bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–CTLA‐4 synergizes with dendritic cell–targeted vaccine to promote IL‐3–dependent CD4+ effector T cell infiltration into murine pancreatic tumors
Authors: Zaidi Neeha , Quezada Sergio A. , Kuroiwa Janelle M.Y. , Zhang Li , Jaffee Elizabeth M. , Steinman Ralph M. , Wang Bei 
Published: April 2019

AbstractOne successful class of cancer immunotherapies, immune checkpoint inhibitory antibodies, disrupts key pathways that regulate immune checkpoints, such as cytotoxic T lymphocyte–associated antigen‐4 (CTLA‐4). These agents unleash the potency of antigen‐experienced T cells that have already been induced as a consequence of the existing tumor. But only 20% of cancers naturally induce T cells. For most cancers, vaccines are require to induce and mobilize T effector cells (Teffs) to traffick into tumors. We evaluated the effects of anti–CTLA‐4 given in combination with an antigen‐specific dendritic cell vaccine on intratumoral Teffs in a murine pancreatic cancer model. The dendritic cell–targeted tumor antigen plus anti–CTLA‐4 significantly increased the number of vaccine‐induced CD4+ Teffs within the tumor. This increase was accompanied by a reduction in the size of the peripheral CD4+ Teff pool. We also found that IL‐3 production by activated CD4+ T cells was significantly increased with this combination. Importantly, the CD4+ Teff response was attenuated in Il3−/− mice, suggesting mediation of the effect by IL‐3. Finally, the induced T cell infiltration was associated with activation of the tumor endothelium by T cell–derived IL‐3. Our findings collectively provide a new insight into the mechanism driving Teff infiltration and vascular activation in a murine pancreatic cancer model, specifically identifying a new role for IL‐3 in the anticancer immune response.
Adiposity in relation to readmission and all‐cause mortality following coronary artery bypass grafting: A systematic review and meta‐analysis
Authors: Zhang Kefeng , Wang Junjie , Yang Yan , An Ruopeng 
Published: April 2019

SummaryThis study systemically reviewed evidence linking adiposity to readmission and all‐cause mortality in post‐coronary artery bypass grafting (CABG) patients. Keyword/reference search was performed in PubMed, Web of Science, CINAHL, and Cochrane Library for articles published before June, 2018. Eligibility criteria included study designs: experimental/observational studies; subjects: adult patients undergoing CABG; and outcomes: hospital/clinic readmissions, and short‐term (≤30 days) and mid‐to‐long‐term (>30 days) all‐cause mortality. Seventy‐two studies were identified. Meta‐analysis showed that the odds of post‐CABG readmission among patients with overweight was 30% lower than their normal‐weight counterparts and the odds of mid‐to‐long‐term post‐CABG mortality among patients with overweight were 20% lower than their normal‐weight counterparts. In contrast, no difference in post‐CABG readmission rate was found between patients with obesity and their nonobese counterparts; no difference in short‐term or in‐hospital post‐CABG mortality rate was found between patients with overweight or obesity and their normal‐weight counterparts; and no difference in mid‐to‐long‐term post‐CABG mortality rate was found between patients with obesity and their normal‐weight counterparts. In conclusion, patients with overweight but not obesity had a lower readmission and mid‐to‐long‐term mortality rate following CABG relative to their normal‐weight counterparts. Preoperative weight loss may not be advised to patients with overweight undergoing CABG.
Nutrition and allergic diseases in urban and rural communities from the South African Food Allergy cohort
Authors: Botha Maresa , Basera Wisdom , Facey‐Thomas Heidi E. , Gaunt Ben , Genuneit Jon , Gray Claudia L. , Kiragu Wanjiku , Ramjith Jordache , Watkins Alexandra , Levin Michael E. 
Published: April 2019

AbstractThis study describes and compares allergic diseases and sensitization in urban and rural children in the SAFFA study cohort as well as infant feeding patterns and nutritional status. We assessed the relationship between nutritional status, breastfeeding, complementary feeding patterns, and atopic diseases including aeroallergen and food allergen sensitization, self‐reported atopic dermatitis, allergic rhinitis, asthma, and challenge‐proven food allergy (FA).MethodologyA total of 1185 urban and 398 rural toddlers aged 12‐36 months were screened for food sensitization (FS) and FA using skin prick testing and oral food challenges. Of these, 535 and 347, respectively, were additionally screened for aeroallergen sensitization. Information was collected on infant feeding practices, and anthropometric measurements and clinical signs for atopy were documented.ResultsMarkedly higher rates of allergy (asthma 9.0% vs 1.0%, eczema 25.6% vs 2.0%, rhinitis 25.3% vs 3.3%, and FA 2.5% vs 0.5%) exist in urban vs rural children. 13.1% unselected urban South African children were sensitized to aeroallergens compared to 3.8% of their rural counterparts and 9.0% to any food compared to 0.5%. Exclusive breastfeeding duration was longer, and there was a later introduction of allergenic foods in rural communities. Obesity rates were similar between the two groups, but rural children were more likely to be stunted. Being overweight was associated with asthma in urban but not rural settings. In the urban cohort, children with FS and allergy were thinner than their peers.ConclusionAllergy and sensitization rates are significantly higher in unselected urban South African toddlers than their rural counterparts. Risk and protective factors for allergy and atopy may differ between urban and rural settings.
MicroRNAs and new biotechnological tools for its modulation and improving stress tolerance in plants
Authors: Basso Marcos Fernando , Ferreira Paulo Cavalcanti Gomes , Kobayashi Adilson Kenji , Harmon Frank G. , Nepomuceno Alexandre Lima , Molinari Hugo Bruno Correa , Grossi‐de‐Sa Maria Fatima 
Published: April 2019

SummaryMicroRNAs (miRNAs) modulate the abundance and spatial–temporal accumulation of target mRNAs and indirectly regulate several plant processes. Transcriptional regulation of the genes encoding miRNAs (MIR genes) can be activated by numerous transcription factors, which themselves are regulated by other miRNAs. Fine‐tuning of MIR genes or miRNAs is a powerful biotechnological strategy to improve tolerance to abiotic or biotic stresses in crops of economic importance. Current approaches for miRNA fine‐tuning are based on the down‐ or up‐regulation of MIR gene transcription and the use of genetic engineering tools to manipulate the final concentration of these miRNAs in the cytoplasm. Transgenesis, cisgenesis, intragenesis, artificial MIR genes, endogenous and artificial target mimicry, MIR genes editing using Meganucleases, ZNF proteins, TALENs and CRISPR/Cas9 or CRISPR/Cpf1, CRISPR/dCas9 or dCpf1, CRISPR13a, topical delivery of miRNAs and epigenetic memory have been successfully explored to MIR gene or miRNA modulation and improve agronomic traits in several model or crop plants. However, advantages and drawbacks of each of these new biotechnological tools (NBTs) are still not well understood. In this review, we provide a brief overview of the biogenesis and role of miRNAs in response to abiotic or biotic stresses, we present critically the main NBTs used for the manipulation of MIR genes and miRNAs, we show current efforts and findings with the MIR genes and miRNAs modulation in plants, and we summarize the advantages and drawbacks of these NBTs and provide some alternatives to overcome. Finally, challenges and future perspectives to miRNA modulating in important crops are also discussed.
Idarucizumab, but not procoagulant concentrates, fully restores dabigatran‐altered platelet and fibrin components of hemostasis
Authors: Arellano‐Rodrigo Eduardo , Fernandez‐Gallego Victor , López‐Vilchez Irene , Molina Patricia , Díaz‐Ricart Maribel , Zafar M. Urooj , Badimon Juan J. , van Ryn Joanne , Escolar Ginés 
Published: April 2019

BACKGROUNDComparative studies on the restoration of hemostasis with different reversal agents after dabigatran therapy have not been performed. We compared the efficacy and prothrombotic potential of the specific antidote idarucizumab with that of previously recommended non‐specific procoagulant concentrates.STUDY DESIGN AND METHODSWe explored the in vitro effects of dabigatran (184 ng/mL) on fibrin and platelet‐aggregate formation onto a damaged vessel under flow conditions (600 s−1). The reversal mechanisms and efficacy of idarucizumab (0.3–3 mg/mL) were compared with that of the non‐specific procoagulant concentrates aPCC (25–75 U/Kg), PCC (70 U/Kg), or rFVIIa (120 μg/Kg). Generation of thrombin and prothrombin fragment (F1 + 2), and thromboelastometry parameters of clot formation were measured.RESULTSDabigatran caused pronounced reductions in fibrin (87%) and platelet interactions (36%) with damaged vessels (p < 0.01) and significantly impaired thrombin generation and thromboelastometric parameters (delayed dynamics and reduced firmness). Idarucizumab completely normalized rates of fibrin and platelet coverage to baseline values in flow studies; and reversed the alterations in thrombin generation, F1 + 2 and thromboelastometry parameters produced by dabigatran. In comparison, aPCC and PCC only partially compensated for the dabigatran‐induced alterations in fibrin deposition, but were unable to fully restore them to baseline values. Reversal with aPCC or PCC improved the majority of alterations in coagulation‐related tests, but tended to overcompensate thrombin generation kinetics and significantly increased F1 + 2 levels.CONCLUSIONIdarucizumab antagonizes alterations of direct and indirect biomarkers of hemostasis caused by dabigatran. In our studies, idarucizumab was clearly more efficacious than strategies with non‐specific procoagulant concentrates and devoid of the excessive procoagulant tendency observed with the latter.
Transfusion Camp: a prospective evaluation of a transfusion education program for multispecialty postgraduate trainees
Authors: Lin Yulia , Tilokee Everad , Chargé Sophie , Alam Asim , Cserti‐Gazdewich Christine , Lau Wendy , Lee Christie , Lieberman Lani , Nixon Paula , Owens Wendy , Pavenski Katerina , Pendergrast Jacob , Saidenberg Elianna , Shehata Nadine , Skeate Robert , Yi Qi‐Long , Conrad David , Dudebout Jill , Hsia Cyrus C. , Murphy Michael , Prokopchuk‐Gauk Oksana , Shah Akshay , Solh Ziad , Trudeau Jacqueline , Zeller Michelle P. , Callum Jeannie 
Published: April 2019

BACKGROUNDThe optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes, and self‐reported behavior was evaluated.METHODSDidactic lectures (delivered locally, by webinar, or recorded) and locally facilitated team‐based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20‐question multiple‐choice exam was conducted before and after Transfusion Camp. Attitudes and self‐reported behavior were collected through a survey.RESULTSOver 2 academic years (July 2016 to June 2018), 390 trainees from 16 different specialties (predominantly anesthesia, 41%; hematology, 14%; and critical care, 7%) attended at least 1 day of Transfusion Camp. The mean pretest score was 10.3 of 20 (±2.9; n = 286) compared with posttest score of 13.0 (±2.8; n = 194; p < 0.0001). Lower pretest score and greater attendance (4–5 days compared with 1–3 days) were associated with larger improvement in posttest score; delivery format, specialty, and postgraduate year were not. Trainees reported an improvement in self‐rated abilities to manage TM scenarios; 95% rated TM knowledge as very or extremely important in providing patient care; and 81% indicated that they had applied learning from Transfusion Camp into clinical practice.CONCLUSIONSTransfusion Camp increased TM knowledge, fostered a positive attitude toward TM, and enabled a self‐reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.
No Dose Adjustment for Isavuconazole Based on Age or Sex
Authors: Desai Amit V. , Han David , Kowalski Donna L. , Lademacher Christopher , Pearlman Helene , Yamazaki Takao 
Published: April 2019

This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (
n
=

12 each in groups of nonelderly males and females and elderly males and females).
Pituitary gigantism: a rare learning opportunity
Authors: Bendor-Samuel Owen Martyn , Pal Aparna , Cudlip Simon , Anderson Gemma , Salgia Sanjay , Makaya Tafadzwa 
Published: April 2019

IntroductionPituitary gigantism is a rare but significant paediatric condition with complexities surrounding diagnosis and management. Transsphenoidal surgery (TSS) is the treatment of choice; however, medical treatment is often considered as adjuvant therapy.CaseA 10½ -year-old boy presented with tall stature and a height velocity of 11 cm/year. His height was 178.7 cm (+5.8 SD above mean) and insulin-like growth factor-1 (IGF-1) was elevated. An oral glucose tolerance test demonstrated non-suppression of growth hormone (GH). Initial contrast MRI was inconclusive, but C-11 methionine functional positron emission tomography CT identified a 6 mm pituitary microadenoma. A multidisciplinary team clinic held with the family allowed discussion about medical and surgical treatment options. Due to a number of factors including the patient’s young age, prepubertal status, a wish to allow him to settle into his new high school and his desire to reach a final height taller than his father’s height, it was decided to try medical therapy first with a somatostatin analogue. Pubertal induction was also commenced and bilateral epiphysiodesis surgery performed. Initial response to octreotide was positive; however, 4 months into therapy his IGF-1 was climbing and a repeat GH profile was not fully suppressed. The patient therefore proceeded to have successful TSS excision of the adenoma.ConclusionRare cases such as this require sharing of knowledge and expertise, so the best possible care is offered. It is often necessary to work across sites and disciplines. Each case requires an individual approach tailored to the patient and their family.
Perceived quality of nursing care and patient education: a cross-sectional study of hospitalised surgical patients in Finland
Authors: Gröndahl Weronica , Muurinen Hanna , Katajisto Jouko , Suhonen Riitta , Leino-Kilpi Helena 
Published: April 2019

ObjectivesThis study aims to analyse the relationship between patient education and the quality of surgical nursing care as perceived by patients. The background of the study lies in the importance of a patient-centred approach for both patient education and quality evaluation.DesignThis was a cross-sectional descriptive correlational study with surgical patients.SettingData were collected in 2013 in one hospital district in Finland.Participants480 hospitalised surgical patients.MethodsThe data were collected using two structured instruments: one measuring the perceived quality of nursing care experienced by patients (Good Nursing Care Scale) and one measuring the received knowledge of hospital patients (RKhp). Data were analysed statistically using descriptive and inferential statistics to describe the sample and study variables. Pearson’s correlation coefficients were used to analyse the association between the scales.ResultsSurgical hospital patients evaluated the level of the quality of nursing care as high; this was especially true with reference to the environment and staff characteristics, but not to collaboration with family members. Most (85%) of the patients had received sufficient knowledge preoperatively and they were familiar with the proceeding of their care and treatment after discharge; in particular, they had received bio-physiological knowledge, consisting of knowledge of the disease, symptoms and the physiological elements of care. The positive correlation between the perceived quality of surgical nursing care and received knowledge was strong, suggesting a positive relationship between patient education and improvement of the quality of nursing care.ConclusionsBased on the results, the quality of nursing care and patient education are interconnected. Thus, by improving patient education, the quality of nursing care can also be improved. It is particularly important to improve collaboration with family members and patients’ own management strategies as well as the multidimensionality of educational knowledge.
Impact of Z′ boson on lepton flavor violating decays
Authors: Maji P. , Nayek P. , Sahoo S. 
Published: April 2019

Recently, some small hints of lepton flavor violating (LFV) decays have been probed in different colliders and accelerators. Although these processes are forbidden in the Standard Model (SM), observation of LFV decays are considered as good probes to test theory beyond the SM. In this paper, we study some LFV decays, e.g. three-body decay channels of [Formula: see text] lepton like [Formula: see text], [Formula: see text] and two-body decays of B meson and [Formula: see text] lepton like [Formula: see text] and [Formula: see text] in [Formula: see text] model. We calculate the branching ratio of the above decays considering the effect of both [Formula: see text] and [Formula: see text]-mediated flavor-changing neutral-current (FCNC).
Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training
Authors: Batra Abhinandan , Vohra Ravneet S. , Chrzanowski Steve M. , Hammers David W. , Lott Donovan J. , Vandenborne Krista , Walter Glenn A. , Forbes Sean C. 
Published: April 2019

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice ( mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T2) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31phosphorus MRS (31P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T2 was attenuated ( P < 0.05) in treated mdx and wild-type mice compared with untreated mdx. During training, resting T2 values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater ( P < 0.05) in treated mdx (>90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater ( P < 0.05) in treated mdx that trained than untreated mdx, with no differences in muscle oxidative capacity, as measured by 31P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function. NEW & NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOSμ.
Angiotensin II suppresses autophagy and disrupts ultrastructural morphology and function of mitochondria in mouse skeletal muscle
Authors: Silva Kleiton Augusto Santos , Ghiarone Thaysa , Schreiber Kathy , Grant DeAna , White Tommi , Frisard Madlyn I. , Sukhanov Sergiy , Chandrasekar Bysani , Delafontaine Patrice , Yoshida Tadashi 
Published: April 2019

Angiotensin II (ANG II)-induced skeletal muscle wasting is characterized by activation of the ubiquitin-proteasome system. However, the potential involvement of proteolytic system macroautophagy/autophagy in this wasting process remains elusive. Autophagy is precisely regulated to maintain cell survival and homeostasis; thus its dysregulation (i.e., overactivation or persistent suppression) could lead to detrimental outcomes in skeletal muscle. Here we show that infusion of ANG II for 7 days in male FVB mice suppressed autophagy in skeletal muscle. ANG II blunted microtubule-associated protein 1 light chain 3B (LC3B)-I-to-LC3B-II conversion (an autophagosome marker), increased p62/SQSTM1 (an autophagy cargo receptor) protein expression, and decreased the number of autophagic vacuoles. ANG II inhibited UNC-51-like kinase 1 via inhibition of 5′-AMP-activated kinase and activation of mechanistic target of rapamycin complex 1, leading to reduced phosphorylation of beclin-1Ser14 and Autophagy-related protein 14Ser29, suggesting that ANG II impairs autophagosome formation in skeletal muscle. In line with ANG II-mediated suppression of autophagy, ANG II promoted accumulation of abnormal/damaged mitochondria, characterized by swelling and disorganized cristae and matrix dissolution, with associated increase in PTEN-induced kinase 1 protein expression. ANG II also reduced mitochondrial respiration, indicative of mitochondrial dysfunction. Together, these results demonstrate that ANG II reduces autophagic activity and disrupts mitochondrial ultrastructure and function, likely contributing to skeletal muscle wasting. Therefore, strategies that activate autophagy in skeletal muscle have the potential to prevent or blunt ANG II-induced skeletal muscle wasting in chronic diseases. NEW & NOTEWORTHY Our study identified a novel mechanism whereby angiotensin II (ANG II) impairs mitochondrial energy metabolism in skeletal muscle. ANG II suppressed autophagosome formation by inhibiting the UNC-51-like kinase 1(ULK1)-beclin-1 axis, resulting in accumulation of abnormal/damaged and dysfunctional mitochondria and reduced mitochondrial respiratory capacity. Therapeutic strategies that activate the ULK1-beclin-1 axis have the potential to delay or reverse skeletal muscle wasting in chronic diseases characterized by increased systemic ANG II levels.