bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioenergetic and inflammatory systemic phenotypes in Alzheimer’s disease APOE ε4‐carriers
Authors: Wilkins Heather M. , Wang Xiaowan , Menta Blaise W. , Koppel Scott J. , Bothwell Rebecca , Becker Annette M. , Anderson Heidi , Schwartz Erin , Pei Dong , Yellapu Nanda K. , Chalise Prabhakar , Gouvion Cynthia M. , Haeri Mohammad , Burns Jeffrey M. , Swerdlow Russell H. 
Published: May 2021

AbstractWe examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean platelet mitochondrial cytochrome oxidase Vmax activity was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. Proteins that mediate mitophagy and energy sensing were higher in APOE ε4 lymphocytes which could represent compensatory changes and recapitulate phenomena observed in post‐mortem AD brains. Analysis of the lipid synthesis pathway found higher AceCSI, ATP CL, and phosphorylated ACC levels in APOE ε4 lymphocytes. Lymphocyte ACC changes were also observed in post‐mortem brain tissue. Lymphocyte RNAseq showed lower APOE ε4 carrier sphingolipid Transporter 3 (SPNS3) and integrin Subunit Alpha 1 (ITGA1) expression. RNAseq pathway analysis revealed APOE ε4 alleles activated inflammatory pathways and modulated bioenergetic signaling. These findings support a relationship between APOE genotype and bioenergetic pathways and indicate platelets and lymphocytes from APOE ε4 carriers exist in a state of bioenergetic stress. Neither medication use nor brain‐localized AD histopathology can account for these findings, which define an APOE ε4‐determined molecular and systemic phenotype that informs AD etiology.
PR interval prolongation is significantly associated with aortic root abscess: An age‐ and gender‐matched study
Authors: Kohli Utkarsh , Obuobi Shirlene , Addetia Karima , Ota Takeyoshi , Nayak Hemal M. 
Published: May 2021

AbstractBackgroundElectrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age‐ and gender‐matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis.MethodsPatients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12‐lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre‐ and post‐admission PR interval, was the primary outcome of interest. The patients in the ARA group were age‐ and gender‐matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed.ResultsEighteen patients with surgically confirmed ARA were enrolled. These patients were age‐ and gender‐matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (−5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003).ConclusionsThe findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement.
Association between lifetime and recent stressful life events and the early course and psychopathology in patients with newly diagnosed bipolar disorder, first‐degree unaffected relatives and healthy controls: Cross‐sectional results from a prospective study
Authors: av Kák Kollsker Stina , Coello Klara , Stanislaus Sharleny , Melbye Sigurd , Lie Kjærstad Hanne , Stefanie Ormstrup Sletved Kimie , Vedel Kessing Lars , Vinberg Maj 
Published: May 2021

AbstractObjectiveThere is an accumulation of stressful life events prior to the first mood episode, but the impact of previous severe life events on psychopathology in patients with bipolar disorder (BD) is not well studied. We aimed to examine the number of recent and lifetime life events in patients with newly diagnosed BD, their unaffected relatives (UR), and healthy controls (HC) as well as the impact of severe lifetime life events on the early course of BD.MethodsWe compared the number of recent and lifetime life events in 398 patients with newly diagnosed BD, 109 UR, and 214 HC. We subsequently dichotomized the patients with BD by >2 lifetime life events to investigate the associations of severe lifetime life events with clinical characteristics and affective symptoms.ResultsPatients with newly diagnosed BD reported significantly more life events in the last 12 months and lifetime before compared with UR and HC. Patients who reported >2 lifetime life events (n = 160) compared with patients with 0–2 life events (n = 238) had a significantly longer diagnostic delay (9.5 years ± 8.2 vs. 6.2 years ± 6.9), presented with more anxiety and depressive symptoms and had at least one previous suicide attempt (30.6% vs. 15.6%) and one previous admission (51.3% vs. 36.6%).ConclusionThe experience of severe lifetime life events seems to impact the early course in BD in terms of longer diagnostic delay, more severe psychopathology including more admissions and a more than doubled risk for previous suicide attempts.
Evaluating the feasibility and acceptability of a mobile‐based health technology for smoking cessation: Mobile Anxiety Sensitivity Program
Authors: Garey Lorra , Hébert Emily T. , Mayorga Nubia A. , Chavez JeanFelix , Shepherd Justin M. , Businelle Michael S. , Zvolensky Michael J. 
Published: May 2021

ObjectivesCigarette smoking is the leading preventable cause of death and disability. Although most US smokers want to quit, more than 95% of cessation attempts end in relapse within 6 months. To improve cessation outcomes, research has turned to targetable mechanisms, such as anxiety sensitivity (AS), which maintain smoking behaviour, impede cessation success, and can be effectively targeted in the context of psychosocial interventions. Although integrated treatment programmes that address AS reduction in the context of smoking cessation have demonstrated promising results, presently, no mobile, technology‐based integrated treatment exists to expressly address smoking and AS. The current study evaluated the initial feasibility and acceptability of a mobile smoking cessation intervention, Mobile Anxiety Sensitivity Program for smoking (MASP).MethodsParticipants were 15 daily adult combustible cigarette smokers (females n = 6, Mage = 46.5 years, SD = 13.3) who completed a 6‐week total intervention period (baseline visit, 2 weeks pre‐quit, 4 weeks post‐quit, follow‐up visit).ResultsMost participants (N = 12) completed the full 6‐week intervention, and participant engagement with MASP was high. Participants reported that MASP was acceptable. Biochemical verification of smoking abstinence indicated 25% of smokers were abstinent for at least 24 hr prior to the in‐person 4 weeks post‐quit follow‐up visit.ConclusionsFindings indicated that MASP has the potential to provide effective assistance to those wanting to quit cigarettes.Practitioner points

Mobile‐based smoking cessation interventions may be a promising treatment option, particularly for those of lower socio‐economic status.

Targeting AS in the context of a mobile‐based smoking cessation app may be a viable way to improve smoking cessation success and treatment outcome.

Due to the pilot nature of this study, there was no control group. Thus, comparative conclusions and generalizability based on the current study must be made with caution.
Improving the laboratory diagnosis of pyruvate kinase deficiency
Authors: Laas Claire , Lambert Christopher , Senior McKenzie Tania , Sheldon Ewart , Davidson Philip , Rees David , Clark Barnaby 
Published: May 2021

SummaryPyruvate kinase (PK) deficiency is an autosomal recessive disease caused by mutations in the PKLR gene, which reduce erythrocyte PK enzyme activity and result in decreased energy synthesis in red cells, causing haemolytic anaemia. Historically, the investigation into pyruvate kinase deficiency (PKD) has been led by a red cell enzyme assay determining PK enzyme activity per unit of haemoglobin. For our laboratory, the reference range was set by Beutler et al. in 1977 when the test was first established. The introduction of genetic testing permitted the creation of reference sample datasets, with positive controls having two pathogenic variants causing disease. This permitted re‐assessment of the enzyme assay’s sensitivity and specificity, and was used to reassess the reference range of the enzyme assay. Using sequenced samples, we have devised an enzyme assay, DNA testing workflow, which minimises false negative/positive results and improves the diagnostic efficiency. This combined enzyme‐DNA testing strategy should improve the diagnostic accuracy whilst limiting the number of expensive DNA tests. During this evaluation, 10 novel genetic variants were identified and are described.
Histopathological patterns in atypical teratoid/rhabdoid tumors are related to molecular subgroup
Authors: Zin Francesca , Cotter Jennifer A. , Haberler Christine , Dottermusch Matthias , Neumann Julia , Schüller Ulrich , Schweizer Leonille , Thomas Christian , Nemes Karolina , Johann Pascal D. , Kool Marcel , Frühwald Michael C. , Paulus Werner , Judkins Alexander , Hasselblatt Martin 
Published: May 2021

AbstractAtypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor that may not only contain rhabdoid tumor cells but also poorly differentiated small‐round‐blue cells as well as areas with mesenchymal or epithelial differentiation. Little is known on factors associated with histopathological diversity. Recent studies demonstrated three molecular subgroups of AT/RT, namely ATRT‐TYR, ATRT‐SHH, and ATRT‐MYC. We thus aimed to investigate if morphological patterns might be related to molecular subgroup status. Hematoxylin‐eosin stained sections of 114 AT/RT with known molecular subgroup status were digitalized and independently categorized by nine blinded observers into four morphological categories, that is, “rhabdoid,” “small‐round‐blue,” “epithelial,” and “mesenchymal.” The series comprised 48 ATRT‐SHH, 40 ATRT‐TYR, and 26 ATRT‐MYC tumors. Inter‐observer agreement was moderate but significant (Fleiss’ kappa = 0.47; 95% C.I. 0.41‐0.53; p < 0.001) and there was a highly significant overall association between morphological categories and molecular subgroups for each of the nine observers (p < 0.0001). Specifically, the category “epithelial” was found to be over‐represented in ATRT‐TYR (p < 0.000001) and the category “small‐round‐blue” to be over‐represented in ATRT‐SHH (p < 0.01). The majority of ATRT‐MYC was categorized as “mesenchymal” or “rhabdoid,” but this association was less compelling. The specificity of the category “epithelial” for ATRT‐TYR was highest and accounted for 97% (range: 88‐99%) whereas sensitivity was low [49% (range: 35%–63%)]. In line with these findings, cytokeratin‐positivity was highly overrepresented in ATRT‐TYR. In conclusion, morphological features of AT/RT might reflect molecular alterations and may also provide a first hint on molecular subgroup status, which will need to be confirmed by DNA methylation profiling.
Self‐harm as the first presentation of attention deficit hyperactivity disorder in adolescents
Authors: Ward John Headley , Curran Sarah 
Published: May 2021

BackgroundSelf‐harm (SH) in adolescence has previously been shown to significantly overlap with both attention deficit hyperactivity disorder (ADHD) and emotional dysregulation (ED). Our objective as such was to investigate the relationship between self‐harm and ADHD in our population and consider its clinical relevance.MethodsThis case series analysis examined 124 presentations of SH in 13‐ to 17 year‐olds to Accident and Emergency Departments in South West London (97F:27M). Strength and Difficulties Questionnaires (SDQs) were used to screen for ADHD/hyperactivity and ED, and scores were compared with reference data obtained from Meltzer et al. (1999, International Review of Psychiatry (Abingdon, England), 15, 185).ResultsMean SDQ ADHD/hyperactivity scores were significantly higher in our SH sample compared to reference data (p < .0001). Furthermore, significantly greater ED scores were found in our sample compared with the control reference data.ConclusionOur findings contribute to the evidence for an important link between ADHD and clinical presentations of SH and suggest there to be value in screening girls presenting to A&E with self‐harm for ADHD. We speculate that ED plays a role in the evolution of SH in dysregulated ADHD. We recommend that clinicians assessing adolescents have self‐harmed to be aware of possible ADHD symptoms and screen as appropriate; however, future research examining the temporal association between ADHD, emotional dysregulation and self‐harm is required to establish causal direction.
Development of humanized mouse with patient‐derived xenografts for cancer immunotherapy studies: A comprehensive review
Authors: Jin Ke‐Tao , Du Wen‐Lin , Lan Huan‐Rong , Liu Yu‐Yao , Mao Chun‐Sen , Du Jin‐Lin , Mou Xiao‐Zhou 
Published: May 2021

AbstractImmunotherapy has revolutionized cancer treatment, however, not all tumor types and patients are completely responsive to this approach. Establishing predictive pre‐clinical models would allow for more accurate and practical immunotherapeutic drug development. Mouse models are extensively used as in vivo system for biomedical research. However, due to the significant differences between rodents and human, it is impossible to translate most of the findings from mouse models to human. Pharmacological development and advancing personalized medicine using patient‐derived xenografts relies on producing mouse models in which murine cells and genes are substituted with their human equivalent. Humanized mice (HM) provide a suitable platform to evaluate xenograft growth in the context of a human immune system. In this review, we discussed recent advances in the generation and application of HM models. We also reviewed new insights into the basic mechanisms, pre‐clinical evaluation of onco‐immunotherapies, current limitations in the application of these models as well as available improvement strategies. Finally, we pointed out some issues for future studies.
Evaluating outcomes of conservation with multidimensional indicators of well‐being
Authors: Mbaru Emmanuel K. , Hicks Christina C. , Gurney Georgina G. , Cinner Joshua E. 
Published: May 2021

AbstractMany conservation interventions are hypothesized to be beneficial for both the environment and people's well‐being, but this has rarely been tested rigorously. We examined the effects of adoption or nonadoption of a conservation intervention on 3 dimensions of people's well‐being (material, relational, and subjective) over time. We focused on a fisheries bycatch management initiative intended to reduce environmental externalities associated with resource extraction. We collected panel data from fishers (n = 250) in villages with (adopters and nonadopters) and without (control) the conservation intervention 3 times over 2 years. We found no evidence that adoption reduced any of the 3 dimensions of well‐being in the local populations affected by the intervention. There were modest improvements in material (t = –1.58) and subjective livelihood well‐being (p = 0.04) for adopters relative to nonadopters over time. The variations in well‐being experiences (in terms of magnitude of change) among adopters, nonadopters, and controls across the different domains over time affirmed the dynamic and social nature of well‐being.
Enabling transformative economic change in the post‐2020 biodiversity agenda
Authors: Turnhout Esther , McElwee Pamela , Chiroleu‐Assouline Mireille , Clapp Jennifer , Isenhour Cindy , Kelemen Eszter , Jackson Tim , Miller Daniel C. , Rusch Graciela M. , Spangenberg Joachim H. , Waldron Anthony 
Published: May 2021

AbstractThe COVID‐19 pandemic, its impact on the global economy, and current delays in the negotiation of the post‐2020 global biodiversity agenda of the Convention on Biological Diversity heighten the urgency to build back better for biodiversity, sustainability, and well‐being. In 2019, the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services (IPBES) concluded that addressing biodiversity loss requires a transformative change of the global economic system. Drawing on the IPBES findings, this policy perspective discusses actions in four priority areas to inform the post‐2020 agenda: (1) Increasing funding for conservation; (2) redirecting incentives for sustainability; (3) creating an enabling regulatory environment; and (4) reforming metrics to assess biodiversity impacts and progress toward sustainable and just goals. As the COVID‐19 pandemic has made clear, and the negotiations for the post‐2020 agenda have emphasized, governments are indispensable in guiding economic systems and must take an active role in transformations, along with businesses and civil society. These key actors must work together to implement actions that combine short‐term impacts with structural change to shift economic systems away from a fixation with growth toward human and ecological well‐being. The four priority areas discussed here provide opportunities for the post‐2020 agenda to do so.
Fifteen years of lessons from the Seascape approach: A framework for improving ocean management at scale
Authors: Murphy Shannon E. , Farmer Ginny , Katz Laure , Troëng Sebastian , Henderson Scott , Erdmann Mark V. , Corrigan Colleen , Gold Barry , Lavoie Christian , Quesada Marco , Díazgranados Cadelo María Claudia , Guzmán Mora Ana Gloria , Nunez Enrique , Montebon Augustus , Meo Semisi , Waqainabete‐Tuisese Susana , Dutra Guilherme , Pereira Renata , Mongdong Meity , Putra Ketut S. 
Published: May 2021

AbstractSeascapes are large, multiple‐use marine areas, defined scientifically and strategically, in which government authorities, private organizations, and other stakeholders cooperate to conserve the diversity and abundance of marine life and promote human well‐being. This approach has been applied by global nonprofit partnerships in five seascapes across eight countries and has drawn on the practical experience of more than 250 partners over 15 years. These experiences have helped define the Seascape approach, consisting of nine essential elements, for achieving effective ocean governance and management from local to regional levels. Lessons learned relate to using integrated planning frameworks, community‐led and locally owned initiatives, and a network of partners and a “backbone” organization for effective Seascape planning and design; promoting diversification in funding sources, private sector engagement, and the transition of nonprofit roles to ensure durability of a Seascape; and ensuring Seascape outcomes are measured through robust monitoring and evaluation frameworks and communicated effectively. Seascapes are unique in their ability to create a pathway toward sustainable development. To ensure support and amplification of the approach, they must align with diversified funding opportunities and global priorities outlined in international United Nations conventions focused on sustainable development and ocean health.
Acetyl‐CoA‐driven respiration in frozen muscle contributes to the diagnosis of mitochondrial disease
Authors: Zuccolotto‐dos‐Reis Felippe Henrique , Escarso Silvia Helena Andrião , Araujo Jackeline Souza , Espreafico Enilza Maria , Alberici Luciane Carla , Sobreira Claudia Ferreira da Rosa 
Published: May 2021

AbstractBackgroundFreezing human biopsies is common in clinical practice for storage. However, this technique disrupts mitochondrial membranes, hampering further analyses of respiratory function. To contribute to laboratorial diagnosis of mitochondrial diseases, this study sought to develop a respirometry approach using O2k (Oroboros Ins.) to measure the whole electron transport chain (ETC) activity in homogenates of frozen skeletal muscle biopsies.Patients and MethodsWe enrolled 16 patients submitted to muscle biopsy in the process of routine diagnostic investigation: four with mitochondrial disease and severe mitochondrial dysfunction; seven with exercise intolerance and multiple deletions of mitochondrial DNA, presenting mild to moderate mitochondrial dysfunction; five without mitochondrial disease, as controls. Whole homogenates of muscle fragments were prepared using grinder‐type equipment. O2 consumption rates were normalized using citrate synthase activity.ResultsTransmission electron microscopy confirmed mitochondrial membrane discontinuation, indicating increased permeability of mitochondrial membranes in homogenates from frozen biopsies. O2 consumption rates in the presence of acetyl‐CoA lead to maximum respiratory rates sensitive to rotenone, malonate and antimycin. This protocol of acetyl‐CoA‐driven respiration (ACoAR), applied in whole homogenates of frozen muscle, was sensitive enough to identify ETC abnormality, even in patients with mild to moderate mitochondrial dysfunction. We demonstrated adequate repeatability of ACoAR and found significant correlation between O2 consumption rates and enzyme activity assays of individual ETC complexes.ConclusionsWe present preliminary data on a simple, low cost and reliable procedure to measure respiratory function in whole homogenates of frozen skeletal muscle biopsies, contributing to diagnosis of mitochondrial diseases in humans.