared with baseline. While 37% of subjects reported at baseline waking up 2‒3 times/night to void, none did so after taking the study product for 60 days. Compliance was very high throughout the study. No adverse events related to the study product were reported. Conclusions The study product might be a safe alternative for individuals willing to explore a non-conventional approach to manage their nocturia. A larger randomized placebo-controlled clinical trial is warranted to confirm these results. Clinical trial registry: Clinical Trials.gov. Registration number (September 1st, 2016): NCT02886832.
Protective effects of acute exercise preconditioning on disuse-induced muscular atrophy in aged muscle: a narrative literature review
Authors: Yoshihara Toshinori , Naito Hisashi 
Published: November 2020

AbstractAging is associated with a progressive loss of skeletal muscle mass and strength, resulting in frailty and lower quality of life in older individuals. At present, a standard of clinical or pharmacological care to prevent the adverse effects of aging does not exist. Determining the mechanism(s) responsible for muscular atrophy in disused aged muscle is a required key step for the development of effective countermeasures. Studies suggest an age-related differential response of genes and signalings to muscle disuse in both rodents and humans, implying the possibility that effective countermeasures to prevent disuse muscle atrophy may be age-specific. Notably, exercise preconditioning can attenuate disuse-induced muscular atrophy in rodent and human skeletal muscles; however, information on age-specific mechanisms of this exercise-induced protection remains limited. This mini-review aimed to summarize the protective effects of acute exercise preconditioning on muscular atrophy in aged muscle and provide potential mechanisms for its preventive effect on skeletal muscle wasting.
Transcriptome and proteome profiling reveal complementary scavenger and immune features of rat liver sinusoidal endothelial cells and liver macrophages
Authors: Bhandari Sabin , Li Ruomei , Simón-Santamaría Jaione , McCourt Peter , Johansen Steinar Daae , Smedsrød Bård , Martinez-Zubiaurre Inigo , Sørensen Karen Kristine 
Published: November 2020

AbstractBackgroundLiver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs; liver resident macrophages) form the body’s most effective scavenger cell system for the removal of harmful blood-borne substances, ranging from modified self-proteins to pathogens and xenobiotics. Controversies in the literature regarding the LSEC phenotype pose a challenge when determining distinct functionalities of KCs and LSECs. This may be due to overlapping functions of the two cells, insufficient purification and/or identification of the cells, rapid dedifferentiation of LSECs in vitro, or species differences. We therefore characterized and quantitatively compared expressed gene products of freshly isolated, highly pure LSECs (fenestrated SE-1/FcγRIIb2+) and KCs (CD11b/c+) from Sprague Dawley, Crl:CD (SD), male rats using high throughput mRNA-sequencing and label-free proteomics.ResultsWe observed a robust correlation between the proteomes and transcriptomes of the two cell types. Integrative analysis of the global molecular profile demonstrated the immunological aspects of LSECs. The constitutive expression of several immune genes and corresponding proteins of LSECs bore some resemblance with the expression in macrophages. LSECs and KCs both expressed high levels of scavenger receptors (SR) and C-type lectins. Equivalent expression of SR-A1 (Msr1), mannose receptor (Mrc1), SR-B1 (Scarb1), and SR-B3 (Scarb2) suggested functional similarity between the two cell types, while functional distinction between the cells was evidenced by LSEC-specific expression of the SRs stabilin-1 (Stab1) and stabilin-2 (Stab2), and the C-type lectins LSECtin (Clec4g) and DC-SIGNR (Clec4m). Many immune regulatory factors were differentially expressed in LSECs and KCs, with one cell predominantly expressing a specific cytokine/chemokine and the other cell the cognate receptor, illustrating the complex cytokine milieu of the sinusoids. Both cells expressed genes and proteins involved in antigen processing and presentation, and lymphocyte co-stimulation.ConclusionsOur findings support complementary and partly overlapping scavenging and immune functions of LSECs and KCs. This highlights the importance of including LSECs in studies of liver immunity, and liver clearance and toxicity of large molecule drugs and nano-formulations.