bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts
Authors: Milaneschi Yuri , Kappelmann Nils , Ye Zheng , Lamers Femke , Moser Sylvain , Jones Peter B. , Burgess Stephen , Penninx Brenda W. J. H. , Khandaker Golam M. 
Published: June 2021

AbstractWe examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05–1.08), altered appetite (OR = 1.25, 95%CI = 1.23–1.28), sleep problems (OR = 1.05, 95%CI = 1.04–1.06), and fatigue (OR = 1.12, 95% CI = 1.11–1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05–1.08) and worrying control (OR = 1.03, 95% CI = 1.02–1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12–1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13–1.43) and IL-6 (OR = 1.26, 95% CI = 1.07–1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08–1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18–1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.
Oral health problems in high-performance athletes at 2019 Pan American Games in Lima: a descriptive study
Authors: Opazo-García Catalina , Moya-Salazar Jeel , Chicoma-Flores Karina , Contreras-Pulache Hans 
Published: June 2021

Abstract
Introduction
Dental care is provided for high-performance athletes at national and international sports events. Elite athletes may seek care for sports-related injuries and pre-existing oral diseases. Previous studies indicate an association between oral health problems and negative performance impacts in elite athletes.

Objectives
To determine the prevalence of the most common oral pathologies in high-performance athletes during the emergency dental care performed at the Lima 2019 Pan American Games (JPL-19).

Methodology
All reports of athletes (≥18 years old, of both sexes, from 41 countries) who received emergency dental care at Pan American Villas during the JPL-19 were included. Injuries and types of oral diseases were classified according to the Injury and Disease Surveillance System proposed by the International Olympic Committee.

Results
Of the 6680 participating athletes, 76 (1.14%) presented as dental emergencies, 90.8% (69/76) of the athletes seen presented pre-existing oral pathological conditions, the most frequent were periodontal diseases (34%, 26/76) and dental caries (29%, 22/76). Among the sports with the most cases, there were 22 (29%) in athletics, 6 (8%) in soccer, and 6 (8%) in taekwondo. The most frequent dental emergencies came from Peru, Puerto Rico, Bahamas, Grenada, and Venezuela.

Conclusions
Pre-existing oral diseases were more frequent than sports-related accidents. The most prevalent diseases were periodontal disease and dental caries disease. It is necessary to implement new care strategies for athletes, based on prevention, before and during sports competitions.
Prophylaxis with intrathecal or high-dose methotrexate in diffuse large B-cell lymphoma and high risk of CNS relapse
Authors: Bobillo Sabela , Joffe Erel , Sermer David , Mondello Patrizia , Ghione Paola , Caron Philip C. , Hamilton Audrey , Hamlin Paul A. , Horwitz Steven M. , Kumar Anita , Matasar Matthew J. , Batlevi Connie L. , Moskowitz Alison , Noy Ariela , Owens Collette N. , Palomba M. Lia , Straus David , von Keudell Gottfried , Dogan Ahmet , Zelenetz Andrew D. , Seshan Venkatraman E. , Younes Anas 
Published: June 2021

AbstractAlthough methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermore, the CNS relapse risk was similar in patients who received IT and HD-MTX (5-year risk 5.6% vs. 5.2%). Collectively, our data indicate the benefit of MTX for CNS prophylaxis is transient, highlighting the need for more effective prophylactic regimens. In addition, our results failed to demonstrate a clinical advantage for the HD-MTX regimen.
Reovirus mutant jin-3 exhibits lytic and immune-stimulatory effects in preclinical human prostate cancer models
Authors: van de Merbel Arjanneke F. , van der Horst Geertje , van der Mark Maaike H. , Bots Selas T. F. , van den Wollenberg Diana J. M. , de Ridder Corrina M. A. , Stuurman Debra , Aalders Tilly , Erkens-Schulz Sigrun , van Montfoort Nadine , Karthaus Wouter R. , Mehra Niven , Smits Minke , Schalken Jack A. , van Weerden Wytske M. , Hoeben Rob C. , van der Pluijm Gabri 
Published: June 2021

AbstractTreatment of castration-resistant prostate cancer remains a challenging clinical problem. Despite the promising effects of immunotherapy in other solid cancers, prostate cancer has remained largely unresponsive. Oncolytic viruses represent a promising therapeutic avenue, as oncolytic virus treatment combines tumour cell lysis with activation of the immune system and mounting of effective anti-tumour responses. Mammalian Orthoreoviruses are non-pathogenic human viruses with a preference of lytic replication in human tumour cells. In this study, we evaluated the oncolytic efficacy of the bioselected oncolytic reovirus mutant jin-3 in multiple human prostate cancer models. The jin-3 reovirus displayed efficient infection, replication, and anti-cancer responses in 2D and 3D prostate cancer models, as well as in ex vivo cultured human tumour slices. In addition, the jin-3 reovirus markedly reduced the viability and growth of human cancer cell lines and patient-derived xenografts. The infection induced the expression of mediators of immunogenic cell death, interferon-stimulated genes, and inflammatory cytokines. Taken together, our data demonstrate that the reovirus mutant jin-3 displays tumour tropism, and induces potent oncolytic and immunomodulatory responses in human prostate cancer models. Therefore, jin-3 reovirus represents an attractive candidate for further development as oncolytic agent for treatment of patients with aggressive localised or advanced prostate cancer.
ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment
Authors: Bharadwaj Thashi , Schrauwen Isabelle , Rehman Sakina , Liaqat Khurram , Acharya Anushree , Giese Arnaud P. J. , Nouel-Saied Liz M. , Nasir Abdul , Everard Jenna L. , Pollock Lana M. , Zhu Shaoyuan , Bamshad Michael J. , Nickerson Deborah A. , Ali Raja Hussain , Ullah Asmat , Wali Abdul , Ali Ghazanfar , Santos-Cortez Regie Lyn P. , Ahmed Zubair M. , McDermott Brian M. , Ansar Muhammad , Riazuddin Saima , Ahmad Wasim , Leal Suzanne M. 
Published: June 2021

AbstractHearing impairment (HI) is a common disorder of sensorineural function with a highly heterogeneous genetic background. Although substantial progress has been made in the understanding of the genetic etiology of hereditary HI, many genes implicated in HI remain undiscovered. Via exome and Sanger sequencing of DNA samples obtained from consanguineous Pakistani families that segregate profound prelingual sensorineural HI, we identified rare homozygous missense variants in four genes (ADAMTS1, MPDZ, MVD, and SEZ6) that are likely the underlying cause of HI. Linkage analysis provided statistical evidence that these variants are associated with autosomal recessive nonsyndromic HI. In silico analysis of the mutant proteins encoded by these genes predicted structural, conformational or interaction changes. RNAseq data analysis revealed expression of these genes in the sensory epithelium of the mouse inner ear during embryonic, postnatal, and adult stages. Immunohistochemistry of the mouse cochlear tissue, further confirmed the expression of ADAMTS1, SEZ6, and MPDZ in the neurosensory hair cells of the organ of Corti, while MVD expression was more prominent in the spiral ganglion cells. Overall, supported by in silico mutant protein analysis, animal models, linkage analysis, and spatiotemporal expression profiling in the mouse inner ear, we propose four new candidate genes for HI and expand our understanding of the etiology of HI.
Effect of COVID-19 response policies on walking behavior in US cities
Authors: Hunter Ruth F. , Garcia Leandro , de Sa Thiago Herick , Zapata-Diomedi Belen , Millett Christopher , Woodcock James , Pentland Alex ’Sandy’ , Moro Esteban 
Published: June 2021

AbstractThe COVID-19 pandemic is causing mass disruption to our daily lives. We integrate mobility data from mobile devices and area-level data to study the walking patterns of 1.62 million anonymous users in 10 metropolitan areas in the United States. The data covers the period from mid-February 2020 (pre-lockdown) to late June 2020 (easing of lockdown restrictions). We detect when users were walking, distance walked and time of the walk, and classify each walk as recreational or utilitarian. Our results reveal dramatic declines in walking, particularly utilitarian walking, while recreational walking has recovered and even surpassed pre-pandemic levels. Our findings also demonstrate important social patterns, widening existing inequalities in walking behavior. COVID-19 response measures have a larger impact on walking behavior for those from low-income areas and high use of public transportation. Provision of equal opportunities to support walking is key to opening up our society and economy.
Sensitive period for rescuing parvalbumin interneurons connectivity and social behavior deficits caused by TSC1 loss
Authors: Amegandjin Clara A. , Choudhury Mayukh , Jadhav Vidya , Carriço Josianne Nunes , Quintal Ariane , Berryer Martin , Snapyan Marina , Chattopadhyaya Bidisha , Saghatelyan Armen , Di Cristo Graziella 
Published: June 2021

AbstractThe Mechanistic Target Of Rapamycin Complex 1 (mTORC1) pathway controls several aspects of neuronal development. Mutations in regulators of mTORC1, such as Tsc1 and Tsc2, lead to neurodevelopmental disorders associated with autism, intellectual disabilities and epilepsy. The correct development of inhibitory interneurons is crucial for functional circuits. In particular, the axonal arborisation and synapse density of parvalbumin (PV)-positive GABAergic interneurons change in the postnatal brain. How and whether mTORC1 signaling affects PV cell development is unknown. Here, we show that Tsc1 haploinsufficiency causes a premature increase in terminal axonal branching and bouton density formed by mutant PV cells, followed by a loss of perisomatic innervation in adult mice. PV cell-restricted Tsc1 haploinsufficient and knockout mice show deficits in social behavior. Finally, we identify a sensitive period during the third postnatal week during which treatment with the mTOR inhibitor Rapamycin rescues deficits in both PV cell innervation and social behavior in adult conditional haploinsufficient mice. Our findings reveal a role of mTORC1 signaling in the regulation of the developmental time course and maintenance of cortical PV cell connectivity and support a mechanistic basis for the targeted rescue of autism-related behaviors in disorders associated with deregulated mTORC1 signaling.
Extracellular mRNA transported to the nucleus exerts translation-independent function
Authors: Tomita Takeshi , Kato Masayoshi , Mishima Taishi , Matsunaga Yuta , Sanjo Hideki , Ito Ken-ichi , Minagawa Kentaro , Matsui Toshimitsu , Oikawa Hiroyuki , Takahashi Satoshi , Takao Toshifumi , Iwai Noriki , Mino Takashi , Takeuchi Osamu , Maru Yoshiro , Hiratsuka Sachie 
Published: June 2021

AbstractRNA in extracellular vesicles (EVs) are uptaken by cells, where they regulate fundamental cellular functions. EV-derived mRNA in recipient cells can be translated. However, it is still elusive whether “naked nonvesicular extracellular mRNA” (nex-mRNA) that are not packed in EVs can be uptaken by cells and, if so, whether they have any functions in recipient cells. Here, we show the entrance of nex-mRNA in the nucleus, where they exert a translation-independent function. Human nex-interleukin-1β (IL1β)-mRNA outside cells proved to be captured by RNA-binding zinc finger CCCH domain containing protein 12D (ZC3H12D)-expressing human natural killer (NK) cells. ZC3H12D recruited to the cell membrane binds to the 3′-untranslated region of nex-IL1β-mRNA and transports it to the nucleus. The nex-IL1β-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-γ production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA.
Genetic variants associated with inherited cardiovascular disorders among 13,131 asymptomatic older adults of European descent
Authors: Lacaze Paul , Sebra Robert , Riaz Moeen , Ingles Jodie , Tiller Jane , Thompson Bryony A. , James Paul A. , Fatkin Diane , Semsarian Christopher , Reid Christopher M. , Tonkin Andrew M. , Winship Ingrid , Schadt Eric , McNeil John J. 
Published: June 2021

AbstractGenetic testing is used to optimise the management of inherited cardiovascular disorders that can cause sudden cardiac death. Yet more genotype–phenotype correlation studies from populations not ascertained on clinical symptoms or family history of disease are required to improve understanding of gene penetrance. We performed targeted sequencing of 25 genes used routinely in clinical genetic testing for inherited cardiovascular disorders in a population of 13,131 asymptomatic older individuals (mean age 75 years) enrolled in the ASPREE trial. Participants had no prior history of cardiovascular disease events, dementia or physical disability at enrolment. Variants were classified following ACMG/AMP standards. Sudden and rapid cardiac deaths were clinically adjudicated as ASPREE trial endpoints, and assessed during mean 4.7 years of follow-up. In total, 119 participants had pathogenic/deleterious variants in one of the 25 genes analysed (carrier rate of 1 in 110 or 0.9%). Participants carried variants associated with hypertrophic cardiomyopathy (N = 24), dilated cardiomyopathy (N = 29), arrhythmogenic right-ventricular cardiomyopathy (N = 22), catecholaminergic polymorphic ventricular tachycardia (N = 4), aortopathies (N = 1), and long-QT syndrome (N = 39). Among 119 carriers, two died from presumed sudden/rapid cardiac deaths during follow-up (1.7%); both with pathogenic variants in long-QT syndrome genes (KCNQ1, SCN5A). Among non-carriers, the rate of sudden/rapid cardiac deaths was significantly lower (0.08%, 11/12936, p < 0.001). Variants associated with inherited cardiovascular disorders are found in asymptomatic individuals aged 70 years and older without a history of cardiovascular disease.
Sounding out falsified medicines from genuine medicines using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)
Authors: Alfarsi Anas , Caillet Céline , Fawbert Garry , Lawrence Simon , Krüse Jacob , McSweeney Seán , O’Mahony Marcus , Dondorp Arjen , Newton Paul N. , Fitzpatrick Dara 
Published: June 2021

AbstractThe trade in falsified medicine has increased significantly and it is estimated that global falsified sales have reached $100 billion in 2020. The EU Falsified Medicines Directive states that falsified medicines do not only reach patients through illegal routes but also via the legal supply chain. Falsified medicines can contain harmful ingredients. They can also contain too little or too much active ingredient or no active ingredient at all. BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy) harnesses an acoustic phenomenon associated with the dissolution of a sample (tablet or powder). The resulting acoustic spectrum is unique and intrinsic to the sample and can be used as an identifier or signature profile. BARDS was evaluated in this study to determine whether a product is falsified or genuine in a rapid manner and at lower cost than many existing technologies. A range of genuine and falsified medicines, including falsified antimalarial tablets from south-east Asia, were tested, and compared to their counterpart genuine products. Significant differences between genuine and falsified doses were found in their acoustic signatures as they disintegrate and dissolve. Principal component analysis was employed to differentiate between the genuine and falsified medicines. This demonstrates that the tablets and capsules included here have intrinsic acoustic signatures which could be used to screen the quality of medicines.
Relationship between Apgar scores and long-term cognitive outcomes in individuals with Down syndrome
Authors: del Hoyo Soriano Laura , Rosser Tracie C. , Hamilton Debra R. , Harvey Danielle J. , Abbeduto Leonard , Sherman Stephanie L. 
Published: June 2021

AbstractThis study examined the contribution of the Apgar score at 1 and 5 min after birth to later cognitive functioning in 168 individuals with Down syndrome who were between 6 and 25 years of age at time of cognitive testing. Our results showed that a lower Apgar score at 1 min was related to a worse performance in later cognitive measures of receptive vocabulary, verbal comprehension and production, visual memory and working memory. Results also showed that a lower Apgar score at 5 min was only related to worse later outcomes of verbal comprehension and production and auditory working memory. Our findings suggest a need for future studies investigating how specific perinatal events reflected in the Apgar score are linked to later cognitive functioning in individuals with Down syndrome.
Advanced mycelium materials as potential self-growing biomedical scaffolds
Authors: Antinori Maria Elena , Contardi Marco , Suarato Giulia , Armirotti Andrea , Bertorelli Rosalia , Mancini Giorgio , Debellis Doriana , Athanassiou Athanassia 
Published: June 2021

AbstractMycelia, the vegetative part of fungi, are emerging as the avant-garde generation of natural, sustainable, and biodegradable materials for a wide range of applications. They are constituted of a self-growing and interconnected fibrous network of elongated cells, and their chemical and physical properties can be adjusted depending on the conditions of growth and the substrate they are fed upon. So far, only extracts and derivatives from mycelia have been evaluated and tested for biomedical applications. In this study, the entire fibrous structures of mycelia of the edible fungi Pleurotus ostreatus and Ganoderma lucidum are presented as self-growing bio-composites that mimic the extracellular matrix of human body tissues, ideal as tissue engineering bio-scaffolds. To this purpose, the two mycelial strains are inactivated by autoclaving after growth, and their morphology, cell wall chemical composition, and hydrodynamical and mechanical features are studied. Finally, their biocompatibility and direct interaction with primary human dermal fibroblasts are investigated. The findings demonstrate the potentiality of mycelia as all-natural and low-cost bio-scaffolds, alternative to the tissue engineering systems currently in place.
Biochemical consequences of two clinically relevant ND-gene mutations in Escherichia coli respiratory complex I
Authors: Nuber Franziska , Schimpf Johannes , di Rago Jean-Paul , Tribouillard-Tanvier Déborah , Procaccio Vincent , Martin-Negrier Marie-Laure , Trimouille Aurélien , Biner Olivier , von Ballmoos Christoph , Friedrich Thorsten 
Published: June 2021

AbstractNADH:ubiquinone oxidoreductase (respiratory complex I) plays a major role in energy metabolism by coupling electron transfer from NADH to quinone with proton translocation across the membrane. Complex I deficiencies were found to be the most common source of human mitochondrial dysfunction that manifest in a wide variety of neurodegenerative diseases. Seven subunits of human complex I are encoded by mitochondrial DNA (mtDNA) that carry an unexpectedly large number of mutations discovered in mitochondria from patients’ tissues. However, whether or how these genetic aberrations affect complex I at a molecular level is unknown. Here, we used Escherichia coli as a model system to biochemically characterize two mutations that were found in mtDNA of patients. The V253AMT-ND5 mutation completely disturbed the assembly of complex I, while the mutation D199GMT-ND1 led to the assembly of a stable complex capable to catalyze redox-driven proton translocation. However, the latter mutation perturbs quinone reduction leading to a diminished activity. D199MT-ND1 is part of a cluster of charged amino acid residues that are suggested to be important for efficient coupling of quinone reduction and proton translocation. A mechanism considering the role of D199MT-ND1 for energy conservation in complex I is discussed.
Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR
Authors: Gudi Radhika , Palanisamy Viswanathan , Vasu Chenthamarakshan 
Published: June 2021

AbstractCentrosomal P4.1-associated protein (CPAP) plays a critical role in restricting the centriole length in human cells. Here, we report a novel, positive regulatory influence for CPAP on endocytic vesicular transport (EVT) and lysosome targeting of internalized-cell surface receptor EGFR. We observed that higher CPAP levels cause an increase in the abundance of multi-vesicular body (MVB) and EGFR is detectable in CPAP-overexpression induced puncta. The surface and cellular levels of EGFR are higher under CPAP deficiency and lower under CPAP overexpression. While ligand-engagement induced internalization or routing of EGFR into early endosomes is not influenced by cellular levels of CPAP, we found that targeting of ligand-activated, internalized EGFR to lysosome is impacted by CPAP levels. Transport of ligand-bound EGFR from early endosome to late endosome/MVB and lysosome is diminished in CPAP-depleted cells. Moreover, CPAP depleted cells appear to show a diminished ability to form MVB structures upon EGFR activation. These observations suggest a positive regulatory effect of CPAP on EVT of ligand-bound EGFR-like cell surface receptors to MVB and lysosome. Overall, identification of a non-centriolar function of CPAP in endocytic trafficking provides new insights in understanding the non-canonical cellular functions of CPAP.