bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic Symptom Disorder, Conversion Disorder, and Chronic Pain: Pediatric Clinician Perspectives
Authors: Edwards Kim R. , McMurtry C. Meghan , Dick Bruce , Lewinson Rebecca , Dhariwal Amrit , Katz Joel 
Published: January 2021

Objectives: The appropriateness and relevance of somatic symptom disorder and conversion disorder ( American Psychiatric Association, 2013 ) diagnoses are in question as they relate to pediatric chronic pain. This survey-based study on pediatric chronic pain explores how these psychiatric diagnoses are made and perceived and how treatment of patients is approached by Canadian health care professionals working in pediatric chronic pain clinics. Method: Health care professionals ( N = 50) completed the survey, which contained both qualitative and quantitative items. Results: Of participants, 88% reported moderate/advanced training in pain, whereas only 26% reported moderate/advanced training in somatic symptom disorder and conversion disorder. Somatic symptom disorder and conversion disorder were reportedly diagnosed in approximately 17% and 5% of young people with chronic pain, respectively; however, overall, the participants were not confident or only slightly confident when diagnosing these disorders. There were no major differences in the reported interventions used to treat pain, somatic symptom disorder, or conversion disorder. Conclusions: These results highlight the need for standardized training in pain and psychiatric assessment, diagnosis, and treatment; diagnostic guidelines; and how to best provide this training to health care staff who work with young people with chronic pain. Implications for Impact Statement These results raise questions about the conceptualization of chronic pain, somatic symptom disorder, and conversion disorder, and point to the need for further research, improved training, clearer differential diagnostic criteria, and effective treatments.
The Role of Pediatric Psychologists in Mitigating Disability-Specific Barriers Among Youth During the COVID-19 Pandemic
Authors: Lund Emily M. , Gabrielli Joy 
Published: January 2021

Objective: The objective of this article is to provide information about the ways in which the COVID-19 pandemic may affect the physical and psychosocial well-being of youth with disabilities, including assessment and intervention considerations for pediatric psychologists and other mental health professionals. Methods: This article reviews the emerging literature on the impact of the COVID-19 pandemic on children and adolescents and connects it to the unique needs of youth with disabilities and their families. Results: The COVID-19 pandemic magnifies the inequalities and barriers faced by youth with disabilities and creates new difficulties in accessing health, education, and other intervention services. In particular, this article discusses how the pandemic has affected (a) access to special education; (b) access to health care and personal care; and (c) mental health, including exposures to traumatic events. Conclusions: The COVID-19 pandemic has the potential to greatly affect the biopsychosocial well-being of youth with disabilities. Pediatric psychologists can play an active role in mitigating these effects at both the individual and system levels. Implications for Impact Statement This article addresses the unique and increased barriers faced by youth with disabilities and their families during the COVID-19 pandemic (e.g., access to education and health care, trauma and mental health concerns) and how pediatric psychologists can help them during these difficult times with effective, culturally responsive, and evidence-based strategies.
Ensemble learning of diffractive optical networks
Authors: Rahman Md Sadman Sakib , Li Jingxi , Mengu Deniz , Rivenson Yair , Ozcan Aydogan 
Published: January 2021

AbstractA plethora of research advances have emerged in the fields of optics and photonics that benefit from harnessing the power of machine learning. Specifically, there has been a revival of interest in optical computing hardware due to its potential advantages for machine learning tasks in terms of parallelization, power efficiency and computation speed. Diffractive deep neural networks (D2NNs) form such an optical computing framework that benefits from deep learning-based design of successive diffractive layers to all-optically process information as the input light diffracts through these passive layers. D2NNs have demonstrated success in various tasks, including object classification, the spectral encoding of information, optical pulse shaping and imaging. Here, we substantially improve the inference performance of diffractive optical networks using feature engineering and ensemble learning. After independently training 1252 D2NNs that were diversely engineered with a variety of passive input filters, we applied a pruning algorithm to select an optimized ensemble of D2NNs that collectively improved the image classification accuracy. Through this pruning, we numerically demonstrated that ensembles of N = 14 and N = 30 D2NNs achieve blind testing accuracies of 61.14 ± 0.23% and 62.13 ± 0.05%, respectively, on the classification of CIFAR-10 test images, providing an inference improvement of >16% compared to the average performance of the individual D2NNs within each ensemble. These results constitute the highest inference accuracies achieved to date by any diffractive optical neural network design on the same dataset and might provide a significant leap to extend the application space of diffractive optical image classification and machine vision systems.
Constrained proteome allocation affects coexistence in models of competitive microbial communities
Authors: Pacciani-Mori Leonardo , Suweis Samir , Maritan Amos , Giometto Andrea 
Published: January 2021

Abstract
Microbial communities are ubiquitous and play crucial roles in many natural processes. Despite their importance for the environment, industry and human health, there are still many aspects of microbial community dynamics that we do not understand quantitatively. Recent experiments have shown that the structure and composition of microbial communities are intertwined with the metabolism of the species that inhabit them, suggesting that properties at the intracellular level such as the allocation of cellular proteomic resources must be taken into account when describing microbial communities with a population dynamics approach. In this work, we reconsider one of the theoretical frameworks most commonly used to model population dynamics in competitive ecosystems, MacArthur’s consumer-resource model, in light of experimental evidence showing how proteome allocation affects microbial growth. This new framework allows us to describe community dynamics at an intermediate level of complexity between classical consumer-resource models and biochemical models of microbial metabolism, accounting for temporally-varying proteome allocation subject to constraints on growth and protein synthesis in the presence of multiple resources, while preserving analytical insight into the dynamics of the system. We first show with a simple experiment that proteome allocation needs to be accounted for to properly understand the dynamics of even the simplest microbial community, i.e. two bacterial strains competing for one common resource. Then, we study our consumer-proteome-resource model analytically and numerically to determine the conditions that allow multiple species to coexist in systems with arbitrary numbers of species and resources.
Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease
Authors: Chatterjee Pratishtha , Pedrini Steve , Stoops Erik , Goozee Kathryn , Villemagne Victor L. , Asih Prita R. , Verberk Inge M. W. , Dave Preeti , Taddei Kevin , Sohrabi Hamid R. , Zetterberg Henrik , Blennow Kaj , Teunissen Charlotte E. , Vanderstichele Hugo M. , Martins Ralph N. 
Published: January 2021

AbstractGlial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−,n = 63) and high (Aβ+,n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (p < 0.00001), and plasma Aβ1–42/Aβ1–40 ratios were significantly lower (p < 0.005), in Aβ+ participants compared to Aβ− participants, adjusted for covariates age, sex, and apolipoprotein E-ε4 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished Aβ+ from Aβ− (area under the curve, AUC = 0.78), but was outperformed when plasma GFAP was added to the base model (AUC = 0.91) and further improved with plasma Aβ1–42/Aβ1–40 ratio (AUC = 0.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain Aβ load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma Aβ1–42/Aβ1–40 ratios) for cognitively normal older adults at risk of AD.
Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence
Authors: Mocking Roel J. T. , Naviaux Jane C. , Li Kefeng , Wang Lin , Monk Jonathan M. , Bright A. Taylor , Figueroa Caroline A. , Schene Aart H. , Ruhé Henricus G. , Assies Johanna , Naviaux Robert K. 
Published: January 2021

AbstractRecurrent major depressive disorder (rMDD) is a relapsing-remitting disease with high morbidity and a 5-year risk of recurrence of up to 80%. This was a prospective pilot study to examine the potential diagnostic and prognostic value of targeted plasma metabolomics in the care of patients with rMDD in remission. We used an established LC-MS/MS platform to measure 399 metabolites in 68 subjects with rMDD (n = 45 females and 23 males) in antidepressant-free remission and 59 age- and sex-matched controls (n = 40 females and 19 males). Patients were then followed prospectively for 2.5 years. Metabolomics explained up to 43% of the phenotypic variance. The strongest biomarkers were gender specific. 80% of the metabolic predictors of recurrence in both males and females belonged to 6 pathways: (1) phospholipids, (2) sphingomyelins, (3) glycosphingolipids, (4) eicosanoids, (5) microbiome, and (6) purines. These changes traced to altered mitochondrial regulation of cellular redox, signaling, energy, and lipid metabolism. Metabolomics identified a chemical endophenotype that could be used to stratify rrMDD patients at greatest risk for recurrence with an accuracy over 0.90 (95%CI = 0.69–1.0). Power calculations suggest that a validation study of at least 198 females and 198 males (99 cases and 99 controls each) will be needed to confirm these results. Although a small study, these results are the first to show the potential utility of metabolomics in assisting with the important clinical challenge of prospectively identifying the patients at greatest risk of recurrence of a depressive episode and those who are at lower risk.
Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis
Authors: Premkumar Vikram J. , Lentzsch Suzanne , Pan Samuel , Bhutani Divaya , Richter Joshua , Jagannath Sundar , Liedtke Michaela , Jaccard Arnaud , Wechalekar Ashutosh D. , Comenzo Raymond , Sanchorawala Vaishali , Royer Bruno , Rosenzweig Michael , Valent Jason , Schönland Stefan , Fonseca Rafael , Wong Sandy , Kapoor Prashant 
Published: January 2021

AbstractVenetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
The role of E3 ubiquitin ligases in the development and progression of glioblastoma
Authors: Humphreys Luke M. , Smith Paul , Chen Zhuoyao , Fouad Shahd , D’Angiolella Vincenzo 
Published: January 2021

AbstractDespite recent advances in our understanding of the disease, glioblastoma (GB) continues to have limited treatment options and carries a dismal prognosis for patients. Efforts to stratify this heterogeneous malignancy using molecular classifiers identified frequent alterations in targetable proteins belonging to several pathways including the receptor tyrosine kinase (RTK) and mitogen-activated protein kinase (MAPK) signalling pathways. However, these findings have failed to improve clinical outcomes for patients. In almost all cases, GB becomes refractory to standard-of-care therapy, and recent evidence suggests that disease recurrence may be associated with a subpopulation of cells known as glioma stem cells (GSCs). Therefore, there remains a significant unmet need for novel therapeutic strategies. E3 ubiquitin ligases are a family of >700 proteins that conjugate ubiquitin to target proteins, resulting in an array of cellular responses, including DNA repair, pro-survival signalling and protein degradation. Ubiquitin modifications on target proteins are diverse, ranging from mono-ubiquitination through to the formation of polyubiquitin chains and mixed chains. The specificity in substrate tagging and chain elongation is dictated by E3 ubiquitin ligases, which have essential regulatory roles in multiple aspects of brain cancer pathogenesis. In this review, we begin by briefly summarising the histological and molecular classification of GB. We comprehensively describe the roles of E3 ubiquitin ligases in RTK and MAPK, as well as other, commonly altered, oncogenic and tumour suppressive signalling pathways in GB. We also describe the role of E3 ligases in maintaining glioma stem cell populations and their function in promoting resistance to ionizing radiation (IR) and chemotherapy. Finally, we consider how our knowledge of E3 ligase biology may be used for future therapeutic interventions in GB, including the use of blood–brain barrier permeable proteolysis targeting chimeras (PROTACs).
BUB1B promotes extrahepatic cholangiocarcinoma progression via JNK/c-Jun pathways
Authors: Jiao Chen Yu , Feng Qin Chao , Li Chang Xian , Wang Dong , Han Sheng , Zhang Yao Dong , Jiang Wang Jie , Chang Jiang , Wang Xuehao , Li Xiang Cheng 
Published: January 2021

AbstractCurrently, the controversy regarding the expression profile and function of BUB1B in different malignancies still exist. In this project, we aimed to explore the role and molecular mechanism of BUB1B in the progression of extrahepatic cholangiocarcinoma (ECC). The expression levels of BUB1B in human ECC were evaluated by immunohistochemistry, western blot, and real-time PCR. The role and mechanism of BUB1B in CCA cell proliferation and invasion were investigated in both in vitro and in vivo functional studies. To indicate the clinical significance, a tissue microarray was performed on 113 ECC patients, followed by univariate and multivariate analyses. The expression of BUB1B was increased in both human CCA tissues and CCA cells. Results from loss-of-function and gain-of-function experiments suggested that the inhibition of BUB1B decreased the proliferation and invasiveness of CCA cells in vitro and in vivo, while overexpression of BUB1B achieved the opposite effect. Furthermore, the activation of c-Jun N-terminal kinase-c-Jun (JNK)-c-Jun pathway was regulated by BUB1B. BUB1B regulated the proliferation and invasiveness of CAA cells in a JNK-c-Jun-dependent manner. Clinically, ECC patients with BUB1B high expression had worse overall survival and recurrence-free survival than those with BUB1B low expression. Multivariate analysis identified that BUB1B was an independent predictor for postoperative recurrence and overall survival of ECC patients. In conclusion, BUB1B promoted ECC progression via JNK/c-Jun pathways. These findings suggested that BUB1B could be a potential therapeutic target and a biomarker for predicting prognosis for ECC patients.
ALKBH5 suppresses tumor progression via an m6A-dependent epigenetic silencing of pre-miR-181b-1/YAP signaling axis in osteosarcoma
Authors: Yuan Ye , Yan Gege , He Mingyu , Lei Hong , Li Linqiang , Wang Yang , He Xiaoqi , Li Guanghui , Wang Quan , Gao Yuelin , Qu Zhezhe , Mei Zhongting , Shen Zhihua , Pu Jiaying , Wang Ao , Zhao Wei , Jiang Huiwei , Du Weijie , Yang Lei 
Published: January 2021

AbstractALKBH5 is the main enzyme for m6A-based demethylation of RNAs and it has been implicated in many biological and pathophysiological processes. Here, we aimed to explore the potential involvement of ALKBH5 in osteosarcoma and decipher the underlying cellular/molecular mechanisms. We discovered downregulated levels of demethylase ALKBH5 were correlated with increased m6A methylation in osteosarcoma cells/tissues compared with normal osteoblasts cells/tissues. ALKBH5 overexpression significantly suppressed osteosarcoma cell growth, migration, invasion, and trigged cell apoptosis. In contrast, inhibition of ALKBH5 produced the opposite effects. Whereas ALKBH5 silence enhanced m6A methylations of pre-miR-181b-1 and YAP-mRNA exerting oncogenic functions in osteosarcoma. Moreover, upregulation of YAP or downregulation of mature miR-181b-5p displayed a remarkable attenuation of anti-tumor activities caused by ALKBH5. Further results revealed that m6A methylated pre-miR-181b-1 was subsequently recognized by m6A-binding protein YTHDF2 to mediate RNA degradation. However, methylated YAP transcripts were recognized by YTHDF1 to promote its translation. Therefore, ALKBH5-based m6A demethylation suppressed osteosarcoma cancer progression through m6A-based direct/indirect regulation of YAP. Thus, ALKBH5 overexpression might be considered a new approach of replacement therapy for osteosarcoma treatment.
A map of copy number variations in the Tunisian population: a valuable tool for medical genomics in North Africa
Authors: Romdhane Lilia , Mezzi Nessrine , Dallali Hamza , Messaoud Olfa , Shan Jingxuan , Fakhro Khalid A. , Kefi Rym , Chouchane Lotfi , Abdelhak Sonia 
Published: January 2021

AbstractCopy number variation (CNV) is considered as the most frequent type of structural variation in the human genome. Some CNVs can act on human phenotype diversity, encompassing rare Mendelian diseases and genomic disorders. The North African populations remain underrepresented in public genetic databases in terms of single-nucleotide variants as well as for larger genomic mutations. In this study, we present the first CNV map for a North African population using the Affymetrix Genome-Wide SNP (single-nucleotide polymorphism) array 6.0 array genotyping intensity data to call CNVs in 102 Tunisian healthy individuals. Two softwares, PennCNV and Birdsuite, were used to call CNVs in order to provide reliable data. Subsequent bioinformatic analyses were performed to explore their features and patterns. The CNV map of the Tunisian population includes 1083 CNVs spanning 61.443 Mb of the genome. The CNV length ranged from 1.017 kb to 2.074 Mb with an average of 56.734 kb. Deletions represent 57.43% of the identified CNVs, while duplications and the mixed loci are less represented. One hundred and three genes disrupted by CNVs are reported to cause 155 Mendelian diseases/phenotypes. Drug response genes were also reported to be affected by CNVs. Data on genes overlapped by deletions and duplications segments and the sequence properties in and around them also provided insights into the functional and health impacts of CNVs. These findings represent valuable clues to genetic diversity and personalized medicine in the Tunisian population as well as in the ethnically similar populations from North Africa.
Integrated genetic and metabolic landscapes predict vulnerabilities of temozolomide resistant glioblastoma cells
Authors: Immanuel Selva Rupa Christinal , Ghanate Avinash D. , Parmar Dharmeshkumar S. , Yadav Ritu , Uthup Riya , Panchagnula Venkateswarlu , Raghunathan Anu 
Published: January 2021

AbstractMetabolic reprogramming and its molecular underpinnings are critical to unravel the duality of cancer cell function and chemo-resistance. Here, we use a constraints-based integrated approach to delineate the interplay between metabolism and epigenetics, hardwired in the genome, to shape temozolomide (TMZ) resistance. Differential metabolism was identified in response to TMZ at varying concentrations in both the resistant neurospheroidal (NSP) and the susceptible (U87MG) glioblastoma cell-lines. The genetic basis of this metabolic adaptation was characterized by whole exome sequencing that identified mutations in signaling pathway regulators of growth and energy metabolism. Remarkably, our integrated approach identified rewiring in glycolysis, TCA cycle, malate aspartate shunt, and oxidative phosphorylation pathways. The differential killing of TMZ resistant NSP by Rotenone at low concentrations with an IC50 value of 5 nM, three orders of magnitude lower than for U87MG that exhibited an IC50 value of 1.8 mM was thus identified using our integrated systems-based approach.