bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Stem Cell DNA Enabled Real‐Time Genotyping with Self‐Functionalized Quantum Superstructures—Overcoming the Barriers of Noninvasive cfDNA Cancer Diagnostics
Authors: Haldavnekar Rupa , Ganesh Swarna , Venkatakrishnan Krishnan , Tan Bo 
Published: March 2022

AbstractCancer diagnosis and determining its tissue of origin are crucial for clinical implementation of personalized medicine. Conventional diagnostic techniques such as imaging and tissue biopsy are unable to capture the dynamic tumor landscape. Although circulating tumor DNA (ctDNA) shows promise for diagnosis, the clinical relevance of ctDNA remains largely undetermined due to several biological and technical complexities. Here, cancer stem cell‐ctDNA is used to overcome the biological complexities like the inability for molecular analysis of ctDNA and dependence on ctDNA concentration rather than the molecular profile. Ultrasensitive quantum superstructures overcome the technical complexities of trace‐level detection and rapid diagnosis to detect ctDNA within its short half‐life. Activation of multiple surface enhanced Raman scattering mechanisms of the quantum superstructures achieved a very high enhancement factor (1.35 × 1011) and detection at ultralow concentration (10−15M) with very high reliability (RSD: 3–12%). Pilot validation with clinical plasma samples from an independent validation cohort achieved a diagnosis sensitivity of ≈95% and specificity of 83%. Quantum superstructures identified the tissue of origin with ≈75–86% sensitivity and ≈92–96% specificity. With large scale clinical validation, the technology can develop into a clinically useful liquid biopsy tool improving cancer diagnostics.
Assessing high‐school students' modeling performance on Newtonian mechanics
Authors: Zhai Xiaoming 
Published: March 2022

AbstractAssessing scientific modeling competence (SMC) is challenging because of the multi‐dimensionality of the construct and the potential variability of student performance across tasks. To deal with the challenges, this study applied Kane's validity framework to assess high‐school students' SMC in Newtonian mechanics and examined how students' performance depended on tasks. We first specified students' SMC in three dimensions: Conceptualization, Deploying Scientific Knowledge, and Representation, incorporating 11 components (e.g., conceptualization of objects). We assessed 305 high‐school students' modeling performance on two Newtonian mechanics tasks, taking task dependency into account. We applied the Many‐facet Rasch measurement (MFRM) to examine students' ability and discriminate students' performance variability across tasks. MFRM analyses revealed that among the three dimensions of SMC, Representation is most challenging for students to achieve compared to Conceptualization and Deploying Scientific Knowledge, especially among higher‐performing students. Five out of the 11 SMC components were task‐dependent, suggesting significant score variance due to the variability of tasks. After excluding task variance, we found that students were grouped into four levels (i.e., primitive non‐model, intuitive model, qualitative model, and quantitative model), and the majority of students were distributed at the medium two levels. We conclude the study by introducing three putative theories that may account for task dependency: depth of cognition, knowledge transfer, and construct irrelevant interest. The study suggests that task dependency does not necessarily compromise the interpretation of scores, as long as assessors appropriately consider potential theories in their interpretive arguments when designing tasks and interpreting scores.
Safety of intravenous iodinated contrast medium injection in rabbits undergoing conscious computed tomography
Authors: Isaac Ingrid , Richardson Jenna , Liuti Tiziana , Longo Maurizio 
Published: March 2022

AbstractBackgroundContrast media in CT is widely used in dogs and cats to provide superior tissue delineation and increase the diagnostic capabilities. These contrast‐enhanced imaging techniques are gaining popularity in rabbits; published studies reporting the safety of doing so are lacking.MethodsThis retrospective observational study aimed to determine the incidence of adverse events following the intravenous administration of iodinated non‐ionic contrast medium in 350 rabbits. The medical records of this subset of rabbits admitted between January 2009 and November 2018, that underwent CT examination and received intravenous contrast media, were evaluated.ResultsFrom the 350 rabbits, 342 rabbits were still alive 7 days after the scan. A total of eight rabbits died within 7 days of the scan, seven of which within the first 24 h. All deaths were presumed to be sequelae to the diseases they were being investigated for and not thought to be related to the administration of intravenous contrast medium.ConclusionsThe results indicated that the use of intravenous non‐iodinated contrast medium was well tolerated and safe in rabbits undergoing conscious CT examination.
Generative models for molecular discovery: Recent advances and challenges
Authors: Bilodeau Camille , Jin Wengong , Jaakkola Tommi , Barzilay Regina , Jensen Klavs F. 
Published: March 2022

AbstractDevelopment of new products often relies on the discovery of novel molecules. While conventional molecular design involves using human expertise to propose, synthesize, and test new molecules, this process can be cost and time intensive, limiting the number of molecules that can be reasonably tested. Generative modeling provides an alternative approach to molecular discovery by reformulating molecular design as an inverse design problem. Here, we review the recent advances in the state‐of‐the‐art of generative molecular design and discusses the considerations for integrating these models into real molecular discovery campaigns. We first review the model design choices required to develop and train a generative model including common 1D, 2D, and 3D representations of molecules and typical generative modeling neural network architectures. We then describe different problem statements for molecular discovery applications and explore the benchmarks used to evaluate models based on those problem statements. Finally, we discuss the important factors that play a role in integrating generative models into experimental workflows. Our aim is that this review will equip the reader with the information and context necessary to utilize generative modeling within their domain.This article is categorized under:
Data Science > Artificial Intelligence/Machine Learning
Flavour alignment of New Physics in light of the (g − 2)μ anomaly
Authors: Isidori Gino , Pagès Julie , Wilsch Felix 
Published: March 2022

Abstract
We investigate the flavour alignment conditions that New Physics (NP) models need to satisfy in order to address the (g − 2)μ anomaly and, at the same time, be consistent with the tight bounds from μ → eγ and τ → μγ. We analyse the problem in general terms within the SMEFT, considering the renormalisation group evolution of all the operators involved. We show that semileptonic four-fermion operators, which are likely to generate a sizeable contribution to the (g − 2)μ anomaly, need to be tightly aligned to the lepton Yukawa couplings and the dipole operators in flavour space. While this tuning can be achieved in specific NP constructions, employing particular dynamical assumptions and/or flavour symmetry hypotheses, it is problematic in a wide class of models with broken flavour symmetries, such as those proposed to address both charged- and neutral-current B anomalies. We quantify this tension both in general terms, and in the context of explicit NP constructions.
Quantifying scrambling in quantum neural networks
Authors: Garcia Roy J. , Bu Kaifeng , Jaffe Arthur 
Published: March 2022

Abstract
We quantify the role of scrambling in quantum machine learning. We characterize a quantum neural network’s (QNNs) error in terms of the network’s scrambling properties via the out-of-time-ordered correlator (OTOC). A network can be trained by minimizing a loss function. We show that the loss function can be bounded by the OTOC. We prove that the gradient of the loss function can be bounded by the gradient of the OTOC. This demonstrates that the OTOC landscape regulates the trainability of a QNN. We show numerically that this landscape is flat for maximally scrambling QNNs, which can pose a challenge to training. Our results pave the way for the exploration of quantum chaos in quantum neural networks.
Assessment of aromatic amides in printed food contact materials: analysis of potential cleavage to primary aromatic amines during simulated passage through the gastrointestinal tract
Authors: Bittner Nataly , Boon Andy , Delbanco Evert H. , Walter Christof , Mally Angela 
Published: March 2022

AbstractRecent analyses conducted by German official food control reported detection of the aromatic amides N-(2,4-dimethylphenyl)acetamide (NDPA), N-acetoacetyl-m-xylidine (NAAX) and 3-hydroxy-2-naphthanilide (Naphthol AS) in cold water extracts from certain food contact materials made from paper or cardboard, including paper straws, paper napkins, and cupcake liners. Because aromatic amides may be cleaved to potentially genotoxic primary amines upon oral intake, these findings raise concern that transfer of NDPA, NAAX and Naphthol AS from food contact materials into food may present a risk to human health. The aim of the present work was to assess the stability of NDPA, NAAX and Naphthol AS and potential cleavage to 2,4-dimethylaniline (2,4-DMA) and aniline during simulated passage through the gastrointestinal tract using static in vitro digestion models. Using the digestion model established by the National Institute for Public Health and the Environment (RIVM, Bilthoven, NL) and a protocol recommended by the European Food Safety Authority, potential hydrolysis of the aromatic amides to the respective aromatic amines was assessed by LC–MS/MS following incubation of the aromatic amides with digestive fluid simulants. Time-dependent hydrolysis of NDPA and NAAX resulting in formation of the primary aromatic amine 2,4-DMA was consistently observed in both models. The highest rate of cleavage of NDPA and NAAX was recorded following 4 h incubation with 0.07 M HCl as gastric-juice simulant, and amounted to 0.21% and 0.053%, respectively. Incubation of Naphthol AS with digestive fluid simulants did not give rise to an increase in the concentration of aniline above the background that resulted from the presence of aniline as an impurity of the test compound. Considering the lack of evidence for aniline formation from Naphthol AS and the extremely low rate of hydrolysis of the amide bonds of NDPA and NAAX during simulated passage through the gastrointestinal tract that gives rise to only very minor amounts of the potentially mutagenic and/or carcinogenic aromatic amine 2,4-DMA, risk assessment based on assumption of 100% cleavage to the primary aromatic amines would appear to overestimate health risks related to the presence of aromatic amides in food contact materials.
Neuropsychiatric Comorbidity in Primary Hyperparathyroidism Before and After Parathyroidectomy: A Population Study
Authors: Koman A. , Bränström R. , Pernow Y. , Bränström R. , Nilsson I.‐L. , Granath Fredrik 
Published: March 2022

AbstractBackgroundPrimary hyperparathyroidism (PHPT) is often accompanied by neuropsychiatric symptoms. This study aimed to map out psychiatric comorbidity as reflected by medical treatment for psychiatric symptoms.MethodsA retrospective case–control analysis and a prospective cohort analysis of psychotropic drug utilization before and after PTX. A total of 8279 PHPT patients treated with parathyroidectomy in Sweden between July 1, 2008 and December 31, 2017 compared to a matched control cohort from the total population (n = 82,790). Information on filled prescriptions was collected from the Swedish Prescribed Drug Register (SDR). Socioeconomic data and diagnoses were added by linkage to national patient and population registers. Regression analyses were used to calculate relative drug utilization (OR) within 3 years prior to PTX and relative incidence of drug treatment (RR) within 3 years postoperatively.ResultsUtilization of antidepressant, anxiolytic and sleep medication was more comprehensive in PHPT patients compared with the controls prior to PTX. The most common were benzodiazepines [OR 1.40 (95% CI: 1.31–1.50)] and selective serotonin reuptake inhibitors [SSRI; OR 1.38 (95% CI: 1.30–1.47)]. Postoperatively, the excess prescription rate for anxiolytic benzodiazepines decreased within three years from a 30 to 19% excess and for benzodiazepines for sleep from 31 to 14%. No corresponding decrease in excess prescription rate was observed for SSRI.ConclusionPHPT is associated with increased utilization of antidepressive medications and benzodiazepines before PTX. This study implies that psychiatric symptoms should be considered in PHPT patients and continuous medication should be reevaluated after PTX.
Phase 1b trial of anti-VEGF/PDGFR vorolanib combined with immune checkpoint inhibitors in patients with advanced solid tumors
Authors: Bagegni Nusayba A. , Park Haeseong , Kraft Katlyn , O-Toole Maura , Gao Feng , Waqar Saiama N. , Ratner Lee , Morgensztern Daniel , Devarakonda Siddhartha , Amin Manik , Baggstrom Maria Q. , Liang Chris , Selvaggi Giovanni , Wang-Gillam Andrea 
Published: March 2022

Abstract
Purpose
Vorolanib is a multi-target tyrosine kinase inhibitor with anti-angiogenic properties. This study aimed to evaluate the tolerability, safety and efficacy of vorolanib when added to checkpoint inhibitors (CPIs) in patients with advanced solid tumors.

Methods
We conducted a phase 1b study of vorolanib (300 or 400 mg orally once daily) plus pembrolizumab or nivolumab using a standard 3 + 3 design to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). The endpoints included safety, toxicity and objective response rate, according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

Results
Sixteen patients (9 in pembrolizumab arm, 7 in nivolumab arm) with gastrointestinal or lung cancers were enrolled. All patients had at least 1 treatment-related adverse event (TRAE). The most common TRAEs across all cohorts were lymphopenia (n = 7), leukopenia (n = 5), fatigue (n = 5), and alanine aminotransferase elevation (n = 5); most toxicities were grade (G) 1–2. DLTs were reported in 3 patients at vorolanib 400 mg dose level, with G3 aspartate aminotransferase elevation, G3 rectal hemorrhage, and G3 rash. Of 13 total response-evaluable patients, 2 patients had confirmed partial responses (1 rectal squamous cell cancer and 1 small cell lung cancer). Two patients achieved prolonged stable disease. Vorolanib 300 mg daily was determined to be the RP2D for either pembrolizumab or nivolumab.

Conclusion
Combination vorolanib 300 mg orally once daily plus CPI appears to be a feasible regimen with manageable toxicity and promising efficacy in select tumor types. NCT03511222. Date of Registration: April 18, 2018.
SCL, Encoding a Chloroplast Signal Recognition Particle Receptor, Affects Chlorophyll Synthesis and Chloroplast Development in Rice
Authors: Ye Jing , Ye Shenghai , Zhai Rongrong , Wu Mingming , Yu Faming , Zhu Guofu , Zhang Xiaoming 
Published: March 2022

AbstractCrop yield is largely determined by the solar energy utilization efficiency of photosynthesis; plants with long stay-green periods have greater total photosynthetic production levels and crop yields. Here, a novel seedling chlorosis and lethality (scl) mutant exhibiting a yellow leaf and seedling-lethal phenotype was identified in rice (Oryza sativa L.). The mutant had deformed chloroplasts and almost no protein complexes in thylakoid membranes. The expression levels of photosynthesis-associated genes were significantly down-regulated in scl compared with the wild-type (WT). Positive transgenic lines generated by Agrobacterium tumefaciens-mediated transformation of the scl mutant with a complementation vector harboring SCL cDNA exhibited the normal green leaf phenotype, whereas the scl seedling harboring the empty vector displayed the yellow leaf phenotype, indicating that SCL is LOC_Os01g72800. A fusion protein expressing SCL with green fluorescent protein revealed the fluorescence signal localized to chloroplasts. The expression patterns of chloroplast development and chlorophyll biosynthesis and degradation-related genes were disordered in scl mutant, possibly resulting in the yellow leaf phenotype. These results indicated that the SCL loss of function impaired chloroplast development, chlorophyll biosynthesis, and light-harvesting chlorophyll-binding protein transportation in rice.
An adaptive approach to quantify weather-within-climate rainfall characteristics
Authors: Martinez Carlos , Muñoz Ángel G. , Goddard Lisa , Kushnir Yochanan , Ting Mingfang 
Published: March 2022

AbstractKnowledge of subseasonal-to-seasonal (S2S) rainfall characteristics such as onset, duration, and demise of the rainfall cycle, and characteristics of dry periods that are between rainfall seasons, can provide important insight for the agriculture, health, disaster, and energy industries. Several methods have attempted to calculate temporal characteristics of rainfall and few have worked with intermittent dry periods and calculate intermittent dry period characteristics. Issues arise when applying these methods for complex rainfall regimes, or regions that have one or more of the following: (1) multiple rainfall seasons in a given year, (2) a relatively wet dry season, (3) unclear transitions between wet and dry seasons. This study develops a new and comprehensive method for calculating S2S rainfall characteristics, especially for regions that have complex annual rainfall cycles. The method consists of three steps: (1) create the annual cycle climatology of rainfall and classify its modality by the presence or absence of intermittent dry period(s), (2) identify seasonal windows of the rainfall cycle based on its climatological modality, (3) calculate yearly intermittent dry period characteristics and calculate temporal rainfall characteristics for each year using information on daily rainfall amount and the concurrent rate of change. Application and results of the method are given for the Caribbean, which exhibits the properties of a region with complex rainfall regimes. The method can be utilized under a meteorological or agronomical lens and is able to delineate false meteorological and agronomical onsets and demises. Meteorological onsets and demises that are calculated via each year’s Early-Rainy Season (ERS) and Late-Rainy Season (LRS) mean thresholds effectively characterize the seasonal evolution of mean onsets and demises in the Caribbean. The year-to-year variability of Mid-Summer Drought (MSD) characteristics, and onsets and demises that are calculated by climatological ERS and LRS mean thresholds resemble the variability of seasonal rainfall totals in the Caribbean and are statistically significantly correlated with the identified dynamical processes that impact each seasonal component of the rainfall cycle. The method has important implications for prediction, modeling capabilities, and understanding the variability of rainfall across timescales.
Continuing versus withholding angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) combination tablets during perioperative periods in patients undergoing minor surgery: a single-blinded randomized controlled trial
Authors: Takeuchi Kazuyo , Hayashida Masakazu , Kudoh Osamu , Niimi Naoko , Kataoka Kumi , Kakemizu-Watanabe Maho , Yamamoto Makiko , Hara Atsuko , Kawagoe Izumi , Yamaguchi Keisuke 
Published: March 2022

Abstract
Purpose
This trial was conducted to compare effects of continuing versus withholding single-pill combination tablets consisting of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on perioperative hemodynamics and clinical outcomes.

Methods
Patients undergoing minor abdominal or urological surgery (n = 106) were randomly assigned to Group C, in which ARB/CCB combination tablets were continued until surgery, or Group W, in which they were withheld within 24 h of surgery. Perioperative hemodynamics and clinical outcomes were compared between the Groups.

Results
The incidence of hypotension during anesthesia requiring repeated treatment with vasoconstrictors was higher in Group C than Group W (p = 0.0052). Blood pressure during anesthesia was generally lower in Group C than Group W (p < 0.05) despite significantly more doses of ephedrine and phenylephrine administrated in Group C (p = 0.0246 and p = 0.0327, respectively). The incidence of postoperative hypertension did not differ between Groups (p = 0.3793). Estimated glomerular filtration rate (eGFR) on the preoperative day did not differ between Groups (p = 0.7045), while eGFR was slightly lower in Group C than Group W on the first and third postoperative days (p = 0.0400 and p = 0.0088, respectively), although clinically relevant acute kidney injury did not develop.

Conclusions
Continuing ARB/CCB combination tablets preoperatively in patients undergoing minor surgery increased the incidence of hypotension during anesthesia, increased requirements of vasoconstrictors to treat hypotension, and might deteriorate postoperative renal function, albeit slightly. These results suggest that withholding ARB/CCB tablets preoperatively is preferable to continuing them.

Clinical trial registration
This trial is registered with the Japan Registry of Clinical Trials (jRCT) at Japanese Ministry of Health, Labour, and Welfare (Trial ID: jRCT1031190027).
Omen: discovering sequential patterns with reliable prediction delays
Authors: Cüppers Joscha , Kalofolias Janis , Vreeken Jilles 
Published: March 2022

AbstractSuppose we are given a discrete-valued time series$$X $$Xof observed events and an equally long binary sequence$$Y $$Ythat indicates whether something of interest happened at that particular point in time. We consider the problem of mining serial episodes, sequential patterns allowing for gaps, from$$X $$Xthat reliably predict those interesting events. Withreliablewe mean patterns that not only predictthatan interesting event is likely to follow, but in particular that we can also accurately tell howhow longuntil that event will happen. In other words, we are specifically interested in patterns with a highly skewed distribution of delays between pattern occurrences and predicted events. As it is unlikely that a single pattern can explain a complex real-world progress, we are after the smallest, least redundant set of such patterns that together explain the interesting events well. We formally define this problem in terms of the Minimum Description Length principle, by which we identify the best patterns as those that describe the occurrences of interesting events$$Y $$Ymost succinctly given the data over$$X $$X. As neither discovering the optimal explanation of$$Y $$Ygiven a set of patterns, nor the discovery of optimal pattern set are problems that allow for straightforward optimization, we break the problem in two and propose effective heuristics for both. Through extensive empirical evaluation, we show that both our main method,Omen, and its fast approximationfOmen, work well in practice and both quantitatively and qualitatively beat the state of the art.