bluuebunny/crossref_metadata_2025 huggingface dataset:
Retention in care in aging adults with a dual diagnosis of HIV infection and type 2 diabetes mellitus: a longitudinal retrospective cross-sectional study
Authors: Zuniga Julie Ann , García Alexandra A. , Lee Junse , Park Jungmin
Published: May 2020

Background

This study aimed to investigate the measures of retention in care (RIC) in persons living with HIV (PLWH) and type 2 diabetes mellitus (T2DM) by age group (younger vs. older adults).

Methods

This was a longitudinal retrospective cross-sectional study that used secondary data from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We examined RIC in 798 adult PLWH + T2DM who visited a CNICS clinic at least once in 2015. Six measures of RIC were examined: missed visits [measured as a continuous variable (total number of missed visits) and dichotomous variable (0 = never missed, 1 = missed)], visit adherence, 6-month visit gap, 4-month visit constancy, and the Health and Resources Services Administration HIV/AIDS Bureau’s RIC measure. We calculated Spearman correlation coefficients and conducted logistic regression and multi-group path analysis.

Results

Most RIC measures were significantly correlated (p < 0.05) with one another; only 4-month visit constancy was not correlated with other measures. Except for the number of missed visits in older adult PLWH + T2DM, we found no significant relationships between RIC measures and CD4 cell count using logistic regression. However, multi-group path analysis demonstrated significant positive relationships between most RIC measures and CD4 cell count in both age groups. In younger adults living with HIV (YALWH) + T2DM, HbA1c level, but not CD4 count, was significantly associated with most RIC measures.

Conclusions

RIC is related to disease control (CD4 cell count and HbA1c level) in PLWH + T2DM and notably, HbA1c level was only significantly affected in YALWH + T2DM. A future study is needed to find more accurate reasons for the fact that only HbA1c level had significant relationships in YALWH + T2DM. The findings from this study provide guidance in measuring RIC in PLWH who have comorbidities.
Going for brokerage: strategies and strains in commercial healthcare facilitation
Authors: Hunter Benjamin M.
Published: May 2020

Background

The formation of domestic and global marketplaces during the past 50 years has opened up new commercial opportunities for third-party activity in healthcare systems. Commercial mediation of access to healthcare is one recent area of activity that sees companies and individuals offering to organise healthcare and travel in return for payment. With varying degrees of control over the location, type, cost and experiences of healthcare provisioning, these intermediaries occupy potentially influential positions in healthcare systems and yet much of their work is poorly understood.

Methods

Drawing on social science theories of brokerage, this article presents a novel analysis of commercial healthcare facilitation. It focuses on facilitation companies and their workers as central, intermediating actors for people to access healthcare in markets characterised by complexity. Semi-structured interviews were conducted with people working in domestic and international healthcare facilitation in London and Delhi, and data were analysed using a framework approach that emphasises the structural features and personal agencies for this area of work.

Results

Findings point to an institutional environment for commercial healthcare facilitation marked by competition and the threat of obsolescence. The activities of rivals, and the risk that users and providers will bypass intermediaries, compels facilitation companies to respond strategically and to continuously pursue new populations and activities to mediate – to go for broke. These pressures percolate into the lives of people who perform facilitation work and who describe a physical and mental burden of labour incurred by onerous processes for generating and completing facilitation work. The need for language interpretation services introduces an additional set of relations and has created further points of tension. It is an environment that engenders mistrust and anxiety, and which incentivises exploitation and a commodification of users whose associated commissions are highly prized.

Conclusion

Brokerage analysis provides valuable insights into the strategies and strains for commercial mediation of access to healthcare, and the findings indicate opportunities for further research on the contributions of interpreters, diplomatic and business networks, and new technologies, and on the growth of new forms of mediation in domestic and overseas settings.
Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study
Authors: Walls G. M. , McConnell L. , McAleese J. , Murray P. , Lynch T. B. , Savage K. , Hanna G. G. , de Castro D. Gonzalez
Published: May 2020

Background

The evaluation of circulating tumour DNA (ctDNA) from clinical blood samples, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously.

Materials and methods

Patients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma samples were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes.

Results

Tumour-specific mutations were found in all patients (1 in 3 patients; 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05–3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline (p = 0.4627).

Conclusion

This study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.
Randomized clinical trials in ANCA-associated vasculitis: a systematic analysis of the WHO - International Clinical Trials Registry Platform
Authors: Iudici Michele , Puéchal Xavier , Brigante Alejandro , Atal Ignacio , Gabay Cem
Published: May 2020

Background

The analysis of the main features of randomized controlled trials (RCTs) on ANCA-associated vasculitis (AAV) can inform future study design.

Methods

We searched within the International Clinical Trials Registry Platform all registered RCTs on AAV from October 2008 to December 2018. Two reviewers selected studies according to pre-specified eligibility criteria. We retrieved information including countries, funding, design, sample sizes, eligibility criteria, primary outcomes (POs), and treatments.

Results

Among the 40 RCTs identified, 22 (55%) were conducted in Europe, 29 (72,5%) in a single country, 14 (35%) were industry-funded. The median number of patients planned to enrol was 68 (IQR 36–138). Only 28% of RCTs targeted a single vasculitis, and ANCA negative patients were not included in about 40% of studies. Interventions investigated were mainly drugs given to induce (40%) or maintain (32.5%) remission. Eighty-five percent of POs were considered being ‘patient-important’, but discrepancies in definition of disease states, such as remission or relapse were observed. Glucocorticoids use was part of the PO in < 25% of studies. The number of trials targeting a single disease, non-industry funded, incorporating glucocorticoids in PO, as well as the planned sample size increased over time.

Conclusion

Despite the important achievements in the field, a better harmonization of eligibility, and outcome criteria across studies is an important objective to pursue in next future.
The first seven years of nationally organized helicopter emergency medical services in Finland – the data from quality registry
Authors: Saviluoto Anssi , Björkman Johannes , Olkinuora Anna , Virkkunen Ilkka , Kirves Hetti , Setälä Piritta , Pulkkinen Ilkka , Laukkanen-Nevala Päivi , Raatiniemi Lasse , Jäntti Helena , Iirola Timo , Nurmi Jouni
Published: May 2020

Background

Helicopter Emergency Medical Services (HEMS) play an important role in prehospital care of the critically ill. Differences in funding, crew composition, dispatch criteria and mission profile make comparison between systems challenging. Several systems incorporate databases for quality control, performance evaluation and scientific purposes. FinnHEMS database was incorporated for such purposes following the national organization of HEMS in Finland 2012. The aims of this study are to describe information recorded in the database, data collection, and operational characteristics of Finnish HEMS during 2012–2018.

Methods

All dispatches of the six Finnish HEMS units recorded in the national database from 2012 to 2018 were included in this observational registry study. Five of the units are physician staffed, and all are on call 24/7. The database follows a template for uniform reporting in physician staffed pre-hospital services, exceeding the recommended variables of relevant guidelines.

Results

The study included 100,482 dispatches, resulting in 33,844 (34%) patient contacts. Variables were recorded with little or no missing data. A total of 16,045 patients (16%) were escorted by HEMS to hospital, of which 2239 (2%) by helicopter. Of encountered patients 4195 (4%) were declared deceased on scene. The number of denied or cancelled dispatches was 66,638 (66%). The majority of patients were male (21,185, 63%), and the median age was 57.7 years. The median American Society of Anesthesiologists Physical Scale classification was 2 and Eastern Cooperative Oncology Group performance class 0. The most common reason for response was trauma representing 26% (8897) of the patients, followed by out-of-hospital cardiac arrest 20% (6900), acute neurological reason excluding stroke 13% (4366) and intoxication and related psychiatric conditions 10% (3318). Blunt trauma (86%, 7653) predominated in the trauma classification.

Conclusions

Gathering detailed and comprehensive data nationally on all HEMS missions is feasible. A national database provides valuable insights into where the operation of HEMS could be improved. We observed a high number of cancelled or denied missions and a low percentage of patients transported by helicopter. The medical problem of encountered patients also differs from comparable systems.
Point-of-care ultrasound induced changes in management of unselected patients in the emergency department - a prospective single-blinded observational trial
Authors: Weile Jesper , Frederiksen Christian A. , Laursen Christian B. , Graumann Ole , Sloth Erik , Kirkegaard Hans
Published: May 2020

Background

Point-of-Care ultrasound (POCUS) changes the management in specific groups of patients in the Emergency Department (ED). It seems intuitive that POCUS holds an unexploited potential on a wide variety of patients. However, little is known about the effect of ultrasound on the broad spectrum of unselected patients in the ED. This study aimed to identify the effect on the clinical management if POCUS was applied on unselected patients. Secondarily the study aimed to identify predictors of ultrasound changing management.

Methods

This study was a blinded observational single center trial. A basic whole body POCUS protocol was performed in extension to the physical examination. The blinded treating physicians were interviewed about the presumptive diagnosis and plan for the patient. Subsequently the physicians were unblinded to the POCUS results and asked to choose between five options regarding the benefit from POCUS results.

Results

A total of 403 patients were enrolled in this study. The treating physicians regarded POCUS examinations influence on the diagnostic workup or treatment as following: 1) No new information: 249 (61.8%), 2) No further action: 45 (11.2%), 3) Further diagnostic workup needed: 52 (12.9%), 4) Presumptive diagnosis confirmed 38 (9.4%), and 5) Immediate treatment needed: 19 (4.7%). Predictors of beneficial ultrasound were: (a) triage > 1, (b) patient comorbidities (cardiac disease, hypertension or lung disease), or (c) patients presenting with abdominal pain, dyspnea, or syncope.

Conclusion

POCUS was found to be potentially beneficial in 27.0% of all patients. High triage score, known cardiac disease, hypertension, pulmonary diseases, a clinical presentation with abdominal pain, dyspnea, or syncope are predictors of this. Future research should focus on patient-important outcomes when applying POCUS on these patients.

Trial registration

The trail was registered prior to patient inclusion with the Danish Data Protection Agency (https://www.datatilsynet.dk/ Case no: 1–16–02-603-14) and Clinical Trials (www.clinicaltrials.gov/ Protocol ID: DNVK1305018).
IL-23 in arthritic and inflammatory pain development in mice
Authors: Lee Kevin M.-C. , Zhang Zihao , Achuthan Adrian , Fleetwood Andrew J. , Smith Julia E. , Hamilton John A. , Cook Andrew D.
Published: May 2020

Background

The cytokine, interleukin-23 (IL-23), can be critical for the progression of inflammatory diseases, including arthritis, and is often associated with T lymphocyte biology. We previously showed that certain lymphocyte-independent, inflammatory arthritis and pain models have a similar requirement for tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF), and C-C motif ligand 17 (CCL17). Given this correlation in cytokine requirements, we explored whether IL-23 might interact with this cytokine cluster in the control of arthritic and inflammatory pain.

Methods

The role of IL-23 in the development of pain-like behaviour was investigated using mouse arthritis models (zymosan-induced arthritis and GM-CSF-, TNF-, and CCL17-driven monoarticular arthritis) and inflammatory pain models (intraplantar zymosan, GM-CSF, TNF, and CCL17). Additionally, IL-23-induced inflammatory pain was measured in GM-CSF−/−, Tnf−/−, and Ccl17E/E mice and in the presence of indomethacin. Pain-like behaviour and arthritis were assessed by relative weight distribution in hindlimbs and histology, respectively. Cytokine mRNA expression in knees and paw skin was analysed by quantitative PCR. Blood and synovial cell populations were analysed by flow cytometry.

Results

We report, using Il23p19−/− mice, that innate immune (zymosan)-driven arthritic pain-like behaviour (herein referred to as pain) was completely dependent upon IL-23; optimal arthritic disease development required IL-23 (P < 0.05). Zymosan-induced inflammatory pain was also completely dependent on IL-23. In addition, we found that exogenous TNF-, GM-CSF-, and CCL17-driven arthritic pain, as well as inflammatory pain driven by each of these cytokines, were absent in Il23p19−/− mice; optimal disease in these mBSA-primed models was dependent on IL-23 (P < 0.05). Supporting this cytokine connection, it was found conversely that IL-23 (200 ng) can induce inflammatory pain at 4 h (P < 0.0001) with a requirement for each of the other cytokines as well as cyclooxygenase activity.

Conclusions

These findings indicate a role for IL-23 in innate immune-mediated arthritic and inflammatory pain with potential links to TNF, GM-CSF, CCL17, and eicosanoid function.
Tonsillar granuloma associated with hypogammaglobulinemia
Authors: Laajala Aleksi , Kuismin Outi , Tastula Mikko , Tiitto Leena , Kauppila Saila , Salo Anna , Åström Pirjo , Nissinen Antti , Glumoff Virpi , Seppänen Mikko R. J. , Hautala Timo
Published: May 2020

Background

Rare tonsillar granulomas may be caused for example by infections, malignancies or sarcoidosis. Granulomas also occur in inborn errors of immunity (IEI) such as common variable immunodeficiency (CVID) with B cell maturation defects and hypogammaglobulinemia. CVID shares various features with sarcoidosis and drug-induced secondary hypogammaglobulinemia; careful consideration of differential diagnosis between these conditions is warranted.

Case presentation

A 29-year-old female with epilepsy developed dysphagia, dyspnea and impaired exercise tolerance. Obstruction caused by swollen lingual tonsil and edema in the epiglottis and arytenoid mucosa were found. Lingual tonsil and epiglottis biopsies displayed non-necrotizing granulomas. There was no evidence of viral, bacterial, mycobacterial or fungal infections. Chest X-ray, computerized tomography of chest and ultrasound of neck and abdomen remained unremarkable. Positron emission tomography/computed tomography (PET/CT) showed laryngeal enhancement. Empiric antimicrobials combined with prednisolone were insufficient to control her disease. In immunological evaluation, the patient had normal counts of B and T cells. Proportions of CD27+ memory B cells (30.3%) and IgD−IgM−CD27+ switched memory B cells (7.2%; normal range 6.5–29.2%) were normal. Percentage of activated CD21low B cells was high (6.6%; normal range 0.6–3.5%). IgG (3.5 g/L; normal range 6.77–15.0 g/l) and all IgG subclass concentrations were low. Anti-polysaccharide responses were impaired, with 3/10 serotypes reaching a level of 0.35 µg/ml after immunization with Pneumovax®. The findings were consistent with hypogammaglobulinemia resembling CVID, possibly secondary to antiepileptic medication. Her dyspnea and dysphagia responded favorably to subcutaneous IgG and rituximab.

Conclusions

Tonsillar granulomas can be the presenting and only clinical feature of B cell deficiency, highlighting the diversity of symptoms and findings in primary or secondary immunodeficiencies.
DeConFuse: a deep convolutional transform-based unsupervised fusion framework
Authors: Gupta Pooja , Maggu Jyoti , Majumdar Angshul , Chouzenoux Emilie , Chierchia Giovanni
Published: May 2020

This work proposes an unsupervised fusion framework based on deep convolutional transform learning. The great learning ability of convolutional filters for data analysis is well acknowledged. The success of convolutive features owes to the convolutional neural network (CNN). However, CNN cannot perform learning tasks in an unsupervised fashion. In a recent work, we show that such shortcoming can be addressed by adopting a convolutional transform learning (CTL) approach, where convolutional filters are learnt in an unsupervised fashion. The present paper aims at (i) proposing a deep version of CTL, (ii) proposing an unsupervised fusion formulation taking advantage of the proposed deep CTL representation, and (iii) developing a mathematically sounded optimization strategy for performing the learning task. We apply the proposed technique, named DeConFuse, on the problem of stock forecasting and trading. A comparison with state-of-the-art methods (based on CNN and long short-term memory network) shows the superiority of our method for performing a reliable feature extraction.
Exploring prevention and mitigation strategies to reduce the health impacts of occupational exposure to wildfires for wildland firefighters and related personnel: protocol of a scoping study
Authors: Koopmans Erica , Fyfe Trina , Eadie Mike , Pelletier Chelsea A.
Published: May 2020

Background

With an increase in wildfire activity across the globe and growing numbers of personnel involved each year, it is necessary to explore the health impacts of occupational exposure to wildfires and the practices and policies that can be implemented to mitigate these effects. The aim of this work is to (1) identify the impact occupational exposure to wildfires has on health outcomes including physical, mental, and social wellbeing; (2) examine the characteristics and effectiveness of mitigation strategies or policies to reduce negative health impacts as reported by current literature and reports; and (3) develop a program of research to address and understand the health impacts of occupational exposure to wildfires based on gaps in the literature and stakeholder priorities.

Methods

This scoping study will be conducted in two phases: (1) scoping literature review and (2) modified Delphi process. The literature review will follow a methodologically rigorous scoping review approach that includes (a) identifying the research question (and protocol development), (b) identifying literature (an iterative process), (c) selecting relevant studies, (d) extracting data into tables, and (e) synthesizing, summarizing, and reporting results. Alongside this, a modified Delphi process will be conducted to define priorities for wildland fire occupational health research. A partnership with the British Columbia (BC) Wildfire Service will enable exploring the appropriateness of identified mitigation strategies and health risks for the BC context.

Discussion

This two-phase approach will provide an in-depth review of the literature of the health impacts of occupational exposure to wildfires and identify mitigation strategies or policies implemented to protect workers and reduce negative health impacts. It is anticipated that these findings may provide recommendations for “quick wins” or initial action that can be implemented within the BC context to reduce negative health outcomes, and inform gaps in context-specific research that needs to be addressed through a strategic, collaborative research program over the next 5 years.

Systematic review registration

Open Science Frameworkosf.io/ugz4
The arbitrary-order fractional hyperbolic nonlinear scalar conservation law
Authors: Shirkhorshidi S. M. Reza , Rostamy D. , Othman W. A. M. , Awang M. A. Omar
Published: May 2020

In this paper, we use a new powerful technique of arbitrary-order fractional (AOF) characteristic method (CM) to solve the AOF hyperbolic nonlinear scalar conservation law (HNSCL) of time and space. We present the existence and uniqueness of this class of equations in time and one-dimensional space of fractional arbitrary order. We extend Jumarie’s modification of Riemann–Liouville and Caputo’s definition of the fractional arbitrary order to introduce some formulae (Appl. Math. Lett. 22:378–385, 2009; Appl. Math. Lett. 18:739–748, 2005). Then, we use these formulae to prove the main theorem. In the application section, we use the analytical technique that is presented in the theorem to solve examples that are given.
Quadratic covariations for the solution to a stochastic heat equation with space-time white noise
Authors: Sun Xichao , Yan Litan , Yu Xianye
Published: May 2020

Let $u(t,x)$u(t,x) be the solution to a stochastic heat equation $$ \frac{\partial }{\partial t}u=\frac{1}{2} \frac{\partial ^{2}}{\partial x^{2}}u+ \frac{\partial ^{2}}{\partial t\,\partial x}X(t,x),\quad t\geq 0, x\in { \mathbb{R}} $$∂∂tu=12∂2∂x2u+∂2∂t∂xX(t,x),t≥0,x∈R with initial condition $u(0,x)\equiv 0$u(0,x)≡0, where Ẋ is a space-time white noise. This paper is an attempt to study stochastic analysis questions of the solution $u(t,x)$u(t,x). In fact, it is well known that the solution is a Gaussian process such that the process $t\mapsto u(t,x)$t↦u(t,x) is a bi-fractional Brownian motion with Hurst indices $H=K=\frac{1}{2}$H=K=12 for every real number x. However, the many properties of the process $x\mapsto u(\cdot ,x)$x↦u(⋅,x) are unknown. In this paper we consider the generalized quadratic covariations of the two processes $x\mapsto u(\cdot ,x),t\mapsto u(t,\cdot )$x↦u(⋅,x),t↦u(t,⋅). We show that $x\mapsto u(\cdot ,x)$x↦u(⋅,x) admits a nontrivial finite quadratic variation and the forward integral of some adapted processes with respect to it coincides with “Itô’s integral”, but it is not a semimartingale. Moreover, some generalized Itô formulas and Bouleau–Yor identities are introduced.
Autumn migration direction of juvenile willow warblers (Phylloscopus t. trochilus and P. t. acredula) and their hybrids assessed by qPCR SNP genotyping
Authors: Zhao Tianhao , Ilieva Mihaela , Larson Keith , Lundberg Max , Neto Júlio M. , Sokolovskis Kristaps , Åkesson Susanne , Bensch Staffan
Published: May 2020

Backgrounds

Geographic regions, where two closely related taxa with different migration routes come into contact, are known as migratory divides. Hybrids originating from migratory divides are hypothesized to migrate intermediately relative to the parental populations. Few studies have tested this hypothesis in wild birds, and only in hybrids that have completed the migration back to the breeding grounds. Here, we make use of the well-established migration routes of willow warblers (Phylloscopus trochilus), for which the subspecies trochilus and acredula have migration-associated genetic markers on chromosomes 1 and 5. The genetic approach enabled us to analyze the geographic distribution of juveniles during their first autumn migration, predicting that hybrids should be more frequent in the central flyway over Italy than along the typical SW routes of trochilus and SE routes of acredula.

Methods

Blood and feather samples were collected from wintering birds in Africa (n = 69), and from juveniles during autumn migration in Portugal (n = 33), Italy (n = 38) and Bulgaria (n = 32). Genotyping was carried out by qPCR SNP assays, on one SNP each on chromosome 1 (SNP 65) and chromosome 5 (SNP 285). Both these SNPs have alternative alleles that are highly fixed (> 97%) in each of the subspecies.

Results

The observed combined genotypes of the two SNPs were associated with the known migration routes and wintering distributions of trochilus and acredula, respectively. We found hybrids (HH) among the juveniles in Italy (5/38) and in Portugal (2/33). The proportion of hybrids in Italy was significantly higher than expected from a background rate of hybrid genotypes (1.5%) in allopatric populations of the subspecies.

Conclusions

Our genetic approach to assign individuals to subspecies and hybrids allowed us to investigate migration direction in juvenile birds on their first migration, which should better reflect the innate migratory direction than studies restricted to successful migrants. The excess of hybrids in Italy, suggests that they employ an intermediate route relative to the parental populations. Our qPCR SNP genotyping method is efficient for processing large sample sizes, and will therefore be useful in migration research of species with known population genetic structure.
TRAF3 can interact with GMEB1 and modulate its anti-apoptotic function
Authors: Kotsaris George , Kerselidou Despoina , Koutsoubaris Dimitrios , Constantinou Elena , Malamas George , Garyfallos Dimitrios A. , Ηatzivassiliou Eudoxia G.
Published: May 2020

Background

Members of Tumor Necrosis Factor (TNF) Receptor-Associated Factors (TRAFs) family interact with the cytoplasmic tails of TNF receptor family members to mediate signal transduction processes. TRAF3 has a major immunomodulatory function and TRAF3 deficiency has been linked to malignancies, such as multiple myeloma and lymphoid defects. In order to characterize the molecular mechanisms of TRAF3 signaling, the yeast two-hybrid system was used to identify proteins that interact with TRAF3.

Results

The yeast two-hybrid screen of a human B cell cDNA library with TRAF3 as bait, identified Glucocorticoid Modulatory Element-Binding Protein 1 (GMEB1) as a TRAF3-interacting protein. Previous studies indicated that GMEB1 functions as a potent inhibitor of caspase activation and apoptosis. The interaction of TRAF3 and GMEB1 proteins was confirmed in mammalian cells lines, using immunoprecipitation assays. The RING and TRAF-C domains of TRAF3 were not essential for this interaction. The overexpression of TRAF3 protein enhanced the anti-apoptotic function of GMEB1 in HeLa cells. On the other hand, downregulation of TRAF3 by RNA interference decreased significantly the ability of GMEB1 to inhibit apoptosis. In addition, LMP1(1–231), a truncated form of the EBV oncoprotein LMP1, that can interact and oligomerize with TRAF3, was also able to cooperate with GMEB1, in order to inhibit apoptosis.

Conclusions

Our protein-interaction experiments demonstrated that TRAF3 can interact with GMEB1, which is an inhibitor of apoptosis. In addition, cell viability assays showed that overexpression of TRAF3 enhanced the anti-apoptotic activity of GMEB1, supporting a regulatory role of TRAF3 in GMEB1-mediated inhibition of apoptosis. Better understanding of the molecular mechanism of TRAF3 function will improve diagnostics and targeted therapeutic approaches for TRAF3-associated disorders.
Malignant adenomyoepithelioma of the breast
Authors: Moro Kazuki , Sakata Eiko , Nakahara Asa , Hashidate Hideki , Gabriel Emmanuel , Makino Haruhiko
Published: May 2020

Background

Adenomyoepithelioma (AME) of the breast is a very rare tumor and is generally considered to be benign. However, some show malignant transformation, which results in local recurrences or distant metastases. The morphological features of AME that might predict malignant potential have not been elucidated. Moreover, there is also no established multidisciplinary treatment for malignant AME aside from complete excision at an early stage.

Case presentation

A 64-year-old female diagnosed with AME of the left breast underwent lumpectomy. The surgical margins were negative. Six months after the operation, however, malignant AME recurred locally in the left breast. MRI showed multiple masses, which invaded the skin. A left mastectomy with axillary lymph node dissection was performed. Additional areas of AME were found in about one third of the entire breast. Eight months after the mastectomy, lung metastases were detected. She underwent chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC) for 9 cycles with little response. Lung metastasectomy was performed. Nine months after lung metastasectomy, the metastases were widespread to the brain, heart, and kidney; she subsequently died 2 months later.

Conclusions

Malignant AME has various morphological features, and in this report, we characterize new findings from both imaging and pathology/autopsy. Malignant potency is related to the tumor size, tumor appearance, and mitoses, even if only a few. Given that ductal spread is one of the morphological features of malignant AME, it is of paramount importance to assess the surgical margins.
Analysis of corporate sustainability performance and corporate financial performance causal linkage in the Indian context
Authors: Jha Milind Kumar , Rangarajan K.
Published: May 2020

This paper aims to explore the relationship between corporate sustainability performance (CSP) and corporate firm performance (CFP) for a sample of the top 500 Indian firms covering the period from 2008 to 2018. CSP variables have been considered at both aggregate and disaggregate levels of environmental, social and governance performance. CFP has been evaluated in both accounting and market-based measures. Rigorous statistical methods have been used to evaluate the bidirectional causality and intensity of the CSP-CFP relationship using the Granger causality test and multiple regression for panel data. A sectoral level trend analysis is presented dividing the firms in various industries and classifying them in ESI vs non-ESI sectors. The findings indicate the absence of causality among CSP and CFP variables in either direction and suggest that the CSP-CFP linkage is mostly insignificant for Indian firms at the aggregate level. At an individual level, some negative association is found between CSP and CFP. This relationship has an adverse impact on CSP-CFP linkage in both cases, which means that Indian firms don’t get the financial performance benefits of investments done for sustainability. Our findings with mostly insignificant results for this relation also means that firms with higher or lower CSP on ESG dimensions will perform likewise in terms of CFP. The findings have practical implications for corporates, academicians, and policymakers alike given sustainability as a high focus area for all.
l-carnitine acts as a neuroprotecor against aspartame injury in Wistar albino rat
Authors: Hamza Reham Z. , Al-Eisa Rasha A. , El-Shenawy Nahla S.
Published: May 2020

Background

l-carnitine(LC) plays an important role in the oxidative/antioxidative balance of different organs. The study has explored the effect of the daily administration of aspartame (ASP) at two different doses for 4 weeks induces oxidative stress, inflammation, and histopathology in the brain of rats. This study also focused on explaining whetherl-carnitine (LC) has potential ameliorative effects against pathophysiology induced by ASP in the brain. Adult male Wistar rats were split into six groups as follows: control animals were administered with vehicle, group of ASP at a low dose (ASP-LD) was given 75 mg/kg B.W., high dose of ASP (ASP-HD; 150 mg/kg), animals were treated with LC (10 mg/kg), ASP-LD + LC group and ASP-HD + LC treated rats.

Results

ASP induced large increments in cytokines of interleukin-6, tumor necrosis factor-α, myeloperoxidase, xanthine oxidase, cyclooxygenase-2, and prostaglandin E2 in a dose-dependent response of the brain. Activities of superoxide dismutase/catalase, glutathione peroxidase, and acetylcholinesterase, besides levels of thiol, glutathione, a brain-derived neurotrophic factor, and neurotransmitters, were decreased in the brain tissue. The inauguration of brain injury by ASP administration was depended on the dose of treatment. Co-administration of LC with ASP significantly reversed and corrected all the abovementioned parameters.

Conclusion

The data confirm that LC attenuated ASP neurotoxicity by suppressing the inflammation, oxidative stress and improving the neurotransmitters, antioxidants coupled with the histological and cellular structure.
Uneven solidarity: the school strikes for climate in global and intergenerational perspective
Authors: Walker Catherine
Published: May 2020

Background

The school strikes for climate (henceforth, the school strikes) initiated by Greta Thunberg have brought young people’s environmental concerns to the global stage. However, there is a danger of considering youth environmental concerns only through the actions of highly mobilised young people who are heavily concentrated in the urban Global North. This article revisits qualitative data collected before the school strikes to consider how 11–14-year-olds in India and England interpreted and responded to environmental hazards and degradation in their everyday lives, and connected their situated experiences to narratives of global environmental crisis. The young people occupied a range of socio-economic positions and were experiencing different degrees of vulnerability to environmental hazards.

Results

All of the research participants were concerned about the future of the planet and their immediate environments. However, for the most environmentally vulnerable participants, future- and globally-oriented environmental concerns were overpowered by more immediate concerns. Although the young people were engaged in responses to environmental concerns, they did not see themselves as acting alone but rather with others around them, often adults. Some young people expressed doubt about the extent to which they as generationally-positioned individuals could make a difference to the problems discussed. These findings in many ways anticipate the school strikes, wherein young people are taking action to call upon adults to respond to environmental problems that young people recognise are beyond their individual capacities to resolve.

Conclusion

The environmental activism of a significant minority of young people is to be applauded, however, the interest in youth activism prompted by the school strikes runs the risk of flattening global inequalities in young people’s exposure to environmental hazards, access to education and global knowledge networks. There is a need to look beyond such high-profile activities to understand how young people around the world are interpreting and responding to environmental concerns as generationally-positioned individuals operating within broader regimes of power.
Potent bioactive methanolic extract of wild orange (Citrus macroptera Mont.) shows antioxidative, anti-inflammatory, and antimicrobial properties in in vitro, in vivo, and in silico studies
Authors: Lala Mousikha , Modak Debabrata , Paul Subhashis , Sarkar Indrani , Dutta Ankita , Kumar Anoop , Bhattacharjee Soumen , Sen Arnab
Published: May 2020

Background

There is always an increasing demand for natural remedies from natural sources which can substitute the synthetic therapeutic drugs and lessen their side effects. The present study aims to investigate the antioxidant, anti-inflammatory, antimicrobial properties and in silico docking study ofCitrus macropteraleaf (CML) extract in both in vivo and in vitro aspect.

Material and methods

The antioxidant and anti-inflammatory potential of crude extract was investigated in vitro and in vivo on Wistar albino rat. The antioxidant potentiality also investigated on HepG2 cell line. Antimicrobial activity was evaluated againstStaphylococcussp. andKlebsiellasp. Chemical compounds of the crude extract were identified by GC-MS analysis. In silico docking was also done against NF-ҡB protein.

Results

At 200 μg/ml concentration, CML significantly scavenges reactive oxygen species (ROS) which was generated on HepG2 cell line. CML showed 71% anti-inflammatory activity (p≤ 0.001) against carrageenan-induced paw edema in albino Wistar rats. CML extract is very effective againststaphylococcussp. thanKlebsiellasp. In the docking analysis, the proximadiol and menthone had − 5.6 kcal/mol and − 5.7 kcal/mol binding affinity with the protein NF-ҡB.

Conclusion

In the present work, CML provided notable antioxidant, anti-inflammatory, and antimicrobial activity. This activity was confirmed by both in vitro and in vivo followed by in silico docking technique. Overall, the experimental results presented in this study suggest that crude extract of CML could be used as a promising antioxidant and anti-inflammatory candidate with potential benefits.
Ysla de Panciteria: a preliminary study on the culinary heritage significance of pancit using the heritage documentation approach—the case of Luzon Island, Philippines
Authors: Mercado Jame Monren T. , Andalecio Avi Ben P.
Published: May 2020

Pancitin the Philippines is known as one of the acculturated dishes of the Filipinos from the Chinese. Filipinos accepted the culinary tradition and became as one of the indigenized culinary identities. This qualitative study explicates the culinary heritage significances ofpancitin Luzon Island, Philippines using the Heritage Documentation Approach. From that context, this paper highlights the different kinds and variations ofpancitbased on cultural and heritage aspects of the community and its related characteristics such as the raw ingredients, selling points, cooking equipment, and tools; process of cooking, consumption, and the disposal and recycling of wastes. The researchers make use of different theoretical frameworks from international and national cultural charters and conventions. In the conduct of the research, the researchers used observation as the documentation process, which was based from the cultural heritage mapping. In-depth interviews were utilized to determine the perspectives of the major stakeholders specifically the local government units (LGUs) specifically the Tourism; and Culture and Arts Office; local culinary historians, owners of the restaurants or people who are known for practicing the culinary tradition; and the non-government organizations (NGOs) who are managing and safeguarding the culinary tradition. All of the gathered data were analyzed through the use of thematic analysis and repertory grid. Documentary evidences were assessed and analyzed to determine the perspectives of the previous and current researchers and authors. From the research, a total of 101 kinds ofpancitdishes were documented from 8 regions in Luzon. These were all differ from its characteristics and significances, but each dish contributes to the context of the community’s story and cultural value. In the end of the research, the researchers identified that the culinary tradition ofpancitin Luzon was developed based from regionalism, indigenization, and significance.
Generalized involute and evolute curves of equiform spacelike curves with a timelike equiform principal normal in $E_{1}^{3}$
Authors: Elsharkawy A.
Published: May 2020

Equiform geometry is considered as a generalization of the other geometries. In this paper, involute and evolute curves are studied in the case of the curve α is an equiform spacelike with a timelike equiform principal normal vector N. Furthermore, the equiform frames of the involute and evolute curves are obtained. Also, the equiform curvatures of the involute and evolute curves are obtained in Minkowski 3-space.
Extending the applicability of a third-order scheme with Lipschitz and Hölder continuous derivative in Banach spaces
Authors: Sharma Debasis , Parhi Sanjaya Kumar
Published: May 2020

We extend the applicability of a cubically convergent nonlinear system solver using Lipschitz continuous first-order Fréchet derivative in Banach spaces. This analysis avoids the usual application of Taylor expansion in convergence analysis and extends the applicability of the scheme by applying the technique based on the first-order derivative only. Also, our study provides the radius of convergence ball and computable error bounds along with the uniqueness of the solution. Furthermore, the generalization of this analysis using Hölder condition is provided. Various numerical tests confirm that our analysis produces better results and it is useful in solving such problems where previous methods can not be implemented.
On the inverse sum indeg index of some graph operations
Authors: Havare Özge Çolakoǧlu
Published: May 2020

Topological indices are the molecular descriptors that describe the structures of chemical compounds. They are used in isomer discrimination, structure-property relationship, and structure-activity relations. The topological indices are used to predict certain physico-chemical properties such as boiling point, enthalpy of vaporization, and stability. In this paper, the inverse sum indeg index is studied. This index (ISI(G)) is defined as $\sum \frac {d_{u}d_{v}}{d_{u}+d_{v}}$∑dudvdu+dv. The inverse sum indeg index of some graph operations is computed. These operations are join, sequential join, cartesian product, lexicographic product, and corona operation.
Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial
Authors: Lin Nancy U. , Borges Virginia , Anders Carey , Murthy Rashmi K. , Paplomata Elisavet , Hamilton Erika , Hurvitz Sara , Loi Sherene , Okines Alicia , Abramson Vandana , Bedard Philippe L. , Oliveira Mafalda , Mueller Volkmar , Zelnak Amelia , DiGiovanna Michael P. , Bachelot Thomas , Chien A. Jo , O’Regan Ruth , Wardley Andrew , Conlin Alison , Cameron David , Carey Lisa , Curigliano Giuseppe , Gelmon Karen , Loibl Sibylle , Mayor JoAl , McGoldrick Suzanne , An Xuebei , Winer Eric P.
Published: May 2020

PURPOSE

In the HER2CLIMB study, patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer with brain metastases (BMs) showed statistically significant improvement in progression-free survival (PFS) with tucatinib. We describe exploratory analyses of intracranial efficacy and survival in participants with BMs.

PATIENTS AND METHODS

Patients were randomly assigned 2:1 to tucatinib or placebo, in combination with trastuzumab and capecitabine. All patients underwent baseline brain magnetic resonance imaging; those with BMs were classified as active or stable. Efficacy analyses were performed by applying RECIST 1.1 criteria to CNS target lesions by investigator assessment. CNS-PFS (intracranial progression or death) and overall survival (OS) were evaluated in all patients with BMs. Confirmed intracranial objective response rate (ORR-IC) was evaluated in patients with measurable intracranial disease.

RESULTS

There were 291 patients with BMs: 198 (48%) in the tucatinib arm and 93 (46%) in the control arm. The risk of intracranial progression or death was reduced by 68% in the tucatinib arm (hazard ratio [HR], 0.32; 95% CI, 0.22 to 0.48; P < .0001). Median CNS-PFS was 9.9 months in the tucatinib arm versus 4.2 months in the control arm. Risk of death was reduced by 42% in the tucatinib arm (OS HR, 0.58; 95% CI, 0.40 to 0.85; P = .005). Median OS was 18.1 versus 12.0 months. ORR-IC was higher in the tucatinib arm (47.3%; 95% CI, 33.7% to 61.2%) versus the control arm (20.0%; 95% CI, 5.7% to 43.7%; P = .03).

CONCLUSION

In patients with HER2-positive breast cancer with BMs, the addition of tucatinib to trastuzumab and capecitabine doubled ORR-IC, reduced risk of intracranial progression or death by two thirds, and reduced risk of death by nearly half. To our knowledge, this is the first regimen to demonstrate improved antitumor activity against BMs in patients with HER2-positive breast cancer in a randomized, controlled trial.