bluuebunny/crossref_metadata_2025_split huggingface dataset:
90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years
Authors: Rieger Kathrin , De Filippi Rosaria , Lindén Ola , Viardot Andreas , Hess Georg , Lerch Kristina , Neumeister Peter , Stroux Andrea , Peuker Caroline A. , Pezzutto Antonio , Pinto Antonello , Keller Ulrich , Scholz Christian W. 
Published: February 2022

AbstractRadioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy. ClinicalTrials.gov Identifier: NCT00772655.
Yeast Stn1 promotes MCM to circumvent Rad53 control of the S phase checkpoint
Authors: Gasparayan Hovik , Caridi Chris , Julius Jeff , Feng Wenyi , Bachant Jeff , Nugent Constance I. 
Published: February 2022

AbstractTreating yeast cells with the replication inhibitor hydroxyurea activates the S phase checkpoint kinase Rad53, eliciting responses that block DNA replication origin firing, stabilize replication forks, and prevent premature extension of the mitotic spindle. We previously found overproduction of Stn1, a subunit of the telomere-binding Cdc13–Stn1–Ten1 complex, circumvents Rad53 checkpoint functions in hydroxyurea, inducing late origin firing and premature spindle extension even though Rad53 is activated normally. Here, we show Stn1 overproduction acts through remarkably similar pathways compared to loss of RAD53, converging on the MCM complex that initiates origin firing and forms the catalytic core of the replicative DNA helicase. First, mutations affecting Mcm2 and Mcm5 block the ability of Stn1 overproduction to disrupt the S phase checkpoint. Second, loss of function stn1 mutations compensate rad53 S phase checkpoint defects. Third Stn1 overproduction suppresses a mutation in Mcm7. Fourth, stn1 mutants accumulate single-stranded DNA at non-telomeric genome locations, imposing a requirement for post-replication DNA repair. We discuss these interactions in terms of a model in which Stn1 acts as an accessory replication factor that facilitates MCM activation at ORIs and potentially also maintains MCM activity at replication forks advancing through challenging templates.
Impact of linewidth enhancement factor and gain suppression on chirp characteristics of high-speed laser diode and performance of 40 Gbps optical fiber links
Authors: Fouad Nada , Mohamed Tarek , Mahmoud Alaa 
Published: February 2022

AbstractWe present a simulation study on the chirping characteristics of a directly modulated 40 Gbps laser diode and evaluate its performance for use in high-speed optical fiber links. The effects of the linewidth enhancement factor (α) and gain suppression on the laser chirp and the maximum fiber transmission length are investigated. The chirp characteristics include the frequency peak-to-peak chirp of the time-varying frequency and shift of the emission wavelength. The performance of 40 Gbps optical fiber link is evaluated in terms of the eye diagram and quality factor of the received signal, which helps in predicting the maximum fiber length that achieves error-free transmission. The results show that whenαincreases from 1 to 10, the overshoots of the relaxation oscillations become strong, resulting in a sharp increase in laser peak-to-peak chirp from 21.8 to 205 GHz. The increase of gain suppression factor formε = 0.5 × 10–17cm3toε = 5 × 10–17cm3dampens out the overshoots and slightly reduces the peak-to-peak chirp from 19.5 to 193.3 GHz. Although the gain suppression works to reduce the laser chirp, it causes a significant wavelength shift relative to the emission wavelength of the non-modulated laser, which degrades the efficiency of the laser diode. On the other hand, the gain suppression is shown to increase the degree of eye-opening and the correspondingQ-factor of the fiber link on a reverse action of the linewidth enhancement factor. As fiber length increases, the influences ofαand ε on chirp characteristics become more significant. The maximum fiber length (Lmax) is shown to decrease with the increase inαand/orε; when α increases from 1 to 10,Lmaxdecreases from 5.89 to 0.78 km atε = 5 × 10–17cm3, and decreases from 2.52 to 0.3 km atε = 0.5 × 10–17cm3.
The radiation adaptive response and priming dose influence: the quantification of the Raper–Yonezawa effect and its three-parameter model for postradiation DNA lesions and mutations
Authors: Fornalski Krzysztof W. , Adamowski Łukasz , Dobrzyński Ludwik , Jarmakiewicz Rafał , Powojska Aleksandra , Reszczyńska Joanna 
Published: February 2022

AbstractThe priming dose effect, called also the Raper–Yonezawa effect or simply the Yonezawa effect, is a special case of the radiation adaptive response phenomenon (radioadaptation), which refers to: (a) faster repair of direct DNA lesions (damage), and (b) DNA mutation frequency reduction after irradiation, by applying a small priming (conditioning) dose prior to the high detrimental (challenging) one. This effect is observed in many (but not all) radiobiological experiments which present the reduction of lesion, mutation or even mortality frequency of the irradiated cells or species. Additionally, the multi-parameter model created by Dr. Yonezawa and collaborators tried to explain it theoretically based on experimental data on the mortality of mice with chronic internal irradiation. The presented paper proposes a new theoretical approach to understanding and explaining the priming dose effect: it starts from the radiation adaptive response theory and moves to the three-parameter model, separately for two previously mentioned situations: creation of fast (lesions) and delayed damage (mutations). The proposed biophysical model was applied to experimental data—lesions in human lymphocytes and chromosomal inversions in mice—and was shown to be able to predict the Yonezawa effect for future investigations. It was also found that the strongest radioadaptation is correlated with the weakest cellular radiosensitivity. Additional discussions were focussed on more general situations where many small priming doses are used.
Evaluation of peripapillary vascular flow in patients with Thyroid-Associated Ophthalmopathy (TAO) by OCT Angiography
Authors: Del Noce Chiara , Roda Matilde , Valsecchi Nicola , Guandalini Sofia , Di Geronimo Natalie , Schiavi Costantino , Traverso Carlo Enrico , Vagge Aldo 
Published: February 2022

Abstract

Purpose
To evaluate changes in peripapillary vascular blood flow indices (PVBFI) in patients with thyroid-associated ophthalmopathy (TAO) using OCT angiography (OCTA) technology.

Methods
Patients with TAO and control subjects matched for age and sex were included in the study. Eye examination, Clinical Activity Score (CAS) evaluation and OCTA scan analysis (Topcon ImageNet 6; DRI OCT Triton, Topcon Corporation) were performed. In particular, PVBFI of the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR) and choriocapillaris (CC) layers were obtained by OCTA and extracted from 8-bit greyscale OCT images using the ImageJ software package.

Results
Twenty-six patients with TAO (19 females, mean age 54.7 ± 5.2 and 7 males, mean age 51.4 ± 16.3) were compared with 26 healthy subjects (15 females, mean age 48.2 ± 14.1 and 11 males, mean age 53.1 ± 15.2). Both DCP-PVBF and CC-PVBFI were significantly reduced in TAO patients compared to control eyes (28.6 ± 2.1 vs. 29.7 ± 0.93, p = 0.002; 46.5 ± 1.72 vs. 47.2 ± 1.2, p = 0.019 respectively); on the other hand, no statistically significant differences were found in SCP-PVBFI and OR-PVBFI in TAO patients compared to healthy subjects (p > 0.05). Also, CC-PVBFI was associated with elevated values of CAS (p = 0.018) and ROC curve showed that patients with elevated CC-PVBFI were correlated with active TAO (CAS > 3) (p = 0.012).

Conclusions
TAO disease may be associated with changes in DCP-PVBFI and CC-PVBFI; also, CC-PVBFI seems to correlate with disease activity.
Implications of the study of subglacial volcanism and glaciovolcanic cave systems
Authors: Sobolewski Linda , Stenner Christian , Williams-Jones Glyn , Anitori Roberto , Davis Richard E. , Pflitsch Andreas 
Published: February 2022

AbstractGlacial environments can have significant impacts on the surrounding landscape and nearby populations when affected by volcanic activity. As such, glaciovolcanic interactions and related hazards have received substantial attention during the last few decades. In contrast, the study of void spaces created by these interactions—glaciovolcanic cave systems—remains underrepresented. This review outlines the global distribution of glaciovolcanic caves and describes examples of both historical and ongoing research advances, most of which are limited to volcanoes of the Cascade Volcanic Arc and Antarctica. Examples range from a largely static fumarolic ice cave system in the crater of Mount Rainier to glaciovolcanic cave genesis and evolution in the crater of Mount St. Helens, where the advancing glacier ice is interacting with ongoing fumarolic activity and generating new cave systems. This review includes various volcanic subfields and also brings together additional disciplines including speleology, microbiology, and astrobiology. Due to the importance of glaciovolcanic caves in the hydrothermal cycle of volcanic systems, the global fight against antibiotic resistance, and their implications for understanding volcano-ice interactions beyond Earth, research on these systems is expanding. Kamchatka, Alaska, and Iceland have notable potential for further studies, while known research sites still hold open questions, including better understanding of the environmental parameters affecting cave genesis and persistence, the effect of glaciovolcanic cave development on underlying hydrothermal systems, and cataloging the biodiversity of glaciovolcanic cave environments.
Revisiting the Evaluation of Hydraulic Transmissivity of Elliptical Rock Fractures in Triaxial Shear-Flow Experiments
Authors: Ji Yinlin , Hofmann Hannes , Rutter Ernest H. , Xiao Fei , Yang Lining 
Published: February 2022

Highlights• A novel numerical approach has been proposed to retrieve the hydraulic transmissivity of elliptical rock fractures in triaxial shear-flow experiments.• The accuracy of different methods for estimation of hydraulic transmissivity of elliptical rock fractures has been evaluated and discussed.• The numerical approach and electrical analogy are recommended for accurate evaluation of hydraulic transmissivity of elliptical rock fractures.
Not just a background: pH buffers do interact with lanthanide ions—a Europium(III) case study
Authors: Mandal Poulami , Kretzschmar Jerome , Drobot Björn 
Published: February 2022

AbstractThe interaction between Eu(III) ion and different pH buffers, popular in biology and biochemistry, viz. HEPES, PIPES, MES, MOPS, and TRIS, has been studied by solution nuclear magnetic resonance spectroscopy (NMR) and time-resolved laser-induced fluorescence spectroscopy (TRLFS) techniques. The Good’s buffers reveal non-negligible interaction with Eu(III) as determined from their complex stability constants, where the sites of interaction are the morpholine and piperazine nitrogen atoms, respectively. In contrast, TRIS buffer shows practically no affinity towards Eu(III). Therefore, when investigating lanthanides, TRIS buffer should be preferred over Good’s buffers.
Graphical abstract
“Passive or interactive virtual reality? The effectiveness for pain and anxiety reduction in pediatric patients”
Authors: Ferraz-Torres Marta , San Martín-Rodríguez Leticia , García-Vivar Cristina , Soto-Ruiz Nelia , Escalada-Hernández Paula 
Published: February 2022

AbstractInvasive techniques such as venipuncture are painful procedures causing stress and anxiety, both in pediatric patients and in their carers. For this reason, efforts are being made to develop mitigating strategies for the patient’s pain and anxiety during the performance. To analyze and evaluate the effectiveness of the use of Virtual Reality distraction techniques as a measure of pain and anxiety reduction in pediatric patients and their parents. In addition, the effects of two modes of Virtual Reality (passive vs. interactive) were compared. A quasi-experimental study was carried out in the pediatric emergency department of a tertiary referral hospital in north Spain. The participants were children who underwent venipuncture for blood extraction and vascular cannulation. From the 124 patients, 51.6% (n = 64) were girls and 48.4% (n = 60) were boys (p = 0.574). The mean age was 8.4 years (SD: 4.1). The mean level of pain experienced was 2.33 (SD: 0.76) in the interactive VR group (n = 88) versus 2.67 (SD: 1.35) in patients with passive VR (n = 36) (p = 0.008); being the presence of anxiety in 27.3% (n = 24) of the cases treated with interactive Virtual Reality and in 88.9% (n = 32) of the patients with passive Virtual Reality (p = 0.000). The virtual reality is an effective method to reduce pain and anxiety levels in pediatric patients, with the effectiveness of interactive virtual reality and its use in the population aged 7–15 years being greater.
In systemic sclerosis TAPSE/sPAP ratio is correlated with ventilatory efficiency and exercise capacity assessed by CPET
Authors: Colalillo Amalia , Pellicano Chiara , Romaniello Antonella , Rosato Edoardo 
Published: February 2022

Abstract
Objectives
The aim of the study was to evaluate the correlation between cardiopulmonary exercise testing (CPET) parameters and right ventricular echocardiographic parameters for pulmonary arterial hypertension screening in a cohort of systemic sclerosis (SSc) patients. Methods forty SSc patients were examined using CPET and resting transthoracic echocardiography. CPET parameters analyzed were minute ventilation/carbon dioxide production (VE/VCO2) slope and maximum oxygen uptake (VO2 max); echocardiographic parameters were systolic pulmonary artery pressure (sPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/sPAP ratio. Results a positive correlation was observed between VE/VCO2 slope and age (r = 0.415, p < 0.01) and sPAP (r = 0.461, p < 0.01), conversely, a negative correlation was found between VE/VCO2 slope and TASPE/sPAP ratio (r = − 0.521, p = 0.001). VO2 max showed an inverse correlation with age (r = − 0.367, p < 0.05) and sPAP (r = − 0.387, p < 0.05) and a positive correlation with TAPSE/sPAP ratio (r = 0.521, p < 0.01). On stepwise linear regression analysis, VE/VCO2 slope was significantly correlated with TAPSE/sPAP ratio (β coefficient = − 0.570; p < 0.0001), as well as VO2 max was significantly correlated with TAPSE/sPAP ratio (β coefficient = 0.518; p = 0.001). Conclusion in SSc patients, TAPSE/sPAP ratio is the echocardiographic parameter of RV function which showed the best correlation with ventilatory efficiency and exercise capacity.
How Large Is the Risk of Stagflation in the Eurozone?
Authors: Demary Markus , Hüther Michael 
Published: February 2022

AbstractThe rapid recovery of demand combined with supply constraints has led to rising prices during the past months. This is evident in oil and gas markets, but also in international trade, which has been thrown out of step by bottlenecks at Asian ports. This situation creates a trade-off for the European Central Bank, because a more expansionary monetary policy cannot mitigate the supply bottlenecks and supply-side restrictions, while a more restrictive monetary policy would slow down the economic recovery. For this reason, key interest rate hikes in the eurozone are not to be expected for 2022. If the supply-side factors become persistent and wage policy tries to pass the price effects on, monetary policy will be forced to become restrictive.
International Inequality and the COVID-19 Pandemic
Authors: Dauderstädt Michael 
Published: February 2022

AbstractThe lockdowns and stimulus programmes that governments have adopted to fight the COVID-19 pandemic and the associated economic crisis have affected the distribution of income and production within and between countries. Considering both, current evidence indicates that the EU-wide and global inequality of disposable income did not change dramatically in 2020. However, the unequal impact on the wealth and health of people is likely to worsen income inequality in the future.
Do the COVID-19 Crisis, Ageing and Climate Change Put Swiss Fiscal Sustainability at Risk?
Authors: Brändle Thomas , Bruchez Pierre-Alain , Colombier Carsten , Baur Martin , Hohl Lukas 
Published: February 2022

AbstractThe ongoing coronavirus pandemic crisis as well as demographic and climate change pose major challenges for public finances. This article deals with the implications of demographic trends in Switzerland, i.e. the progressive ageing of the population and its impact on the country’s public finances in the long run. As the analysis shows, the brunt of the demographic burden is borne by the old-age pension scheme, health and long-term care. This article also addresses the financial ramifications of the COVID-19 crisis and shows the need for economic policy action over the longer term to ensure the sustainability of public finances in Switzerland. Furthermore, a qualitative assessment of climate change is included, as it constitutes an additional major long-term challenge for public finances.
Measuring the relative development and integration of EU countries’ capital markets using composite indicators and cluster analysis
Authors: Gucciardi Gianluca 
Published: February 2022

AbstractThe paper proposes a set of metrics and a methodology to measure the progress that European Union Member States are making towards the development and integration of capital markets. It identifies a set of indicators and analyzes the performance of these countries over the 2007–2018 period using a composite indicator approach (in both a static and dynamic environment), based on the six priorities related to achieving a well-functioning and integrated European capital market included in the European Commission Capital Markets Union Action Plan. The author uses robust clustering to identify groups of countries and tracks their development over time. He finds that the process of capital market development and integration process has started but is not completed and that it is mainly associated with countries’ adherence to European increasing trends driven by the benchmarks rather than the policy actions of countries aimed at catching up with the best performers.
Pseudo-T2 mapping for normalization of T2-weighted prostate MRI
Authors: Sørland Kaia Ingerdatter , Sunoqrot Mohammed R. S. , Sandsmark Elise , Langørgen Sverre , Bertilsson Helena , Trimble Christopher G. , Lin Gigin , Selnæs Kirsten M. , Goa Pål E. , Bathen Tone F. , Elschot Mattijs 
Published: February 2022

Abstract
Objective
Signal intensity normalization is necessary to reduce heterogeneity in T2-weighted (T2W) magnetic resonance imaging (MRI) for quantitative analysis of multicenter data. AutoRef is an automated dual-reference tissue normalization method that normalizes transversal prostate T2W MRI by creating a pseudo-T2 map. The aim of this study was to evaluate the accuracy of pseudo-T2s and multicenter standardization performance for AutoRef with three pairs of reference tissues: fat/muscle (AutoRefF), femoral head/muscle (AutoRefFH) and pelvic bone/muscle (AutoRefPB).

Materials and methods
T2s measured by multi-echo spin echo (MESE) were compared to AutoRef pseudo-T2s in the whole prostate (WP) and zones (PZ and TZ/CZ/AFS) for seven asymptomatic volunteers with a paired Wilcoxon signed-rank test. AutoRef normalization was assessed on T2W images from a multicenter evaluation set of 1186 prostate cancer patients. Performance was measured by inter-patient histogram intersections of voxel intensities in the WP before and after normalization in a selected subset of 80 cases.

Results
AutoRefFH pseudo-T2s best approached MESE T2s in the volunteer study, with no significant difference shown (WP: p = 0.30, TZ/CZ/AFS: p = 0.22, PZ: p = 0.69). All three AutoRef versions increased inter-patient histogram intersections in the multicenter dataset, with median histogram intersections of 0.505 (original data), 0.738 (AutoRefFH), 0.739 (AutoRefF) and 0.726 (AutoRefPB).

Discussion
All AutoRef versions reduced variation in the multicenter data. AutoRefFH pseudo-T2s were closest to experimentally measured T2s.
Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors
Authors: Waqar Saiama N. , Robinson Clifford , Olszanski Anthony J. , Spira Alexander , Hackmaster Melissa , Lucas Luisa , Sponton Laura , Jin Hulin , Hering Ursula , Cronier Damien , Grinberg Marianna , Seithel-Keuth Annick , Diaz-Padilla Ivan , Berlin Jordan 
Published: February 2022

SummaryBackground. Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM. Methods. This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50–300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic regression model with overdose control. Results. Doses of M3541 up to 300 mg/fraction day were well tolerated. One patient (200 mg group) experienced two dose-limiting toxicities (urinary tract infection, febrile neutropenia) that resolved with antibiotics. All patients reported ≥ 1 treatment-emergent adverse event (TEAE) but none led to treatment discontinuation. No grade ≥ 4 TEAEs were reported and there was no indication of a dose effect for any TEAE. Three patients (20.0%; 95% confidence interval 4.3–48.1) had confirmed complete or partial response. M3541 total plasma levels did not increase with dose following single or repeated dosing. No relationship was observed between dose and changes in the ratio of phosphorylated to total ATM or in immune cell counts. Conclusions. The MTD and RP2D could not be established as the study closed early due to the absence of a dose–response relationship and non-optimal PK profile. No further clinical development of M3541 was pursued. (Trial registration number ClinicalTrials.gov NCT03225105. Registration date July 21, 2017).