bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated image curation in diabetic retinopathy screening using deep learning
Authors: Nderitu Paul , Nunez do Rio Joan M. , Webster Ms Laura , Mann Samantha S. , Hopkins David , Cardoso M. Jorge , Modat Marc , Bergeles Christos , Jackson Timothy L. 
Published: July 2022

AbstractDiabetic retinopathy (DR) screening images are heterogeneous and contain undesirable non-retinal, incorrect field and ungradable samples which require curation, a laborious task to perform manually. We developed and validated single and multi-output laterality, retinal presence, retinal field and gradability classification deep learning (DL) models for automated curation. The internal dataset comprised of 7743 images from DR screening (UK) with 1479 external test images (Portugal and Paraguay). Internal vs external multi-output laterality AUROC were right (0.994 vs 0.905), left (0.994 vs 0.911) and unidentifiable (0.996 vs 0.680). Retinal presence AUROC were (1.000 vs 1.000). Retinal field AUROC were macula (0.994 vs 0.955), nasal (0.995 vs 0.962) and other retinal field (0.997 vs 0.944). Gradability AUROC were (0.985 vs 0.918). DL effectively detects laterality, retinal presence, retinal field and gradability of DR screening images with generalisation between centres and populations. DL models could be used for automated image curation within DR screening.
Core cysteine residues in the Plasminogen-Apple-Nematode (PAN) domain are critical for HGF/c-MET signaling
Authors: Pal Debjani , De Kuntal , Shanks Carly M. , Feng Kai , Yates Timothy B. , Morrell-Falvey Jennifer , Davidson Russell B. , Parks Jerry M. , Muchero Wellington 
Published: July 2022

AbstractThe Plasminogen-Apple-Nematode (PAN) domain, with a core of four to six cysteine residues, is found in > 28,000 proteins across 959 genera. Still, its role in protein function is not fully understood. The PAN domain was initially characterized in numerous proteins, including HGF. Dysregulation of HGF-mediated signaling results in multiple deadly cancers. The binding of HGF to its cell surface receptor, c-MET, triggers all biological impacts. Here, we show that mutating four core cysteine residues in the HGF PAN domain reduces c-MET interaction, subsequent c-MET autophosphorylation, and phosphorylation of its downstream targets, perinuclear localization, cellular internalization of HGF, and its receptor, c-MET, and c-MET ubiquitination. Furthermore, transcriptional activation of HGF/c-MET signaling-related genes involved in cancer progression, invasion, metastasis, and cell survival were impaired. Thus, targeting the PAN domain of HGF may represent a mechanism for selectively regulating the binding and activation of the c-MET pathway.
Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
Authors: Hu Xiaoming , Niu Yuguo , Luo Peixiang , Xiao Fei , Yuan Feixiang , Yin Hanrui , Chen Shanghai , Guo Feifan 
Published: July 2022

AbstractAngiotensin-converting enzyme 2 (ACE2) has been identified as a primary receptor for severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2). Here, we investigated the expression regulation of ACE2 in enterocytes under amino acid deprivation conditions. In this study, we found that ACE2 expression was upregulated upon all or single essential amino acid deprivation in human colonic epithelial CCD841 cells. Furthermore, we found that knockdown of general control nonderepressible 2 (GCN2) reduced intestinal ACE2 mRNA and protein levels in vitro and in vivo. Consistently, we revealed two GCN2 inhibitors, GCN2iB and GCN2-IN-1, downregulated ACE2 protein expression in CCD841 cells. Moreover, we found that increased ACE2 expression in response to leucine deprivation was GCN2 dependent. Through RNA-sequencing analysis, we identified two transcription factors, MAFB and MAFF, positively regulated ACE2 expression under leucine deprivation in CCD841 cells. These findings demonstrate that amino acid deficiency increases ACE2 expression and thereby likely aggravates intestinal SARS-CoV-2 infection.
Secure random number generation from parity symmetric radiations
Authors: Tsurumaru Toyohiro , Sasaki Toshihiko , Tsutsui Izumi 
Published: July 2022

AbstractThe random number generators (RNGs) are an indispensable tool for information security. Among various approaches, the radioactive decay has been considered as a promising candidate of RNGs for over half a century, on account of its seemingly unpredictable decay timings as quantum phenomena. However, the security of these radioactive RNGs has not been proven so far. Here we prove the security by a change of tactics, that is, by rewriting decay timings into decay directions, which allows us to ensure the secrecy with the help of the parity invariance deeply rooted in the fundamental law of nature. Our result demonstrates that the foundational properties of particle physics, such as the symmetry of interactions, can be used as a firm basis for the RNGs.
Universal multilayer network exploration by random walk with restart
Authors: Baptista Anthony , Gonzalez Aitor , Baudot Anaïs 
Published: July 2022

AbstractThe amount and variety of data have been increasing drastically for several years. These data are often represented as networks and explored with approaches arising from network theory. Recent years have witnessed the extension of network exploration approaches to capitalize on more complex and richer network frameworks. Random walks, for instance, have been extended to explore multilayer networks. However, current random walk approaches are limited in the combination and heterogeneity of networks they can handle. New analytical and numerical random walk methods are needed to cope with the increasing diversity and complexity of multilayer networks. We propose here MultiXrank, a method and associated Python package that enables Random Walk with Restart on any kind of multilayer network. We evaluate MultiXrank with leave-one-out cross-validation and link prediction, and measure the impact of the addition or removal of network data on prediction performances. Finally, we measure the sensitivity of MultiXrank to input parameters by in-depth exploration of the parameter space.
Mechanism for particle fractionalization and universal edge physics in quantum Hall fluids
Authors: Bochniak Arkadiusz , Nussinov Zohar , Seidel Alexander , Ortiz Gerardo 
Published: July 2022

AbstractAdvancing a microscopic framework that rigorously unveils the underlying topological hallmarks of fractional quantum Hall (FQH) fluids is a prerequisite for making progress in the classification of strongly-coupled topological matter. We present a second-quantization framework that reveals an exact fusion mechanism for particle fractionalization in FQH fluids, and uncovers the fundamental structure behind the condensation of non-local operators characterizing topological order in the lowest-Landau-level. We show the first exact analytic computation of the quasielectron Berry connections leading to its fractional charge and exchange statistics, and perform Monte Carlo simulations that numerically confirm the fusion mechanism for quasiparticles. We express the sequence of (bosonic and fermionic) Laughlin second-quantized states, highlighting the lack of local condensation, and present a rigorous constructive subspace bosonization dictionary for the bulk fluid. Finally, we establish universal long-distance behavior of edge excitations by formulating a conjecture based on the DNA, or root state, of the FQH fluid.
Over a third of groundwater in USA public-supply aquifers is Anthropocene-age and susceptible to surface contamination
Authors: Jurgens Bryant C. , Faulkner Kirsten , McMahon Peter B. , Hunt Andrew G. , Casile Gerolamo , Young Megan B. , Belitz Kenneth 
Published: July 2022

AbstractThe distribution of groundwater age is useful for evaluating the susceptibility and sustainability of groundwater resources. Here, we compute the aquifer-scale cumulative distribution function to characterize the age distribution for 21 Principal Aquifers that account for ~80% of public-supply pumping in the United States. The aquifer-scale cumulative distribution function for each Principal Aquifer was derived from an ensemble of modeled age distributions (~60 samples per aquifer) based on multiple tracers: tritium, tritiogenic helium-3, sulfur hexafluoride, chlorofluorocarbons, carbon-14, and radiogenic helium-4. Nationally, the groundwater is 38% Anthropocene (since 1953), 34% Holocene (75 – 11,800 years ago), and 28% Pleistocene (>11,800 years ago). The Anthropocene fraction ranges from <5 to 100%, indicating a wide range in susceptibility to land-surface contamination. The Pleistocene fraction of groundwater exceeds 50% in 7 eastern aquifers that are predominately confined. The Holocene fraction of groundwater exceeds 50% in 5 western aquifers that are predominately unconfined. The sustainability of pumping from these Principal Aquifers depends on rates of recharge and release of groundwater stored in fine-grained layers.
Spatio-temporal monitoring of health facility-level malaria trends in Zambia and adaptive scaling for operational intervention
Authors: Lubinda Jailos , Bi Yaxin , Haque Ubydul , Lubinda Mukuma , Hamainza Busiku , Moore Adrian J. 
Published: July 2022

Abstract
Background
The spatial and temporal variability inherent in malaria transmission within countries implies that targeted interventions for malaria control in high-burden settings and subnational elimination are a practical necessity. Identifying the spatio-temporal incidence, risk, and trends at different administrative geographies within malaria-endemic countries and monitoring them in near real-time as change occurs is crucial for developing and introducing cost-effective, subnational control and elimination intervention strategies.

Methods
This study developed intelligent data analytics incorporating Bayesian trend and spatio-temporal Integrated Laplace Approximation models to analyse high-burden over 32 million reported malaria cases from 1743 health facilities in Zambia between 2009 and 2015.

Results
The results show that at least 5.4 million people live in catchment areas with increasing trends of malaria, covering over 47% of all health facilities, while 5.7 million people live in areas with a declining trend (95% CI), covering 27% of health facilities. A two-scale spatio-temporal trend comparison identified significant differences between health facilities and higher-level districts, and the pattern observed in the southeastern region of Zambia provides the first evidence of the impact of recently implemented localised interventions.

Conclusions
The results support our recommendation for an adaptive scaling approach when implementing national malaria monitoring, control and elimination strategies and a particular need for stratified subnational approaches targeting high-burden regions with increasing disease trends. Strong clusters along borders with highly endemic countries in the north and south of Zambia underscore the need for coordinated cross-border malaria initiatives and strategies.
Patient-derived tumor organoids for personalized medicine in a patient with rare hepatocellular carcinoma with neuroendocrine differentiation: a case report
Authors: Meier Marie-Anne , Nuciforo Sandro , Coto-Llerena Mairene , Gallon John , Matter Matthias S. , Ercan Caner , Vosbeck Jürg , Terracciano Luigi M. , Soysal Savas D. , Boll Daniel , Kollmar Otto , Delaloye Raphaël , Piscuoglio Salvatore , Heim Markus H. 
Published: July 2022

Abstract
Background
Hepatocellular carcinoma with neuroendocrine differentiation (HCC-NED) is a very rare subtype of primary liver cancer. Treatment allocation in these patients therefore remains a challenge.

Methods
We report the case of a 74-year-old man with a HCC-NED. The tumor was surgically removed in curative intent. Histopathological work-up revealed poorly differentiated hepatocellular carcinoma (Edmondson-Steiner grade IV) with diffuse expression of neuroendocrine markers synaptophysin and chromogranin. Three months after resection, multifocal recurrence of the HCC-NED was observed. In the meantime, tumor organoids have been generated from the resected HCC-NED and extensively characterized. Sensitivity to a number of drugs approved for the treatment of HCC or neuroendocrine carcinomas was tested in vitro.

Results
Based on the results of the in vitro drug screening, etoposide and carboplatin are used as first line palliative combination treatment. With genomic analysis revealing a NTRK1-mutation of unknown significance (kinase domain) and tumor organoids found to be sensitive to entrectinib, a pan-TRK inhibitor, the patient was treated with entrectinib as second line therapy. After only two weeks, treatment is discontinued due to deterioration of the patient’s general condition.

Conclusion
The rapid establishment of patient-derived tumor organoids allows in vitro drug testing and thereby personalized treatment choices, however clinical translation remains a challenge. To the best of our knowledge, this report provides a first proof-of-principle for using organoids for personalized medicine in this rare subtype of primary liver cancer.
Dual Language Profiles in Spanish-Speaking English Learners
Authors: Su Pumpki Lei , Rojas Raúl , Iglesias Aquiles 
Published: July 2022

Purpose:
The purpose of this study was to identify and describe latent dual language profiles in a large sample of school-age Spanish–English bilingual children designated as English learners (ELs) by their school district.

Method:
Data for this study include 847 Spanish-speaking ELs from kindergarten to third grade. Spanish and English narrative retell language samples were collected from all participants. Four oral language measures were calculated in Spanish and English, including the subordination index, moving average type–token ratio, narrative structure scheme (NSS), and words per minute using Systematic Analysis of Language Transcript. These indicator measures were used in a latent profile analysis to identify dual language profiles.

Results:
The optimal model represents a four-profile solution, including a Spanish-dominant group (average Spanish, low English), an English-dominant group (low Spanish, average English), and two balanced groups (a balanced-average group and a balanced-high group). Additionally, participants displayed uneven performance across language domains and distinct patterns of unique strength or weakness in a specific domain in one of their two languages.

Conclusions:
Findings from this study highlight the large variability in English and Spanish oral language abilities in school-age Spanish-speaking ELs and suggest that a dichotomous classification of ELs versus English-proficient students may not be sufficient to determine the type of educational program that best fits a specific bilingual child's need. These findings highlight the need to assess both languages across multiple language domains to paint a representative picture of a bilingual child's language abilities. The dual language profiles identified may be used to guide the educational program selection process to improve the congruence among the linguistic needs of an individual child, teachers' use of instructional language, and the goals of the educational program (i.e., improving English proficiency vs. supporting dual language development).

Supplemental Material:

https://doi.org/10.23641/asha.20151836
New conditions for finite‐time stability of impulsive dynamical systems via piecewise quadratic functions
Authors: Ambrosino Roberto , Ariola Marco , Garone Emanuele , Amato Francesco , Tartaglione Gaetano 
Published: July 2022

AbstractIn this paper, the use of time‐varying piecewise quadratic functions is investigated to characterize the finite‐time stability of state‐dependent impulsive dynamical linear systems. Finite‐time stability defines the behavior of a dynamic system over a bounded time interval. More precisely, a system is said to be finite‐time stable if, given a set of initial conditions, its state vector does not exit a predefined domain for a certain finite interval of time. This paper presents new sufficient conditions for finite‐time stability based on time‐varying piecewise quadratic functions. These conditions can be reformulated as a set of Linear Matrix Inequalities that can be efficiently solved through convex optimization solvers. Different numerical analysis are included in order to prove that the presented conditions are able to improve the results presented so far in the literature.
Implementation and analysis of deflection switched reluctance generator for underwater flow generation applications
Authors: Li Zheng , Wang Xueting , Wei Xiaopeng , Liu Libo , Gao Menghai , Cheng Liyuan , Liu Mengjie , Liu Huixian , Sun Hexu 
Published: July 2022

AbstractThis paper proposes a dual‐stator switched reluctance generator (DSSRG) which can be applied to underwater power generation. DSSRG is connected with the propeller. When the propeller deflects, it can drive the generator to deflect for underwater power generation and improve the conversion efficiency of the motor. Firstly, taking the underwater propeller as the research object, the pressure and torque characteristics of the propeller at different deflection angles are studied by using CFX software. Then, the structure of DSSRG is modelled and analysed, and the voltage and current characteristics of DSSRG at different speeds and deflection angles are analysed. Finally, an underwater generator prototype is established to verify the rationality of the underwater DSSRG and the feasibility and stability of the power generation system.
Hüft-Totalendoprothese
Authors: Grasmück Jürgen , Buekens Jo 
Published: July 2022

ZUSAMMENFASSUNGDie Implantation von Hüft-Totalendoprothesen ist eine der häufigsten
Operationen weltweit. Wir zeigen eine Möglichkeit auf, um die Struktur zu
behandeln, die für die Integration der Totalendoprothese eine
bestmögliche biologische Funktion aufweisen muss: der Knochen.
(−)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality
Authors: Chun Ji Hye , Henckel Melissa M. , Knaub Leslie A. , Hull Sara E. , Pott Greg B. , Ramirez David G. , Reusch Jane E.-B. , Keller Amy C. 
Published: July 2022

AbstractDiabetes is a life-threatening and debilitating disease with pathological hallmarks, including glucose intolerance and insulin resistance. Plant compounds are a source of novel and
effective therapeutics, and the flavonoid (−)-epicatechin, common to popular foods worldwide, has been shown to improve carbohydrate metabolism in both clinical studies and preclinical
models. We hypothesized that (−)-epicatechin would alleviate thermoneutral housing-induced glucose intolerance. Male rats were housed at either thermoneutral (30 °C) or room temperature
(24 °C) for 16 weeks and gavaged with either 1 mg/kg body weight or vehicle for the last 15 days before sacrifice. Rats housed at thermoneutrality had a significantly elevated serum glucose
area under the curve (p < 0.05) and reduced glucose-mediated insulin secretion. In contrast, rats at thermoneutrality treated with (−)-epicatechin had improved glucose tolerance and
increased insulin secretion (p < 0.05). Insulin tolerance tests revealed no differences in insulin sensitivity in any of the four groups. Pancreatic immunohistochemistry staining showed
significantly greater islet insulin positive cells in animals housed at thermoneutrality. In conclusion, (−)-epicatechin improved carbohydrate tolerance via increased insulin secretion in
response to glucose challenge without a change in insulin sensitivity.
Stage 1 Hypertension in Nulliparous Pregnant Patients and Risk of Unplanned Cesarean Delivery
Authors: Natenzon Anna , Parrott Caitlin W. , Manem Nihita , Zelig Craig M. 
Published: July 2022

Objective The aim of the study is to determine whether stage 1 hypertension is a risk factor for cesarean at ≥390/7 weeks.
Study Design This is a retrospective cohort study of nulliparas delivering at ≥390/7weeks. Exposure was defined as stage 1 hypertension and compared with normotension. The primary outcome was unplanned cesarean. Statistical analysis was performed using SPSS 27.
Results Two hundred and fifty patients had stage 1 hypertension and 250 had normotension. Thirty-eight percent of the patients with stage 1 hypertension required cesarean as did 22% of controls (risk ratio [RR]=1.55, 95% confidence interval [CI]: 1.23–1.96, p <0.001). This remained significant after controlling for confounders in a logistic regression (odds ratio [OR]=1.61, 95% confidence interval [CI]: 1.02–2.55, p <0.040). Upon secondary analysis, these results were statistically significant for gestational age ≥395/7 weeks (adjusted odds ratio [AOR]=1.89, 95% CI: 1.05–3.39, p=0.033) but not from 390/7 to 394/7weeks (AOR=0.68, 95% CI: 0.31–1.50, p=0.34).
Conclusion In nulliparas, stage 1 hypertension is an independent risk factor for unplanned cesarean.
Key Points
No Differences in Cerebral Immunohistochemical Markers following Remote Ischemic Postconditioning in Newborn Piglets with Hypoxia–Ischemia
Authors: Andersen Hannah B. , Andersen Mads , Bennedsgaard Kristine , Kerrn-Jespersen Sigrid , Kyng Kasper J. , Holm Ida E. , Henriksen Tine B. 
Published: July 2022

Abstract
Background Despite therapeutic hypothermia, neonates with hypoxic–ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia–ischemia (HI). The aim of this study was to further investigate potential effects of RIPC on cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis.
Methods Brain expression of aquaporin 4, caspase-3, B-cell lymphoma 2, and vascular endothelial growth factor was analyzed by immunohistochemistry in 23 piglets, randomly selected from a larger study of RIPC after HI. Twenty animals were subjected to 45 minutes of HI and randomized to treatment with and without RIPC, while three animals were randomized to sham procedures. RIPC was conducted by four conditioning cycles of 5-minute ischemia and reperfusion. Piglets were euthanized 72 hours after the HI insult.
Results Piglets subjected to HI treated with and without RIPC were similar at baseline and following the HI insult. However, piglets randomized to HI alone had longer duration of low blood pressure during the insult. We found no differences in the brain expression of the immunohistochemical markers in any regions of interest or the whole brain between the two HI groups.
Conclusion RIPC did not influence brain expression of markers related to edema, apoptosis, or angiogenesis in newborn piglets at 72 hours after HI. These results support previous findings of limited neuroprotective effect by this RIPC protocol. Our results may have been affected by the time of assessment, use of fentanyl as anesthetic, or limitations related to our immunohistochemical methods.