bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18FDG-PET studies in schizophrenia
Authors: Townsend Leigh , Pillinger Toby , Selvaggi Pierluigi , Veronese Mattia , Turkheimer Federico , Howes Oliver 
Published: June 2022

AbstractBackgroundImpaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown.MethodsWe searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using 18FDG-PET, in schizophrenia/first-episode psychosis v. controls. Effect sizes (Hedges g) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus.ResultsThirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's g = −0.74 ± 0.54, p = 0.01; I2 = 67%) and metabolism relative to whole brain (g = −0.44 ± 0.34, p = 0.01; I2 = 55%) were lower in schizophrenia v. controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic (g = −1.18 ± 0.73) v. first-episode patients (g = −0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (−1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia v. controls (−0.25 ± 0.24, p = 0.049; I2 = 5%). Studies identified reporting voxel-based morphometry measures of absolute 18FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower 18FDG uptake in the left anterior cingulate gyrus (Z = −4.143; p = 0.007) and the left inferior orbital frontal gyrus (Z = −4.239; p = 0.02) in schizophrenia.ConclusionsWe report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.
Methods and criteria for the assessment of orphan drugs: a scoping review
Authors: Mohammadshahi Marita , Olyaeemanesh Alireza , Ehsani-Chimeh Elham , Mobinizadeh Mohammadreza , Fakoorfard Zeinab , Akbari Sari Ali , Aghighi Mohammad 
Published: June 2022

Abstract

Objectives
This study aimed to identify different criteria for priority setting of rare diseases to help policy makers in making evidence-informed decisions.

Methods
A scoping review was conducted to comprehensively examine the existing various methods and criteria for prioritizing orphan drugs and rare diseases. We performed searching in Scopus, PubMed, Embase, and websites of health technology assessment (HTA) agencies, 2000–21, and data were extracted.

Results
From the 1,580 identified publications, eleven articles were included. Multicriteria decision analysis was the most frequent method (seven out of eleven studies) used for priority setting. The extracted criteria for priority setting of orphan products were analyzed based on six main categories as follows: health outcomes and clinical implications (six subsets which showed clinical implications), economic aspects (four subsets that indicated the economic effects of orphan drugs and rare diseases), disease and population characteristics (six subsets that included the characteristics of the rare diseases), therapeutic alternatives and uniqueness of orphan technologies (two subsets which discussed the alternatives and uniqueness of orphan technologies), evidence (three subsets which regarded the quality and availability of evidence), and other criteria (three subsets dealing with social and organizational criteria). Cost-effectiveness, budget impact, and disease severity were the most frequent criteria in the studies.

Conclusions
Because of the high price of orphan drugs and limitations of using HTA for reimbursement of them, it is critical to explore them by precise technical methods like multiple criteria decision making in priority setting.
Joint programmes in paediatric cardiac surgery: an update and descriptive analysis
Authors: Toomey Nikia T. , Ulysse James , DeCampli William M. 
Published: June 2022

AbstractObjective:Joint programmes are an alternative model that may aid in improving congenital cardiac surgery outcomes while avoiding the potential resource and accessibility challenges that could result from regionalisation. This study aims to characterise current joint programmes, identify factors that are associated with joint programme success and failure, and gauge attitudes within the profession regarding joint programmes as an alternative.Methods:A multiple choice survey with 23 standard questions for all programmes and additional 42 additional questions for each participant hospital in a joint programme was addressed to paediatric cardiac surgeons in the United States of America. Questions were designed to qualitatively and quantitatively characterise congenital cardiac surgery joint programmes.Results:Of the 34 unique congenital cardiac surgery programmes identified in this survey, 14 have participated in a joint programme and 50% of those joint programmes existed for more than 10 years. Most joint programmes (86%) participate or participated in a model where the hospital participants are engaged in a “mother–daughter” relationship in both perception and case volume distribution. In three out of four defunct joint programmes, there were case complexity limitations placed on partner institutions, but the now independent partner institutions operate with no limitation on complexity. Most (71%) hospital participants in a joint programme felt that the joint programme produced better outcomes than two separate programmes; however, among those who participate or have participated in a joint programme, only 18% felt that joint programmes were the optimal model for delivery of congenital cardiac surgical care.
Quality of life after Ross procedure in children
Authors: Chau Peter , Uzark Karen C. , Goldberg Caren S. , Donohue Janet E. , Schumacher Kurt R. 
Published: June 2022

AbstractIntroduction:Health-related quality of life in children who have undergone the Ross procedure has not been well characterised. The aim of this study was to characterise health-related quality of life in this cohort and compare to children with other CHD.Method:In this cross sectional, single-centre study, health-related quality of life was assessed in patients who underwent a non-neonatal Ross procedure using the Pediatric Quality of Life Inventory. Ross cohort scores were compared with healthy norms, patients with CHD requiring no surgical intervention or had curative surgery (Severity 2, S2) and patients who were surgically repaired with ≥1 surgical procedure and with significant residual lesion or need for additional surgery (Severity 3, S3). Associations between Pediatric Quality of Life Inventory score and patient factors were also examined.Results:68 patients completed surveys. Nearly one-sixth of patients had overall scores below the cut-off for at-risk status for impaired health-related quality of life. There was no difference in overall health-related quality of life score between the Ross cohort and healthy children (p = 0.56) and S2 cohort (p = 0.97). Health-related quality of life was significantly higher in the Ross cohort compared to S3 cohort (p = 0.02). This difference was driven by a higher psychosocial health-related quality of life in the Ross cohort as compared to S3 cohort (p = 0.007). Anxiety scores were significantly worse in the Ross cohort compared to both S2 (p = 0.001) and S3 (p = 0.0017), respectively.Conclusion:Children who have undergone a Ross procedure report health-related quality of life equivalent to CHD not requiring therapy and superior to CHD with residual lesions. Despite these reassuring results, providers should be aware of potential anxiety among Ross patients.
Sex and gender in treatment response to dialectical behaviour therapy: current knowledge, gaps, and future directions
Authors: Penta S. , Correia S. , Schneider M.A. , Holshausen K. , Nicholson A.A. , Haefner S.A. , Mutschler C. , Ferdossifard A. , Boylan K. , Hewitt J. , Roth S.L. , Wilson R. , Hatchard T. 
Published: June 2022

Abstract
Borderline personality disorder (BPD) is a mental health condition characterized by emotion dysregulation, interpersonal impairment, and high suicidality. Dialectical behaviour therapy (DBT) is the most widely studied psychotherapeutic treatment for BPD. To date, the vast majority of DBT research has focused on cisgender women, with a notable lack of systematic investigation of sex and/or gender differences in treatment response. In order to encourage effective, equitable treatment of BPD, further investigation into treatment targets in this population is critical. Here, we employed a systematic strategy to delineate gaps in the DBT literature pertaining to sex and gender differences and propose directions for future research. Findings demonstrate a significant discrepancy in measurement of sex and gender, particularly among gender-diverse individuals. Exploring DBT treatment response across the full spectrum of genders will facilitate the provision of more tailored, impactful care to all individuals who suffer from BPD.

Key learning aims

(1)
To date, DBT treatment literature has focused almost exclusively on cisgender women, with only two of 253 DBT studies in current literature accounting for transgender and gender diverse (TGD) individuals.

(2)
Recognize how gender minority stress may impact the prevalence of BPD among TGD individuals.

(3)
Learn how future research initiatives can be employed to rectify this gap in the DBT literature.
Increasing Frequency of Mid‐Depth Salinity Maximum Intrusions in the Middle Atlantic Bight
Authors: Gawarkiewicz G. , Fratantoni P. , Bahr F. , Ellertson A. 
Published: June 2022

AbstractShelfbreak exchange processes have been studied extensively in the Middle Atlantic Bight. An important process occurring during stratified conditions is the Salinity Maximum Intrusion. These features are commonly observed at the depth of the seasonal pycnocline, and less frequently at the surface and bottom. Data collected from NOAA's National Marine Fisheries Service Ecosystem Monitoring program as well as data collected from the fishing industry in Rhode Island show that the middepth intrusions are now occurring much more frequently than was reported in a previous climatology of the intrusions (Lentz, 2003, https://doi.org/10.1029/2003JC001859). The intrusions have a greater salinity difference from ambient water and penetrate large distances shoreward of the shelf break relative to the earlier climatology. The longer term data from the Ecosystem Monitoring program indicates that the increase in frequency occurred in 2000, and thus may be linked to a recent regime shift in the annual formation rate of Warm Core Rings by the Gulf Stream. Given the increased frequency of these salty intrusions, it will be necessary to properly resolve this process in numerical simulations in order to account for salt budgets for the continental shelf and slope.
Modeling the Transport and Deposition of 10Be Produced by the Strongest Solar Proton Event During the Holocene
Authors: Spiegl T. C. , Yoden S. , Langematz U. , Sato T. , Chhin R. , Noda S. , Miyake F. , Kusano K. , Schaar K. , Kunze M. 
Published: June 2022

AbstractProminent excursions in the number of cosmogenic nuclides (e.g., 10Be) around 774 CE/775 document the most severe solar proton event (SPE) throughout the Holocene. Its manifestation in ice cores is valuable for geochronology, but also for solar‐terrestrial physics and climate modeling. Using the ECHAM/MESSy Atmospheric Chemistry (EMAC) climate model in combination with the Warning System for Aviation Exposure to SEP (WASAVIES), we investigate the transport, mixing, and deposition of the cosmogenic nuclide 10Be produced by the 774 CE/775 SPE. By comparing the model results to the reconstructed 10Be time series from four ice core records, we study the atmospheric pathways of 10Be from its stratospheric source to its sink at Earth's surface. The reconstructed post‐SPE evolution of the 10Be surface fluxes at the ice core sites is well captured by the model. The downward transport of the 10Be atoms is controlled by the Brewer‐Dobson circulation in the stratosphere and cross‐tropopause transport via tropopause folds or large‐scale sinking. Clear hemispheric differences in the transport and deposition processes are identified. In both polar regions the 10Be surface fluxes peak in summertime, with a larger influence of wet deposition on the seasonal 10Be surface flux in Greenland than in Antarctica. Differences in the peak 10Be surface flux following the 774 CE/775 SPE at the drilling sites are explained by specific meteorological conditions depending on the geographic locations of the sites.
OTUB1 augments hypoxia signaling via its non-canonical ubiquitination inhibition of HIF-1α during hypoxia adaptation
Authors: Liu Xing , Deng Hongyan , Tang Jinhua , Wang Zixuan , Zhu Chunchun , Cai Xiaolian , Rong Fangjing , Chen Xiaoyun , Sun Xueyi , Jia Shuke , Ouyang Gang , Li Wenhua , Xiao Wuhan 
Published: June 2022

AbstractAs a main regulator of cellular responses to hypoxia, the protein stability of hypoxia-inducible factor (HIF)-1α is strictly controlled by oxygen tension dependent of PHDs-catalyzed protein hydroxylation and pVHL complex-mediated proteasomal degradation. Whether HIF-1α protein stability as well as its activity can be further regulated under hypoxia is not well understood. In this study, we found that OTUB1 augments hypoxia signaling independent of PHDs/VHL and FIH. OTUB1 binds to HIF-1α and depletion of OTUB1 reduces endogenous HIF-1α protein under hypoxia. In addition, OTUB1 inhibits K48-linked polyubiquitination of HIF-1α via its non-canonical inhibition of ubiquitination activity. Furthermore, OTUB1 promotes hypoxia-induced glycolytic reprogramming for cellular metabolic adaptation. These findings define a novel regulation of HIF-1α under hypoxia and demonstrate that OTUB1-mediated HIF-1α stabilization positively regulates HIF-1α transcriptional activity and benefits cellular hypoxia adaptation.
Chronic inhibition of the mitochondrial ATP synthase in skeletal muscle triggers sarcoplasmic reticulum distress and tubular aggregates
Authors: Sánchez-González Cristina , Herrero Martín Juan Cruz , Salegi Ansa Beñat , Núñez de Arenas Cristina , Stančič Brina , Pereira Marta P. , Contreras Laura , Cuezva José M. , Formentini Laura 
Published: June 2022

AbstractTubular aggregates (TA) are honeycomb-like arrays of sarcoplasmic-reticulum (SR) tubules affecting aged glycolytic fibers of male individuals and inducing severe sarcomere disorganization and muscular pain. TA develop in skeletal muscle from Tubular Aggregate Myopathy (TAM) patients as well as in other disorders including endocrine syndromes, diabetes, and ageing, being their primary cause unknown. Nowadays, there is no cure for TA. Intriguingly, both hypoxia and calcium dyshomeostasis prompt TA formation, pointing to a possible role for mitochondria in their setting. However, a functional link between mitochondrial dysfunctions and TA remains unknown. Herein, we investigate the alteration in muscle-proteome of TAM patients, the molecular mechanism of TA onset and a potential therapy in a preclinical mouse model of the disease. We show that in vivo chronic inhibition of the mitochondrial ATP synthase in muscle causes TA. Upon long-term restrained oxidative phosphorylation (OXPHOS), oxidative soleus experiments a metabolic and structural switch towards glycolytic fibers, increases mitochondrial fission, and activates mitophagy to recycle damaged mitochondria. TA result from the overresponse of the fission controller DRP1, that upregulates the Store-Operate-Calcium-Entry and increases the mitochondria-SR interaction in a futile attempt to buffer calcium overloads upon prolonged OXPHOS inhibition. Accordingly, hypoxic muscles cultured ex vivo show an increase in mitochondria/SR contact sites and autophagic/mitophagic zones, where TA clusters grow around defective mitochondria. Moreover, hypoxia triggered a stronger TA formation upon ATP synthase inhibition, and this effect was reduced by the DRP1 inhibitor mDIVI. Remarkably, the muscle proteome of TAM patients displays similar alterations in mitochondrial dynamics and in ATP synthase contents. In vivo edaravone treatment in mice with restrained OXPHOS restored a healthy phenotype by prompting mitogenesis and mitochondrial fusion. Altogether, our data provide a functional link between the ATP synthase/DRP1 axis and the setting of TA, and repurpose edaravone as a possible treatment for TA-associated disorders.
Association between DNA methylation variability and self-reported exposure to heavy metals
Authors: Freydenzon Anna , Nabais Marta F. , Lin Tian , Williams Kelly L. , Wallace Leanne , Henders Anjali K. , Blair Ian P. , Wray Naomi R. , Pamphlett Roger , McRae Allan F. 
Published: June 2022

AbstractIndividuals encounter varying environmental exposures throughout their lifetimes. Some exposures such as smoking are readily observed and have high personal recall; others are more indirect or sporadic and might only be inferred from long occupational histories or lifestyles. We evaluated the utility of using lifetime-long self-reported exposures for identifying differential methylation in an amyotrophic lateral sclerosis cases-control cohort of 855 individuals. Individuals submitted paper-based surveys on exposure and occupational histories as well as whole blood samples. Genome-wide DNA methylation levels were quantified using the Illumina Infinium Human Methylation450 array. We analyzed 15 environmental exposures using the OSCA software linear and MOA models, where we regressed exposures individually by methylation adjusted for batch effects and disease status as well as predicted scores for age, sex, cell count, and smoking status. We also regressed on the first principal components on clustered environmental exposures to detect DNA methylation changes associated with a more generalised definition of environmental exposure. Five DNA methylation probes across three environmental exposures (cadmium, mercury and metalwork) were significantly associated using the MOA models and seven through the linear models, with one additionally across a principal component representing chemical exposures. Methylome-wide significance for four of these markers was driven by extreme hyper/hypo-methylation in small numbers of individuals. The results indicate the potential for using self-reported exposure histories in detecting DNA methylation changes in response to the environment, but also highlight the confounded nature of environmental exposure in cohort studies.
High efficacy of intensive immunochemotherapy for primary mediastinal B-cell lymphoma with prolonged follow up
Authors: Romejko-Jarosinska Joanna , Ostrowska Beata , Dabrowska-Iwanicka Anna , Domanska-Czyz Katarzyna , Rymkiewicz Grzegorz , Paszkiewicz-Kozik Ewa , Konecki Robert , Borawska Anna , Druzd-Sitek Agnieszka , Lampka Elzbieta , Osiadacz Wlodzimierz , Osowiecki Michal , Popławska Lidia , Swierkowska Monika , Targonski Lukasz , Tajer Joanna , Lapinska Grazyna , Smorczewska Malwina , Walewski Jan 
Published: June 2022

AbstractPrimary mediastinal B-cell lymphoma (PMBL) is currently curable in 85–95% of patients. Treatment regimens frequently used include RCHOP ± radiotherapy, DAEPOCH-R, or occasionally more intensive protocols. Here we present results of treatment of 124 patients with PMBL over a period between 2004 and 2017 with the use of a protocol designed for aggressive B-cell lymphoma GMALL/B-ALL/NHL2002 including 6 cycles of alternating immunochemotherapy with intermediate-dose methotrexate in each cycle, and reduced total doxorubicin dose (100 mg/m2 for whole treatment). Majority of patients (77%) received consolidative radiotherapy. A median (range) age of patients was 30 (18–59) years, and 60% were female. With a median (range) follow up of 9 (1–17) years, 5-year overall survival (OS) and 5-year progression free survival (PFS) were 94% and 92%, respectively. Positron emission tomography—computed tomography (PET-CT) results at the end of chemotherapy were predictive for outcome: OS and PFS at 5 year were 96% and 94% in PET-CT negative patients, respectively, and 70% and 70% in PET-CT-positive patients (p = 0.004 for OS, p = 0.01 for PFS). Eight (6%) patients had recurrent/refractory disease, however, no central nervous system (CNS) relapse was observed. Acute toxicity included pancytopenia grade 3/4, neutropenic fever, and treatment related mortality rate of 0.8%. Second malignancies and late cardiotoxicity occurred in 2.4% and 2.4% of patients, respectively. Intensive alternating immunochemotherapy protocol GMALL/B-ALL/NHL2002 is curative for more than 90% of PMBL patients and late toxicity in young patients is moderated. The attenuated dose of doxorubicin and intermediate dose of methotrexate may contribute to low incidence of late cardiotoxicity and effective CNS prophylaxis.
Association between migraine and risk of ocular motor cranial nerve palsy
Authors: Rhiu Soolienah , Han Kyungdo , Yoo Juhwan , Park Kyung-Ah , Oh Sei Yeul 
Published: June 2022

AbstractTo assess association between migraines and development of ocular motor cranial nerve palsy (CNP) and finding risk factors using the National Sample Cohort database from the Korea National Health Insurance Service. Data was analyzed from 4,234,341 medical screening examinees aged 20–90 years in 2009. Cox proportional hazard regression analysis was used to the adjusted hazard ratios (HR) for ocular motor CNP according to presence of migraine. Subgroup analysis was performed to evaluate effect of other factors on association of migraine with ocular motor CNP. A total of 5806 participants (0.14% of subjects) developed ocular motor CNP and were assigned to CNP group, 4,048,018 were assigned to control group, with an average of 8.22 ± 0.93 years of follow-up. Incidence of ocular motor CNP increased in migraine group compared to control. After adjusting potential confounding variables, HR for ocular motor CNP was 1.166 (confidence interval [CI] 1.013–1.343) in migraine group. Subgroups of relatively younger age less than 65 years (HR = 1.267, 95% CI 1.067–1.504), male gender (HR = 1.228, 95% CI 1.000–1.122), smokers (HR 1.426, 95% CI 1.127–1.803), and diabetes mellitus patients (HR = 1.378, 95% CI 1.045–1.378) showed a stronger association between migraines and development of ocular motor CNP. Our population-based cohort study demonstrated a significant association between presence of migraines and incidence of ocular motor CNP. Especially, relatively younger age, males, smokers, and diabetes patients with migraines could have a higher risk of developing ocular motor CNP.