bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors that influence women’s enrolment and ongoing participation in a partially decentralised randomised controlled dermatology trial: a qualitative interview study with participants in the SAFA (Spironolactone for Adult Female Acne) trial
Authors: Boxall Cherish , Renz Susanne , Eminton Zina , Nuttall Jacqui , Saji Alan , Cluff Charlotte , Wilcox Christopher , Muller Ingrid , Layton Alison , Soulsby Irene , Santer Miriam 
Published: June 2023

Abstract
Background
The use of decentralised clinical trials (which bring trials to patients through remote processes and technology versus central on-site visits) has been thought to be a potential solution to common recruitment and retention barriers. However, there is a lack of evidence to understand the experiences, needs and preferences of the public to inform trial methodologies that appeal to different populations. We report participant experiences of SAFA, a partially decentralised randomised clinical trial, to inform the methodology used in future dermatology trials that aim to appeal to women aged 18 and over.
Methods
Participants of the SAFA (Spironolactone for Adult Female Acne) trial were invited to take part in a qualitative semi-structured interview to explore their experience and perspectives of taking part in the trial. Questions focused on their experience of using decentralised methods to access and enrol in the trial (e.g. social media advertising), in addition to the decentralised trial visit and data collection methods used throughout. Interviews were conducted remotely, recorded, and transcribed. Data were analysed using reflexive Thematic Analysis.
Results
Twelve SAFA participants (all women, age range 22-36) were interviewed. Initially, participants were influenced to enrol by trusted online information, the feeling of validation the trial provided and the convenience and flexibility offered by the decentralised methods and research staff made participants feel valued and enabled them to engage in the trial with minimal interference to existing commitments. SAFA participants were generally accepting of trial demands, such as the text-heavy paperwork and on-site visits for blood collection and highlighted several areas relevant for trial conduct going forwards including where decentralised methods may (and may not) be accepted and how trial accessibility and understanding could be improved.
Conclusions
The study has shown that decentralised methods used by responsive and approachable staff were widely accepted in the SAFA trial. Interviewees found the methods adopted in the SAFA trial helped the trial to fit with their needs and promoted a sense of feeling valued that encouraged ongoing trial engagement. Decentralised methods should be considered favourably when designing a dermatology trial as they can potentially enhance both recruitment and retention.
Trial registration number: ISRCTN number: 12892056
Lidocaine promoted cuproptosis in laryngeal cancer through long noncoding RNA DNMBP-AS1
Authors: Yu Yi , Lv Meihong 
Published: June 2023

AbstractBackground:Lidocaine is a traditional local anesthetic, which has been reported to trigger apoptosis through the mitochondrial pathway, independent of death receptor signaling. Cuproptosis is a copper triggered mitochondrial cell death mode. In this study, we explored the biological effects of lidocaine on laryngeal cancer and studied the relevant mechanisms of cuproptosisMethods:quantitative RT-PCR weas used to measure the expression level of long noncoding RNA (IncRNA) DNMBP-AS1. DNMBP-AS1 siRNA (si-DNMBP-AS1) were transfected into Hep-2 cells to verify the roles of DNMBP-AS1 in cuproptosis. 24 hours treatment with 20 nM elesclomol and 2 µM CuCl2 was performed to promote the occurrence of Cuproptosis. Cell proliferation and apoptosis assays ware utilized to analyze biological effect of lidocaine on Hep-2 cells.Results:DNMBP-AS1 was significantly upregulated during cuproptosis in Hep-2 cells. The si-DNMBP-AS1 significantly increased the cell viability, and suppress the cuproptosis. Lidocaine was cytotoxic to the Hep-2 cells in a dose- and time-dependent manner. Exposure to 10 μM of lidocaine for 24 hours did not reduce the viability, but significantly increased the expression of DNMBP-AS1, and promote the cuproptosis. Anymore, si-DNMBP-AS1 reverse the pro-cuproptosis function of lidocaine.Conclusions:lidocaine was cytotoxic to human laryngeal cancer cells in a time- and dose-dependent manner, promoted the cuproptosis through up-regulating DNMBP-AS1. The results of this study offer initial optimism that lidocaine can be used in an adjuvant or neoadjuvant fashion in laryngeal cancer treatment.
ApoER2-Dab1 disruption as the origin of pTau-related neurodegeneration in sporadic Alzheimer's disease
Authors: Ramsden Christopher E , Zamora Daisy , Horowitz Mark , Jahanipour Jahandar , Keyes Gregory , Li Xiufeng , Murray Helen C , Curtis Maurice A , Faull Richard M , Sedlock Andrea , Maric Dragan 
Published: June 2023

Abstract
BACKGROUND
Sporadic Alzheimer’s disease (sAD) is not a global brain disease. Specific regions, layers and neurons degenerate early while others remain untouched even in advanced disease. The prevailing model used to explain this selective neurodegeneration—prion-like Tau spread—has key limitations and is not easily integrated with other defining sAD features. Instead, we propose that in humans Tau hyperphosphorylation occurs locally via disruption in ApoER2-Dab1 signaling and thus the presence of ApoER2 in neuronal membranes confers vulnerability to degeneration. Further, we propose that disruption of the Reelin/ApoE/ApoJ-ApoER2-Dab1-P85α-LIMK1-Tau-PSD95 (RAAAD-P-LTP) pathway induces deficits in memory and cognition by impeding neuronal lipoprotein internalization and destabilizing actin, microtubules, and synapses. This new model is based in part on our recent finding that ApoER2-Dab1 disruption is evident in entorhinal-hippocampal terminal zones in sAD. Here, we hypothesized that neurons that degenerate in the earliest stages of sAD (1) strongly express ApoER2 and (2) show evidence of ApoER2-Dab1 disruption through co-accumulation of multiple RAAAD-P-LTP components.
METHODS
We applied in situ hybridization and immunohistochemistry to characterize ApoER2 expression and accumulation of RAAAD-P-LTP components in five regions that are prone to early pTau pathology in 64 rapidly autopsied cases spanning the clinicopathological spectrum of sAD.
RESULTS
We found that: (1) selectively vulnerable neuron populations strongly express ApoER2; (2) numerous RAAAD-P-LTP pathway components accumulate in neuritic plaques and abnormal neurons; and (3) RAAAD-P-LTP components were higher in MCI and sAD cases and correlated with histological progression and cognitive deficits. Multiplex-IHC revealed that Dab1, pP85αTyr607, pLIMK1Thr508, pTau and pPSD95Thr19 accumulated together within dystrophic dendrites and soma of ApoER2-expressing neurons in the vicinity of ApoE/ApoJ-enriched extracellular plaques. These observations provide evidence for molecular derangements that can be traced back to ApoER2-Dab1 disruption, in each of the sampled regions, layers, and neuron populations that are prone to early pTau pathology.
CONCLUSION
Findings support the RAAAD-P-LTP hypothesis, a unifying model that implicates dendritic ApoER2-Dab1 disruption as the major driver of both pTau accumulation and neurodegeneration in sAD. This model provides a new conceptual framework to explain why specific neurons degenerate and identifies RAAAD-P-LTP pathway components as potential mechanism-based biomarkers and therapeutic targets for sAD.
Multimodal imaging of the optic nerve head in retinitis pigmentosa
Authors: Wada Naoko , Takagi Seiji , Yoshikawa Akiko , Itokawa Takashi , Maruyama Takahiro , Hori Yuichi 
Published: June 2023

Abstract

Background: A pallor optic nerve head (ONH) is one of the three features in retinitis pigmentosa (RP). This study aimed to assess the ONH by color tone, presence of hyper-reflective structure, blood flow, and retinal nerve fiber layer (RNFL) thickness, and investigate the change in these parameters with and without ONH pallor.
Methods: The presence of ONH pallor was assessed by three independent examiners through careful examination using fundus photographs. The presence of a hyper-reflective structure on the ONH was carefully evaluated using a volume scan optical coherence tomography (OCT). RNFL thickness and ellipsoid zone (EZ) width around the macula were also evaluated by OCT. Laser speckle flowgraphy was used to measure the mean blur rate of the entire ONH area, which was subsequently divided into the vessel area (MV) and tissue area (MT).
Results: Twenty-eight eyes of 28 patients with RP (55.4±16.23 years old) were included. The pale ONH was observed in 10 (35%) eyes. Hyper-reflective structures were observed in 7 (25%) eyes. No significant correlation was found between the pale ONH and presence of a hyper-reflective structure (Pearson’s chi-squared test, p=0.364). The average of the ONH area, MV, and MT was 8.65±3.08 AU, 17.81±7.54 AU, and 6.4±2.66 AU, respectively, which significantly decreased in patients with pallor ONH (all p<0.05). The global RNFL thickness was 73.54±18.82 μm. The nasal and superior quadrants and global RNFL thickness in patients with a pale ONH were significantly thinner than in patients without a pale ONH (all p<0.05). There was no difference in the EZ width between patients with and without a pale ONH (p=0.107).
Conclusion: We conducted multiple assessments of the ONH in patients with RP and investigated its clinical significance. Our findings suggest that ONH pallor may indicate a comprehensive change that emerges alongside the progression of retinal degeneration in RP.
Trial registration: This trial was retrospectively registered in the UMIN Clinical Trial Registry(UMIN000048168 01/07/2022).
Molecular identification and validation of four stable QTL for slow-mildewing resistance in Chinese wheat cultivar Bainong 64
Authors: Xu Xiaowan , Sun Daojie , Ni Zhongqiu , Zou Xinyu , Xu Xiaoting , Sun Mengjing , Cao Qiang , Tong Jingyang , Ding Fugong , Zhang Yelun , Wang Fengju , Dong Yachao , Zhang Luyan , Wang Jiankang , Xia Xianchun , He Zhonghu , Hao Yuanfeng 
Published: June 2023

Abstract
Wheat powdery mildew, caused by Blumeria graminis f. sp tritici (Bgt), is a devastating fungal disease. Seedlings of Chinese winter wheat cultivar Bainong 64 are susceptible to Bgt but adult plants have maintained slow-mildewing resistance since it was released in 1996. A population of 171 recombinant inbred lines (RILs) developed from cross Jingshuang 16/Bainong 64 (JS16/BN64) was used to dissect genetic components of powdery mildew resistance. A genetic map comprising 5,383 polymorphic markers was constructed using the 15K SNP chip and kompetitive allele-specific PCR (KASP) markers. Composite interval mapping identified four stable QTL on chromosome arms 1DL, 2BS, 2DL, and 6BL in all five environments and their favorable alleles were inherited from BN64. The QTL accounted for 8.3%, 13.8%, 14.4%, and 9.0% of the total phenotypic variances in maximum, respectively. QPmjbr.caas-1DL,situated about 22 Mb from centromere, is probably a new QTL. QPmjbr.caas-2DL located near the end of arm 2DL. Using genetic maps populated with KASP markers, QPmjbr.caas-2BS and QPmjbr.caas-6BL were fine mapped to a 1.8 cM genetic intervals spanning 13.6 Mb (76.0–89.6 Mb) and 1.7 cM and 4.9 Mb (659.9–664.8 Mb), respectively. The four QTL were all independent of stripe rust and leaf rust resistance and were validated for slow-mildewing in another RIL population related to BN64 and a cultivar panel using representative KASP markers spanning each QTL. Since BN64 has been a leading cultivar and an important breeding parent, the QTL and markers reported in this study will be useful for marker-assisted selection of slow-mildewing resistance.
Gender Difference and Job Quality: Application in Cameroon
Authors: Meka'a cosmas bernard , fotso silvain raoul 
Published: June 2023

Abstract
The objective of this article is to examine to what extent gender differences exist in the quality of employment in the labor market in Cameroon. For this, we use data from the fourth Cameroon Household Survey (ECAM4). This survey has the advantage of covering the national territory and providing information on the socio-demographic characteristics of workers as well as on the dimensions of job quality. In addition to examining gender inequalities in the different dimensions of job quality, a principal component analysis was carried out to construct a composite index of overall job quality. The results establish that the probability for women to hold a better job is lower compared to men. The only possibilities that women have of accessing quality jobs exist when they have managerial status and when they work in large companies. Inequalities in access to better quality jobs to their disadvantage are more the result of differences in unobservable characteristics rather than differences in individual characteristics.
JEL Rating: J16, J23, C25, C35
Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal spinal infections: a retrospective observational study
Authors: Lombès Amélie , Fernandez-Gerlinger Marie-Paule , Khalifé Marc , Kassis-Chikhani Najiby , Jomli Amira , Mainardi Jean-Luc , Lebeaux David , Dubert Marie 
Published: June 2023

Abstract
Background
Post-surgical spinal infections (pSSIs) are a serious complication of spinal surgeries, with Staphylococcus spp. being one of the most prominent bacteria identified. Optimal antimicrobial therapy for staphylococcal spinal infections without spinal implants is not well documented.
Methods
This single center retrospective 7-year observational study described and compared the outcome (treatment failure or mortality at 1 year) of 20 patients with staphylococcal-implant-free pSSI treated with single or combination antibiotics.
Results
Median duration of treatment was 40 days (IQR 38–42), with 6 days (IQR 5–7) on intravenous antibiotics and 34 days (IQR 30–36) on oral therapy. Four patients (20%) underwent new surgical debridement, all due to surgical failure, and 1 patient died within the first year without statistical differences between both group of treatment.
Conclusion
This study raises the possibility of single antibiotic therapy for patients with implant-free post-surgical spinal infections due to Staphylococcus spp.
Direct regeneration and Genetic transformation studies in Hemidesmus indicus (L.) R. Br. (Indian Sarasaprilla)
Authors: Ranganatha Manjula , sharma ashwani , BE Rangaswamy , Kumar Shashi , Rao Nagashree N 
Published: June 2023

Abstract
Since ages, plants continue to provide new remedies to mankind. Hemidesmus indicus L. R. Br. is one such plant belonging to family Apocynaceae, showing potent medicinal properties known through traditional knowledge. Hemidesmus is also explored for the presence of flavoring compound namely 2-hydroxy-4-methoxybenzaldehyde (HMB) which is used in pharmaceutical and nutraceutical industries. Due to anthropogenic activities, the plant has been exploited till the ridge for its ethnobotanical properties for mankind. Biotechnological intervention to conserve this endangered sps through in vitro plant cultures, micropropogation and genetic transformation studies is the pre-requite to maintain it from extinction. The objective of the study is to improve the regeneration potential and optimize the genetic transformation in Hemidesmus indicus. The direct regeneration of Hemidesmus indicus through leaf explants, nodal explants with subsequent plant regeneration using Murashige and Skoog (MS) medium supplemented with various plant growth regulators (auxins, cytokinins, and gibberellic acid), adenine sulphate, TRIA. The Agrobacterium tumefaciens mediated genetic transformation studies in Hemidesmus indicus was carried out in callus cultures using the plant expression vector pCAMBIA 1301. The caulogenic response of 78.8%, 73.3% and 71.4% was observed when the leaf explant was inoculated on MS media containing 2.3 mgL− 1 BAP + 0.2 mgL− 1 2,4-D, 0.02 mgL− 1 TRIA + 2 mgL− 1 BAP, 1 mgL− 1 KIN + 1 mgL− 1 NAA respectively with creamish yellow nodular friable callus by the 4 weeks. The initiation of shoot bud was observed within three days after inoculation of nodal explant on media supplemented with 1 mgL− 1 BAP + 0.1 mgL− 1 NAA, 1 mgL− 1 BAP + 0.1 mgL− 1 NAA + 40 mgL− 1 AgNO3, 1 mgL− 1 BAP + 0.1 mgL− 1 NAA + 40 mgL− 1 AgNO3 + 40 mgL− 1 adenine sulphate respectively and incubated in the dark for 2 weeks. Shoot regeneration from the leaf explants was also observed within 4 weeks after inoculation in MS medium with 1 mgL− 1 BAP + 0.1 mgL− 1 NAA. Agrobacterium mediated genetic transformation was carried out successfully in callus cultures of H. indicus. The transformation efficiency was found to be 26%. The efficient shoot regeneration was observed within 4 weeks and transformation study can be further applied for over expression of biosynthetic genes to enhance the bioactive components that have immense significance in pharmaceutical, nutraceutical and cosmetic industries.
Thousands of domestic and public supply wells face failure despite groundwater sustainability reform in California’s Central Valley
Authors: Bostic Darcy , Mendez-Barrientos Linda , Pauloo Richard , Dobbin Kristin , MacClements Victoria 
Published: June 2023

Abstract
Declining groundwater levels are causing wells to run dry, increasing water and food insecurity, and often acutely impacting marginalized communities across the world. Despite the ubiquitousness and severity of impacts, groundwater research has focused on piecemeal policy instruments or quantified groundwater depletion. How sustainability definitions shape the fate of sustainability reforms and their outcomes is unexplored. Here, we examine one of the world’s large-scale sustainability reforms, the California Sustainable Groundwater Management Act (SGMA), and estimate the impact of sustainability criteria on well failure. We show that proposed sustainability measures accommodate business as usual groundwater level decline, impacting over 10,000 drinking water wells, and 14,000-120,000 domestic well users who could lose access to their source of drinking water. These findings highlight the necessity of carefully and critically engaging in the evaluation of sustainability definitions and their operationalization to prevent detrimental impacts, like threats to household and municipal water supply.
An Acute Increase in TGF beta Increases Permeability of 70 kDa Molecular Tracer from the Heart to Cells Inhabiting Tissue Compartments of the Osteoarthritic Guinea Pig Knee Joint
Authors: Ngo Lucy , Tate Melissa L. Knothe 
Published: June 2023

Abstract
A recent pilot study showed that a spike in the inflammatory cytokines TNF-α or TGF-β, delivered via the heart in mature Dunkin-Hartley guinea pigs with osteoarthritis, results in diminished barrier function between the vascular (blood vessels) and respective tissue compartments of bone and muscle [1]. Here we aim to probe effects of TNF-α and TGF-β on barrier function at the vascular interface in different tissue compartments of the knee joint using the same animal model, and with higher resolution imaging modalities including confocal and electron microscopy. First we quantified the intensity of a fluorescent-tagged 70 kDa tracer, similar in size to albumin, the largest transporter protein in the blood, in tissue compartments of bone (periosteum, marrow space, compact bone and epiphyseal bone) and cartilage (articular cartilage, calcified cartilage, and the interface between, i.e. the epiphyseal line), as well as at sites of tendon attachment to bone. We then examined tracer presence and intensity in the respective pericellular and extracellular matrix zones of bone and cartilage. Confirming the previous study, acute exposure to both cytokines reduced barrier function (increased permeability) at vascular interfaces with tissue compartments of the knee joint, with a significant effect in the TGF-β group. Furthermore, this increase in permeability, observed at the length scale of tissue compartments, was also observed at the cellular length scale; the observation of pericellular transport of the albumin-sized molecules to osteocytes contrasts with previous observations of barrier function in healthy, untreated animals and is indicative of reduced barrier function in pericellular regions of cytokine treated animals. The acute, cytokine-induced changes to molecular transport between and within the tissue compartments of the joint, and their respective cellular inhabitants, is of particular relevance for a systems biology understanding of articular joint physiology and interactions between the vascular, musculoskeletal and immune systems, providing impetus for further studies.
A New Sensitivity Based Mapping Scheme for Topology Optimization of Graded TPMS Designs
Authors: Parlayan Onur , Ozdemir Mirhan , Gayir Cemal Efe , Simsek Ugur , Kiziltas Gullu 
Published: June 2023

Abstract
Graded TPMS topologies display excellent mechanical and thermal properties. Design schemes targeting optimal performance exist, but final reconstructed designs still suffer from performance degradation. To overcome this challenge, we propose an automated design framework based on the integration of a homogenization-based topology optimization scheme and a new mapping strategy. Optimized designs obtained using a modified SIMP technique are reconstructed as graded gyroid structures. Unlike mapping strategies using relative density values prior to TPMS infill, for the first time we make use of readily available adjoint sensitivities for mapping optimal densities to graded gyroid structures. Results show that the proposed framework delivers performance preserving graded designs when compared to original optimized designs obtained using OPTISTRUCT and superior performance in comparison to standard density-based mapping methods. The resulting graded design is manufactured using additive manufacturing and three-point bending tests are performed confirming simulation results and demonstrating the applicability of presented design scheme.