bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution and long‐term outcomes of combined immunodeficiency due to CARMIL2 deficiency
Authors: Kolukisa Burcu , Baser Dilek , Akcam Bengu , Danielson Jeffrey , Bilgic Eltan Sevgi , Haliloglu Yesim , Sefer Asena Pinar , Babayeva Royale , Akgun Gamze , Charbonnier Louis‐Marie , Schmitz‐Abe Klaus , Kendir Demirkol Yasemin , Zhang Yu , Gonzaga‐Jauregui Claudia , Jimenez Heredia Raul , Kasap Nurhan , Kiykim Ayca , Ozek Yucel Esra , Gok Veysel , Unal Ekrem , Pac Kisaarslan Aysenur , Nepesov Serdar , Baysoy Gokhan , Onal Zerrin , Yesil Gozde , Celkan Tulin Tiraje , Cokugras Haluk , Camcioglu Yildiz , Eken Ahmet , Boztug Kaan , Lo Bernice , Karakoc‐Aydiner Elif , Su Helen C. , Ozen Ahmet , Chatila Talal A. , Baris Safa 
Published: July 2021

AbstractBackgroundBiallelic loss‐of‐function mutations in CARMIL2 cause combined immunodeficiency associated with dermatitis, inflammatory bowel disease (IBD), and EBV‐related smooth muscle tumors. Clinical and immunological characterizations of the disease with long‐term follow‐up and treatment options have not been previously reported in large cohorts. We sought to determine the clinical and immunological features of CARMIL2 deficiency and long‐term efficacy of treatment in controlling different disease manifestations.MethodsThe presenting phenotypes, long‐term outcomes, and treatment responses were evaluated prospectively in 15 CARMIL2‐deficient patients, including 13 novel cases. Lymphocyte subpopulations, protein expression, regulatory T (Treg), and circulating T follicular helper (cTFH) cells were analyzed. Three‐dimensional (3D) migration assay was performed to determine T‐cell shape.ResultsMean age at disease onset was 38 ± 23 months. Main clinical features were skin manifestations (n = 14, 93%), failure to thrive (n = 10, 67%), recurrent infections (n = 10, 67%), allergic symptoms (n = 8, 53%), chronic diarrhea (n = 4, 27%), and EBV‐related leiomyoma (n = 2, 13%). Skin manifestations ranged from atopic and seborrheic dermatitis to psoriasiform rash. Patients had reduced proportions of memory CD4+ T cells, Treg, and cTFH cells. Memory B and NK cells were also decreased. CARMIL2‐deficient T cells exhibited reduced T‐cell proliferation and cytokine production following CD28 co‐stimulation and normal morphology when migrating in a high‐density 3D collagen gel matrix. IBD was the most severe clinical manifestation, leading to growth retardation, requiring multiple interventional treatments. All patients were alive with a median follow‐up of 10.8 years (range: 3–17 years).ConclusionThis cohort provides clinical and immunological features and long‐term follow‐up of different manifestations of CARMIL2 deficiency.
Immunological effects of adjuvanted low‐dose allergoid allergen‐specific immunotherapy in experimental murine house dust mite allergy
Authors: Heldner Alexander , Alessandrini Francesca , Russkamp Dennis , Heine Sonja , Schnautz Benjamin , Chaker Adam , Mwange Juliet , Carreno Velazquez Thalia L. , Heath Matthew D. , Skinner Murray A. , Kramer Matthias F. , Zissler Ulrich M. , Schmidt‐Weber Carsten B. , Blank Simon 
Published: July 2021

AbstractBackgroundNative allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen‐specific immunotherapy (AIT), although mechanistic side‐by‐side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high‐dose HDM extract and low‐dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy.MethodsCellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant‐free intranasal sensitization followed by subcutaneous AIT.ResultsWhile low‐dose allergoid and high‐dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2‐type cytokine secretion of lung‐resident lymphocytes and draining lymph node cells, low‐dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low‐dose allergoid AIT with MCT or MCT and dose‐adjusted MPL promoted Th1‐inducing mechanisms and robust B‐cell activation counterbalancing the allergic Th2 immune response.ConclusionLow allergen doses induce cellular and humoral mechanisms counteracting Th2‐driven inflammation by using allergoids and dose‐adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low‐dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses.
Identification of novel biomarkers to distinguish bradykinin‐mediated angioedema from mast cell‐/histamine‐mediated angioedema
Authors: Bindke Gesa , Gehring Manuela , Wieczorek Dorothea , Kapp Alexander , Buhl Timo , Wedi Bettina 
Published: July 2021

AbstractBackgroundThe pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood.MethodsTo identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE‐inhibitor induced (ACE‐AE), and 12 mast cell‐mediated without wheals in chronic spontaneous urticaria (CSU‐AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin‐lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme‐linked immunosorbent assay.ResultsNew routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin‐mediated (BK‐) AE (ie, HAE and ACE‐AE) from mast cell‐/histamine‐mediated CSU‐AE. However, FAP‐α and tPA were significantly increased in all AE compared to controls. In HAE, FAP‐ α, tPA, uPAR, pentraxin‐3, Tie‐2, sE‐selectin, and VE‐cadherin were significantly increased compared to controls. In HAE compared to CSU‐AE and ACE‐AE, sE‐Selectin, Tie‐2, and VE‐Cadherin were significantly increased, whereas for Ang‐2 the difference was significant compared to CSU‐AE only. Tie‐2 correlated strongly negatively with C4, C1‐INH activity, and C1‐INH function.ConclusionsThis study is the first to compare HAE, ACE‐AE, and CSU‐AE. Although significance is limited by small sample size, Tie‐2 was identified as a new promising biomarker candidate for HAE. FAP‐ α and tPA might serve as a marker for AE in general, whereas sE‐selectin and Ang‐2 were increased in BK‐AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.
A Heuristic Model for Designing Interventions in Multicultural Mental Health Encounters: The Case of a Community Mental Health Center among the Mapuche of Chile
Authors: Wiencke Markus 
Published: July 2021

AbstractIn this paper, I develop the integrative concept of “shared experience of sense” as a heuristic model to design interventions in multicultural health encounters in the field of mental health promotion. For this purpose, I use extensive ethnographic material from the Mapuche’s territory in Chile, analyzing the interactions between an outpatient community mental health center and deinstitutionalized patients in their home settings. The patients and their families navigate the medical pluralism of their domestic settings and make varying use of each of the different therapeutic options that are available to them, offered by the outpatient community mental health center, Indigenous healers, and Pentecostalism.The concept of “shared experience of sense” characterizes a specific form of meaning‐making that may be beneficial to health in mental illness. This “positive” meaning making is made possible by a person's emotional and physical participation in the social events of therapeutic settings. In this regard, I highlight the bridges that the community mental health center builds to the everyday lives of patients and their families. Because of the support and access to resources provided by such therapeutic settings, persons are able to cope with their illness in everyday life, which can mean different things depending on the context. This is what I mean when I refer to “health promotion” in this article.
The Sensory Deprivation Tank – A Time Machine
Authors: Phillips Matthew T 
Published: July 2021

AbstractThis paper explores Henri Bergson’s understanding of time in relation to the experience of the sensory deprivation tank. In this exploration, the tank is presented as a time machine: a machine that separates time from space and takes the floater into an experience of what Bergson describes as pure time. At the same time, the tank acts as a kind of phenomenological epoché that, through the disabling of the floater’s sensory‐motor schema, literally suspends the human being outside of the world and forces them to reconsider their previous judgements and understandings of consciousness and time. The tank is tied in with contemporary scientific and philosophical discourses on consciousness, such as those of David Chalmers and what he has described as the hard problem of consciousness. As Chalmers discusses, the hard problem requires a radically new type of thinking beyond contemporary science and its inherent materialistic and mechanistic worldview. The tank is presented as a machine that could play a part in this radical rethinking of consciousness—a literal black box working through the black box problems of consciousness.
Synthesis of coagulation factors during long‐term ex situ liver perfusion
Authors: Eshmuminov Dilmurodjon , Hefti Max , Mueller Matteo , Schuler Martin J. , Bautista Borrego Lucia , Schneider Marcel André , Koch Karin , Weisskopf Miriam , Tibbitt Mark W. , Dutkowski Philipp , Rudolf von Rohr Philipp , Studt Jan‐Dirk , Becker Dustin , Clavien Pierre‐Alain 
Published: July 2021

AbstractRobust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood‐based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti‐FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate.
Acute gastrointestinal bleeding: proposed study outcomes for new randomised controlled trials
Authors: Jensen Dennis M. , Barkun Alan , Cave David , Gralnek Ian M. , Jutabha Rome , Laine Loren , Lau James Y. W. , Saltzman John R. , Soetikno Roy , Sung Joseph J. Y. 
Published: July 2021

SummaryBackgroundAcute gastrointestinal bleeding (GIB) remains a common cause of hospitalisation. However, interpretation and comparisons of published studies in GIB have been hampered by disparate study methodology.AimsTo make recommendations about outcome measures to be used in future randomised controlled trials (RCTs) of patients with acute bleeding from any GI source (nonvariceal UGI, variceal, small bowel, or colon) and suggest new RCTs in acute GIB for future peer‐reviewed funding.MethodsAs part of a National Institutes of Health conference entitled “Hemostatic Outcomes in Clinical Trials”, a group of GIB experts performed targeted critical reviews of available evidence with the goal of proposing a bleeding outcome that could potentially be applied to different disciplines. In addition, the panel sought to develop a clinically meaningful primary endpoint specifically for acute GIB, potentially allowing a more contemporary regrouping of clinically relevant outcomes.ResultsThe primary endpoint proposed was a composite outcome of further bleeding within 30 days after randomisation leading to red blood cell transfusion, urgent intervention (repeat endoscopy; interventional radiology or surgery), or death. Secondary outcomes may include the individual components of the primary outcome, length of hospitalisation, serious adverse events, and health care resource utilisation.ConclusionThe proposed endpoint may help move the GIB field forward by focusing on the most clinically relevant outcomes for patients with acute GIB of all types and informing study design and importance of sample size determination for future RCTs in GIB.
Personality as a moderator of immediate and delayed ostracism distress
Authors: Yaakobi Erez 
Published: July 2021

AbstractAlthough ostracism is known to have negative consequences, individuals are affected to differing extents and show different patterns of recovery. To better understand these differences, the Big Five personality model was used to examine the moderating role of personality on immediate and delayed ostracism distress. In this laboratory study, 408 participants played Cyberball and completed batteries on needs satisfaction and mood distress. The results show that more Agreeable or Conscientious individuals experienced greater distress on the immediate and the delayed distress measures (needs satisfaction and mood). Greater Openness to experience was related to greater effects of Agreeableness or Conscientious on distress experienced after being ostracized than when included. The discussion centres on the steps that can be taken to achieve greater relief after ostracism. This research contributes new theoretical insights and presents practical implications leading to a better understanding of those individuals who are at greater risk of being affected by ostracism, the personality characteristics that moderate ostracism distress, and when.
Transplantation of kidneys after normothermic perfusion: A single center experience
Authors: Pearson Robert , Geddes Colin , Mark Patrick , Clancy Marc , Asher John 
Published: July 2021

AbstractBackgroundIn order to expand the pool of usable donors from circulatory death (DCD) there is increasing interest in normothermic regional perfusion (NRP) to assess and improve liver viability.1,2 NRP may also improve outcomes in kidney transplantation.We present our single center experience of outcomes in imported kidneys following NRP.MethodsData was obtained from a prospectively maintained database between December 2012 and September 2018. Primary endpoints were incidence of delayed graft function (DGF) and estimated glomerular filtration rate (eGFR).ResultsSix‐hundred and thirty‐two decease donor kidneys were transplanted, 229 from DCD donors, 29 of which had NRP. The DGF rate was lower for NRP versus DCD (six of 29, 20.7% vs. 70 of 200, 35.0%) with reduced duration of DGF. Multivariate analysis demonstrated transplant type to be a statistically significant independent predictor of eGFR at 7 and 14 days. Early transplant function in NRP kidneys was comparable to DBD. There were no graft losses within 30 days in the NRP group. One‐year graft loss rate was 3.4% for NRP and 6.0% for standard DCD.ConclusionThis data suggests NRP is safe, and reduces rates of DGF and improves early renal transplant function.
Doing violence to evidence on violence? How the alcohol industry created doubt in order to influence policy
Authors: Bartlett Andrew , McCambridge Jim 
Published: July 2021

AbstractIntroductionIn 2015/2016 controversy followed the publication of a report on an anthropological study of Australian and New Zealand night‐time economies funded by a major alcohol producer. This paper explores the background, moments of public controversy and political uses of the report.MethodsInformed by the sociology of scientific controversies, we review the available relevant work of the author of the report, associated material such as press releases, newspaper articles (n = 18) and industry submissions to government (n = 12). Attention was paid to the ways in which claims were made about the relationship between alcohol and violence, and the ways in which credibility and legitimacy were constructed.ResultsThe author of the report has longstanding associations with alcohol industry organisations. Claims made regarding alcohol and violence have remained highly consistent over time, and appear oblivious to developments in the evidence. In the media, the story was largely framed as a contest of credibility between compromised parties. The report continues to be used in alcohol industry submissions to government.Discussion and ConclusionsThis analysis suggests that this is a ‘counterfeit scientific controversy’; in our assessment, the report has had value not as a contribution to the scientific literature, but as a resource in the claims‐making practices of the alcohol industry. Studies of the ways in which industry actors foster science‐related content conducted at significant social and conceptual distance from the core of the relevant research community will enhance understandings of the ways in which industry actors engage with science and policy.
Genetic and environmental influences on executive functions and intelligence in middle childhood
Authors: Freis Samantha M. , Morrison Claire L. , Lessem Jeffrey M. , Hewitt John K. , Friedman Naomi P. 
Published: July 2021

AbstractExecutive functions (EFs) and intelligence (IQ) are phenotypically correlated. In twin studies, latent variables for EFs and IQ display moderate to high heritability estimates; however, they show variable genetic correlations in twin studies spanning childhood to middle age. We analyzed data from over 11,000 children (9‐ to 10‐year‐olds, including 749 twin pairs) in the Adolescent Brain Cognitive Development (ABCD) Study to examine the phenotypic and genetic relations between EFs and IQ in childhood. We identified two EF factors—Common EF and Updating‐Specific—which were both related to IQ (rs = 0.64–0.81). Common EF and IQ were heritable (53%–67%), and their genetic correlation (rG = 0.86) was not significantly different than 1. These results suggest that EFs and IQ are phenotypically but not genetically separable in middle childhood, meaning that this phenotypic separability may be influenced by environmental factors.
The brain basis of handwriting deficits in Chinese children with developmental dyslexia
Authors: Yang Yang , Zuo Zhentao , Tam Fred , Graham Simon J. , Li Junjun , Ji Yuzhu , Meng Zelong , Gu Chanyuan , Bi Hong‐Yan , Ou Jian , Xu Min 
Published: July 2021

AbstractAbundant behavioral studies have demonstrated high comorbidity of reading and handwriting difficulties in developmental dyslexia (DD), a neurological condition characterized by unexpectedly low reading ability despite adequate nonverbal intelligence and typical schooling. The neural correlates of handwriting deficits remain largely unknown; however, as well as the extent that handwriting deficits share common neural bases with reading deficits in DD. The present work used functional magnetic resonance imaging to examine brain activity during handwriting and reading tasks in Chinese dyslexic children (n = 18) and age‐matched controls (n = 23). Compared to controls, dyslexic children exhibited reduced activation during handwriting tasks in brain regions supporting sensory‐motor processing (including supplementary motor area and postcentral gyrus) and visual‐orthography processing (including bilateral precuneus and right cuneus). Among these regions, the left supplementary motor area and the right precuneus also showed a trend of reduced activation during reading tasks in dyslexics. Moreover, increased activation was found in the left inferior frontal gyrus and anterior cingulate cortex in dyslexics, which may reflect more efforts of executive control to compensate for the impairments of motor and visual‐orthographic processing. Finally, dyslexic children exhibited aberrant functional connectivity among brain areas for cognitive control and sensory‐motor processes during handwriting tasks. Together, these findings suggest that handwriting deficits in DD are associated with functional abnormalities of multiple brain regions implicated in motor execution, visual‐orthographic processing, and cognitive control, providing important implications for the diagnosis and treatment of dyslexia.
Long‐term outcome in patients with follicular lymphoma following high‐dose therapy and autologous stem cell transplantation
Authors: Metzner Bernd , Pott Christiane , Müller Thomas H. , Casper Jochen , Kimmich Christoph , Petershofen Eduard K. , Renzelmann Andrea , Rosien Bernd , Thole Ruth , Voß Andreas , Köhne Claus Henning , Wellnitz Dominique 
Published: July 2021

AbstractObjectiveTo contribute data on long‐term outcome and potential curative impact of ASCT in FL, especially following HDT with the BEAM protocol (BCNU, etoposide, cytarabine and melphalan), given very limited data on this topic in the literature.Patients and methodsPatients with FL (n = 76) were treated in our institution with HDT and ASCT. In the case of long‐term remission (≥8 years), peripheral blood was tested for minimal residual disease by t(14;18)‐ and IGH‐PCR, including the last follow‐up.Results10‐year overall survival, progression‐free survival, and freedom from progression (FFP) after first‐line ASCT (n = 20) were 80%, 60%, and 69%, after second‐line ASCT (n = 48, following BEAM) 66%, 38%, and 41%, after third/fourth‐line ASCT (n = 8) 33%, 25%, and 25%, respectively. Prognostic factors for FFP were treatment line and FLIPI (Follicular Lymphoma International Prognostic Index). 10‐year FFP for second‐line ASCT and low‐risk FLIPI at relapse was 69%, intermediate‐risk 28%, and high‐risk 25% (P < .05). 26 patients developed sustained long‐term clinical and molecular remissions of up to 27 years.ConclusionsSustained long‐term clinical and molecular complete remissions up to 27 years can be achieved following ASCT (including HDT with BEAM in second treatment line), indicating a potential curative impact of ASCT in FL.