bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double‐blind, randomized, placebo‐controlled, phase 2 clinical trial
Authors: Kato Masaki , Nakagome Kazuyuki , Baba Takamichi , Sonoyama Takuhiro , Okutsu Daiki , Yamanaka Hideki , Shimizu Ryosuke , Motomiya Tomoko , Inoue Takeshi 
Published: May 2023

[Corrections added on 20 December 2024, after first online publication: The Results section in the Abstract has been revised to report on updated data following the re‐analysis of the study results using revised numbers of patients in the three groups ‐ zuranolone 20 mg [N=84], zuranolone 30 mg [N=79], and placebo [N=79] ‐ that were included in the full analyses set and the safety analysis set.]AimTo evaluate the efficacy and safety of an oral, once‐daily, 14‐day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD).MethodsThis multicenter, randomized, double‐blind, placebo‐controlled study randomized eligible patients (1:1:1) to receive oral zuranolone 20 mg, zuranolone 30 mg, or placebo once daily for 14 days (treatment‐period), followed by two 6‐week follow‐up periods. The primary endpoint was change from baseline in the 17‐item Hamilton Depression Rating Scale (HAMD‐17) total score on Day 15.ResultsOverall, 250 patients (enrolled: 07/07/2020–05/26/2021) were randomized, of whom 79 in the placebo group, 84 in the zuranolone 20‐mg group, and 79 in the zuranolone 30‐mg group were included in the full analysis set (FAS) population. The demographic and baseline characteristics were balanced between groups. The adjusted mean (standard error) change from baseline in the HAMD‐17 total score on Day 15 was −6.09 (0.64), −8.18 (0.63), and − 8.33 (0.65) in the placebo, zuranolone 20‐mg, and zuranolone 30‐mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for the zuranolone 20‐mg versus placebo (−2.09; [−3.86, −0.33]; P = 0.0204) and zuranolone 30‐mg versus placebo (−2.24; [−4.03, −0.45]; P = 0.0146) groups were observed on Day 15, and also as early as Day 3 for zuranolone 30 mg. A nonsignificant yet distinct drug‐placebo separation was observed in the zuranolone 30‐mg group during follow‐up. Somnolence (placebo [3.8%], zuranolone 20 mg [10.7%], and zuranolone 30 mg [21.5%]) and dizziness (2.5%, 9.5%, and 8.9%, respectively) were more common drug reactions in the treatment period with zuranolone.ConclusionOral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by the HAMD‐17 total score change from baseline over 14 days in Japanese patients with MDD.
Suppressing plant defense: Scavenge the ROS!
Authors: Prasad Ashish , Sharma Shambhavi , Prasad Manoj 
Published: May 2023

AbstractReactive oxygen species (ROS)‐mediated defense against fungal pathogens is an essential arm of plant immunity. As a counter defense, these pathogens synthesize antioxidant enzymes that scavenge the ROS produced by plants. The molecular mechanism behind the upregulation of these enzymes in fungal pathogens was unknown. A recent study by Zhang et al. (2023, https://doi.org/10.15252/embj.2022112634) has shed light on the mechanism, and it has been shown that deacetylation of FolSrpk1 protein on the K304 residue following oxidative stress is an important event in the signaling cascade leading to ROS detoxification in Fusarium oxysporum f. sp. lycopersici. Deacetylated FolSrpk1 moves to the nucleus where it hyperphosphorylates FolSr1, which further regulates the transcription of antioxidant enzymes. This mechanism of ROS detoxification is conserved in Botrytis cinerea as well. Several other phytopathogenic fungi have a corresponding K304 site and NLS present in their Srpk1, suggesting a similar mechanism of ROS detoxification and suppression of plant defense. In this article, we have presented our views on how future studies can be synthesized based on the pathway deciphered by Zhang et al. (2023, https://doi.org/10.15252/embj.2022112634).
Salivary 3‐methoxy‐4‐hydroxyphenylglycol and MRI‐based volume change of the precuneus in community‐dwelling elderly people
Authors: Ohishi‐Fukuchi Junko , Imamura Yoshiomi , Orihashi Ryuzo , Kunitake Hiroko , Kunitake Yutaka , Tateishi Hiroshi , Yamada Shigeto , Monji Akira , Mizoguchi Yoshito 
Published: May 2023

BackgroundThe noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long‐term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer's disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3‐methoxy‐4‐hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community.MethodsThe survey was conducted twice in Kurokawa‐cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005–2007). Follow‐up brain MRIs were taken at Time 2 (2009–2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel‐based morphometry implemented with statistical parametric mapping.ResultsIn participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found.ConclusionOur results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function.
Understanding oral health from the point of view of adults with disabilities and/or complex medical conditions: A scoping review
Authors: Bogner Marie‐Sophie , Faulks Denise 
Published: May 2023

AbstractAimThis study aimed to review the qualitative scientific literature investigating experience of the mouth and oral health amongst adults with disabilities and/or complex health conditions.MethodsA scoping review methodology was applied in accordance with the methodological framework of Arksey & O'Malley and the PRISMA‐SCR checklist. Electronic searching was performed using the databases Pubmed, Embase, and PsychInfo.ResultsThirty articles were included in the final selection. The populations included in the selected studies were very varied in terms of health conditions and disabilities. Three major themes relating to the experience and understanding of the mouth, oral health, and function were highlighted in the review: the representation of oral health, the influence of oral health on the participant's life, and the influence of the socio‐environmental context on oral health. No study explicitly described the functional, social, and psychological roles of the mouth in a comprehensive manner.ConclusionsPerception of the mouth and oral health differs depending on the individual and their health condition. Oral health is described as dependent on the socio‐environmental context, however, outside of the experience of dental care services, this context is not investigated in the literature. This scoping review demonstrated that exhaustive understanding of the dimensions of the mouth and oral health has not been explored in published research for this population.
Optical coherence tomography confirms non‐malignant pigmented lesions in phacomatosis pigmentokeratotica using a support vector machine learning algorithm
Authors: Lee Jenna , Beirami Mohammad Javad , Ebrahimpour Reza , Puyana Carolina , Tsoukas Maria , Avanaki Kamran 
Published: May 2023

AbstractIntroductionPhacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an extensive range of atypical nevi of different morphologies may manifest. Pigmented lesions may fulfill the ABCDE criteria for melanoma, which may prompt a physician to perform a full‐thickness biopsy.MotivationExcisions result in pain, mental distress, and physical disfigurement. For patients with a significant number of nevi with morphologic atypia, it may not be physically feasible to biopsy a large number of lesions. Optical coherence tomography (OCT) is a non‐invasive imaging modality that may be used to visualize non‐melanoma and melanoma skin cancers.Materials and MethodIn this study, we used OCT to image pigmented lesions with morphologic atypia in a patient with PPK and assessed their quantitative optical properties compared to OCT cases of melanoma. We implement a support vector machine learning algorithm with Gabor wavelet transformation algorithm during post‐image processing to extract optical properties and calculate attenuation coefficients.ResultsThe algorithm was trained and tested to extract and classify textural data.ConclusionWe conclude that implementing this post‐imaging machine learning algorithm to OCT images of pigmented lesions in PPK has been able to successfully confirm benign optical properties. Additionally, we identified remarkable differences in attenuation coefficient values and tissue optical characteristics, further defining separating benign features of pigmented lesions in PPK from malignant features.
A defence of conceptual analysis as a linguistic endeavour
Authors: Grindrod Jumbly 
Published: May 2023

AbstractIn this paper, I outline and defend a traditional yet controversial view of conceptual analysis, particularly as it is used in epistemology. I will defend the view against a number of objections, all of which focus on the idea that conceptual analysis relies upon linguistic intuitions. Rather than trying to deny this claim, I will seek to vindicate the use of conceptual analysis within epistemology even given its reliance on linguistic intuitions. To do so, I first outline the view of conceptual analysis I have in mind and then respond to three broad objections from Quill Kukla, Allan Hazlett and Stephen Stich.
Applications of the algebraic geometry of the Putman–Wieland conjecture
Authors: Landesman Aaron , Litt Daniel 
Published: May 2023

AbstractWe give two applications of our prior work toward the Putman–Wieland conjecture. First, we deduce a strengthening of a result of Marković–Tošić on virtual mapping class group actions on the homology of covers. Second, let and let be a finite ‐cover of topological surfaces. We show the virtual action of the mapping class group of on an ‐isotypic component of has nonunitary image.
Sensory training system for use at home by people with complex regional pain syndrome in England: protocol for a proof-of-concept study
Authors: Coggins Jessica , Grieve Sharon , Hart Darren , Llewellyn Alison , Palmer Mark , Boichat Charlotte , McCabe Candy 
Published: May 2023

IntroductionComplex regional pain syndrome (CRPS) is a disabling and distressing chronic pain condition characterised by a range of sensory, motor, autonomic and trophic symptoms. UK guidelines recommend therapy interventions to help normalise touch perception through self-administered tactile and thermal desensitisation activities. Interventions have been developed, aiming to help individuals broaden their sensory experience, thereby relieving chronic pain. However, therapy-led interventions often experience practical constraints and poor adherence. In response, a sensory training system (STS) device has been designed for unsupervised independent home-use.MethodsThis proof-of-concept study aims to explore whether people with CRPS use the device at home for 30 minutes a day for 30 days. Secondary aims are to determine whether the STS device will change tactile acuity and perceived levels of pain intensity, pain interference, sensitivity or feelings towards the affected limb. We will seek to recruit 20 eligible participants. Participants will be asked to measure tactile acuity using a two-point discrimination assessment, complete an online questionnaire before and after use of the device and complete a daily diary. On completion of the 30-day use, participants will be invited to take part in a semi-structured interview to explore their experiences of using the device.AnalysisPain intensity and pain interference will be scored using the online Assessment Center Scoring Service or using the look-up table in the PROMIS scoring manual. The remaining questionnaire data, including tactile acuity results, and device-use data, including frequency and duration of use, will be analysed using descriptive statistics. Qualitative data will be thematically analysed.Ethics and disseminationLondon-Stanmore Research Ethics Committee provided a favourable opinion on 19 April 2021 (ref 21/LO/0200). The NHS Health Research Authority, UK, approved this study on 7 June 2021. Dissemination will include peer-reviewed publications, presentations at conferences, social media and reports to the funder and patient charities.Trial registration numberISRCTN89099843.
Tumour stemness and poor clinical outcomes in haemochromatosis patients with hepatocellular carcinoma
Authors: Di Capua Daniel M , Shanahan William , Bourke Michele , Ramlaul Navneet , Appel Josh , Canney Aoife , Docherty Neil G , McGrath Erinn , Ring Eabha , Jones Fiona , Boyle Marie , McCormack Janet , Gallagher Tom , Hoti Emir , Nolan Niamh , Ryan John D , Houlihan Diarmaid D , Fabre Aurelie 
Published: May 2023

AimsPatients with haemochromatosis (HFE) are known to have an increased risk of developing hepatocellular carcinoma (HCC). Available data are conflicting on whether such patients have poorer prognosis, and there is lack of data regarding the biology of HFE-HCC. We compared the course of HFE-HCC with a matched non-HFE-HCC control group and examined tumour characteristics using immunohistochemistry.MethodsIn this tertiary care-based retrospective analysis, 12 patients with HFE and 34 patients with alcohol/non-alcoholic steatohepatitis who underwent initially successful curative HCC therapy with ablation or resection were identified from our registry. Time to tumour progression was compared. Resected liver tissue from a separate cohort of 11 matched patients with HFE-HCC and without HFE-HCC was assessed for the expression of progenitor and epithelial–mesenchymal transition markers using immunohistochemistry.ResultsThe median follow-up was 24.39 and 24.28 months for patients with HFE-HCC and those without HFE-HCC, respectively (p>0.05). The mean time to progression was shorter in the HFE group compared with the non-HFE group (12.87 months vs 17.78 months; HR 3.322, p<0.05). Patients with HFE-HCC also progressed to more advanced disease by the end of follow-up (p<0.05). Immunohistochemical analysis of matched HFE-HCC and non-HFE-HCC explants demonstrated increased expression of the cancer stem cell markers EpCAM (epithelial cell adhesion molecule) and EpCAM/SALL4 (spalt-like transcription factor 4) coexpression in HFE-HCC specimens (p<0.05). There was a high frequency of combined tumour subtypes within the HFE cohort.ConclusionsThis study demonstrates that the clinical course of patients with HFE-HCC is more aggressive and provides the first data indicating that their tumours have increased expression of progenitor markers. These findings suggest patients with HFE-HCC may need to be considered for transplant at an earlier stage.
Flow diversion for basilar quadrifurcation aneurysms
Authors: Srinivasan Visish M , Jubran Jubran H , Stonnington Henry O , Catapano Joshua S , Scherschinski Lea , Hendricks Benjamin K , Winkler Ethan A , Rudy Robert F , Nguyen Brandon A , Dabrowski Stephen J , Jadhav Ashutosh P , Ducruet Andrew F , Albuquerque Felipe C 
Published: May 2023

BackgroundFlow-diverting devices (FDDs), such as the Pipeline Embolization Device, have been gaining traction for treating challenging posterior circulation aneurysms. Few previous studies have focused on using FDDs to treat aneurysms of the basilar quadrifurcation.MethodsWe retrospectively reviewed the use of FDDs to treat patients with basilar quadrifurcation aneurysms. Patients were assessed for aneurysm type, previous aneurysm treatment, technical success, periprocedural complications, and long-term aneurysm occlusion.Results34 patients were assessed; aneurysms of the basilar apex (n=23) or superior cerebellar artery (SCA) (n=7), or both (n=1), and posterior cerebral artery (PCA) (n=3). The mean (SD) largest aneurysm dimension was 8.7 (6.1) mm (range 1.9–30.8 mm). 14 aneurysms were previously surgically clipped or endovascularly coiled. All aneurysms had a saccular morphology. Complete or near-complete occlusion was achieved in 30 of 34 patients (88%) at final angiographic follow-up, a mean (SD) of 6.6 (5.4) months (range 0–19 months) postoperatively. No patient experienced postoperative symptomatic occlusions of the SCA or PCA; 4 patients developed asymptomatic posterior communicating artery occlusions; 28 patients (82%) experienced no complications; whereas 3 (9%) experienced major complications and 3 (9%) experienced minor complications; and 1 patient died as a result of subarachnoid hemorrhage.ConclusionFlow diversion may be a safe and effective option to treat basilar quadrifurcation aneurysms. Previously treated basilar quadrifurcation aneurysms with recurrence or residual lesion may benefit from additional treatment with an FDD. Further prospective studies should be directed toward validating these findings.
Extent of illicit cigarette sales in Nepal: findings from a retail survey
Authors: Shakya Sangita , Lamichhane Anjana , Karki Pranav , Gurung Jaya Kumar , Pradhan Pranil Man Singh 
Published: May 2023

Introduction
Increasing the tax on cigarettes is widely considered the most effective method to reduce its consumption. However, Nepal has a low cigarette tax as policymakers in Nepal are concerned about illicit trade of cigarettes if taxes are increased.

Methods
The study employed a retail survey approach used in India suitable for countries with prevalent loose cigarette sales, with improved methodology. In 2021, empty cigarette packs generated in a day’s loose cigarette sales were collected directly from cigarette retailers from 23 primary sampling units covering rural/urban, geographic divisions, border/non-border to India and tobacco factory locations. The central points of each primary sampling unit were identified, and retailers were selected for the survey. A cigarette pack was classified as illicit if it had at least one of the following attributes: (a) no authentic excise duty sticker, (b) no graphic health warning, (c) no mention of ‘maximum retail price/MRP’ and (d) no production date, name, address and trademark.

Findings
We collected 4307 empty cigarette packs from 1204 retailers and 0.33% of them were classified as illicit. The estimates varied across location with the highest prevalence of illicit packs in Kathmandu (1.25%). All the illicit cigarettes were imported and were high-priced brands (>90%), mostly found in urban areas and not bordering India.

Conclusion
Our estimate of the illicit cigarette market share of 0.33% suggests that the industry’s statement of 25% is grossly overstated.
Evolution of channel flow and Darcy’s law beyond the critical Reynolds number
Authors: Deng Xiaohui , Sheng Ping 
Published: May 2023

AbstractFor incompressible channel flow, there is a critical state, characterized by a critical Reynolds number Rec and a critical wavevector mc along the channel direction, beyond which the channel flow becomes unstable in the linear regime. In this work, we investigate the channel flow beyond the critical state and find the existence of a new fluctuating, quasi-stationary flow that comprises the laminar Poiseuille flow superposed with a counter-flow component, accompanied by vortices and anti-vortices. The net flow rate is reduced by  ~ 15% from the linear, laminar regime. Our study is facilitated by the analytical solution of the linearized, incompressible, three-dimensional (3D) Navier–Stokes (NS) equation in the channel geometry, with the Navier boundary condition, alternatively denoted as the hydrodynamic modes (HMs). By using the HMs as the complete mathematical basis for expanding the velocity in the NS equation, the Rec is evaluated to 5-digit accuracy when compared to the well-known Orszag result, without invoking the standard Orr-Sommerfeld equation. Beyond Rec, the analytical solution is indispensable in offering physical insight to those features of the counter-flow component that differs from any of the pressure-driven channel flows. In particular, the counter flow is found to comprise multiple HMs, some with opposite flow direction, that can lead to a net boundary reaction force along the counter-flow direction. The latter is analyzed to be necessary for satisfying Newton’s law. Experimental verification of the predictions is discussed.
Graphical Abstract
Printed circuit heat exchangers and fast neutron radiography
Authors: Vrban B. , Čerba Š. , Lüley J. , Filová V. , Nečas V. 
Published: May 2023

AbstractNon-destructive testing is capable of detecting defects of important components, where a failure could pose a significant hazard and cause severe economic losses. Currently, imaging techniques utilizing gamma or X-ray sources are mainly used and allow to examine of devices ranging in size from units to tens of centimetres, but for industrial-sized large components, these methods usually fail. The utilization of fast neutrons in radiography is a promising alternative, especially for industrial applications. Currently, due to the higher neutron-matter interaction probabilities, most neutron-imaging systems use thermal neutrons originating from research reactors. Due to the intention of on-site inspection of revealing the possible ruptures and failures, this option is not applicable. The paper presents the newly developed neutronic models of printed circuit heat exchangers where the specific ruptures are defined. Next, neutron transport simulations are performed to investigate the different irradiation geometries, various neutron sources, and backfill materials to access the principal detectability of these ruptures in the industrial environment. Finally, conclusions are drawn, and the best backfill material and neutron source are identified in the simplified model.
About this title - Geological Hazards in the UK: Their Occurrence, Monitoring and Mitigation – Engineering Group Working Party Report
Authors: Giles D. P. , Griffiths J. S. 
Published: May 2023

The UK is perhaps unique globally in that it presents the full spectrum of geological time, stratigraphy and associated lithologies within its boundaries. With this wide range of geological assemblages comes a wide range of geological hazards, whether they be geophysical (earthquakes, effects of volcanic eruptions, tsunami, landslides), geotechnical (collapsible, compressible, liquefiable, shearing, swelling and shrinking soils), geochemical (dissolution, radon and methane gas hazards) or georesource related (coal, chalk and other mineral extraction). An awareness of these hazards and the risks that they pose is a key requirement of the engineering geologist.
The Geological Society considered that a Working Party Report would help to put the study and assessment of geohazards into the wider social context, helping the engineering geologist to better communicate the issues concerning geohazards in the UK to the client and the public. This volume sets out to define and explain these geohazards, to detail their detection, monitoring and management and to provide a basis for further research and understanding.