bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute effects of breaking up sitting time with isometric exercise on cardiovascular health: Randomized crossover trial
Authors: Silva Gustavo O. , Carvalho Juliana F. , Kanegusuku Hélcio , Farah Breno Q. , Correia Marilia A. , Ritti‐Dias Raphael M. 
Published: July 2021

The objective of this study was to analyze the acute effects of breaking up prolonged sitting with isometric exercise on the cardiovascular health of sedentary adults. This is a three‐condition randomized crossover trial. The sample was comprised of 17 subjects (11 women; 29 ± 10 years old; 25,1 ± 5,1 kg/m2). The participants completed, in randomized order, three experimental conditions (control, breaks with isometric leg extension exercise, and breaks with walking), with the order of the conditions determined through simple automatic randomization. All the conditions had in common a sitting period of 3 h. During the conditions with isometric exercise and walking breaks the participants performed breaks with isometric leg extension exercise and with walking every 30 min, while in the control condition they remained seated with no breaks. Before and after this period, vascular function (primary outcome), blood pressure, and cardiac autonomic modulation (secondary outcomes) were measured. Generalized estimated equations were used to analyze the data. The results did not indicate significant interaction effects for vascular function among experimental conditions (p > 0,05 for all). We also did not find significant interaction effects for systolic or diastolic blood pressure among the conditions (p > 0,05 for all). The heart rate variability parameters did not present significant interaction effects among conditions (p > 0,05 for all). In conclusion, breaking up sitting with isometric exercise does not seem to lead to significant effects on the cardiovascular health of sedentary adults.
Adolescent Health Series: Adolescent neurocognitive development in Western and Sub‐Saharan African contexts
Authors: Pozuelo Julia R. , Kilford Emma J. 
Published: July 2021

AbstractThe transitional period of adolescence has long been associated with physical, social and behavioural change. During this time, adolescents start to develop their own self‐identity, make important life decisions and acquire the necessary skills to successfully transition to adulthood. More recently, advances in brain imaging technology have enabled increased understanding of structural and functional changes in the human brain during this developmental period, and how they relate to social, emotional, motivational and cognitive development. The ability to integrate these developing cognitive processes in increasingly complex social contexts is a key aspect of mature decision‐making, which has implications for adolescent health, educational, economic and social outcomes. Insights from the field of developmental cognitive neuroscience could increase our understanding of this influential stage of life and thus inform potential interventions to promote adolescent health, a critical goal for global health research. Many social changes occur during adolescence and the social environment shapes both brain and cognitive development and the decisions adolescents make. Thus, it is important to study adolescent neurocognitive development in socio‐cultural context. Yet, despite evidence from Western studies that socio‐cultural and economic factors impact on adolescent neurocognitive development, existing studies of adolescent neurocognitive development in sub‐Saharan Africa are relatively scarce. We summarise research findings from Western and sub‐Saharan African contexts and highlight areas where research is lacking. Longitudinal studies from more diverse global samples will be needed to build a comprehensive model of adolescent development, that characterises both commonalities in developmental trajectories, as well as the way these can meaningfully differ between both individuals and contexts.
Ex vivo hemostatic and immuno‐inflammatory profiles of freeze‐dried plasma
Authors: Peng Henry T. , Rhind Shawn G. , Devine Dana , Jenkins Craig , Beckett Andrew 
Published: July 2021

AbstractBackgroundHemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze‐dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze‐dried plasma product (TFDP).Study design and methodsRotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta‐machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at −80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at −80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One‐way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties.ResultsNo significant differences in ROTEM variables (coagulation time [CT], clot formation time, α‐angle, maximum clot firmness, and lysis index 30) between the TFDP‐producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno‐inflammatory mediators were similar between frozen plasma and TFDP.ConclusionsTFDP is equivalent to frozen plasma with respect to global hemostatic and immuno‐inflammatory mediator profiles. Further investigations of TFDP in trauma‐induced coagulopathy models and bleeding patients are warranted.
Emerging gene therapies for enhancing the hemostatic potential of platelets
Authors: Leung Jerry , Cau Massimo F. , Kastrup Christian J. 
Published: July 2021

AbstractPlatelet transfusions are an integral component of balanced hemostatic resuscitation protocols used to manage severe hemorrhage following trauma. Enhancing the hemostatic potential of platelets could lead to further increases in the efficacy of transfusions, particularly for non‐compressible torso hemorrhage or severe hemorrhage with coagulopathy, by decreasing blood loss and improving overall patient outcomes. Advances in gene therapies, including RNA therapies, are leading to new strategies to enhance platelets for better control of hemorrhage. This review will highlight three approaches for creating modified platelets using gene therapies: (i) direct transfection of transfusable platelets ex vivo, (ii) in vitro production of engineered platelets from platelet‐precursor cells, and (iii) modifying the bone marrow for in vivo production of modified platelets. In summary, modifying platelets to enhance their hemostatic potential is an exciting new frontier in transfusion medicine, but more preclinical development as well as studies testing the safety and efficacy of these agents are needed.
DEHT is a suitable plasticizer option for phthalate‐free storage of irradiated red blood cells
Authors: Larsson Linda , Ohlsson Sara , Derving Julia , Diedrich Beatrice , Sandgren Per , Larsson Stella , Uhlin Michael 
Published: July 2021

AbstractBackground and ObjectivesDue to increasing concerns about possible endocrine‐disrupting properties, the use of the plasticizer di(2‐ethylhexyl) phthalate (DEHP) will be banned in future blood storage. Di(2‐ethylhexyl) terephthalate (DEHT) provides sufficient red blood cell (RBC) quality during conventional blood bank storage. It is important that a new plasticizer also maintains acceptable quality during exposure to high cell stress, such as irradiation, which is commonly used to prevent graft‐versus‐host disease.Materials and MethodsA total of 59 RBC units were collected and processed in polyvinyl chloride (PVC)‐DEHT or PVC‐DEHP blood bags combined with either saline‐adenine‐glucose‐mannitol (SAGM) or phosphate‐adenine‐glucose‐guanosine‐saline‐mannitol (PAGGSM) additive solution. All units were X‐ray irradiated on day 2 post‐collection. Sampling for assessment of parameters of storage lesion was performed on day 2 pre‐irradiation and day 14 and 28 post‐irradiation.ResultsThough irradiation increased cell stress, DEHT/PAGGSM and current common European preference DEHP/SAGM were equally affected up to 14 days post‐irradiation for all measured parameters. At day 28, haemolysis and microvesicle count were slightly increased in DEHT, whereas extracellular potassium ions, glucose, lactate, pH, mean corpuscular volume and microvesicle phosphatidylserine remained unaffected by plasticizer choice throughout storage. No individual unit exceeded 0.8% haemolysis, not even in DEHT/SAGM, the combination overall most affected by irradiation. Of the four combinations, membrane stability was least impacted in DEHP/PAGGSM.ConclusionWe demonstrate that DEHT is a suitable plasticizer for storage of RBCs after X‐ray irradiation cell stress. This strengthens the option of DEHT as a viable non‐phthalate substitute for DEHP.
Long‐term impact of legume‐based cropping with chemical and integrated fertilisation on viable weed seed density, diversity and community structure
Authors: Nath Chaitanya P. , Hazra Kali K. , Praharaj Chandra S. , Singh Ummed , Singh Sati S. , Kumar Narendra , Nandan Rajiv , Singh Narendra P. 
Published: July 2021

AbstractDominance, evenness and diversity of weeds in the seedbank have been recommended as potential indicators for monitoring the sustainability of cropping systems. We aimed to investigate viable seed density and diversity in soil after 13 years of diversified cropping and nutrient management practices. The long‐term field experiment comprised four cropping sequences: maize (Zea mays L.)–wheat (Triticum aestivum L.) (M‐W), maize–wheat–mungbean (Vigna radiata L.) (M‐W‐Mb), maize–wheat–maize–chickpea (Cicer arietinum L.) (M‐W‐M‐C) and pigeonpea (Cajanus cajan L.)–wheat (P‐W) in main plots and three nutrient management regimes: without fertilisation (CT), recommended inorganic fertilisers (RDF) and integrated nutrient management (INM) in subplots. The importance value index (IVI), the sum of relative frequency, density and abundance, was used to measure how dominant a species was in a given treatment. The M‐W rotation recorded a higher IVI of Phyllanthus niruri L. and Medicago denticulata L. compared with legume‐based cropping (M‐W‐Mb, M‐W‐M‐C and P‐W). INM also resulted in higher IVI of these species than RDF in the 0–15 cm soil layer. The P‐W rotation resulted in 33%–40% (at 0–7.5 cm), 16%–26% (at 7.5–15 cm) and 27%–36% (at 0–15 cm) higher seed density compared to the remaining rotations (expressed as the mean of other rotations). However, the sequence of seed density was INM = CT > RDF for the nutrient management. Weed species diversity (Shannon and richness indices) in the seedbank was higher in legume‐based cropping than the M‐W. The M‐W rotation also had higher ecological dominance than legume‐based rotations throughout the soil profile. Averaged across depths, RDF had 16% higher ecological dominance than the INM practice. Above‐ground weed density in wheat at harvest was significantly lower in M‐W‐Mb and M‐W‐M‐C than the M‐W rotation indicating that weed pressure and competition in wheat are reduced when systems were diversified with mungbean and chickpea. However, the P‐W rotation and INM can increase both weed seed density and species diversity compared with continuous cereal–cereal rotation (M‐W) and chemical fertilisation (RDF) in the long term. Thus, diversification of M‐W with legume (chickpea and mungbean) can be an important strategy to enhance species diversity vis‐à‐vis to reduce weed competition, herbicide inputs and avoiding the evolution of herbicide resistance.
Effect of Passive Flow Control Devices on Base Pressure for Mach Numbers Between 0.5 and 1.4
Authors: Murugan Jayaprakash N. , Chutkey Kiran , Sri Raghu R. , Verma Shashi B. 
Published: July 2021

Abstract
Experimental studies are carried out on an axisymmetric cylindrical base body for six freestream Mach numbers between 0.54 and 1.41. Unsteady pressure is measured on the base surface using high-frequency response Kulite pressure transducers. The effect of passive flow control devices on the mean base pressure and the unsteady characteristics of base pressure have been studied. A blunt base, a conventional cavity device, and three different ventilated cavity devices have been tested along with four different rounded base lip devices. A total of 20 different base geometric modifications are tested at 6 freestream Mach numbers resulting in 120 test cases. The cavity devices improve the base pressure as compared to the blunt base case, particularly for freestream Mach numbers more than 0.98. Among all the cases considered, a maximum increase of 8.6% in the base pressure coefficient is noticed for the normal ventilated cavity device as compared to the blunt base case for freestream Mach number of 1.22. The power spectral density of base pressure fluctuations revealed the dominant peaks on the base surface. The Strouhal number associated with the coherent structures developing in the shear layer varies between 0.2 and 0.27 for the six freestream Mach numbers considered. In the presence of cavity devices, dominant peaks are observed for Strouhal numbers between 1 and 5. The root-mean-square, skewness, kurtosis of the base pressure fluctuations for all the cases are presented. Maximum reduction in base pressure fluctuation is observed for the normal and inclined ventilated cavity device configuration test cases.
Survival in colon and rectal cancers in Finland and Sweden through 50 years
Authors: Hemminki Kari , Försti Asta , Hemminki Akseli 
Published: July 2021

ObjectivesGlobal survival studies have shown favourable development in colon and rectal cancers but few studies have considered extended periods or covered populations for which medical care is essentially free of charge.DesignWe analysed colon and rectal cancer survival in Finland and Sweden over a 50-year period (1967–2016) using data from the Nordcan database. In addition to the standard 1-year and 5-year survival rates, we calculated the difference between these as a novel measure of how well survival was maintained between years 1 and 5.ResultsRelative 1-year and 5-year survival rates have developed favourably without major shifts for men and women in both countries. For Finnish men, 1-year survival in colon cancer increased from 50% to 82%, and for rectal cancer from 62% to 85%. The Swedish survival was a few per cent unit better for 1-year survival but for 5-year survival the results were equal. Survival of female patients for both cancers was somewhat better than survival in men through 50 years. Overall the survival gains were higher in the early compared with the late follow-up periods, and were the smallest in the last 10 years. The difference between 1-year and 5-year survival in colon cancer was essentially unchanged over the 50-year period while in rectal cancer there was a large improvement.ConclusionsThe gradual positive development in survival suggests a contribution by many small improvements rather than single breakthroughs. The improvement in 5-year survival in colon cancer was almost entirely driven by improvement in 1-year survival while in rectal cancer the positive development extended to survival past year 1, probably due to successful curative treatments. The current challenges are to reinvigorate the apparently stalled positive development and to extend them to old patients. For colon cancer, survival gains need to be extended past year 1 of diagnosis.
Clinical decision support system to optimise symptom management in palliative medicine: focus group study
Authors: van der Stap Lotte , de Heij Albert H , van der Heide Agnes , Reyners Anna KL , van der Linden Yvette M 
Published: July 2021

ObjectivesSuboptimal symptom control in patients with life-limiting illnesses is a major issue. A clinical decision support system (CDSS) that combines a patient-reported symptom assessment scale (SAS) and guideline-based individualised recommendations has the potential to improve symptom management. However, lacking end-user acceptance often prevents CDSS use in daily practice.We aimed to evaluate the acceptability and feasibility of a palliative care CDSS according to its targeted end-users.MethodsSix focus groups with different groups of stakeholders were conducted: (1) patient representatives; (2) community nurses; (3) hospital nurses; (4) general practitioners; (5) hospital physicians and (6) palliative care specialists. Audiotapes were transcribed verbatim and thematically analysed.ResultsFifty-one stakeholders (6–12 per focus group) participated. Six themes were discussed: effect, validity, continuity, practical usability, implementation and additional features. All participants expected a CDSS to improve symptom management, for example, by reminding clinicians of blind spots and prompting patient participation. They feared interference with professional autonomy of physicians, doubted the validity of using a patient-reported SAS as CDSS input and thought lacking care continuity would complicate CDSS use. Clinicians needed clear criteria for when to use the CDSS (eg, life-limiting illness, timing in illness trajectory). Participants preferred a patient-coordinated system but were simultaneously concerned patients may be unwilling or unable to fill out an SAS.ConclusionsA palliative care CDSS was considered useful for improving symptom management. To develop a feasible system, barriers for successful implementation must be addressed including concerns about using a patient-reported SAS, lacking care continuity and unclear indications for use.
Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma
Authors: Bao Riyue , Spranger Stefani , Hernandez Kyle , Zha Yuanyuan , Pytel Peter , Luke Jason J , Gajewski Thomas F , Volchenboum Samuel L , Cohn Susan L , Desai Ami V 
Published: July 2021

BackgroundTumor-infiltrating CD8+ T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion.MethodsA defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group, MYCN amplification, and survival were analyzed by Cox proportional hazards models. Additional survival analysis was conducted after integrating neoantigen load predicted from somatic mutations. Pathways activated in non-T cell-inflamed relative to T cell-inflamed tumors were analyzed using causal network analysis.ResultsPatients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p<0.05), independent of MYCN amplification status, in both TARGET and GMKF cohorts. Higher neoantigen load was also associated with better event-free and overall survival (p<0.005) and was independent of the T cell-inflamed signature. Activation of MYCN, ASCL1, SOX11, and KMT2A transcriptional programs was inversely correlated with the T cell-inflamed signature in both cohorts.ConclusionsOur results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.
Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells
Authors: Dalla Pietà Anna , Cappuzzello Elisa , Palmerini Pierangela , Ventura Annavera , Visentin Andrea , Astori Giuseppe , Chieregato Katia , Mozzo Valentina , Perbellini Omar , Tisi Maria Chiara , Trentin Livio , Visco Carlo , Ruggeri Marco , Sommaggio Roberta , Rosato Antonio 
Published: July 2021

BackgroundPatients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Indeed, CIK cells are an effector population endowed with antitumor activity, which can be further improved and antigen-specifically redirected by clinical-grade mAb triggering antibody-dependent cell-mediated cytotoxicity.MethodsCIK cells were generated from peripheral blood of patients affected by different B-cell malignancies using a blinatumomab-based cell culture protocol. Effector cells were combined with the anti-CD20 mAb obinutuzumab and their therapeutic activity was assessed both in vitro and in vivo.ResultsCIK cells were successfully expanded in clinically relevant numbers, starting from small volumes of peripheral blood with extremely low CD3+ counts and high tumor burden. This relied on the addition of blinatumumab in culture, which leads to the simultaneous expansion of effector cells and the complete elimination of the neoplastic component. Moreover, CIK cells were highly cytotoxic in vitro against both B-cell tumor cell lines and autologous neoplastic targets, and had a significant therapeutic efficacy against a B-cell malignancy patient-derived xenograft on in vivo transfer.ConclusionsThe combination of an easily expandable CIK cell effector population with a mAb already in clinical use establishes a tumor antigen-specific redirection strategy that can be rapidly translated into clinical practice, providing an effective therapeutic alternative for B-cell malignancies without any need for genetic modifications. Additionally, the approach can be potentially applied to an extremely vast array of different tumors by simply substituting the targeting mAb.