bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA): a cross-sectional study
Authors: Chung Deborah Xin Yi , Loo Ying Ern , Kwan Yu Heng , Phang Jie Kie , Woon Ting Hui , Goh Wei Rui , Angkodjojo Stanley , Fong Warren 
Published: May 2023

ObjectivesTo evaluate the association between anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA).DesignCross-sectional evaluation of baseline data from a prospective cohort study, with recruitment from January 2018 to March 2021.SettingOutpatient clinic in a tertiary hospital in Singapore.ParticipantsPatients aged 21 years and above who were diagnosed with axSpA.Outcome measuresThe Hospital Anxiety and Depression Scale (HADS) was used for assessing anxiety and depression, 10-item Connor Davidson Resilience Scale (CD-RISC-10) for resilience, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for disease activity, Bath Ankylosing Spondylitis Functional Index (BASFI) for functional limitation and Assessment of SpondyloArthritis International Society Health Index (ASAS HI) for overall health and functioning. Univariable and multivariable linear regression analyses were performed to assess the association between anxiety, depression and resilience with health and functioning.ResultsWe included 296 patients in this study. The median (IQR) score for HADS-Anxiety was 5.0 (2.0–8.0), with 13.5% and 13.9% having borderline abnormal and abnormal anxiety, respectively. The median (IQR) score for HADS-Depression was 3.0 (1.0–7.0), with 12.8% and 8.4% having borderline abnormal and abnormal depression, respectively. The median (IQR) CD-RISC-10 score was 29.0 (23.0–32.0) while the median (IQR) ASAS HI score was 4.0 (2.0–7.0). Apart from BASDAI, BASFI and disease duration, anxiety and depression were associated with overall health and functioning (β: 0.12, 95% CI 0.03, 0.20; β: 0.20, 95% CI 0.09, 0.31) in the multivariable linear regression. Level of resilience was not associated with health and functioning.ConclusionAnxiety and depression, but not resilience, were associated with poorer health and functioning. Clinicians could consider routinely screening for anxiety and depression in their patients, especially in patients with more severe symptoms.
Randomised, double-blind, placebo-controlled trial of glycopyrronium in children and adolescents with severe sialorrhoea and neurodisabilities: protocol of the SALIVA trial
Authors: Fayoux Pierre , Dinomais Mickael , Shaw Helen , Probert Nick , Villain Frédéric , Pouchain Denis , Texier Nathalie , Auvin Stéphane 
Published: May 2023

IntroductionSevere sialorrhoea is a common, distressing problem in children/adolescents with neurodisabilities, which has adverse health and social consequences. The SALIVA trial is designed to evaluate the efficacy and safety of a paediatric-specific oral solution of glycopyrronium along with its impact on quality-of-life (QoL), which has been lacking from previous trials of sialorrhoea treatments.Methods and analysisA double-blind, placebo-controlled, randomised phase IV trial is ongoing in several centres across France. Eighty children aged 3–17 years with severe sialorrhoea (≥6 on the modified Teachers Drooling Scale) related to chronic neurological disorders in whom non-pharmacological standard of care has already been implemented or has failed, will be recruited. Patients will be randomised 1:1 to receive a 2 mg/5 mL solution of glycopyrronium bromide (Sialanar 320 µg/mL glycopyrronium) or placebo three times daily during a 3-month blinded period. After Day 84, participants will be invited into a 6-month, open-label study extension period, where they will all receive glycopyrronium. The primary endpoint of the double-blind period will be the change from baseline to Day 84 in the Drooling Impact Scale (DIS), a validated measure to assess sialorrhoea. A series of secondary efficacy endpoints involving change in total DIS, specific DIS items and response (DIS improvement ≥13.6 points) will be analysed in a prespecified hierarchy. QoL data will be collected from parents, caregivers and patients where possible using specific DIS questions and DISABKIDS questionnaires. Safety endpoints, including adverse events, will be assessed throughout the trial periods.Ethics and disseminationIn total, 87 children have been recruited and recruitment is now complete. Final results are expected by the end of 2023. Findings will be presented at conferences and published in peer-reviewed journals.Trial registration numberEudraCT 2020-005534-15.
Beyond direct costs: individual and societal financial burden of asthma in young adults in a Danish nationwide study
Authors: Håkansson Kjell Erik Julius , Løkke Anders , Ibsen Rikke , Hilberg Ole , Backer Vibeke , Ulrik Charlotte Suppli 
Published: May 2023

IntroductionAs a common chronic disease seen across all ages, asthma has the potential to incur high societal and individual costs from both direct healthcare costs and loss of productivity. Most previous studies use smaller, selected populations to assess the cost of asthma, possibly reducing generalisability. We, therefore, aimed to assess the total, nationwide economic burden of asthma by severity from both an individual and a societal perspective.MethodsThe annual cost of asthma was assessed in a Danish nationwide cohort of patients aged 18–45 during 2014–2016 as excess healthcare costs, loss of income and welfare expenditure compared with controls (matched 1:4) using national registries. Asthma severity was defined as mild-to-moderate (steps 1–3 or step 4 without exacerbations) or severe (step 4 with exacerbations or step 5).ResultsAcross 63 130 patients (mean age 33, 55% female), the annual excess cost of asthma compared with controls was predicted to €4095 (95% CI €3856 to €4334) per patient. Beyond direct costs related to treatment and hospitalisations (€1555 (95% CI €1517 to €1593)), excess indirect costs related to loss of income (€1060 (95% CI €946 to €1171)) and welfare expenditure (eg, sick pay and disability pensions) (€1480 (95% CI €1392 to €1570)) were seen. Crude pooling of excess costs resulted in an annual societal cost of €263 million for all included patients.Severe asthma (4.5%) incurred 4.4 times higher net costs (€15 749 (95% CI 13 928 to €17 638)) compared with mild-to-moderate disease (€3586 (95% CI €3349 to €3824)). Furthermore, patients with severe asthma experienced an annual loss of income of €3695 (95% CI €4106 to €3225) compared with controls.ConclusionIn young adults with asthma, a significant societal and individual financial burden of disease was seen across severities. Expenditure was mainly driven by loss of income and welfare utilisation, rather than direct healthcare costs.
Effects of an electric charge on Casimir wormholes: changing the throat size
Authors: Garattini Remo 
Published: May 2023

AbstractIn this paper we continue the investigation of the connection between Casimir energy and the traversability of a wormhole. In addition to the negative energy density obtained by a Casimir device, we include the effect of an electromagnetic field generated by an electric charge. This combination defines an electrovacuum source which has an extra parameter related to the size of the throat. Even if the electromagnetic energy density is positive, the null energy condition is still violated. The main reason is that the electromagnetic field satisfies the property $$\rho =-p_{r}$$

ρ
=
-

p
r

. As a consequence, the traversable wormhole throat can be changed as a function of the electric charge. This means that the throat is no longer Planckian and the traversability is slightly less in principle but slightly greater in practice.
Rodinia without Baltica? Constraints from Sveconorwegian orogenic style and palaeomagnetic data
Authors: Slagstad Trond , Kulakov Evgeniy V. 
Published: May 2023

Abstract
The core of the Rodinia supercontinent has long been considered to have consisted of three cratons – Baltica, Laurentia and Amazonia – amalgamated along the late Mesoproterozoic Sveconorwegian, Grenville and Sunsas orogens. In recent years, however, it has become increasingly clear that the metamorphic and magmatic evolution of the Sveconorwegian orogen is inconsistent with a collisional model. Although geological data alone do not rule out proximity to Rodinia, palaeomagnetic data indicate significant latitudinal separation of Baltica and Laurentia during supercontinent assembly. In this contribution, we briefly review two recently proposed and mutually exclusive tectonic models for the Sveconorwegian orogeny and present a compilation of previously published and new chemical and isotopic data. A lack of crustal thickening throughout much of the orogen and few if any changes in lower-crustal sources and melting conditions between 1.3 and 0.9 Ga suggest that the western part of the Sveconorwegian orogeny represents a change from a dominantly extensional to a compressional back-arc regime, but without a significant change in overall tectonic setting. This orogenic evolution is incompatible with amalgamation into Rodinia and suggests that Baltica may have been isolated until the Silurian Caledonian orogeny.
ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma
Authors: Jackson Evangeline R. , Duchatel Ryan J. , Staudt Dilana E. , Persson Mika L. , Mannan Abdul , Yadavilli Sridevi , Parackal Sarah , Game Shaye , Chong Wai Chin , Jayasekara W. Samantha N. , Grand Marion Le , Kearney Padraic S. , Douglas Alicia M. , Findlay Izac J. , Germon Zacary P. , McEwen Holly P. , Beitaki Tyrone S. , Patabendige Adjanie , Skerrett-Byrne David A. , Nixon Brett , Smith Nathan D. , Day Bryan , Manoharan Neevika , Nagabushan Sumanth , Hansford Jordan R. , Govender Dinisha , McCowage Geoff B. , Firestein Ron , Howlett Meegan , Endersby Raelene , Gottardo Nicholas G. , Alvaro Frank , Waszak Sebastian M. , Larsen Martin R. , Colino-Sanguino Yolanda , Valdes-Mora Fatima , Rakotomalala Andria , Meignan Samuel , Pasquier Eddy , André Nicolas , Hulleman Esther , Eisenstat David D. , Vitanza Nicholas A. , Nazarian Javad , Koschmann Carl , Mueller Sabine , Cain Jason E. , Dun Matthew D. 
Published: May 2023

Abstract

Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9 to 11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA mutations showed increased sensitivity to ONC201, whereas those harboring TP53 mutations were more resistant. Metabolic adaptation and reduced sensitivity to ONC201 was promoted by redox-activated PI3K/Akt signaling, which could be counteracted using the brain penetrant PI3K/Akt inhibitor, paxalisib. Together, these discoveries coupled with the powerful anti-DIPG/DMG pharmacokinetic and pharmacodynamic properties of ONC201 and paxalisib have provided the rationale for the ongoing DIPG/DMG phase II combination clinical trial NCT05009992.

Significance:
PI3K/Akt signaling promotes metabolic adaptation to ONC201-mediated disruption of mitochondrial energy homeostasis in diffuse intrinsic pontine glioma, highlighting the utility of a combination treatment strategy using ONC201 and the PI3K/Akt inhibitor paxalisib.
Critical Role of the cGAS-STING Pathway in Doxorubicin-Induced Cardiotoxicity
Authors: Luo Wei , Zou Xiaoyi , Wang Yidan , Dong Zheng , Weng Xinyu , Pei Zhiqiang , Song Shuai , Zhao Yongchao , Wei Zilun , Gao Rifeng , Zhang Beijian , Liu Liwei , Bai Peiyuan , Liu Jin , Wang Xiang , Gao Tingwen , Zhang Yang , Sun Xiaolei , Chen Hang , Hu Kai , Du Shisuo , Sun Aijun , Ge Junbo 
Published: May 2023

Background:
Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation of the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator of interferon genes) pathway plays a critical role in cardiovascular destruction. Here, we investigate the involvement of this mechanism in doxorubicin-induced cardiotoxicity (DIC).

Methods:

Mice were treated with low-dose doxorubicin to induce chronic DIC. The role of the cGAS-STING pathway in DIC was evaluated in
cGAS
-deficiency (c
GAS
−/−
),
Sting
-deficiency (
Sting
−/−
), and interferon regulatory factor 3 (
Irf3
)-deficiency (
Irf3
−/−
) mice. Endothelial cell (EC)-specific conditional
Sting
deficiency (
Sting
flox/flox
/Cdh5-Cre
ERT
) mice were used to assess the importance of this pathway in ECs during DIC. We also examined the direct effects of the cGAS-STING pathway on nicotinamide adenine dinucleotide (NAD) homeostasis in vitro and in vivo.

Results:

In the chronic DIC model, we observed significant activation of the cGAS-STING pathway in cardiac ECs. Global
cGAS
,
Sting
, and
Irf3
deficiency all markedly ameliorated DIC. EC-specific
Sting
deficiency significantly prevented DIC and endothelial dysfunction. Mechanistically, doxorubicin activated the cardiac EC cGAS-STING pathway and its target, IRF3, which directly induced CD38 expression. In cardiac ECs, the cGAS-STING pathway caused a reduction in NAD levels and subsequent mitochondrial dysfunction via the intracellular NAD glycohydrolase (NADase) activity of CD38. Furthermore, the cardiac EC cGAS-STING pathway also regulates NAD homeostasis and mitochondrial bioenergetics in cardiomyocytes through the ecto-NADase activity of CD38. We also demonstrated that pharmacological inhibition of TANK-binding kinase 1 or CD38 effectively ameliorated DIC without compromising the anticancer effects of doxorubicin.

Conclusions:
Our findings indicate a critical role of the cardiac EC cGAS-STING pathway in DIC. The cGAS-STING pathway may represent a novel therapeutic target for preventing DIC.
Role of Dickkopf-3 in Blood Pressure Regulation in Mice and Hypertensive Rats
Authors: Busceti Carla Letizia , Carrizzo Albino , Bianchi Franca , De Lucia Massimiliano , Damato Antonio , Cazzin Chiara , Venturini Eleonora , Di Pietro Paola , Ginerete Roxana Paula , Di Menna Luisa , Cotugno Maria , Stanzione Rosita , Marchitti Simona , Migliarino Serena , Ciccarelli Michele , Sciarretta Sebastiano , Bruno Valeria , Battaglia Giuseppe , Fornai Francesco , Volpe Massimo , Rubattu Speranza , Nicoletti Ferdinando , Vecchione Carmine 
Published: May 2023

Background:

Dkk3 (Dickkopf-3) is a secreted glycoprotein known for its proapoptotic and angiogenic activity. The role of Dkk3 in cardiovascular homeostasis is largely unknown. Remarkably, the
Dkk3
gene maps within a chromosome segment linked to the hypertensive phenotype in spontaneously hypertensive rats (SHR).

Methods:

We used Dkk3
−/−
mice or stroke-resistant (sr) and stroke-prone (sp) SHR to examine the role of Dkk3 in the central and peripheral regulation of blood pressure (BP). We used lentiviral expression vector to rescue Dkk3 in knockout mice or to induce Dkk3 overexpression or silencing in SHR.

Results:

Genetic deletion of
Dkk3
in mice enhanced BP and impaired endothelium-dependent acetylcholine-induced relaxation of resistance arteries. These alterations were rescued by restoring Dkk3 expression either in the periphery or in the central nervous system (CNS). Dkk3 was required for the constitutive expression of VEGF (vascular endothelium growth factor), and the action of Dkk3 on BP and endothelium-dependent vasorelaxation was mediated by VEGF-stimulated phosphatidylinositol-3-kinase pathway, leading to eNOS (endothelial NO synthase) activation both in resistance arteries and the CNS. The regulatory function of Dkk3 on BP was confirmed in SHR stroke-resistant and SHR stroke-prone in which was blunted in both resistance arteries and brainstem. In SHR stroke-resistant, lentiviral expression vector–induced Dkk3 expression in the CNS largely reduced BP, whereas
Dkk3
knock-down further enhanced BP. In SHR stroke-prone challenged with a hypersodic diet, lentiviral expression vector–induced Dkk3 expression in the CNS displayed a substantial antihypertensive effect and delayed the occurrence of stroke.

Conclusions:
These findings demonstrate that Dkk3 acts as peripheral and central regulator of BP by promoting VEGF expression and activating a VEGF/Akt (protein kinase B)/eNOS hypotensive axis.
Sympathetic Nervous Hyperactivity Impairs Microcirculation Leading to Early Brain Injury After Subarachnoid Hemorrhage
Authors: Demura Munehiro , Ishii Hiroshi , Takarada-Iemata Mika , Kamide Tomoya , Yoshikawa Akifumi , Nakada Mitsutoshi , Hori Osamu 
Published: May 2023

Background:
Although early brain injury (EBI) is recognized as a critical step following subarachnoid hemorrhage (SAH), its pathophysiology and underlying mechanisms remain poorly understood. Herein, we investigated the role of cerebral circulation in the acute phase using patient data and a mouse SAH model and evaluated its regulation via the sympathetic nervous system.

Methods:
The cerebral circulation time and neurological outcomes in the human body were retrospectively examined in 34 SAH cases with ruptured anterior circulation aneurysms and 85 cases with unruptured anterior circulation cerebral aneurysms at Kanazawa University Hospital from January 2016 to December 2021. In a mouse study, a SAH model was created via endovascular perforation, and India-ink angiography was performed over time. Additionally, bilateral superior cervical ganglionectomy was performed immediately before surgery, and neurological scores and brain water content were evaluated after SAH.

Results:
Cerebral circulation time was prolonged in the acute phase of SAH compared with that in the unruptured cerebral aneurysm group, especially in those with electrocardiographic changes. Furthermore, it was more prolonged in the poor prognosis group (modified Rankin Scale scores 3–6) than in the good prognosis group (modified Rankin Scale scores 0–2) at discharge. In mice, cerebral perfusion was significantly reduced at 1 and 3 hours after SAH and recovered at 6 hours. superior cervical ganglionectomy improved cerebral perfusion without altering the diameter of the middle cerebral artery at 1 hour and improved neurological outcomes at 48 hours after SAH. Consistently, brain edema, quantified by brain water content, was improved by superior cervical ganglionectomy 24 hours after SAH.

Conclusions:
Sympathetic hyperactivity may play a critical role in the development of EBI by impairing cerebral microcirculation and edema in the acute phase following SAH.
Bridging the Gap between Synthetic and Natural Questions via Sentence Decomposition for Semantic Parsing
Authors: Niu Yilin , Huang Fei , Liu Wei , Cui Jianwei , Wang Bin , Huang Minlie 
Published: May 2023

Abstract
Semantic parsing maps natural language questions into logical forms, which can be executed against a knowledge base for answers. In real-world applications, the performance of a parser is often limited by the lack of training data. To facilitate zero-shot learning, data synthesis has been widely studied to automatically generate paired questions and logical forms. However, data synthesis methods can hardly cover the diverse structures in natural languages, leading to a large gap in sentence structure between synthetic and natural questions. In this paper, we propose a decomposition-based method to unify the sentence structures of questions, which benefits the generalization to natural questions. Experiments demonstrate that our method significantly improves the semantic parser trained on synthetic data (+7.9% on KQA and +8.9% on ComplexWebQuestions in terms of exact match accuracy). Extensive analysis demonstrates that our method can better generalize to natural questions with novel text expressions compared with baselines. Besides semantic parsing, our idea potentially benefits other semantic understanding tasks by mitigating the distracting structure features. To illustrate this, we extend our method to the task of sentence embedding learning, and observe substantial improvements on sentence retrieval (+13.1% for Hit@1).
One step closer but still far from solving the puzzle – The phylogeny of marine associated mites (Acari, Oribatida, Ameronothroidea) inferred from morphological and molecular genetic data
Authors: Pfingstl Tobias , Bardel-Kahr Iris , Schliep Klaus 
Published: May 2023

Abstract
Marine associated oribatid mites belong mainly to the Ameronothroidea which represent a very small percentage of all Oribatida. Over the last decades the systematics and evolutionary history of this group has been discussed controversially and still there is no consensus concerning several issues. The extreme marine environment may have resulted in parallel morphologies complicating the classification and estimation of phylogeny based on discrete morphological traits. In the present study, we performed a molecular genetic study using a mitochondrial and two nuclear markers to infer the phylogeny of this group. Additionally, we reconstructed the phylogeny of Ameronothroidea based on morphological data using different algorithms. Both methods resulted in largely congruent topologies and highlight the following important points: the Ameronothroidea represent a paraphyletic assemblage; the Podacaridae are a distinct family and should be excluded from Ameronothridae; the Fortuyniidae, Selenoribatidae and Tegeocranellidae constitute a monophyletic lineage; and certain genera of Selenoribatidae need a revision. These results demonstrate that the classification of Ameronothroidea and certain positions within this group need to be thoroughly reconsidered and revised. The present study also shows that phylogenetic estimates based on coded morphological data can be a very helpful tool for verifying and supporting molecular phylogenies.