bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma
Authors: Hamilton Erika P. , Wang Judy S. , Oza Amit M. , Patel Manish R. , Ulahannan Susanna V. , Bauer Todd , Karlix Janet L. , Zeron-Medina Jorge , Fabbri Giulia , Marco-Casanova Paola , Moorthy Ganesh , Hattersley Maureen M. , Littlewood Gillian M. , Mitchell Patrick , Saeh Jamal , Pouliot Gayle P. , Moore Kathleen N. 
Published: July 2023

Abstract
AZD5153, a reversible, bivalent inhibitor of the bromodomain and extraterminal family protein BRD4, has preclinical activity in multiple tumors. This first-in-human, phase I study investigated AZD5153 alone or with olaparib in patients with relapsed/refractory solid tumors or lymphoma. Adults with relapsed tumors intolerant of, or refractory to, prior therapies received escalating doses of oral AZD5153 once daily or twice daily continuously (21-day cycles), or AZD5153 once daily/twice daily continuously or intermittently plus olaparib 300 mg twice daily, until disease progression or unacceptable toxicity. Between June 30, 2017 and April 19, 2021, 34 patients received monotherapy and 15 received combination therapy. Dose-limiting toxicities were thrombocytopenia/platelet count decreased (n = 4/n = 2) and diarrhea (n = 1). The recommended phase II doses (RP2D) were AZD5153 30 mg once daily or 15 mg twice daily (monotherapy) and 10 mg once daily (intermittent schedule) with olaparib. With AZD5153 monotherapy, common treatment-emergent adverse events (TEAE) included fatigue (38.2%), thrombocytopenia, and diarrhea (each 32.4%); common grade ≥ 3 TEAEs were thrombocytopenia (14.7%) and anemia (8.8%). With the combination, common TEAEs included nausea (66.7%) and fatigue (53.3%); the most common grade ≥ 3 TEAE was thrombocytopenia (26.7%). AZD5153 had dose-dependent pharmacokinetics, with minimal accumulation, and demonstrated dose-dependent modulation of peripheral biomarkers, including upregulation of HEXIM1. One patient with metastatic pancreatic cancer receiving combination treatment had a partial response lasting 4.2 months. These results show AZD5153 was tolerable as monotherapy and in combination at the RP2Ds; common toxicities were fatigue, hematologic AEs, and gastrointestinal AEs. Strong evidence of peripheral target engagement was observed.
Ventricular Electrograms Duration Map to Detect Ventricular Arrhythmia Substrate: the VEDUM Project Study
Authors: Rossi Pietro , Cauti Filippo Maria , Niscola Marta , Magnocavallo Michele , Polselli Marco , Capone Silvia , Della Rocca Domenico Giovanni , Rodriguez-Garrido Jorge , Piccirillo Gianfranco , Anguera Ignasi , Dallaglio Paolo , Bianchi Stefano 
Published: July 2023

BACKGROUND:
The analysis of the wave-front activation patterns is crucial for the comprehension and treatment of ventricular tachycardia (VT). The ventricular electrograms duration map (VEDUM) is a potential method to identify areas (VEDUM area) with slow and inhomogeneous activation. There is no available data on the characteristics and the arrhythmogenic role of VEDUM areas identified during sinus/paced rhythm.

METHODS:
Patients referred for VT ablation were enrolled at 3 different centers. VEDUM maps during sinus/paced rhythm as well as substrate and functional maps were created; activation mapping was performed for all hemodynamically tolerated VT.

RESULTS:

Thirty-two patients (mean age:70.1±9.4 years; males 93.8%) were enrolled. The VEDUM approach was achieved in all patients and the mean size of the VEDUM area was 12.1±6.9 cm
2
(interquartile range, 7.8–14.9 cm
2
). A significative difference was observed between the electrogram duration in the VEDUM area and the normal tissue (163.7 ms [interquartile range, 142.3–199.2 ms]; versus 65.5 ms [interquartile range, 59.5–76.2 ms];
P
<0.001). The VEDUM area was visualized in a dense scar (<0.5 mV) in 19 (59.4%) patients. A deceleration zone and late potentials were recorded inside the VEDUM area in 56.3% and 81.3%, respectively. When a complete VT activation mapping was available, the isthmus projected in the VEDUM area in 93.5% of patients; 8 of them had multiple VTs mapped and in the 87.5% all VT isthmuses were included in the VEDUM area.

CONCLUSIONS:
VEDUM maps allow the identification of discrete areas of inhomogeneous and slow conduction. They represent a potential target for VT ablation, including patients with multiple morphologies.
Indoleamine 2,3-Dioxygenase 1 Deletion-Mediated Kynurenine Insufficiency Inhibits Pathological Cardiac Hypertrophy
Authors: Wang Yinhui , Song Jia , Yu Kun , Nie Daan , Zhao Chengcheng , Jiao Liping , Wang Ziyi , Zhou Ling , Wang Feng , Yu Qilin , Zhang Shu , Wen Zheng , Wu Junfang , Wang Cong-Yi , Wang Dao Wen , Cheng Jia , Zhao Chunxia 
Published: July 2023

BACKGROUND:
Aberrant amino acid metabolism is implicated in cardiac hypertrophy, while the involvement of tryptophan metabolism in pathological cardiac hypertrophy remains elusive. Herein, we aimed to investigate the effect and potential mechanism of IDO1 (indoleamine 2,3-dioxygenase) and its metabolite kynurenine (Kyn) on pathological cardiac hypertrophy.

METHODS:
Transverse aortic constriction was performed to induce cardiac hypertrophy in IDO1-knockout (KO) mice and AAV9-cTNT-shIDO1 mice. Liquid chromatography–mass spectrometry was used to detect the metabolites of tryptophan-Kyn pathway. Chromatin immunoprecipitation assay and dual luciferase assay were used to validate the binding of protein and DNA.

RESULTS:
IDO1 expression was upregulated in both human and murine hypertrophic myocardium, alongside with increased IDO1 activity and Kyn content in transverse aortic constriction-induced mice’s hearts using liquid chromatography–mass spectrometry analysis. Myocardial remodeling and heart function were significantly improved in transverse aortic constriction-induced IDO1-KO mice, but were greatly exacerbated with subcutaneous Kyn administration. IDO1 inhibition or Kyn addition confirmed the alleviation or aggravation of hypertrophy in cardiomyocyte treated with isoprenaline, respectively. Mechanistically, IDO1 and metabolite Kyn contributed to pathological hypertrophy via the AhR (aryl hydrocarbon receptor)-GATA4 (GATA binding protein 4) axis.

CONCLUSIONS:
This study demonstrated that IDO1 deficiency and consequent Kyn insufficiency can protect against pathological cardiac hypertrophy by decreasing GATA4 expression in an AhR-dependent manner.
Sex-Specific Effects of Blood Pressure Lowering Pharmacotherapy for the Prevention of Cardiovascular Disease: An Individual Participant-Level Data Meta-Analysis
Authors: Bidel Zeinab , Nazarzadeh Milad , Canoy Dexter , Copland Emma , Gerdts Eva , Woodward Mark , Gupta Ajay K. , Reid Christopher M. , Cushman William C. , Wachtell Kristian , Teo Koon , Davis Barry R. , Chalmers John , Pepine Carl J. , Rahimi Kazem ,   on behalf of the Blood Pressure Lowering Treatment Trialists’ Collaboration
Published: July 2023

BACKGROUND:
Whether the relative effects of blood pressure (BP)–lowering treatment on cardiovascular outcomes differ by sex, particularly when BP is not substantially elevated, has been uncertain.

METHODS:
We conducted an individual participant-level data meta-analysis of randomized controlled trials of pharmacological BP lowering. We pooled the data and categorized participants by sex, systolic BP categories in 10-mm Hg increments from <120 to ≥170 mm Hg, and age categories spanning from <55 to ≥85 years. We used fixed-effect one-stage individual participant-level data meta-analyses and applied Cox proportional hazard models, stratified by trial, to analyze the data.

RESULTS:

We included data from 51 randomized controlled trials involving 358 636 (42% women) participants. Over 4.2 years of median follow-up, a 5-mm Hg reduction in systolic BP decreased the risk of major cardiovascular events both in women and men (hazard ratio [95% CI], 0.92 [0.89–0.95] for women and 0.90 [0.88–0.93] for men;
P
for interaction, 1). There was no evidence for heterogeneity of relative treatment effects by sex for the major cardiovascular disease, its components, or across the different baseline BP categories (all
P
for interaction, ≥0.57). The effects in women and men were consistent across age categories and the types of antihypertensive medications (all
P
for interaction, ≥0.14).

CONCLUSIONS:
The effects of BP reduction were similar in women and men across all BP and age categories at randomization and with no evidence to suggest that drug classes had differing effects by sex. This study does not substantiate sex-based differences in BP-lowering treatment.
Clinical Penetrance of the Transthyretin V122I Variant in Older Black Patients With Heart Failure: The SCAN‐MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study
Authors: Madhani Avni , Sabogal Natalia , Massillon Daniel , Paul Ludwine D. , Rodriguez Carlos , Fine Denise , Helmke Stephen , Winburn Morgan , Kurian Damian , Raiszadeh Farbod , Teruya Sergio , Cohn Elizabeth , Einstein Andrew J. , Miller Edward J. , Connors Lawreen H. , Maurer Mathew S. , Ruberg Frederick L. 
Published: July 2023

Background
Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an underdiagnosed cause of heart failure (HF) among patients ≥60 years of age. Although the V122I (valine to isoleucine substitution at position 122 of the transthyretin protein) variant associated with hereditary ATTR‐CM is present in 3.4% of self‐identified Black individuals in the United States (or 1.5 million people), the phenotypic penetrance is not known.

Methods and Results

The SCAN‐MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) study is a currently accruing prospective multisite study designed to determine the prevalence of ATTR‐CM using technetium‐99m‐pyrophosphate imaging in older (≥60 years of age) self‐identified Black and Hispanic individuals with HF. Calculations of the penetrance and prevalence of the V122I allele, along with analyses of functional, biochemical, and echocardiographic parameters, were performed for the first 278 Black participants in SCAN‐MP. The prevalence of ATTR‐CM was 6.8% (95% CI, 4.2–10.5; n=19 cases), of whom 63% were ATTR wild‐type. The prevalence of V122I was 6.5% (n=18 carriers), of whom 7 had ATTR‐CM, yielding a phenotypic penetrance of 39% (95% CI, 17–64). V122I carriers with ATTR‐CM evidenced more advanced HF than carriers without ATTR‐CM. Prealbumin concentration was lowest among V122I carriers with ATTR‐CM (12.9 mg/dL) versus carriers without ATTR‐CM (21.0 mg/dL) and HF controls (25.0 mg/dL,
P
<0.0001).

Conclusions
Among older Black individuals with HF and increased left ventricular wall thickness, of those with ATTR‐CM, 63% had wild‐type, and of those with V122I, the phenotypic penetrance of ATTR‐CM was 39% (95% CI, 17–64), suggesting that genotype alone is insufficient for diagnosis. Prealbumin concentration may be useful to identify V122I carriers with ATTR‐CM.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03812172.
Longitudinal Assessment of Sleep Apnea in the Year After Stroke in a Population-Based Study
Authors: Lisabeth Lynda D. , Zhang Guanghao , Chervin Ronald D. , Shi Xu , Morgenstern Lewis B. , Campbell Morgan , Tower Susan , Brown Devin L. 
Published: July 2023

BACKGROUND:
The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project.

METHODS:
First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors.

RESULTS:

Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (
P
=0.35) but obstructive apnea index increased over time (
P
<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (
P
=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons.

CONCLUSIONS:
Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.
IOHexperimenter: Benchmarking Platform for Iterative Optimization Heuristics
Authors: de Nobel Jacob , Ye Furong , Vermetten Diederick , Wang Hao , Doerr Carola , Bäck Thomas 
Published: July 2023

Abstract
We present IOHexperimenter, the experimentation module of the IOHprofiler project. IOHexperimenter aims at providing an easy-to-use and customizable toolbox for benchmarking iterative optimization heuristics such as local search, evolutionary and genetic algorithms, and Bayesian optimization techniques. IOHexperimenter can be used as a stand-alone tool or as part of a benchmarking pipeline that uses other modules of the IOHprofiler environment.
IOHexperimenter provides an efficient interface between optimization problems and their solvers while allowing for granular logging of the optimization process. Its logs are fully compatible with existing tools for interactive data analysis, which significantly speeds up the deployment of a benchmarking pipeline. The main components of IOHexperimenter are the environment to build customized problem suites and the various logging options that allow users to steer the granularity of the data records.
Noun Sequence Statistics Affect Serial Recall and Order Recognition Memory
Authors: Schwering Steven C. , MacDonald Maryellen C. 
Published: July 2023

Abstract
Most theories of verbal working memory recognize that language comprehension and production processes play a role in word memory for familiar sequences, but not for novel lists of nouns. Some language emergent theories propose that language processes can support verbal working memory even for novel sequences. Through corpus analyses, we identify sequences of two nouns that resemble patterns in natural language, even though the sequences are novel. We present 2 experiments demonstrating better recall in college students for these novel sequences over the same words in reverse order. In a third experiment, we demonstrate better recognition of the order of these sequences over a longer time scale. These results suggest verbal working memory and recognition of order over a delay are influenced by language knowledge processes, even for novel memoranda that approximate noun lists typically employed in memory experiments.
Frazeologia polskiej gwary mieszkańców wsi Wierszyna na Syberii na początku XXI wieku
Authors: Grupa-Dolińska Magdalena 
Published: July 2023

This is the corrected version of the retracted article under the same title, which was published with the following DOI: https://doi.org/10.11649/sfps.2787
Phraseology of the Polish Dialect of the Inhabitants of Vershina Village in Siberia at the Beginning of the Twenty-First Century
The first Polish voluntary settlers appeared in the area of present-day Vershina village at the beginning of the twentieth century. Despite functioning in isola­tion from their linguistic homeland, the inhabitants of Vershina still use their dialectal Polish, which displays a combination of various features of the Lesser Polish dialectal area. The speech of the inhabitants of Vershina also displays the increasingly stronger influence of the Russian language. Despite the relatively rich literature on the language of Poles in Vershina, its phraseology has not as yet been described. This article is an attempt to partially fill this gap by showing the state of this phraseology in the first decades of the twenty-first century. The study presents Polish phraseologisms preserved in the speech of the Poles in Vershina as well as the units which are a consequence of the influence of the Russian language on their dialectal Polish in the field of phraseology.

To jest poprawiona wersja wycofanego artykułu o tym samym tytule, który był opublikowany pod następującym numerem DOI: https://doi.org/10.11649/sfps.2787
Frazeologia polskiej gwary mieszkańców wsi Wierszyna na Syberii na początku XXI wieku
Pierwsi polscy dobrowolni osadnicy pojawili się na obszarze dzisiejszej Wierszyny na początku XX wieku. Mimo funkcjonowania w oderwaniu od ojczyzny językowej, mieszkańcy Wierszyny do dziś posługują się polską gwarą, stanowiącą połączenie cech różnych gwar dialektu małopolskiego. W mowie wierszynian widoczny jest także coraz silniejszy wpływ języka rosyjskiego. Mimo stosunkowo bogatej literatury na temat języka Polaków w Wierszynie, frazeologia do tej pory nie doczekała się opisu. Niniejszy artykuł stanowi próbę częściowego uzupełnienia tej luki poprzez ukazanie stanu zarejestrowanego w pierwszych dekadach XXI wieku. W artykule zostały zaprezentowane zachowane w mowie wierszynian frazeologizmy znane w polszczyźnie oraz te jednostki, które stanowią konsekwencję wpływu języka rosyjskiego na polską gwarę w zakresie frazeologii.
Generation of Multiple Gravity Wave Couplets from Convection
Authors: Yang Hongpei , Du Yu , Wei Junhong 
Published: July 2023

Abstract
The generation of multiple wave couplets with deep tropospheric downdrafts/updrafts by convection is explored through idealized 2D moist numerical simulations as well as dry experiments with prescribed artificial latent heating. These wave couplets are capable of horizontally propagating over a long distance at a fast speed with vertical motions spanning the entire troposphere. The timing of wave generation is determined by the variation in the local heating rate, which arose from the imbalances among latent heating, nonlinear advection, and adiabatic heating/cooling. The amplitudes of wave couplets also correspond well with the strength of the local heating rate. The heat budget analysis highlights the crucial roles of both latent heating and nonlinear advection in the generation of the tropospheric wave couplets. Strong latent heating induces the thermodynamic imbalance and thus triggers waves. Meanwhile, latent heating also increases vertical motion in the source region and thus enhances nonlinear advection through transferring heat upward. Nonlinear advection, which has a comparable magnitude to latent heating in the upper troposphere, partially offsets the balancing effect of adiabatic heating/cooling, and results in a more persistent imbalance at high levels, allowing for the emission of consecutive waves even when latent heating becomes weak. In the simulation with weak nonlinear advection, fewer wave couplets are found, as the effect of latent heating is more easily offset by adiabatic cooling before it weakens.

Significance Statement
The generation of gravity waves in the troposphere by convection is of significant importance in the fields of atmospheric science and meteorology. The waves play a crucial role in the initiation and organization of convection, and the parameterization of wave momentum flux in global numerical models. This study aimed to investigate the generation of wave couplets in the troposphere through idealized numerical simulations with varying prescribed latent heating. The results showed that gravity wave couplets were generated in succession as a result of the imbalances among latent heating, nonlinear advection, and adiabatic heating/cooling. This study highlighted an important but yet complex issue of gravity waves being generated within convection by nonlinear sources other than latent heating, which had been neglected in many recent studies on the topic. These findings deepened our understanding of convectively generated gravity waves and paved the way for coupled wave–convection relationship studies.
A Closer Look at the Evolution of Supercooled Cloud Droplet Temperature and Lifetime in Different Environmental Conditions with Implications for Ice Nucleation in the Evaporating Regions of Clouds
Authors: Roy Puja , Rauber Robert M. , Di Girolamo Larry 
Published: July 2023

Abstract
This study investigates the evolution of temperature and lifetime of evaporating, supercooled cloud droplets considering initial droplet radius (r0) and temperature (), and environmental relative humidity (RH), temperature (T∞), and pressure (P). The time (tss) required by droplets to reach a lower steady-state temperature (Tss) after sudden introduction into a new subsaturated environment, the magnitude of ΔT = T∞ − Tss, and droplet survival time (tst) at Tss are calculated. The temperature difference (ΔT) is found to increase with T∞, and decrease with RH and P. ΔT was typically 1–5 K lower than T∞, with highest values (∼10.3 K) for very low RH, low P, and T∞ closer to 0°C. Results show that tss is <0.5 s over the range of initial droplet and environmental conditions considered. Larger droplets (r0 = 30–50 μm) can survive at Tss for about 5 s to over 10 min, depending on the subsaturation of the environment. For higher RH and larger droplets, droplet lifetimes can increase by more than 100 s compared to those with droplet cooling ignored. Tss of the evaporating droplets can be approximated by the environmental thermodynamic wet-bulb temperature. Radiation was found to play a minor role in influencing droplet temperatures, except for larger droplets in environments close to saturation. The implications for ice nucleation in cloud-top generating cells and near cloud edges are discussed. Using Tss instead of T∞ in widely used parameterization schemes could lead to enhanced number concentrations of activated ice-nucleating particles (INPs), by a typical factor of 2–30, with the greatest increases (≥100) coincident with low RH, low P, and T∞ closer to 0°C.

Significance Statement
Cloud droplet temperature plays an important role in fundamental cloud processes like droplet growth and decay, activation of ice-nucleating particles, and determination of radiative parameters like refractive indices of water droplets. Near cloud boundaries such as cloud tops, dry air mixes with cloudy air exposing droplets to environments with low relative humidities. This study examines how the temperature of a cloud droplet that is supercooled (i.e., has an initial temperature < 0°C) evolves in these subsaturated environments. Results show that when supercooled cloud droplets evaporate near cloud boundaries, their temperatures can be several degrees Celsius lower than the surrounding drier environment. The implications of this additional cooling of droplets near cloud edges on ice particle formation are discussed.