bluuebunny/crossref_metadata_2025_split huggingface dataset:
ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment
Authors: Ponce Santiago , Cedrés Susana , Ricordel Charles , Isambert Nicolas , Viteri Santiago , Herrera-Juarez Mercedes , Martinez-Marti Alex , Navarro Alejandro , Lederlin Mathieu , Serres Xavier , Zugazagoitia Jon , Vetrhus Sylvia , Jaderberg Magnus , Hansen Thomas Birkballe , Levitsky Victor , Paz-Ares Luis 
Published: September 2023

BackgroundONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.MethodsIn this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.ResultsIn total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.ConclusionsONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.
Biallelic truncating variants inVGLL2cause syngnathia in humans
Authors: Agostini Valeria , Tessier Aude , Djaziri Nabila , Khonsari Roman Hossein , Galliani Eva , Kurihara Yukiko , Honda Masahiko , Kurihara Hiroki , Hidaka Kyoko , Tuncbilek Gokhan , Picard Arnaud , Konas Ersoy , Amiel Jeanne , Gordon Christopher T 
Published: September 2023

BackgroundSyngnathia is an ultrarare craniofacial malformation characterised by an inability to open the mouth due to congenital fusion of the upper and lower jaws. The genetic causes of isolated bony syngnathia are unknown.MethodsWe used whole exome and Sanger sequencing and microsatellite analysis in six patients (from four families) presenting with syngnathia. We used CRISPR/Cas9 genome editing to generatevgll2aandvgll4lgermline mutant zebrafish, and performed craniofacial cartilage analysis in homozygous mutants.ResultsWe identified homozygous truncating variants in vestigial-like family member 2 (VGLL2) in all six patients. Two alleles were identified: one in families of Turkish origin and the other in families of Moroccan origin, suggesting a founder effect for each. A shared haplotype was confirmed for the Turkish patients. TheVGLLfamily of genes encode cofactors of TEAD transcriptional regulators.Vgll2is regionally expressed in the pharyngeal arches of model vertebrate embryos, and morpholino-based knockdown ofvgll2ain zebrafish has been reported to cause defects in development of pharyngeal arch cartilages. However, we did not observe craniofacial anomalies invgll2aorvgll4lhomozygous mutant zebrafish nor in fish with double knockout ofvgll2aandvgll4l. InVgll2−/−mice, which are known to present a skeletal muscle phenotype, we did not identify defects of the craniofacial skeleton.ConclusionOur results suggest that although loss ofVGLL2leads to a striking jaw phenotype in humans, other vertebrates may have the capacity to compensate for its absence during craniofacial development.
Time to TAVI: streamlining the pathway to treatment
Authors: Hewitson Lynsey Jane , Cadiz Suzane , Al-Sayed Sameeha , Fellows Sarah , Amin Alaaeldin , Asimakopoulos George , Barnes Edward , Beale Andrew , Browne Suzy , Chandrasekaran Badrinathan , Dalby Miles , Foley Paul , Hawkins Mark , Haynes Douglas , Heng Ee Ling , Hyde Tom , Kabir Tito , Khavandi Ali , Mirsadraee Saeed , McCrea William , Petrou Mario , Senior Roxy , Smith David , Smith Robert , Spartera Marco , Wamil Malgorzata , Panoulas Vasileios , Rahbi Hazim 
Published: September 2023

IntroductionSevere aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI.MethodsThe centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed.ResultsMean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p<0.00001). The total pathway time from echocardiographic diagnosis to TAVI for the centre performing local workup was 89.9±67.6 days, which was also significantly shorter than referral to TAVI time from all other centres (p<0.003). Centres without local workup had a significantly lower percentage of patients accepted for TAVI (49.5% vs 97.8%, p<0.00001).DiscussionA novel TAVI pathway with emphasis on local workup within a non-surgical centre significantly reduced both the time to TAVI and rejection rates from a Heart Valve Centre. If adopted across the other centres, this approach may help improve access to TAVI.
On stability issues of the HEOM method
Authors: Krug Malte , Stockburger Jürgen 
Published: September 2023

AbstractThe Hierarchical Equations of Motion (HEOM) method has become one of the cornerstones in the simulation of open quantum systems and their dynamics. It is commonly referred to as a non-perturbative method. Yet, there are certain instances, where the necessary truncation of the hierarchy of auxiliary density operators seems to introduce errors which are not fully controllable. We investigate the nature and causes of this type of critical error both in the case of pure decoherence, where exact results are available for comparison, and in the spin-boson system, a full system-reservoir model. We find that truncating the hierarchy to any finite size can be problematic for strong coupling to a dissipative reservoir, in particular when combined with an appreciable reservoir memory time.
Entanglement analysis of photoinduced $$\eta$$-pairing states
Authors: Ejima Satoshi , Lange Florian , Fehske Holger 
Published: September 2023

AbstractSimulating the von Neumann and second-order Rényi entropies of driven Mott insulators, we examine the entanglement dynamics of the $$\eta$$
η
-pairing state in the one-dimensional half-filled Hubbard model after pulse irradiation. Corresponding data are obtained by means of the infinite time-evolving block decimation technique directly in the thermodynamic limit. For optimal pump-pulse parameters the temporal course of the entanglement entropies shows the characteristic entanglement growth due to the increase of $$\eta$$
η
-pairing correlations.
Regularity Conditions for Iterated Shuffle on Commutative Regular Languages
Authors: Hoffmann Stefan 
Published: September 2023

We introduce the class [Formula: see text] of commutative regular languages that is a positive variety closed under binary shuffle and iterated shuffle (also called shuffle closure). This class arises out of the known positive variety [Formula: see text] by superalphabet closure, an operation on positive varieties we introduce and describe in the present work. We state alternative characterizations for both classes, that the shuffle of any language (resp. any commutative language) with a language from [Formula: see text] gives a regular language (resp. a language from [Formula: see text]) and that [Formula: see text] is also closed for iterated shuffle. Then we introduce the wider class [Formula: see text] that is also closed under iterated shuffle, but fails to be closed for binary shuffle and is not a positive variety. Furthermore, we give an automata-theoretical characterization for the regularity of the iterated shuffle of a regular commutative language. We use this result to show that, for a fixed alphabet, it is decidable in polynomial time whether the iterated shuffle of a commutative regular language given by a deterministic automaton is regular. Lastly, we state some normal form results for the aperiodic, or star-free, commutative languages and the commutative group languages.
Effects of Daphnetin on Experimental Acute Pancreatitis-Associated Acute Lung Injury in Mice
Authors: Chen Tao , Chen Ou , Zhao Ming , Chen Xia 
Published: September 2023

Background and Aim. Daphnetin, an active monomer ingredient extracted from D. marginata, is proved to have anti-inflammatory and antioxidant effect. The aim of this study is to explore the effect and possible mechanism of daphnetin on acute lung injury (ALI) associated with acute pancreatitis (AP) in mice. Methods. A total of 36 mice were randomly assigned into three groups: control group, AP group, and daphnetin group. The mouse model of AP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 6 and 12 h after daphnetin treatment, respectively. The pathological changes of lung and pancreas were determined by hematoxylin-eosin staining and the pathological scores. Levels of IL-1β, IL-6, and TNF-α in serum and lung and the activity of myeloperoxidase (MPO) in lung tissue homogenate were detected by ELISA. The protein level of toll-like receptor 4 (TLR4), phospho-nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor-kappa B p65 (NF-κB p65), and hypoxia-inducible factor 1 alpha (HIF-1α) in the lung was detected by Western blot. Results. Results showed extensive neutrophil infiltration, hemorrhage, and edema in the pancreas tissues or lung tissues in mice with AP. The daphnetin treatment improved pathological changes in the lung tissues of AP mice. The MPO activity and the levels of inflammatory cytokines including IL-1β, TNF-α, and IL-6 of lung tissues and serum in the AP group were significantly higher than those in the control group (

P

< 0.05), and daphnetin intervention significantly reversed the changes (

P

< 0.05). Compared with the control mice, the protein levels of TLR4, p-NF-κB p65, and HIF-1α were significantly higher in the lung tissue of the AP mice (

P

< 0.05), while daphnetin treatment decreased these protein expression levels. No significant difference was observed in the NF-κB p65 level among control, AP, and daphnetin groups (

P

> 0.05). Conclusions. Daphnetin exerted a protective effect on the acute lung injury induced by SAP in mice. The mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α pathway to reduce the release of inflammatory factors.
Relation between Baroclinity, Horizontal Vorticity, and Mesocyclone Evolution in the 6–7 April 2018 Monroe, Louisiana, Tornadic Supercell during VORTEX-SE
Authors: Hosek Michael J. , Ziegler Conrad L. , Biggerstaff Michael I. , Murphy Todd A. , Wang Zhien 
Published: September 2023

Abstract
This case study analyzes a tornadic supercell observed in northeast Louisiana as part of the Verification of the Origins of Rotation in Tornadoes Experiment Southeast (VORTEX-SE) on 6–7 April 2018. One mobile research radar (SR1-P), one WSR-88D equivalent (KULM), and two airborne radars (TAFT and TFOR) have sampled the storm at close proximity for ∼70 min through its mature phase, tornadogenesis at 2340 UTC, and dissipation and subsequent ingestion into a developing MCS segment. The 4D wind field and reflectivity from up to four Doppler analyses, combined with 4D diabatic Lagrangian analysis (DLA) retrievals, has enabled kinematic and thermodynamic analysis of storm-scale boundaries leading up to, during, and after the dissipation of the NWS-surveyed EF0 tornado. The kinematic and thermodynamic analyses reveal a transient current of low-level streamwise vorticity leading into the low-level supercell updraft, appearing similar to the streamwise vorticity current (SVC) that has been identified in supercell simulations and previously observed only kinematically. Vorticity dynamical calculations demonstrate that both baroclinity and horizontal stretching play significant roles in the generation and amplification of streamwise vorticity associated with this SVC. While the SVC does not directly feed streamwise vorticity to the tornado–cyclone, its development coincides with tornadogenesis and an intensification of the supercell’s main low-level updraft, although a causal relationship is unclear. Although the mesoscale environment is not high-shear/low-CAPE (HSLC), the updraft of the analyzed supercell shares some similarities to past observations and simulations of HSLC storms in the Southeast United States, most notably a pulse-like updraft that is maximized in the low- to midlevels of the storm.

Significance Statement
The purpose of this study is to analyze the airflow and thermodynamics of a highly observed tornado-producing supercell. While computer simulations can provide us with highly detailed looks at the complicated evolution of supercells, it is rare, due to the difficulty of data collection, to collect enough data to perform a highly detailed analysis on a particular supercell, especially in the Southeast United States. We identified a “current” of vorticity—rotating wind—that develops at the intersection of the supercell’s rain-cooled outflow and warm inflow, similar to previous simulations. This vorticity current develops and feeds the storm’s updraft as its tornado develops and the storm intensifies, although it does not directly enter the tornado.
The impact of housing-price-related indices on suicide rates in Taiwan
Authors: Chen Yi-Lung , Li Dian-Jeng , Chen Ying-Yeh , Yen Cheng-Fang 
Published: September 2023

Background: While certain socioeconomic factors have been studied in relation to suicide, housing-price-related indexes have rarely been investigated. Aims: This article aims to examine the impact of housing-price-related indexes on suicide rates in the general population of Taiwan, a country with high housing costs and suicide rates. Methods: The study utilized three national housing-price-related indexes from 2012 to 2019: (1) housing price index, (2) housing price to income ratio, and (3) housing rental index. Cause of Death Data was employed to calculate suicide rate. A linear regression model with autoregressive errors was used to analyze the association between housing-price-related indexes and suicide rates among different sex and age groups. Results: The findings revealed that higher housing rental index values were associated with increased suicide rates in young and middle-aged adults compared to the elderly population, regardless of sex. However, this association was not observed with the other two housing-price-related indexes (i.e. housing price index and housing price to income ratio). Conclusion: These results offer valuable insights for policymakers, mental health professionals, and housing advocates to improve housing affordability and reduce the burden of suicide in the general population, particularly among younger generations.
Short stature is a risk factor for heart transplant morbidity and mortality
Authors: Weingarten Noah , Iyengar Amit , Patel Mrinal , Kim Samuel T , Shin Max , Atluri Pavan 
Published: September 2023

Background Short stature is associated with mortality after cardiac surgery and may increase size mismatch risk among transplant recipients. Yet, stature's impact on heart transplant outcomes is not well-characterized. Methods The Scientific Registry of Transplant Recipients was queried for data on all adult heart transplants in the United States from 2000 to 2022. Recipients were stratified into five cohorts by sex-corrected stature. Morbidity was assessed with Kruskal–Wallis and chi-squared tests. Mortality was analyzed using Kaplan–Meier estimation. Risk factors for mortality were assessed with multivariable Cox regression. Results Among 43,420 transplant recipients, 5321 (12.2%) had short stature (females >4′11″ & ≤5′1″; males >5′4″ & ≤5′7″) and 765 (1.8%) had very short stature (females ≤4′11″; males ≤5′4″). Very short stature patients had higher waitlist status (1A and 1), more congenital heart disease, and received more oversized donor hearts than other cohorts (all p < 0.05). Very short stature patients had decreased 30-day, 1-, 5-, and 10-year survival (94.6%, 84.3%, 69.3% and 52.5%, respectively, all p < 0.001), but less acute rejection ( p = 0.005) and comparable stroke rates ( p = 0.107). On multivariable regression adjusting for congenital heart disease and oversized donor hearts, very short and short stature were associated with 10-year mortality (hazard ratios: 1.40 and 1.12, respectively, both p < 0.005). Conclusions Short stature confers increased mortality risk for heart transplant recipients and merits inclusion in prognostic models.
The value of multimodal functional magnetic resonance imaging in differentiating p53abn from p53wt endometrial carcinoma
Authors: Shifeng Tian , Yue Wang , Wen Zhu , Lihua Chen , Nan Wang , Liangjie Lin , Ailian Liu 
Published: September 2023

Background Endometrial carcinoma (EC) is the sixth most common cancer in women. P53 gene expression in patients with endometrial cancer can predict the efficacy and prognosis of patients with neoadjuvant therapy. Purpose To explore the value of multimodal magnetic resonance imaging (MRI) in differentiating p53 abnormal (p53abn) from p53 wild-type (p53wt) EC. Material and Methods Data from 47 EC patients, including 14 p53abn cases and 33 p53wt cases, were retrospectively analyzed. The preoperative MRI sequences included amide proton transfer weighted (APTw) imaging, T2 mapping, mDIXON-Quant imaging and diffusion-weighted imaging (DWI). After post-processing, APT, T2, transverse relaxation rate (R2*), fat fraction (FF) and apparent diffusion coefficient (ADC) maps were obtained. The APT, T2, R2*, FF and ADC values for lesions of the two groups of cases were measured by two observers who were blind to the pathological data. Results The APT value and R2* value in the p53abn group were higher than those in the p53wt group, while the ADC value was lower (all P < 0.05). There was no statistically significant difference in T2 value and FF value between the two groups (all P > 0.05). The area under curve of APT, R2*, ADC and combined APT + R2*+ADC values for identification of p53abn and p53wt EC were 0.739, 0.689, 0.718 and 0.820, respectively (all P > 0.05). Conclusion APTw, mDIXON-Quant and DWI techniques can be usedfor quantitative identification of p53abn and p53wt EC. The multimodal MRI provides a new way for preoperative quantitative evaluation of EC molecular typing, which has certain clinical application value.
Prediction of Neonatal Hyperbilirubinemia from Cord Blood Bilirubin and Cord Blood Albumin Ratio in Healthy Term Indian Neonates
Authors: Kosigi Anusha , R. Gokul Krishnan 
Published: September 2023

Background Neonatal jaundice affects 85% term and most of the preterm infants. Unconjugated bilirubin is bound by albumin, which promotes its transit and lessens bilirubin toxicity, thereby serves as early determinant for the risk of pathological hyperbilirubinemia among neonates. Present study was undertaken to know the utility of cord blood bilirubin (CBB), cord blood albumin (CBA), and their ratio at time of birth for the development of significant neonatal hyperbilirubinemia. Objectives To evaluate CBB/CBA ratio at the time of delivery as potential predictive factor for the development of significant neonatal hyperbilirubinemia and compare this with CBB and CBA alone. Study Design Prospective observational analytical study. Participants Total 178 inborn term neonates delivered during 3-month time period (22nd October, 2022–22nd January, 2023). Interventions Cord blood sample was collected at birth for CBA, CBB, and blood grouping/phenotyping. Transcutaneous bilirubin (TCB) measurements were done 12 hourly in all babies for the first 7 days of life/till discharge, and also in the case of development of significant clinical jaundice. For TCB values above cut-off, serum total bilirubin was done and need for phototherapy (PT) decided based on cut offs suggested in AAP 2004 nomograms. Results Cut-off values of CBB and CBA as obtained by the receiver operating characteristic (ROC) curves were 1.98 mg/dL and 3.14 g/dL, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CBB were 83.33%, 63.15%, 41.66%, and 92.30%, while for CBA, 41.66%, 71.05%, 31.25%, and 79.41%. CBB/CBA cutoff ratio was 0.630 with 91.66% sensitivity, 86.84% specificity, 68.75% PPV, and 97.05% NPV. Conclusions Compared to CBB and CBA alone, CBB/CBA ratio has greater sensitivity, specificity, PPV, and NPV and it may serve as a better indicator for prediction of pathological hyperbilirubinemia in neonates.
Predictive factors of development of dysthyroid optic neuropathy among individuals with thyroid-eye disease
Authors: Kemchoknatee Parinee , Thongsawangchai Nicha , Srisombut Thansit , Tangon Duanghathai , Chantra Somporn 
Published: September 2023

Purpose Dysthyroid optic neuropathy (DON) is a severe visual loss condition in thyroid eye disease (TED). This study aimed to identify factors affecting moderate-to-severe TED or DON in Thai populations. Methods We retrospectively reviewed the records of 230 TED patients at Rajavithi Hospital between January 1, 2017, and October 31, 2022. Results Mild, moderate-to-severe TED, and DON were found in 60.43%, 22.61%, and 16.96% of participants, respectively. Female predominance was noted in all groups. The proportion of older age, hyperthyroidism, current smokers, and type 2 diabetes mellitus (T2DM) participants were significantly higher in the DON group. Multivariable logistic-regression analysis revealed that hyperthyroidism and current smoking significantly increased the risk of developing moderate-to-severe TED (OR = 3.001, p = 0.010, and OR = 4.153, p = 0.015, respectively). Exophthalmos was the strongest predictor (OR = 6.834, p < 0.001). Regarding DON risk factors, older age (≥55 years) had OR = 3.206 ( p = 0.003), hyperthyroidism had OR = 3.228 ( p = 0.005), and being a current smoker had OR = 3.781 ( p = 0.011). T2DM posed the greatest risk of DON development (OR = 4.111, p = 0.004). Conclusions Hyperthyroidism and current smoking are significant risk factors for moderate-to-severe TED and DON. TED patients with diabetes mellitus or older age should be closely monitored and informed about their risk of developing DON.