bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of spectacle refraction uncertainties with discrete IOL power steps and manufacturing tolerances according to ISO using a Monte Carlo model
Authors: Langenbucher Achim , Szentmáry Nóra , Cayless Alan , Bolz Matthias , Hoffmann Peter , Wendelstein Jascha 
Published: July 2023

PurposeThe purpose of this study was to develop a concept for predicting the effects of both discrete intraocular lens (IOL) power steps (PS) and power labelling tolerances (LT) on the uncertainty of the refractive outcome (REFU).DesignRetrospective non-randomised cross-sectional Monte Carlo simulation study.MethodsWe evaluated a dataset containing 16 669 IOLMaster 700 preoperative biometric measurements. The PS and the delivery range of two modern IOLs (Bausch and Lomb enVista and Alcon SA60AT) were considered for this Monte Carlo simulation. The uncertainties from PS or LT were assumed to be normally distributed according to ±½ the IOL PS or the ISO 11979 LT. REFU was recorded and analysed for all simulations.ResultsWith both lenses the REFU from discrete PS ranged from 0.11 to 0.12 dpt. Due to the larger PS for low/high power lenses with the enVista/SA60AT, REFU is more dominant in initially myopic/hyperopic eyes. REFU from LT ranged from 0.18 to 0.19 dpt for both lenses. Since LT increases stepwise with IOL power, REFU is more prevalent in initially hyperopic eyes requiring high IOL power values, and for lenses with a wide delivery range towards higher powers.ConclusionsSince surgeons and patients are typically aware of the effect of discrete PS on REFU, these might be tolerated in cataract surgery. However, REFU resulting from LT is inevitable while the true measured IOL power is not reported on the package, leading to background noise in postoperative achieved refraction.
Implications of rapid population growth on survey design and HIV estimates in the Rakai Community Cohort Study (RCCS), Uganda
Authors: Khalifa Aleya , Ssekubugu Robert , Lessler Justin , Wawer Maria , Santelli John S , Hoffman Susie , Nalugoda Fred , Lutalo Tom , Ndyanabo Anthony , Ssekasanvu Joseph , Kigozi Godfrey , Kagaayi Joseph , Chang Larry W , Grabowski Mary Kathryn 
Published: July 2023

ObjectiveSince rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia.Design, setting and participantsData were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15–49 years who were censused from 2019 to 2020.MeasuresWe fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates.ResultsOf the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)—somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15–24 years was 4.9% (95% CI: 3.6% to 6.1%)—significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25–49 years was 15.0% (95% CI: 13.3% to 16.4%)—significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%).ConclusionsExclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected.
How and why educational interventions work to increase knowledge of delirium among healthcare professionals in nursing homes: a protocol for a realist review
Authors: Molitor Vincent , Busse Theresa Sophie , Giehl Chantal , Lauer Romy , Otte Ina Carola , Vollmar Horst Christian , Thürmann Petra , Holle Bernhard , Palm Rebecca 
Published: July 2023

BackgroundDelirium is a neuropathological condition that impairs cognitive performance, attention and consciousness and can be potentially life-threatening. Nursing home residents are particularly vulnerable to developing delirium, but research thus far tends to focus on the acute hospital setting. Healthcare professionals (HCPs) working in nursing homes seem to be little aware of delirium. To improve healthcare for affected or at-risk individuals, increasing knowledge among HCPs is highly relevant. Using the realist review method helps to understand how and why an educational intervention for HCPs on delirium in nursing homes works.Methods and analysisIn accordance with the Realist And Meta-narrative Evidence Syntheses: Evolving Standards publication standards for realist syntheses, the review process will include the following five steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis and (5) development of an initial programme theory. The literature search will be conducted in the databases Medline (PubMed), CINAHL (Ebsco), Scopus, Web of Science, GeroLit and Carelit. Additional focuses are on snowballing techniques, hand research and grey literature. Studies of any design will be included to develop the initial programme theory. The literature will be selected by two researchers independently. In addition, the experiences of HCPs from nursing homes will be reflected in group discussions. To this end, Context–Mechanism–Outcome configurations (CMOcs) will be established to develop an initial programme theory.Ethics and disseminationThe results will be disseminated within the scientific community. For this purpose, presentations at scientific conferences as well as publications in peer-reviewed journals are scheduled. In the next step, the CMOcs could serve for the development of a complex educational intervention to increase the knowledge of HCPs on delirium in nursing homes.Registration detailsThis protocol has been registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/HTFU4).
Integrating RNA-Seq into genome sequencing workflow enhances the analysis of structural variants causing neurodevelopmental disorders
Authors: Riquin Kevin , Isidor Bertrand , Mercier Sandra , Nizon Mathilde , Colin Estelle , Bonneau Dominique , Pasquier Laurent , Odent Sylvie , Le Guillou Horn Xavier Maximin , Le Guyader Gwenaël , Toutain Annick , Meyer Vincent , Deleuze Jean-François , Pichon Olivier , Doco-Fenzy Martine , Bézieau Stéphane , Cogné Benjamin 
Published: July 2023

BackgroundMolecular diagnosis of neurodevelopmental disorders (NDDs) is mainly based on exome sequencing (ES), with a diagnostic yield of 31% for isolated and 53% for syndromic NDD. As sequencing costs decrease, genome sequencing (GS) is gradually replacing ES for genome-wide molecular testing. As many variants detected by GS only are in deep intronic or non-coding regions, the interpretation of their impact may be difficult. Here, we showed that integrating RNA-Seq into the GS workflow can enhance the analysis of the molecular causes of NDD, especially structural variants (SVs), by providing valuable complementary information such as aberrant splicing, aberrant expression and monoallelic expression.MethodsWe performed trio-GS on a cohort of 33 individuals with NDD for whom ES was inconclusive. RNA-Seq on skin fibroblasts was then performed in nine individuals for whom GS was inconclusive and optical genome mapping (OGM) was performed in two individuals with an SV of unknown significance.ResultsWe identified pathogenic or likely pathogenic variants in 16 individuals (48%) and six variants of uncertain significance. RNA-Seq contributed to the interpretation in three individuals, and OGM helped to characterise two SVs.ConclusionOur study confirmed that GS significantly improves the diagnostic performance of NDDs. However, most variants detectable by GS alone are structural or located in non-coding regions, which can pose challenges for interpretation. Integration of RNA-Seq data overcame this limitation by confirming the impact of variants at the transcriptional or regulatory level. This result paves the way for new routinely applicable diagnostic protocols.
Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma
Authors: Peel Adam , Wang Ran , Ahmed Waqar , White Iain , Wilkinson Maxim , Loke Yoon K , Wilson Andrew M , Fowler Stephen J 
Published: July 2023

BackgroundInhaled mannitol provokes bronchoconstrictionviamediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin.MethodsParticipants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography–mass spectrometry.ResultsForty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge.ConclusionInhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.
Fluid evolution and ore genesis of Huaduoshan Cu–Mo prospect, Duobaoshan ore field, northeastern China: evidence from fluid inclusions, H–O–S–Pb isotopes, geochronology, and geochemistry
Authors: Li Hao-ming , Wang Ke-yong , Geng Jian-zhen , Tang Wen-hao , Sun Qing-fei , Wang Xue 
Published: July 2023

The Huaduoshan Cu–Mo prospect is in the Duobaoshan orefield, northeast China. The Cu–Mo mineralization occurs in the granodiorites as veinlet-disseminated. The ore-forming process can be divided into four mineralization stages: (I) quartz–pyrite–magnetite; (II) quartz–pyrite–chalcopyrite ± molybdenite; (III) quartz–pyrite–molybdenite–chalcopyrite–sphalerite; and (IV) quartz–calcite–minor pyrite. Liquid-rich two-phase aqueous (L-type), vapour-rich aqueous (V-type) and daughter-minerals three-phase (S-type) fluid inclusions (FIs) were identified at Huaduoshan. The last two types of FIs are absent in stages III and IV. The homogenization temperatures of FIs from stages I to IV are 375–438, 335–378, 283–335, and 223–267 ℃, with corresponding salinities of 2.4–50.4, 2.1–44.9, 2.7–10.1, and 1.7–7.3 wt. % NaCl eqv., respectively. The H–O isotope data of quartz in stages I (δ18OH2O = 6.1–8.0‰, δDH2O = −102.4–−94.6‰) show a magmatic origin of ore-forming fluid; the decreasing δ18OH2O (−6.8–3.2‰) and δDH2O (−117.1–−98.5‰) values of quartz in stage II–IV show the fluid mixing with meteoric water. The S–Pb isotopic values (δ34S = −2.7–0.8; 206Pb/204Pb = 18.236–18.599; 207Pb/204 Pb = 15.504–15.557; 208Pb/204Pb = 37.816–38.629) of pyrites indicate that the ore-forming materials are of magmatic origin. Fluid boiling and mixing may be the major mechanisms of ore precipitation. Zircon U–Pb age (172.1 ± 0.5 Ma) and geochemical data indicate that the ore-related granodiorites are I-type rocks formed in the subduction setting of the Paleo-Pacific Ocean Plate in the Early–Middle Jurassic. In conclusion, we propose that the Huaduoshan Cu–Mo prospect is a porphyry deposit and has potential for further exploration of porphyry Cu–Mo prospecting.
Erratum: QED-based derivation of the general forms of the relativistic Doppler effect and of the relativistic aberration for uniformly rotating frames and for uniformly accelerated frames
Authors: Sfarti A. 
Published: July 2023

The current paper corrects an error that occurred in a previously published paper. The error starts from Sec. 3 , Eq. ( 3.2 ) whereby the scalar value of the wave-vector needs to be corrected. The net result is that the final formulas for the relativistic Doppler effect and for aberration get simplified. The source of the error is an extra multiplication factor by “[Formula: see text]”. We need to replace the incorrect [Formula: see text] in [A. Sfarti, MPLA 37, 2250238 (2022)] with the correct expression [Formula: see text].
Sag-Free Initialization for Strand-Based Hybrid Hair Simulation
Authors: Hsu Jerry , Wang Tongtong , Pan Zherong , Gao Xifeng , Yuksel Cem , Wu Kui 
Published: July 2023

Lagrangian/Eulerian hybrid strand-based hair simulation techniques have quickly become a popular approach in VFX and real-time graphics applications. With Lagrangian hair dynamics, the inter-hair contacts are resolved in the Eulerian grid using the continuum method, i.e., the MPM scheme with the granular Drucker-Prager rheology, to avoid expensive collision detection and handling. This fuzzy collision handling makes the authoring process significantly easier. However, although current hair grooming tools provide a wide range of strand-based modeling tools for this simulation approach, the crucial sag-free initialization functionality remains often ignored. Thus, when the simulation starts, gravity would cause any artistic hairstyle to sag and deform into unintended and undesirable shapes.
This paper proposes a novel four-stage sag-free initialization framework to solve stable quasistatic configurations for hybrid strand-based hair dynamic systems. These four stages are split into two global-local pairs. The first one ensures static equilibrium at every Eulerian grid node with additional inequality constraints to prevent stress from exiting the yielding surface. We then derive several associated closed-form solutions in the local stage to compute segment rest lengths, orientations, and particle deformation gradients in parallel. The second global-local step solves along each hair strand to ensure all the bend and twist constraints produce zero net torque on every hair segment, followed by a local step to adjust the rest Darboux vectors to a unit quaternion. We also introduce an essential modification for the Darboux vector to eliminate the ambiguity of the Cosserat rod rest pose in both initialization and simulation. We evaluate our method on a wide range of hairstyles, and our approach can only take a few seconds to minutes to get the rest quasistatic configurations for hundreds of hair strands. Our results show that our method successfully prevents sagging and has minimal impact on the hair motion during simulation.
Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors
Authors: Vieito Maria , Moreno Victor , Spreafico Anna , Brana Irene , Wang Judy S. , Preis Meir , Hernández Tatiana , Genta Sofia , Hansen Aaron R. , Doger Bernard , Galvao Vladimir , Lenox Laurie , Brown Regina J. , Kalota Anna , Mehta Jaydeep , Pastore Friederike , Patel Bharvin , Mistry Pankaj , Gu Junchen , Lauring Josh , Patel Manish R. 
Published: July 2023

AbstractPurpose:In this first-in-human, Phase 1, open-label, multicenter study, we evaluated JNJ-64619178, a selective and potent PRMT5 inhibitor, in patients with advanced malignant solid tumors or non-Hodgkin lymphomas (NHL). The primary objective was to evaluate the safety and to identify a recommended Phase 2 dose (RP2D) of JNJ-64619178.Patients and Methods:Adult patients with treatment-refractory advanced solid tumors or NHL and measurable disease received escalating doses of JNJ-64619178 following two schedules (Schedule A: 14 days on/7 days off; Schedule B: every day on a 21-day cycle). Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.Results:Ninety patients received JNJ-64619178. Thrombocytopenia was identified as the only dose-limiting toxicity. JNJ-64619178 showed dose-proportional PK and robust target engagement, as measured by plasma symmetric dimethylarginine, across all dose levels. The objective response rate was 5.6% (5 of 90). Patients with adenoid cystic carcinoma (ACC) had an ORR of 11.5% (3 of 26) and a median progression-free survival of 19.1 months.Conclusions:JNJ-64619178 demonstrated manageable dose-dependent toxicity and preliminary evidence of antitumor activity in ACC and other tumor types. Plasma exposure was dose dependent, and target inhibition was maintained with intermittent and continuous dosing. On the basis of safety, clinical activity, PK, and PD findings, two provisional RP2Ds were selected: 1.5 mg intermittently and 1.0 mg once daily. Aside from ACC, clinical benefit was limited, and biomarkers to enrich for responsiveness to PRMT5 inhibition will be needed for further development.
Prognostic Markers of DNA Methylation and Next-Generation Sequencing in Progressive Glioblastoma from the EORTC-26101 Trial
Authors: Kessler Tobias , Schrimpf Daniel , Doerner Laura , Hai Ling , Kaulen Leon D. , Ito Jakob , van den Bent Martin , Taphoorn Martin , Brandes Alba A. , Idbaih Ahmed , Dômont Julien , Clement Paul M. , Campone Mario , Bendszus Martin , von Deimling Andreas , Sahm Felix , Platten Michael , Wick Wolfgang , Wick Antje 
Published: July 2023

Abstract

Purpose:
The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma.

Experimental Design:
We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival.

Results:
Of patients' samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment.

Conclusions:
Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.
Preclinical Development of Brain Permeable ERβ Agonist for the Treatment of Glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K. 
Published: July 2023

Abstract
Glioblastoma (GBM) is the most prevalent and aggressive type of adult brain tumors with low 5-year overall survival rates. Epidemiologic data suggest that estrogen may decrease brain tumor growth, and estrogen receptor beta (ERβ) has been demonstrated to exert antitumor functions in GBM. The lack of potent, selective, and brain permeable ERβ agonist to promote its antitumor action is limiting the therapeutic promise of ERβ. In this study, we discovered that Indanone and tetralone-keto or hydroxyl oximes are a new class of ERβ agonists. Because of its high activity in ERβ reporter assays, specific binding to ERβ in polar screen assays, and potent growth inhibitory activity in GBM cells, CIDD-0149897 was discovered as a possible hit by screening a library of compounds. CIDD-0149897 is more selective for ERβ than ERα (40-fold). Treatment with CIDD-0149897 markedly reduced GBM cell viability with an IC50 of ∼7 to 15 μmol/L, while having little to no effect on ERβ-KO cells and normal human astrocytes. Further, CIDD-0149897 treatment enhanced expression of known ERβ target genes and promoted apoptosis in established and patient-derived GSC models. Pharmacokinetic studies confirmed that CIDD-0149897 has systemic exposure, and good bioavailability in the brain. Mice tolerated daily intraperitoneal treatment of CIDD-0149897 (50 mg/kg) with a 7-day repeat dosage with no toxicity. In addition, CIDD-0149897 treatment significantly decreased tumor growth in U251 xenograft model and extended the survival of orthotopic GBM tumor-bearing mice. Collectively, these findings pointed to CIDD-0149897 as a new class of ERβ agonist, offering patients with GBM a potential means of improving survival.
Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma
Authors: Shinada Masahiro , Kato Daiki , Motegi Tomoki , Tsuboi Masaya , Ikeda Namiko , Aoki Susumu , Iguchi Takaaki , Li Toshio , Kodera Yuka , Ota Ryosuke , Hashimoto Yuko , Takahashi Yosuke , Chambers James , Uchida Kazuyuki , Kato Yukinari , Nishimura Ryohei , Nakagawa Takayuki 
Published: July 2023

AbstractMucosal melanoma metastasizes at an early stage of the disease in human and dog. We revealed that overexpression of podoplanin in tumor invasion fronts (IF) was related to poor prognosis of dogs with mucosal melanoma. Moreover, podoplanin expressed in canine mucosal melanoma cells promotes proliferation and aggressive amoeboid invasion by activating Rho-associated kinase (ROCK)-myosin light chain 2 (MLC2) signaling. PDPN-ROCK-MLC2 signaling plays a role in cell-cycle arrest and cellular senescence escape as a mechanism for regulating proliferation. Podoplanin induces amoeboid invasion in the IFs of mouse xenografted tumor tissues, similar to canine mucosal melanoma clinical samples. We further identified that podoplanin expression was related to poor prognosis of human patients with mucosal melanoma, and human mucosal melanoma with podoplanin-high expression enriched gene signatures related to amoeboid invasion, similar to canine mucosal melanoma. Overall, we propose that podoplanin promotes canine and human mucosal melanoma metastasis by inducing aggressive amoeboid invasion and naturally occurring canine mucosal melanoma can be a novel research model for podoplanin expressing human mucosal melanoma.Implications:Podoplanin could be a new therapeutic target to restrict the metastatic dissemination of canine and human mucosal melanoma.