bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study
Authors: Español-Rego Marta , Fernández-Martos Carlos , Elez Elena , Foguet Carles , Pedrosa Leire , Rodríguez Nuria , Ruiz-Casado Ana , Pineda Estela , Cid Joan , Cabezón Raquel , Oliveres Helena , Lozano Miquel , Ginés Angels , García-Criado Angeles , Ayuso Juan Ramon , Pagés Mario , Cuatrecasas Miriam , Torres Ferràn , Thomson Timothy , Cascante Marta , Benítez-Ribas Daniel , Maurel Joan 
Published: September 2022

Abstract
Background
Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not in mismatch repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination has the potential to achieve synergistic effects.

Methods
This was a Phase I/II multicentric study with translational sub-studies, to evaluate the safety, pharmacodynamics and anti-tumor effects of Avelumab plus ADC vaccine in heavily pre-treated MSS mCRC patients. Primary objective was to determine the maximum tolerated dose and the efficacy of the combination. The primary end-point was 40% progression-free survival at 6 months with a 2 Simon Stage.

Results
A total of 28 patients were screened and 19 pts were included. Combined therapy was safe and well tolerated. An interim analysis (Simon design first-stage) recommended early termination because only 2/19 (11%) patients were disease free at 6 months. Median PFS was 3.1 months [2.1–5.3 months] and overall survival was 12.2 months [3.2–23.2 months]. Stimulation of immune system was observed in vitro but not clinically. The evaluation of basal RNA-seq noted significant changes between pre and post-therapy liver biopsies related to lipid metabolism and transport, inflammation and oxidative stress pathways.

Conclusions
The combination of Avelumab plus ADC vaccine is safe and well tolerated but exhibited modest clinical activity. Our study describes, for the first-time, a de novo post-therapy metabolic rewiring, that could represent novel immunotherapy-induced tumor vulnerabilities.
Critical Parameters for Singular Perturbation Reductions of Chemical Reaction Networks
Authors: Feliu Elisenda , Walcher Sebastian , Wiuf Carsten 
Published: September 2022

AbstractWe are concerned with polynomial ordinary differential systems that arise from modelling chemical reaction networks. For such systems, which may be of high dimension and may depend on many parameters, it is frequently of interest to obtain a reduction of dimension in certain parameter ranges. Singular perturbation theory, as initiated by Tikhonov and Fenichel, provides a path towards such reductions. In the present paper, we discuss parameter values that lead to singular perturbation reductions (so-called Tikhonov–Fenichel parameter values, or TFPVs). An algorithmic approach is known, but it is feasible for small dimensions only. Here, we characterize conditions for classes of reaction networks for which TFPVs arise by turning off reactions (by setting rate parameters to zero) or by removing certain species (which relates to the classical quasi-steady state approach to model reduction). In particular, we obtain definitive results for the class of complex-balanced reaction networks (of deficiency zero) and first-order reaction networks.
Temporal trends in incidence, patient characteristics, microbiology and in-hospital mortality in patients with infective endocarditis: a contemporary analysis of 86,469 cases between 2007 and 2019
Authors: Becher Peter Moritz , Goßling Alina , Fluschnik Nina , Schrage Benedikt , Seiffert Moritz , Schofer Niklas , Blankenberg Stefan , Kirchhof Paulus , Westermann Dirk , Kalbacher Daniel 
Published: September 2022

Abstract
Background
Infective endocarditis (IE) is characterized by high morbidity and mortality rates, despite recent improvements in diagnostics and treatment. We aimed to investigate incidence, clinical characteristics, and in-hospital mortality in a large-scale nationwide cohort.

Methods
Using data from the German Federal Bureau of Statistics, all IE cases in Germany between 2007 and 2019 were analyzed. Logistic regression models were fitted to assess associations between clinical factors and in-hospital mortality.

Results
In total, 86,469 patients were hospitalized with IE between 2007 and 2019. The mean age was 66.5 ± 14.7 years and 31.8% (n = 27,534/86,469) were female. Cardiovascular (CV) comorbidities were common. The incidence of IE in the German population increased from 6.3/100,000 to 10.2/100,000 between 2007 and 2019. Staphylococcus (n = 17,673/86,469; 20.4%) and streptococcus (n = 17,618/86,469; 20.4%) were the most common IE-causing bacteria. The prevalence of staphylococcus gradually increased over time, whereas blood culture-negative IE (BCNIE) cases decreased. In-hospital mortality in patients with IE was 14.9%. Compared to BCNIE, staphylococcus and Gram-negative pathogens were associated with higher in-hospital mortality. In multivariable analysis, factors associated with higher likelihood of in-hospital mortality were advanced age, female sex, CV comorbidities (e.g., heart failure, COPD, diabetes, stroke), need for dialysis or invasive ventilation, and sepsis.

Conclusions
In this contemporary cohort, incidence of IE increased over time and in-hospital mortality remained high (~ 15%). While staphylococcus and streptococcus were the predominant microorganisms, bacteremia with staphylococcus and Gram-negative pathogens were associated with higher likelihood of in-hospital mortality. Our results highlight the need for new preventive strategies and interventions in patients with IE.

Graphical abstract
Factors associated with change in the need for recovery and subjective listening effort in employees with hearing loss receiving aural rehabilitation
Authors: van der Hoek-Snieders Hanneke E. M. , Boymans Monique , Dreschler Wouter A. 
Published: September 2022

Abstract
Objective
Compared to normally-hearing employees, those with hearing loss suffer from higher Need For Recovery (NFR) after work. The aims of this study are to assess the NFR of employees with hearing loss before and after aural rehabilitation and to examine to what extent change in the NFR can be explained by changes in subjective listening effort, personal adjustments, communication strategies, auditory work demands, and self-reported hearing ability.

Methods
We included patients who received aural rehabilitation in two audiological centers in the Netherlands because of hearing complaints in their work situation. Outcomes were measured by questionnaires at baseline and 3 month follow-up. The NFR before and after the rehabilitation was compared with a t test. Hierarchical multiple analyses were performed.

Results
In total, 60 patients (aged 22–63, working hours ≥8 per week) participated in the study, of which 50 completed the follow-up questionnaires. The NFR was significantly lower after the aural rehabilitation (M = 45.03) compared to before the aural rehabilitation (M = 51.89), t = −3.43, p < 0.01). Change in NFR could best be explained by the change in personal adjustments (R2 = 0.45, B = −1.23, p < 0.01).

Conclusion
The NFR of employees with hearing loss can be improved by aural rehabilitation, but this study shows that current practices reduce the NFR only in part of the employees. Therefore, improving current practices should be considered and evaluated, for example by applying a different combination of rehabilitation components. Especially, interventions that affect personal adjustments may be promising to further reduce the NFR in employees with hearing loss.
Increased use of high-flow nasal cannulas after the pandemic in bronchiolitis: a more severe disease or a changed physician’s attitude?
Authors: Ghirardo Sergio , Cozzi Giorgio , Tonin Giovanna , Risso Francesco Maria , Dotta Laura , Zago Alessandro , Lupia Daniela , Cogo Paola , Ullmann Nicola , Coretti Antonella , Badolato Raffaele , Amaddeo Alessandro , Barbi Egidio , Cutrera Renato 
Published: September 2022

AbstractAfter the SARS-CoV-2 pandemic, we noticed a marked increase in high-flow nasal cannula use for bronchiolitis. This study aims to report the percentage of children treated with high-flow nasal cannula (HFNC) in various seasons. The secondary outcomes were admissions for bronchiolitis, virological results, hospital burden, and NICU/PICU need. We conducted a retrospective study in four Italian hospitals, examining the medical records of all infants (< 12 months) hospitalized for bronchiolitis in the last four winter seasons (1 September–31 March 2018–2022). In the 2021–2022 winter season, 66% of admitted children received HFNC versus 23%, 38%, and 35% in the previous 3 years. A total of 876 patients were hospitalized in the study periods. In 2021–2022, 300 infants were hospitalized for bronchiolitis, 22 in 2020–2021, 259 in 2019–2020, and 295 in 2018–2019. The percentage of patients needing intensive care varied from 28.7% to 18%, 22%, and 15% in each of the four considered periods (p < 0.05). Seventy-seven percent of children received oxygen in the 2021–2022 winter; vs 50%, 63%, and 55% (p < 0.01) in the previous 3 years. NIV/CPAP was used in 23%, 9%, 16%, and 12%, respectively. In 2021–2020, 2% of patients were intubated; 0 in 2020–2021, 3% in 2019–2020, and 1% in 2018–2019.Conclusion: This study shows a marked increase in respiratory support and intensive care admissions this last winter. While these severity indexes were all driven by medical choices, more reliable indexes such as intubation rate and length of stay did not change. Therefore, we suggest that there is a more aggressive treatment attitude rather than a more severe disease.

What is Known:• COVID-19 pandemic deeply impacted bronchiolitis epidemiology, reducing hospitalizations to onetenth. In the 2021-2022 winter, bronchiolitis resurged to pre-pandemic numbers in Europe.

What is New:• Bronchiolitis hospitalization rose much faster in the 2021-2022 winter period, peaking at a higher level. Respiratory supports and high-flow nasal cannula increased significantly compared to the pre-pandemic era.
Expanding Rehabilitation Options for Dysphagia: Skill-Based Swallowing Training
Authors: Huckabee Maggie-Lee , Flynn Ruth , Mills Madeline 
Published: September 2022

AbstractOver the past four decades, our understanding of swallowing neural control has expanded dramatically. However, until recently, advances in rehabilitation approaches for dysphagia have not kept pace, with a persistent focussing on strengthening peripheral muscle. This approach is no doubt very appropriate for some if not many of our patients. But what if the dysphagia is not due to muscles weakness? The purpose of this clinical manuscript is to reflect on where we have been, where we are now and perhaps where we need to go in terms of our understanding of swallowing motor control and rehabilitation of motor control impairments. This compilation is presented to clinicians in the hope that suggesting approaches “outside the box” will inspire clinicians to focus their attention “inside the box” to ultimately improve rehabilitation and long-term outcomes for patients with dysphagia.
On the mean square displacement of intruders in freely cooling granular gases
Authors: Abad Enrique , Yuste Santos Bravo , Garzó Vicente 
Published: September 2022

AbstractWe compute the mean square displacement (MSD) of intruders immersed in a freely cooling granular gas made up of smooth inelastic hard spheres. In general, intruders and particles of the granular gas are assumed to have different mechanical properties, implying that non-equipartition of energy must be accounted for in the computation of the diffusion coefficientD. In the hydrodynamic regime, the time decay of the granular temperatureTof the cooling granular gas is known to be dictated by Haff’s law; the corresponding decay of the intruder’s collision frequency entails a time decrease of the diffusion coefficientD. Explicit knowledge of this time dependence allows us to determine the MSD by integrating the corresponding diffusion equation. As in previous studies of self-diffusion (intruders mechanically equivalent to gas particles) and the Brownian limit (intruder’s mass much larger than the grain’s mass), we find a logarithmic time dependence of the MSD as a consequence of Haff’s law. This dependence extends well beyond the two aforementioned cases, as it holds in all spatial dimensions for arbitrary values of the mechanical parameters of the system (masses and diameters of intruders and grains, as well as their coefficients of normal restitution). Our result for self-diffusion in a three-dimensional granular gas agrees qualitatively, but not quantitatively, with that recently obtained by Blumenfeld [arXiv: 2111.06260] in the framework of a random walk model. Beyond the logarithmic time growth, we find that the MSD depends on the mechanical system parameters in a highly complex way. We carry out a comprehensive analysis from which interesting features emerge, such a non-monotonic dependence of the MSD on the coefficients of normal restitution and on the intruder-grain mass ratio. To explain the observed behaviour, we analyze in detail the intruder’s random walk, consisting of ballistic displacements interrupted by anisotropic deflections caused by the collisions with the hard spheres. We also show that the MSD can be thought of as arising from an equivalent random walk with isotropic, uncorrelated steps. Finally, we derive some results for the MSD of an intruder inmersed in a driven granular gas and compare them with those obtained for the freely cooling case. In general, we find significant quantitative differences in the dependence of the scaled diffusion coefficient on the coefficient of normal restitution for the grain-grain collisions.Graphic abstract
Robust convex optimization: A new perspective that unifies and extends
Authors: Bertsimas Dimitris , Hertog Dick den , Pauphilet Jean , Zhen Jianzhe 
Published: September 2022

AbstractRobust convex constraints are difficult to handle, since finding the worst-case scenario is equivalent to maximizing a convex function. In this paper, we propose a new approach to deal with such constraints that unifies most approaches known in the literature and extends them in a significant way. The extension is either obtaining better solutions than the ones proposed in the literature, or obtaining solutions for classes of problems unaddressed by previous approaches. Our solution is based on an extension of the Reformulation-Linearization-Technique, and can be applied to general convex inequalities and general convex uncertainty sets. It generates a sequence of conservative approximations which can be used to obtain both upper- and lower- bounds for the optimal objective value. We illustrate the numerical benefit of our approach on a robust control and robust geometric optimization example.
Höchste Zeit für einen Gaspreisdeckel: ein wichtiges Instrument im Kampf gegen Energiepreisbelastung
Authors: Dullien Sebastian , Weber Isabella M. 
Published: September 2022

AbstractThe explosive increase of the price of natural gas is a key driver of inflation in Germany. At the same time, physical gas shortages in the fall or winter are a plausible scenario. A policy response is urgently needed that protects households from skyrocketing heating costs while at the same time maintaining price incentives to save gas. We have proposed a gas price cap for households’ basic consumption and market prices for all demand above that guaranteed base. Our proposal has been widely discussed by economists and policy makers. In this article, we respond to some criticisms, provide details on the feasibility of our proposal, and urge for swift political action.
Linkage to HIV Care Following HIV Self-testing Among Men: Systematic Review of Quantitative and Qualitative Studies from Six Countries in Sub-Saharan Africa
Authors: Hlongwa Mbuzeleni , Hlongwana Khumbulani , Makhunga Sizwe , Choko Augustine T. , Dzinamarira Tafadzwa , Conserve Donaldson , Tsai Alexander C. 
Published: September 2022

AbstractGender disparities are pervasive throughout the HIV care continuum in sub-Saharan Africa, with men testing, receiving treatment, and achieving viral suppression at lower rates, and experiencing mortality at higher rates, compared with women. HIV self-testing (HIVST) has been shown to be highly acceptable among men in sub-Saharan Africa. However, evidence on linkage to HIV care following a reactive HIVST result is limited. In this systematic review, we aimed to synthesize the quantitative and qualitative literature from sub-Saharan Africa on men’s rates of linkage to HIV care after receiving a reactive HIVST result. We systematically searched 14 bibliometric databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram was used to document the screening results. The Mixed Methods Appraisal Tool (MMAT) was used to assess the methodological quality of the included studies. Of 22,446 references screened, 15 articles were eligible for inclusion in this review. Linkage to HIV care following a reactive HIVST result was subject to several barriers: financial constraints due to travelling costs, potential long waiting hours at the clinics, stigma, discrimination, and privacy concerns. Men’s rates of seeking confirmatory testing and linking to HIV care following a reactive HIVST result were inconsistent across studies. Combining financial incentives with HIVST was found to increase the likelihood of linking to HIV care following a reactive HIVST result. The variable rates of linkage to HIV care following a reactive HIVST result suggest a need for further research and development into strategies to increase linkage to HIV care.
Molecular detection of spotted fever group rickettsiae in hedgehogs (Erinaceus amurensis) and hedgehog-attached ticks in Xuyi County, Southeast China
Authors: Zhu Changqiang , Ai Lele , Qi Yong , Liu Yunsheng , Li Hong , Ye Fuqiang , Wang Qiuwei , Luo Yizhe , Tan Weilong , Shi Chunmeng 
Published: September 2022

AbstractTick-borne diseases like Rickettsia, Anaplasma and Ehrlichia are widespread infectious zoonoses that threaten the health of both humans and animals worldwide. Ticks and their hosts, such as hedgehogs, can play a crucial role in transmitting tick-borne diseases and the cycle of Rickettsia. To investigate the presence and identity of Rickettsia in hedgehogs and hedgehog-attached ticks in Xuyi County, Southeast China, 114 ticks were collected from 45 hedgehogs captured totally. Via morphological and molecular methods, all these ticks were identified as two species: Haemaphysalis flava (110/114, 96.5%) and Haemaphysalis longicornis (4/114, 3.5%). Rickettsia spp. were genotypically characterized by PCR targeting rrs, gltA, ompA, ompB, and sca4 gene fragments. The prevalence of spotted fever group rickettsiae (SFGR) infection found in hedgehogs and ticks was 17.8% (8/45) and 78.1% (89/114), respectively. Phylogenetic analyses demonstrated that those Rickettsia spp. belong to two species: Rickettsia heilongjiangensis (R. heilongjiangensis XY-1) and a potential new species, Candidatus Rickettsia xuyiensis XY-2. The present study gave the first evidence of R. heilongjiangensis and Candidatus R. xuyiensis in ticks and hedgehogs of Southeast China. Our findings suggest that hedgehogs might be involved in the natural transmission cycle of Rickettsia species.
Reliability and Validity of the Colombian Version of the Revised Sociosexual Orientation Inventory
Authors: Romero Duban , Mebarak Moisés , Millán Anthony , Tovar-Castro Juan Camilo , Martinez Martha , Rodrigues David L. 
Published: September 2022

AbstractSociosexuality refers to an individual’s disposition to have casual sex without establishing affective bonds and has been widely studied worldwide using the Revised Sociosexual Orientation Inventory (SOI-R; Penke & Asendorpf, 2008). Despite its many validations in different cultural contexts, no psychometric analyses of this instrument have been conducted in Spanish-speaking Latin American countries. To address this gap in the literature, we examined the psychometric properties of the SOI-R in Colombia. In a cross-sectional study with a large sample of participants (N = 812; 64% women), we conducted exploratory and confirmatory factor analyses to identify different factor structures and determine which had the best fit for our sample and examined the reliability of the scale. Results showed that a three-factor structure, with sociosexual behaviors, attitudes, and desire as first-order factors, and global sociosexuality as a second-order factor, had the best fit indexes. Each factor presented good reliability indexes. Replicating already established gender differences, we also found that men scored higher on each factor when compared to women. These findings show that the SOI-R is a reliable and valid instrument to assess sociosexuality in countries where sociosexuality research is underrepresented.
Tobacco as an efficient metal accumulator
Authors: Kozak Katarzyna , Antosiewicz Danuta Maria 
Published: September 2022

AbstractTobacco (Nicotiana tabacum L.) is an important industrial crop plant. However, it efficiently accumulates metals, primarily cadmium (Cd) and also zinc (Zn), in its leaves. Therefore, it could be a source of cadmium intake by smokers. On the other hand, as a high leaf metal accumulator, it is widely used for phytoremediation of metal-contaminated soil. Both issues provide an important rationale for investigating the processes regulating metal homeostasis in tobacco. This work summarizes the results of research to date on the understanding of the molecular mechanisms determining the effective uptake of Zn and Cd, their translocation into shoots and accumulation in leaves. It also discusses the current state of research to improve the phytoremediation properties of tobacco through genetic modification and to limit leaf Cd content for the tobacco industry.
Graphical Abstract