bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovative need-based low-cost kangaroo mother care (KMC) chair
Authors: Jain Ashish , Sekhar Jerin C , Kumari Nisha , Jain Nidhi 
Published: June 2020

ObjectivesLow birthweight neonates contribute substantially to mortality and morbidity. Their management in low-income countries is difficult due to shortage of skilled staff and limited resources. Kangaroo mother care (KMC) is an effective way of providing warmth, stimulation and protection against infection, thereby decreasing mortality. We intended to perform a need-based survey among mothers and to develop an economic and comfortable chair to facilitate and optimise KMC. We also evaluated the level of satisfaction among mothers using the developed chair.DesignIterative product development.SettingA tertiary teaching hospital having level 3 neonatal intensive care and KMC ward.MethodsAn initial design for KMC chair was developed based on the structured response of 40 mothers to a need-based questionnaire. The prototype was reviewed by experts, including nursing staff, and a comfortable chair with minimum logistics was developed. A formative assessment of satisfaction was done using a questionnaire after introducing it in clinical practice.Results67.5% of mothers were satisfied with the head rest, inclination and height, while 72.5% were satisfied with the in-built KMC cloth and platform for placing utensils. 86.6% of nurses found the chair helpful to mothers; 83.3% were satisfied with the length of in-built KMC cloth; and 80% expressed their overall satisfaction in the KMC chair. 70% of nurses found the chair to facilitate safe position for the baby and to improve breast feeding.ConclusionThis innovative and need-based KMC chair would help mothers of different builds perform KMC comfortably. This might prolong the duration of KMC, thereby having beneficial effects on the neonate.
Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma
Authors: Blondy Thibaut , d'Almeida Sènan Mickael , Briolay Tina , Tabiasco Julie , Meiller Clément , Chéné Anne-Laure , Cellerin Laurent , Deshayes Sophie , Delneste Yves , Fonteneau Jean-François , Boisgerault Nicolas , Bennouna Jaafar , Grégoire Marc , Jean Didier , Blanquart Christophe 
Published: June 2020

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.MethodsPleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.ResultsWe observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression ofCSF1was correlated with ‘M2-like macrophages’ markers, whereas this was not the case withIL34expression, suggesting two distinct modes of action of these cytokines. Expression ofIL34was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression ofIL34was observed in MPM cells with an alteration ofCDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8+T cells.ConclusionsThe M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.
CD3xCD19 DART molecule treatment induces non-apoptotic killing and is efficient against high-risk chemotherapy and venetoclax-resistant chronic lymphocytic leukemia cells
Authors: Martens Anne W J , Janssen Susanne R , Derks Ingrid A M , Adams III Homer C , Izhak Liat , van Kampen Roel , Tonino Sanne H , Eldering Eric , van der Windt Gerritje J W , Kater Arnon P 
Published: June 2020

BackgroundBispecific antibodies are promising new therapeutics in B cell malignancies. Whether they lead to potent T cell activation despite described T cell dysfunction in chronic lymphocytic leukemia (CLL), and are able to effectively target high-risk or venetoclax-resistant samples, is currently unknown.MethodsCD19+cell lines or primary (high-risk) CLL were cocultured in vitro with healthy donor (HD) or CLL-derived T cells in the presence of a CD3xCD19 dual affinity retargeting molecule (CD3xCD19 DART). Cell cytotoxicity, T cell activation, proliferation and effector molecule production were analyzed using flow cytometry.ResultsHere, we report that a bispecific CD3xCD19 DART mediates efficient killing by HD T cells of CD19+cell-lines and primary CLL cells, regardless of immunoglobulin heavy chain variable region (IGHV) mutational status TP53 status or chemotherapy, ibrutinib or venetoclax sensitivity. Whereas TCR stimulation of CLL-derived T cells resulted in dysfunctional T cell activation and proliferation, treatment with CD3xCD19 DART led to a similar activation profile in CLL-derived and HD-derived T cells. Consistently, co-culture of CLL derived T cells with JeKo-1 or CLL cells in the presence of CD3xCD19 DART resulted in significant cytotoxicity by both CD4+and CD8+T cells. On stimulation of CLL cells with CD40L, CLL cells become resistant to the specific inhibitor of anti-apoptotic Bcl-2 protein venetoclax, due to upregulation of Bcl-2 family members such as Bcl-XL. Nevertheless, CD40L stimulated CLL cells were as efficiently lysed on CD3xCD19 DART treatment as unstimulated CLL cells. Further examination of the mechanism of CD3xCD19 DART mediated killing showed that lysis was dependent on granules, but was independent of BAX/BAK or caspase activity, indicating non-apoptotic cell death.ConclusionsThese data show that CD3xCD19 DART in CLL leads to robust T cell activation and lysis of high-risk venetoclax resistant CLL cells through a non-apoptotic mechanism.
Ipilimumab plus nivolumab for patients with metastatic uveal melanoma: a multicenter, retrospective study
Authors: Najjar Yana G , Navrazhina Kristina , Ding Fei , Bhatia Roma , Tsai Katy , Abbate Kelly , Durden Barbara , Eroglu Zeynep , Bhatia Shailender , Park Song , Chowdhary Akansha , Chandra Sunandana , Kennedy Jonathan , Puzanov Igor , Ernstoff Marc , Vachhani Pankit , Drabick Joseph , Singh Arun , Xu Tan , Yang Jessica , Carvajal Richard , Manson Daniel , M Kirkwood John , Cohen Justine , Sullivan Ryan , Johnson Douglas , Funchain Pauline , Shoushtari Alexander 
Published: June 2020

BackgroundUveal melanoma (UM) is the most common intraocular malignancy in adults. In contrast to cutaneous melanoma (CM), there is no standard therapy, and the efficacy and safety of dual checkpoint blockade with nivolumab and ipilimumab is not well defined.MethodsWe conducted a retrospective analysis of patients with metastatic UM (mUM) who received treatment with ipilimumab plus nivolumab across 14 academic medical centers. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methodology.Results89 eligible patients were identified. 45% had received prior therapy, which included liver directed therapy (29%), immunotherapy (21%), targeted therapy (10%) and radiation (16%). Patients received a median 3 cycles of ipilimumab plus nivolumab. The median follow-up time was 9.2 months. Overall response rate was 11.6%. One patient achieved complete response (1%), 9 patients had partial response (10%), 21 patients had stable disease (24%) and 55 patients had progressive disease (62%). Median OS from treatment initiation was 15 months and median PFS was 2.7 months. Overall, 82 (92%) of patients discontinued treatment, 34 due to toxicity and 27 due to progressive disease. Common immune-related adverse events were colitis/diarrhea (32%), fatigue (23%), rash (21%) and transaminitis (21%).ConclusionsDual checkpoint inhibition yielded higher response rates than previous reports of single-agent immunotherapy in patients with mUM, but the efficacy is lower than in metastatic CM. The median OS of 15 months suggests that the rate of clinical benefit may be larger than the modest response rate.
Regional hyperperfusion in cognitively normalAPOE ε4allele carriers in mid-life: analysis of ASL pilot data from the PREVENT-Dementia cohort
Authors: McKiernan Elizabeth Frances , Mak Elijah , Dounavi Maria-Eleni , Wells Katie , Ritchie Craig , Williams Guy , Su Li , O'Brien John 
Published: June 2020

BackgroundRegional cerebral hypoperfusion is characteristic of Alzheimer’s disease (AD). Previous studies report conflicting findings in cognitively normal individuals at high risk of AD. Understanding early preclinical perfusion alterations may improve understanding of AD pathogenesis and lead to new biomarkers and treatment targets.Methods3T arterial spin labelling MRI scans from 162 participants in the PREVENT-Dementia cohort were analysed (cognitively normal participants aged 40–59, stratified by future dementia risk). Cerebral perfusion was compared vertex-wise according toAPOE ε4status and family history (FH). Correlations between individual perfusion, age and cognitive scores (COGNITO battery) were explored.ResultsRegional hyperperfusion was found inAPOE ε4+group (left cingulate and lateral frontal and parietal regions p<0.01, threshold-free cluster enhancement, TFCE) and in FH +group (left temporal and parietal regions p<0.01, TFCE). Perfusion did not correlate with cognitive test scores.ConclusionsRegional cerebral hyperperfusion in individuals at increased risk of AD in mid-life may be a very early marker of functional brain change related to AD. Increased perfusion may reflect a functional ‘compensation’ mechanism, offsetting the effects of early neural damage or may itself be risk factor for accelerating spread of degenerative pathology.
Prognostic value of systemic immune–inflammation index in acute/subacute patients with cerebral venous sinus thrombosis
Authors: Li Shen , Liu Kai , Gao Yuan , Zhao Lu , Zhang Rui , Fang Hui , Tao Yongli , Liu Hongbing , Zhao Jiawei , Xia Zongping , Xu Yuming , Song Bo 
Published: June 2020

ObjectiveTo evaluate the prognosis values of systemic immune–inflammation index (SII) in non-chronic cerebral venous sinus thrombosis (CVST).Methodspatients with CVST, admitted to the First Affiliated Hospital of Zhengzhou University, were retrospectively identified from January 2013 to December 2018. We selected patients in acute/subacute phase from database. Functional outcomes of patients were evaluated with the modified Rankin Scale (mRS)—mRS 3–6 as poor outcomes and mRS 6 as death. The overall survival time was defined as the date of onset to the date of death or last follow-up date. Survival analysis was described by the Kaplan-Meier curve and Cox regression analysis. Multivariate logistic regression analysis assessed the relationship between SII and poor functional outcome. The area under the Receiver Operating Curve curve (AUC) was estimated to evaluate the ability of SII in prediction.ResultsA total of 270 patients were included and their duration of follow-up was 22 months (6–66 months), of whom 31 patients had poor outcomes and 24 patients dead. Cox regression analysis showed that SII (HR=1.304, 95% CI: 1.101 to 1.703, p=0.001) was a predictor of death in non-chronic CVST. Patients with higher SII presented lower survival rates (p=0.003). The AUC of SII was 0.792 (95% CI: 0.695 to 0.888, p=0.040) with a sensitivity of 69.6% and specificity of 80.1%. Subgroups analysis demonstrated that SII was an important predictor of poor outcomes in male (OR=1.303, 95% CI: 1.102 to 1.501, p=0.011) and pregnancy/puerperium female (OR=1.407, 95% CI: 1.204 to 1.703, p=0.034).ConclusionsSII was a potential predictor in the poor prognosis of patients with acute/subacute CVST, especially in male and pregnancy/puerperium female.
Carbon dioxide narcosis due to human error in a dog
Authors: Phillips Victoria , Mathis Alessandra 
Published: June 2020

Incorrect assembly of a parallel Lack (Mapleson A) breathing system resulted in carbon dioxide narcosis in a dog due to rebreathing of expiratory gases. A seven‐year‐old, male neutered Rottweiler, weighing 49 kg, failed to recover after discontinuation of inhalational anaesthesia following a forequarter amputation for osteosarcoma. During recovery, the endotracheal tube had been connected to a parallel Lack anaesthetic breathing system delivering 100 per cent oxygen at 5 l/minute. Although a prolonged recovery, 30 minutes, all vital parameters were considered within normal limits until a severe increase in respiratory effort was noted. Capnography revealed rebreathing with an end‐tidal carbon dioxide tension of >150 mm Hg (>19.9 kPa). The dog was transferred to a circle breathing system, and with normalisation of the capnogram, recovery proceeded without further complications. Visual inspection of the parallel Lack breathing system revealed misassembly which had resulted in rebreathing of expiratory gases, extreme hypercapnia causing prolonged recovery due to narcosis.
Prevalence of Infective Endocarditis in Streptococcal Bloodstream Infections Is Dependent on Streptococcal Species
Authors: Chamat-Hedemand Sandra , Dahl Anders , Østergaard Lauge , Arpi Magnus , Fosbøl Emil , Boel Jonas , Oestergaard Louise Bruun , Lauridsen Trine K. , Gislason Gunnar , Torp-Pedersen Christian , Bruun Niels Eske 
Published: June 2020

Background:
Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs.

Methods:
We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device.

Results:

Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5–7.8). The lowest IE prevalence was found with
Streptococcus pneumoniae
(
S pneumoniae
) 1.2% (0.8–1.6) and
Spyogenes
1.9% (0.9–3.3). An intermediary IE prevalence was found with
Sanginosus
4.8% (3.0–7.3),
Ssalivarius
5.8% (2.9–10.1), and
Sagalactiae
9.1% (6.6–12.1). The highest IE prevalence was found with
Smitis/oralis
19.4% (15.6–23.5),
Sgallolyticus
(formerly
Sbovis
) 30.2% (24.3–36.7),
Ssanguinis
34.6% (26.6–43.3),
Sgordonii
44.2% (34.0–54.8), and
Smutans
47.9% (33.3–62.8). In multivariable analysis using
S pneumoniae
as reference, all species except
S pyogenes
were associated with significantly higher IE risk, with the highest risk found with
S gallolyticus
odds ratio (OR) 31.0 (18.8–51.1),
S mitis/oralis
OR 31.6 (19.8–50.5),
S sanguinis
OR 59.1 (32.6–107),
S gordonii
OR 80.8 (43.9–149), and
S mutans
OR 81.3 (37.6–176).

Conclusions:

The prevalence of IE in streptococcal BSIs is species dependent with
S mutans, S gordonii, S sanguinis, S gallolyticus
, and
S mitis/oralis
having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.
Why the Enculturative Context of Moral Education Matters
Authors: Mapana Kedmon Elisha 
Published: June 2020

Abstract
Auto-ethnography is an effective methodology to reflect upon the moral values and their acquisition among the Wagogo people in central Tanzania against the background of postmodernity. In so doing I have identified the enculturative contexts within which I came to acquire the moral values that I live by, in particular my immediate family (i.e. my parents), the religion I was brought up in, and traditional school experiences (i.e. my initiation). I argue that despite contemporary theories of African character formation generating from the impact in Africa of cultural diversity and neuroscientific research, our traditional enculturative contexts of parenting, religious upbringing, and indigenous initiation ceremonies continue to have a central and enduring impact on the development of moral values among the Wagogo people of central Tanzania.
COVID-19 and Total Laryngectomy—A Report of Two Cases
Authors: Paderno Alberto , Fior Milena , Berretti Giulia , Del Bon Francesca , Schreiber Alberto , Grammatica Alberto , Mattavelli Davide , Deganello Alberto 
Published: June 2020

Objective: To date, no cases have been reported on the effects of COVID-19 in laryngectomees. Case Presentation: We herein presented two clinical cases of laryngectomized patients affected by COVID-19, detailing their clinical course and complications. Discussion: In our experience, permanent tracheostomy did not significantly affect the choice of treatment. However, dedicated devices and repeated tracheal toilettes may be needed to deal with oxygen-therapy-related tracheal crusting. Conclusion: In conclusion, laryngectomees should be considered a vulnerable population that may be at risk for worse outcomes of COVID-19 due to anatomical changes in their airways. The role of the ENT specialist is to guide airway management and inform the support-staff regarding specific needs of these patients.
The effect of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric parameters, body composition and angiogenesis factor, sirtunin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α in obese people under a weight loss regime: A study protocol for a randomized controlled clinical trial
Authors: Mohammadshahi Majid , Zakizadeh Elahe , Ahmadi-Angali Kambiz , Ravanbakhsh Majid , Helli Bijan 
Published: June 2020

Background: Obesity is defined as a chronic disease, and is known as a public health problem in developed and developing countries. Several studies have shown the effects of anti-obesity of α-lactalbumin. Aim: This study was designed to investigate the effect of alpha-lipoic acid supplementation and electrical isotonic contraction on anthropometric parameters, body composition and angiogenesis factor, sirtunin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in obese people under a weight loss regime. Methods: Obese people who meet the inclusion criteria are included. Participants are randomly divided into four groups (alpha-lipoic (1200 mg) +weight loss regime group; Faradic (three 1 hour sessions) + weight loss regime group; alpha-lipoic (1200 mg) + Faradic (three 1 hour sessions) + weight loss regime group; control group (1200 mg placebo) for 2 months. At the beginning and the end of the study, demographic information, dietary intake, anthropometric parameters, body composition and serum levels of the angiogenesis factor (sirtunin-1, PGC1α and nitric oxide) are measured. Conclusion: Recent studies reported the anti-obesity effects of alpha-lipoic acid. This study is novel, since a similar study has not yet been carried out. This study evaluates the effect of 600 mg of alpha-lipoic acid supplementation or having three sessions of 1 hour per week electrical isotonic contraction induced by Faradic for 2 months alone or in combination in obese people that are undergoing a weight loss regime. Trial registration: Iran Clinical Trials Registry, ID: IRCT20131117015424N2. Registered 2018-04-02
The Efficacy of Botulinum Toxin in Pediatric Chronic Migraine: A Literature Review
Authors: Marcelo Raymundo , Freund Brin 
Published: June 2020

Aims: To conduct a review of the literature on the use of botulinum toxin for the treatment of pediatric chronic migraine. Methods: A review of the literature was performed using EMBASE, PubMed, and Cochrane/Ovid. Using our inclusion and exclusion criteria, we targeted any study, published before April 2020, evaluating the efficacy of botulinum toxin in migraineurs younger than 18 years. Results: Seven studies were included: 2 retrospective analyses, 3 case series, a case report, and a randomized control trial. Studies included 1 to 125 patients, with the number of botulinum toxin treatments ranging from 1 to 11 treatments. The results of the randomized controlled trial showed nonsuperiority between placebo and botulinum toxin. Results of the other studies were generally favorable but were difficult to compare because of lack of standardization of botulinum toxin dosing, injection paradigm, frequency and duration of treatment, usage of accompanying prophylaxis, and variation in outcome measures across studies. There was low-quality evidence that botulinum toxin improved headache frequency and intensity, though some studies demonstrated efficacy in treatment with botulinum toxin. Conclusion: This review is the first of its kind, updating the literature on the efficacy of botulinum toxin in pediatric patients. Given evidence of its utility in treating pediatric migraines, off-label use should be considered in certain cases. Further study is warranted to better characterize injection paradigms and patient selection because of the limited and inconsistent data available.
Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy
Authors: Padala Sandeep A , Patel Shivam K , Vakiti Anusha , Patel Nikhil , Gani Imran , Kapoor Rajan , Muhammad Saeed 
Published: June 2020

Introduction Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. Case report We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome. Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. Discussion As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.