bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacodynamic, pharmacokinetic, and phase 1a study of bisthianostat, a novel histone deacetylase inhibitor, for the treatment of relapsed or refractory multiple myeloma
Authors: Zhou Yu-bo , Zhang Yang-ming , Huang Hong-hui , Shen Li-jing , Han Xiao-feng , Hu Xiao-bei , Yu Song-da , Gao An-hui , Sheng Li , Su Ming-bo , Wei Xiao-li , Zhang Yue , Zhang Yi-fan , Gao Zhi-wei , Chen Xiao-yan , Nan Fa-jun , Li Jia , Hou Jian 
Published: August 2021

AbstractHDAC inhibitors (HDACis) have been intensively studied for their roles and potential as drug targets in T-cell lymphomas and other hematologic malignancies. Bisthianostat is a novel bisthiazole-based pan-HDACi evolved from natural HDACi largazole. Here, we report the preclinical study of bisthianostat alone and in combination with bortezomib in the treatment of multiple myeloma (MM), as well as preliminary first-in-human findings from an ongoing phase 1a study. Bisthianostat dose dependently induced acetylation of tubulin and H3 and increased PARP cleavage and apoptosis in RPMI-8226 cells. In RPMI-8226 and MM.1S cell xenograft mouse models, oral administration of bisthianostat (50, 75, 100 mg·kg-1·d-1, bid) for 18 days dose dependently inhibited tumor growth. Furthermore, bisthianostat in combination with bortezomib displayed synergistic antitumor effect against RPMI-8226 and MM.1S cell in vitro and in vivo. Preclinical pharmacokinetic study showed bisthianostat was quickly absorbed with moderate oral bioavailability (F% = 16.9%–35.5%). Bisthianostat tended to distribute in blood with Vss value of 0.31 L/kg. This distribution parameter might be beneficial to treat hematologic neoplasms such as MM with few side effects. In an ongoing phase 1a study, bisthianostat treatment was well tolerated and no grade 3/4 nonhematological adverse events (AEs) had occurred together with good pharmacokinetics profiles in eight patients with relapsed or refractory MM (R/R MM). The overall single-agent efficacy was modest, stable disease (SD) was identified in four (50%) patients at the end of first dosing cycle (day 28). These preliminary in-patient results suggest that bisthianostat is a promising HDACi drug with a comparable safety window in R/R MM, supporting for its further phase 1b clinical trial in combination with traditional MM therapies.
Rising levels of antioxidative phyllobilins in stored agricultural produce and their impact on consumer acceptance
Authors: Karg Cornelia A. , Neubig Christina M. , Roosen Jutta , Moser Simone 
Published: August 2021

AbstractConsumers often throw away faded greens, because taste and appearance are less appealing compared to fresh ones. We report here a family of antioxidants, the phyllobilins, which increase during storage in iceberg lettuce and cucumber. We show that informing consumers about rising levels of phyllobilins leads to a longer willingness to consume faded lettuce and to an improved health and safety perception.
Quorum sensing systems and related virulence factors in Pseudomonas aeruginosa isolated from chicken meat and ground beef
Authors: İnat Gökhan , Sırıken Belgin , Başkan Ceren , Erol İrfan , Yıldırım Tuba , Çiftci Alper 
Published: August 2021

AbstractThe objective of this study was to evaluate 50 [chicken meat (n = 45) and ground beef (n = 5)] Pseudomonas aeruginosa isolates to determine the expression of the lasI and rhl QS systems, related virulence factors, and the presence of N-3-oxo-dodecanoyl homoserine lactone (AHL: 3-O-C12-HSL). For the isolation and identification of P. aeruginosa, conventional culture and oprL gene-based molecular techniques were used. In relation to QS systems, eight genes consisting of four intact and four internal (lasI/R, rhlI/R) genes were analyzed with PCR assay. The two QS systems genes in P. aeruginosa isolates from ground beef (80.00%) and chicken meat (76.00%) were present at quite high levels. The 3-O-C12-HSL was detected in 14.00% of the isolates. Both biofilm formation and motility were detected in 98.00% of the isolates. Protease activity was determined in 54.00% of the isolates. Pyocyanin production was detected in 48.00% of the isolates. The las system scores strongly and positively correlated with the rhl system (p ˂ .01). PYA moderately and positively correlated with protease (p ˂ .05). In addition, there was statistically significance between lasI and protease activity (p < .10), and rhlI and twitching motility (p < .10). In conclusion, the high number of isolates having QS systems and related virulence factors are critical for public health. Pyocyanin, protease, and biofilm formation can cause spoilage and play essential role in food spoilage and food safety.
Simulation of solute transport behaviors in saturated karst aquifer system
Authors: Chu Xuewei , Ding Hanghang , Zhang Xuemei 
Published: August 2021

AbstractThe karst development makes aquifer have strong anisotropy and heterogeneity. In order to reveal the characteristics of solute transport in the karst fissure–conduit aquifer system, this study presents a physical model of fissure–conduit in laboratory experiments to carry out the solute transport simulation. In this paper, the tracer tests of fissure–conduit combination, fissure, and conduit solute transport process in saturated flow are designed. We found that different aquifer structures and tracer injection points have an influence on the shape of the breakthrough curve. Besides, the two-dimensional dispersion model of tracer injection of the instantaneous point was used to calculate the dispersion parameters of each group of experiments. Then, the dynamic responses of the linear distance (x) between the injection point and the receiving point, initial time (t0), peak time (tm), peak concentration (cm), average tracer transport velocity (V), and porosity (p) of aqueous media to the longitudinal dispersion coefficient are discussed. In addition, according to the measured data, Gaussian multi-peak fitting can be used to reflect the overall shape and change trend of the multi-peak BTC. These results demonstrate the solute transport behaviors in the saturated karst aquifer system, which have important reference significance for solving the engineering environmental problems in the karst area.
Longitudinal stability of urinary extracellular vesicle protein patterns within and between individuals
Authors: Erozenci Leyla A. , Piersma Sander R. , Pham Thang V. , Bijnsdorp Irene V. , Jimenez Connie R. 
Published: August 2021

AbstractThe protein content of urinary extracellular vesicles (EVs) is considered to be an attractive non-invasive biomarker source. However, little is known about the consistency and variability of urinary EV proteins within and between individuals over a longer time-period. Here, we evaluated the stability of the urinary EV proteomes of 8 healthy individuals at 9 timepoints over 6 months using data-independent-acquisition mass spectrometry. The 1802 identified proteins had a high correlation amongst all samples, with 40% of the proteome detected in every sample and 90% detected in more than 1 individual at all timepoints. Unsupervised analysis of top 10% most variable proteins yielded person-specific profiles. The core EV-protein-interaction network of 516 proteins detected in all measured samples revealed sub-clusters involved in the biological processes of G-protein signaling, cytoskeletal transport, cellular energy metabolism and immunity. Furthermore, gender-specific expression patterns were detected in the urinary EV proteome. Our findings indicate that the urinary EV proteome is stable in longitudinal samples of healthy subjects over a prolonged time-period, further underscoring its potential for reliable non-invasive diagnostic/prognostic biomarkers.
The effect of electrode shape on Schottky barrier and electric field distribution of flexible ZnO photodiode
Authors: Jezeh Zahra Aminrayai , Efafi Babak , Ghafary Bijan 
Published: August 2021

AbstractIn this study, the effect of electrode shape difference on the height of the Schottky barrier and the electric field in flexible photodiodes (PDs) has been investigated. For this purpose, three different electrode designs were prepared on three flexible FR4 layers that were coated with Zinc Oxide (ZnO). The printing circuit board (PCB) method was used to create these copper electrodes. The asymmetry of the PD electrodes and the difference in the height of the Schottky barrier has led to the creation of self-powered PDs. The effect of the amount and shape of the distribution of internal electric fields generated in the PDs and its effect on the parameters of the PDs has been investigated with the help of simulations performed in COMSOL software. The photocurrent of the sample with circular and rectangular electrodes was equal to 470 µA in 15 V bias, which was twice as good as a sample with an interdigitated MSM structure. Also, this sample had the best response time among these three samples, which was equal to 440 ms.
No association between serum uric acid and lumbar spine bone mineral density in US adult males: a cross sectional study
Authors: Li Xiaoli , Li Lianju , Yang Lixian , Yang Jiaxun , Lu Hua 
Published: August 2021

AbstractAvailable evidence linking serum uric acid (SUA) and bone mineral density (BMD) remains controversial, and data on this association are limited among adult men in the general population. Thus, the aim of this study was to evaluate the association of SUA with lumbar spine BMD in US adult males. A cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES, 1999–2006) database. Multivariate linear regression analyses were employed to assess the association of SUA with lumbar spine BMD, considering complex survey design and sampling weights. Through rigorous eligibility criteria, a total of 6704 individuals were yielded for final data analysis (average age, 40.5 years; 70.6% white). After fully adjusting potential confounders, no associations were detected between SUA and lumbar spine BMD [β (95% confidence interval, CI), − 0.003 (− 0.007, 0.002)]. Additionally, similar results were observed in all stratification analyses, and no interactions were found based on all priori specifications. In brief, our findings did not provide an inspiring clue for the hypothesis that SUA may be beneficial to lumbar spine BMD. Future more prospective studies are needed to further explore the causal relationship of SUA with lumbar spine BMD.
Clinical outcomes of combined Preserflo Microshunt implantation and cataract surgery in open-angle glaucoma patients
Authors: Martínez-de-la-Casa José M. , Saenz-Francés Federico , Morales-Fernandez Laura , Perucho Lucia , Mendez Carmen , Fernandez-Vidal Ana , Garcia-Saenz Sofía , Sanchez-Jean Ruben , García-Feijoo Julian 
Published: August 2021

AbstractTo assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months. Success was defined as an intraocular pressure (IOP) ≤ 18 mmHg and a reduction of at least 20% without (complete) or with (qualified) hypotensive medication. Fifty-eight eyes were included in the study, 35 eyes underwent PMS alone and 23 underwent PMS + Phaco. In the overall study sample, mean IOP was significantly lowered from 21.5 ± 3.3 mmHg at baseline to 14.6 ± 3.5 mmHg at month 12 (p < 0.0001). The IOP was significantly reduced in both groups; p < 0.0001 each, respectively. Ocular hypotensive medication was significantly reduced (p < 0.0001) in both groups. No significant differences were observed in IOP lowering or medication reduction between groups. At month 12, 62.1% eyes were considered as complete success and 82.8% eyes as qualified success. The most common adverse events were device close-to-endothelium, conjunctival fibrosis, and wound leakage. PMS, either alone or in combination with phacoemulsification, may be considered as a valuable option for treating OAG patients.
Habitat suitability mapping of the black coral Leiopathes glaberrima to support conservation of vulnerable marine ecosystems
Authors: Lauria V. , Massi D. , Fiorentino F. , Milisenda G. , Cillari T. 
Published: August 2021

AbstractThe black coral Leiopathes glaberrima is an important habitat forming species that supports benthic biodiversity. Due to its high sensitivity to fishing activities, it has been classified as indicator of Vulnerable Marine Ecosystems (VMEs). However, the information on its habitat selection and large-scale spatial distribution in the Mediterranean Sea is poor. In this study a thorough literature review on the occurrence of L. glaberrima across the Mediterranean Sea was undertaken. Predictive modelling was carried out to produce the first continuous map of L. glaberrima suitable habitat in the central sector of the Mediterranean Sea. MaxEnt modeling was used to predict L. glaberrima probability of presence as a function of seven environmental predictors (bathymetry, slope, aspect North–South and East–West, kinetic energy due to currents at the seabed, seabed habitat types and sea bottom temperature). Our results show that bathymetry, slope and aspect are the most important factors driving L. glaberrima spatial distribution, while in less extent the other environmental variables. This study adds relevant information on the spatial distribution of vulnerable deep water corals in relation to the environmental factors in the Mediterranean Sea. It provides an important background for marine spatial planning especially for prioritizing areas for the conservation of VMEs.
A tree of leaves: Phylogeny and historical biogeography of the leaf insects (Phasmatodea: Phylliidae)
Authors: Bank Sarah , Cumming Royce T. , Li Yunchang , Henze Katharina , Le Tirant Stéphane , Bradler Sven 
Published: August 2021

AbstractThe insect order Phasmatodea is known for large slender insects masquerading as twigs or bark. In contrast to these so-called stick insects, the subordinated clade of leaf insects (Phylliidae) are dorso-ventrally flattened and therefore resemble leaves in a unique way. Here we show that the origin of extant leaf insects lies in the Australasian/Pacific region with subsequent dispersal westwards to mainland Asia and colonisation of most Southeast Asian landmasses. We further hypothesise that the clade originated in the Early Eocene after the emergence of angiosperm-dominated rainforests. The genusPhylliumto which most of the ~100 described species pertain is recovered as paraphyletic and its three non-nominate subgenera are recovered as distinct, monophyletic groups and are consequently elevated to genus rank. This first phylogeny covering all major phylliid groups provides the basis for future studies on their taxonomy and a framework to unveil more of their cryptic and underestimated diversity.
In vitro assay for single-cell characterization of impaired deformability in red blood cells under recurrent episodes of hypoxia
Authors: Qiang Yuhao , Liu Jia , Dao Ming , Du E. 
Published: August 2021

In vitro single-cell testing of mechanical degradation of red blood cells (RBCs) after undergoing hypoxia fatigue cycles in the microfluidic device, mimicking cyclic oxygen tension variations RBCs experience during in vivo blood circulation.
The Use of Same-Day Hearing Aid Fitting with Telehealth Follow-up Care: A Case Study of a Veteran Presenting with Tinnitus and Auditory Processing Disorder Symptoms
Authors: Jedlicka David P. 
Published: August 2021

AbstractProviding same-day hearing aid fitting appointments to patients being seen in an audiology clinic for an audiometric evaluation may help decrease clinic wait times and reduce the need for future in-person appointments. Prior to 2020, the Veterans Administration (VA) Healthcare System did not allow hearing aid manufacturers to provide functional demonstration (demo) hearing aids to VA audiology clinics. Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic, this rule was changed to minimize the number of required in-person VA audiology appointments. The audiology clinic at the Pittsburgh VA Healthcare System developed a hearing aid fitting protocol using demo hearing aids to provide same-day hearing aid fitting appointments. This case study pertains to a female Veteran who presented to the clinic with complaints of decreased hearing and bothersome tinnitus. The patient completed a comprehensive audiometric evaluation, auditory processing disorder screening, hearing aid evaluation, and hearing aid fitting in the clinic. All follow-up appointments were scheduled to be completed via telehealth. The initial findings in this case study indicate that same-day hearing aid fittings can be successful for some patients. Future telehealth follow-up appointments will determine this patient's level of success using hearing aid–related outcome measures.
Troubleshooting Cochlear Implant Processors via Tele-Audiology
Authors: Boss Benjamin 
Published: August 2021

AbstractThis case study examines the methods used to troubleshoot a cochlear implant processor via video visit with a nonagenarian (90+ years old) with a bimodal cochlear implant system. This article will discuss the evaluation and management as well as which specific issues could be addressed virtually and how they were resolved. Examples will be provided about how to virtually connect with the patient and how to best facilitate communication during a video visit. Additionally, this article will examine the captioning apps and other hearing assistive technology available for smartphones that can provide further assistance during a cell phone call along with their benefits and limitations.
Evaluation and Management of Misophonia Using a Hybrid Telecare Approach: A Case Report
Authors: Zitelli Lori 
Published: August 2021

AbstractDecreased sound tolerance (DST) is a negative reaction to environmental sounds and is estimated to affect 3.5% of the population. This case report presents the evaluation and management of an adult female with severe, longstanding misophonia. Her evaluation included comprehensive audiometric testing (including uncomfortable loudness levels) and a detailed assessment of the impact of DST on her life. She enrolled in tinnitus retraining therapy and began receiving treatment aiming to facilitate habituation of bothersome environmental sounds. This case was complicated by the advent of the coronavirus disease 2019 (COVID-19) pandemic and a telemedicine hybrid approach was employed to increase access to audiologic care. Using this structure, some appointments occurred in person in the clinic and others occurred via a telemedicine video visit format. Telemedicine video visits facilitated in-depth discussions, afforded the opportunity to answer questions, and provided the option of cloud-based remote programming of on-ear devices. Future care will continue to employ a hybrid approach.
Training wicked scientists for a world of wicked problems
Authors: Kawa Nicholas C. , Arceño Mark Anthony , Goeckner Ryan , Hunter Chelsea E. , Rhue Steven J. , Scaggs Shane A. , Biwer Matthew E. , Downey Sean S. , Field Julie S. , Gremillion Kristen , McCorriston Joy , Willow Anna , Newton Elizabeth , Moritz Mark 
Published: August 2021

AbstractHumanity faces a number of wicked problems, from global climate change and the coronavirus pandemic to systemic racism and widening economic inequality. Since such complex and dynamic problems are plagued by disagreement among stakeholders over their nature and cause, they are notoriously difficult to solve. This commentary argues that if humanity truly aspires to address the grand challenges of today and tomorrow, then graduate education must be redesigned. It is no longer sufficient to train students only to be experts in their respective fields. They also must hone the interpersonal and professional skills that allow them to collaborate successfully within diverse teams of researchers and other stakeholders. Here the conceptual framework of wicked science is proposed, including what a graduate program in wicked science would achieve and why such training matters both to researchers and the communities where they work. If humanity hopes to effectively tackle the world’s wicked problems, then it is time to train a generation of wicked scientists.
Field-angle-dependent multi-frequency electron spin resonance spectroscopy in submillimeter wave range based on thermal detection
Authors: Takahashi Hideyuki , Sakurai Takahiro , Ohmichi Eiji , Ohta Hitoshi 
Published: August 2021

We report the thermally detected electron spin resonance (ESR) spectroscopy in the frequency range of millimeter and submillimeter waves. Under high vacuum conditions, a cantilever-shaped device detects ESR absorption of a mounted sample as a temperature difference in its beam direction. Despite the simple experimental setup, the spin sensitivity of the order of 1012 spins/G was achieved at 10 K. The developed sample stage is small enough to be used in a 10 T split-pair superconducting magnet with a bore of 25 mm, enabling precise field-angle-dependent ESR measurements at multi-frequencies above 500 GHz. We demonstrate its usefulness by studying the field-angle dependence of the excitation energy of the dimer triplet state in the Shastry–Sutherland magnet SrCu2(BO3)2.
The symbolic role of the underground world among Middle Paleolithic Neanderthals
Authors: Pitarch Martí Africa , Zilhão João , d’Errico Francesco , Cantalejo-Duarte Pedro , Domínguez-Bella Salvador , Fullola Josep M. , Weniger Gerd C. , Ramos-Muñoz José 
Published: August 2021

SignificanceThe emergence of symbolic behavior in our genus is a controversial issue. The dating of paintings in three caves from the Iberian Peninsula supports the view that Neanderthals developed a form of cave art more than 20,000 years before the emergence of anatomical modernity in Europe. In this study, we confirm that the paintings on a large speleothem from one of these sites, Cueva de Ardales, were human made, and we show that the pigments do not come from the outcrops of colorant material known inside the cave. Variations in the composition of the paint correspond to differences in the age of the paintings, supporting the hypothesis that Neanderthals used the speleothems symbolically over an extended time span.
Examining the consumption of radical content on YouTube
Authors: Hosseinmardi Homa , Ghasemian Amir , Clauset Aaron , Mobius Markus , Rothschild David M. , Watts Duncan J. 
Published: August 2021

Significance
Daily share of news consumption on YouTube, a social media platform with more than 2 billion monthly users, has increased in the last few years. Constructing a large dataset of users’ trajectories across the full political spectrum during 2016–2019, we identify several distinct communities of news consumers, including “far-right” and “anti-woke.” Far right is small and not increasing in size over the observation period, while anti-woke is growing, and both grow in consumption per user. We find little evidence that the YouTube recommendation algorithm is driving attention to this content. Our results indicate that trends in video-based political news consumption are determined by a complicated combination of user preferences, platform features, and the supply-and-demand dynamics of the broader web.