bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative multiomics-histopathology analysis for breast cancer classification
Authors: Ektefaie Yasha , Yuan William , Dillon Deborah A. , Lin Nancy U. , Golden Jeffrey A. , Kohane Isaac S. , Yu Kun-Hsing 
Published: November 2021

AbstractHistopathologic evaluation of biopsy slides is a critical step in diagnosing and subtyping breast cancers. However, the connections between histology and multi-omics status have never been systematically explored or interpreted. We developed weakly supervised deep learning models over hematoxylin-and-eosin-stained slides to examine the relations between visual morphological signal, clinical subtyping, gene expression, and mutation status in breast cancer. We first designed fully automated models for tumor detection and pathology subtype classification, with the results validated in independent cohorts (area under the receiver operating characteristic curve ≥ 0.950). Using only visual information, our models achieved strong predictive performance in estrogen/progesterone/HER2 receptor status, PAM50 status, and TP53 mutation status. We demonstrated that these models learned lymphocyte-specific morphological signals to identify estrogen receptor status. Examination of the PAM50 cohort revealed a subset of PAM50 genes whose expression reflects cancer morphology. This work demonstrates the utility of deep learning-based image models in both clinical and research regimes, through its ability to uncover connections between visual morphology and genetic statuses.
Implementing asthma management guidelines in public primary care clinics in Malaysia
Authors: Cheong Ai Theng , Lee Ping Yein , Shariff-Ghazali Sazlina , Salim Hani , Hussein Norita , Ramli Rizawati , Pinnock Hilary , Liew Su May , Hanafi Nik Sherina , Abu Bakar Ahmad Ihsan , Mohd Ahad Azainorsuzila , Pang Yong Kek , Chinna Karuthan , Khoo Ee Ming 
Published: November 2021

AbstractImplementing asthma guideline recommendations is challenging in low- and middle-income countries. We aimed to explore healthcare provider (HCP) perspectives on the provision of recommended care. Twenty-six HCPs from six public primary care clinics in a semi-urban district of Malaysia were purposively sampled based on roles and experience. Focus group discussions were guided by a semi-structured interview guide and analysed thematically. HCPs had access to guidelines and training but highlighted multiple infrastructure-related challenges to implementing recommended care. Diagnosis and review of asthma control were hampered by limited access to spirometry and limited asthma control test (ACT) use, respectively. Treatment decisions were limited by poor availability of inhaled combination therapy (ICS/LABA) and free spacer devices. Imposed Ministry of Health programmes involving other non-communicable diseases were prioritised over asthma. Ministerial policies need practical resources and organisational support if quality improvement programmes are to facilitate better management of asthma in public primary care clinics.
Surface area in the insula was associated with 28-month functional outcome in first-episode psychosis
Authors: Koike Shinsuke , Fujioka Mao , Satomura Yoshihiro , Koshiyama Daisuke , Tada Mariko , Sakakibara Eisuke , Okada Naohiro , Takano Yosuke , Iwashiro Norichika , Natsubori Tatsunobu , Zhu Yinghan , Abe Osamu , Kirihara Kenji , Yamasue Hidenori , Kasai Kiyoto 
Published: November 2021

AbstractMany studies have tested the relationship between demographic, clinical, and psychobiological measurements and clinical outcomes in ultra-high risk for psychosis (UHR) and first-episode psychosis (FEP). However, no study has investigated the relationship between multi-modal measurements and long-term outcomes for >2 years. Thirty-eight individuals with UHR and 29 patients with FEP were measured using one or more modalities (cognitive battery, electrophysiological response, structural magnetic resonance imaging, and functional near-infrared spectroscopy). We explored the characteristics associated with 13- and 28-month clinical outcomes. In UHR, the cortical surface area in the left orbital part of the inferior frontal gyrus was negatively associated with 13-month disorganized symptoms. In FEP, the cortical surface area in the left insula was positively associated with 28-month global social function. The left inferior frontal gyrus and insula are well-known structural brain characteristics in schizophrenia, and future studies on the pathological mechanism of structural alteration would provide a clearer understanding of the disease.
Short-read and long-read RNA sequencing of mouse hematopoietic stem cells at bulk and single-cell levels
Authors: Zheng Xiuran , Zhang Dan , Xu Mengying , Zeng Wanqin , Zhou Ran , Zhang Yiming , Tang Chao , Chen Li , Chen Lu , Lin Jing-wen 
Published: November 2021

AbstractHematopoietic stem cells (HSCs) lie at the top of the differentiation hierarchy. Although HSC and their immediate downstream, multipotent progenitors (MPP) have full multilineage differentiation capacity, only long-term (LT-) HSC has the capacity of long-term self-renewal. The heterogeneity within the HSC population is gradually acknowledged with the development of single-cell RNA sequencing and lineage tracing technologies. Transcriptional and post-transcriptional regulations play important roles in controlling the differentiation and self-renewal capacity within HSC population. Here we report a dataset comprising short- and long-read RNA sequencing for mouse long- and short-term HSC and MPP at bulk and single-cell levels. We demonstrate that integrating short- and long-read sequencing can facilitate the identification and quantification of known and unannotated isoforms. Thus, this dataset provides a groundwork for comprehensive and comparative studies on transcriptional diversity and heterogeneity within different HSC cell types.
Hemodialysis biocompatibility mathematical models to predict the inflammatory biomarkers released in dialysis patients based on hemodialysis membrane characteristics and clinical practices
Authors: Abdelrasoul Amira , Westphalen Heloisa , Saadati Shaghayegh , Shoker Ahmed 
Published: November 2021

AbstractChronic kidney disease affects millions of people around the globe and many patients rely on hemodialysis (HD) to survive. HD is associated with undesired life-threatening side effects that are linked to membrane biocompatibility and clinical operating conditions. The present study develops a mathematical model to predict the inflammatory biomarkers released in HD patients based on membrane morphology, chemistry, and interaction affinity. Based on the morphological characteristics of two clinical-grade HD membrane modules (CTA and PAES-PVP) commonly used in Canadian hospitals, a molecular docking study, and the release of inflammatory cytokines during HD and in vitro incubation experiments, we develop five sets of equations that describe the concentration of eight biomarkers (serpin/antithrombin-III, properdin, C5a, 1L-1α, 1L-1β, C5b-9, IL6, vWF). The equations developed are functions of membrane properties (pore size, roughness, chemical composition, affinity to fibrinogen, and surface charge) and HD operating conditions (blood flow rate, Qb, and treatment time, t). We expand our model based on available clinical data and increase its range of applicability in terms of flow rate and treatment time. We also modify the original equations to expand their range of applicability in terms of membrane materials, allowing the prediction and validation of the inflammatory response of several clinical and synthesized membrane materials. Our affinity-based model solely relies on theoretical values of molecular docking, which can significantly reduce the experimental load related to the development of more biocompatible materials. Our model predictions agree with experimental clinical data and can guide the development of novel materials and support evidence-based membrane synthesis of HD membranes, reducing the need for trial-and-error approaches.
Winter diet of Japanese macaques from Chubu Sangaku National Park, Japan incorporates freshwater biota
Authors: Milner Alexander M. , Wood Susanna A. , Docherty Catherine , Biessy Laura , Takenaka Masaki , Tojo Koji 
Published: November 2021

AbstractThe Japanese macaque (Macaca fuscata) is native to the main islands of Japan, except Hokkaido, and is the most northerly living non-human primate. In the Chubu Sangaku National Park of the Japanese Alps, macaques live in one of the coldest areas of the world, with snow cover limiting the availability of preferred food sources. Winter is typically a bottleneck for food availability potentially resulting in marked energy deficits, and mortality may result from famine. However, streams with groundwater upwelling flow during the winter with a constant water temperature of about 5 °C are easily accessible for Japanese macaques to search for riverine biota. We used metabarcoding (Cytochrome c oxidase I) of fecal samples from Japanese macaques to determine their wintertime diet. Here we provide the first robust evidence that Japanese macaques feed on freshwater biota, including brown trout, riverine insects and molluscs, in Chubu Sangaku National Park. These additional food sources likely aid their winter survival.
Revealing the efficacy-toxicity relationship of Fuzi in treating rheumatoid arthritis by systems pharmacology
Authors: Feng Wuwen , Liu Juan , Zhang Dandan , Tan Yuzhu , Cheng Hao , Peng Cheng 
Published: November 2021

AbstractIn recent decades, herbal medicines have played more and more important roles in the healthcare system in the world because of the good efficacy. However, with the increasing use of herbal medicines, the toxicity induced by herbal medicines has become a global issue. Therefore, it is needed to investigate the mechanism behind the efficacy and toxicity of herbal medicines. In this study, using Aconiti Lateralis Radix Praeparata (Fuzi) as an example, we adopted a systems pharmacology approach to investigate the mechanism of Fuzi in treating rheumatoid arthritis and in inducing cardiac toxicity and neurotoxicity. The results showed that Fuzi has 25 bioactive compounds that act holistically on 61 targets and 27 pathways to treat rheumatoid arthritis, and modulation of inflammation state is one of the main mechanisms of Fuzi. In addition, the toxicity of Fuzi is linked to 32 compounds that act on 187 targets and 4 pathways, and the targets and pathways can directly modulate the flow of Na+, Ca2+, and K+. We also found out that non-toxic compounds such as myristic acid can act on targets of toxic compounds and therefore may influence the toxicity. The results not only reveal the efficacy and toxicity mechanism of Fuzi, but also add new concept for understanding the toxicity of herbal medicines, i.e., the compounds that are not directly toxic may influence the toxicity as well.
Role of the trace amine associated receptor 5 (TAAR5) in the sensorimotor functions
Authors: Kalinina D. S. , Ptukha M. A. , Goriainova A. V. , Merkulyeva N. S. , Kozlova A. A. , Murtazina R. Z. , Shemiakova T. S. , Kuvarzin S. R. , Vaganova A. N. , Volnova A. B. , Gainetdinov R. R. , Musienko P. E. 
Published: November 2021

AbstractClassical monoamines are well-known modulators of sensorimotor neural networks. However, the role of trace amines and their receptors in sensorimotor function remains unexplored. Using trace amine-associated receptor 5 knockout (TAAR5-KO) mice, that express beta-galactosidase mapping its localization, we observed TAAR5 expression in the Purkinje cells of the cerebellum and the medial vestibular nucleus, suggesting that TAAR5 might be involved in the vestibular and motor control. Accordingly, in various behavioral tests, TAAR5-KO mice demonstrated lower endurance, but better coordination and balance compared to wild-type controls. Furthermore, we found specific changes in striatal local field potentials and motor cortex electrocorticogram, such as a decrease in delta and an increase in theta oscillations of power spectra, respectively. The obtained data indicate that TAAR5 plays a considerable role in regulation postural stability, muscle force, balance, and motor coordination during active movements, likely via modulation of monoaminergic systems at different levels of sensorimotor control involving critical brain areas such as the brainstem, cerebellum, and forebrain.
Ultrawideband electromagnetic metamaterial absorber utilizing coherent absorptions and surface plasmon polaritons based on double layer carbon metapatterns
Authors: Kim Yongjune , Park Pyoungwon , Jo Jeongdai , Lee Joonsik , Jeong Leekyo , Shin Jonghwa , Lee Jeong-Hae , Lee Hak-Joo 
Published: November 2021

AbstractAn ultrawideband electromagnetic metamaterial absorber is proposed that consists of double-layer metapatterns optimally designed by the genetic algorithm and printed using carbon paste. By setting the sheet resistance of the intermediate carbon metapattern to a half of that of the top one, it is possible to find an optimal intermediate metapattern that reflects and absorbs the EM wave simultaneously. By adding an absorption resonance via a constructive interference at the top metapattern induced by the reflection from the intermediate one, an ultrawideband absorption can be achieved without increasing the number of layers. Moreover, it is found that the metapatterns support the surface plasmon polaritons which can supply an additional absorption resonance as well as boost the absorption in a broad bandwidth. Based on the simulation, the$$90\%$$90%absorption bandwidth is confirmed from 6.3 to 30.1 GHz of which the fractional bandwidth is 130.77$$\%$$%for the normal incidence. The accuracy is verified via measurements well matched with the simulations. The proposed metamaterial absorber could not only break though the conventional concept that the number of layers should be increased to extend the bandwidth but also provide a powerful solution to realize a low-profile, lightweight, and low cost electromagnetic absorber.
Schizotypal personality traits and the social learning of fear
Authors: González-Rodríguez Antonio , García-Pérez Ángel , Godoy-Giménez Marta , Carmona Isabel , Estévez Ángeles F. , Sayans-Jiménez Pablo , Cañadas Fernando 
Published: November 2021

AbstractSchizotypy can be defined as a combination of traits qualitatively similar to those found in schizophrenia, but milder in their expression, that can be found in clinical and non-clinical populations. In this research, we explore, to our knowledge, for the first time, whether schizotypal personality traits may affect the acquisition of conditioned fear by social means only. Apart from being an essential capacity to ensure learning in safe environments, social fear learning shares important characteristics with direct fear acquisition, which also makes it a great candidate for developing successful extinction procedures. Undergraduate students (n = 72) performed a task of social fear learning. In this task, participants watched a video of a person that simulated to receive electric shocks (unconditioned stimulus; US) paired with a coloured square (conditioned stimulus plus; CS+), while another coloured square was never paired (conditioned stimulus minus; CS−) with the shock. After that, they were presented with a similar sequence of coloured screens. Their Skin Conductance Responses (SCRs) were registered during the whole process. Once they finished, they completed the Schizotypal Personality Questionnaire (SPQ). Our results revealed that participants with a low score in the Cognitive-Perceptual factor of the SPQ exhibited higher SCRs when they saw the US than when they saw the CS− (all ps < 0.01) during the learning phase. Nevertheless, those with higher scores did not present any difference in their SCRs toward both stimuli (all ps > 0.05), a pattern that has been similarly found in schizophrenia. During the final trials of the test phase, participants with the highest scores in the Disorganized factor were the only ones that maintained a higher SCR towards the CS+ than towards the CS− (p = 0.006), which could be associated with an impairment in their extinction processes.
Computer aided designing of novel pyrrolopyridine derivatives as JAK1 inhibitors
Authors: Keretsu Seketoulie , Ghosh Suparna , Cho Seung Joo 
Published: November 2021

AbstractJanus kinases (JAKs) are a family of non-receptor kinases that play a key role in cytokine signaling and their aberrant activities are associated with the pathogenesis of various immune diseases. The JAK1 isoform plays an essential role in the types 1 and II interferon signaling and elicits signals from the interleukin-2, interleukin-4, gp130, and class 2 receptor families. It is ubiquitously expressed in humans and its overexpression has been linked with autoimmune diseases such as myeloproliferative neoplasm. Although JAK1 inhibitors such as Tofacitinib have been approved for medical use, the low potency and off-target effects of these inhibitors have limited their use and calls for the development of novel JAK1 inhibitors. In this study, we used computational methods on a series of pyrrolopyridine derivatives to design new JAK1 inhibitors. Molecular docking and molecular dynamics simulation methods were used to study the protein-inhibitor interactions. 3D-quantitative structure–activity relationship models were developed and were used to predict the activity of newly designed compounds. Free energy calculation methods were used to study the binding affinity of the inhibitors with JAK1. Of the designed compounds, seventeen of the compounds showed a higher binding energy value than the most active compound in the dataset and at least six of the compounds showed higher binding energy value than the pan JAK inhibitor Tofacitinib. The findings made in this study could be utilized for the further development of JAK1 inhibitors.
A comprehensive county level model to identify factors affecting hospital capacity and predict future hospital demand
Authors: Bhowmik Tanmoy , Eluru Naveen 
Published: November 2021

AbstractThe sustained COVID-19 case numbers and the associated hospitalizations have placed a substantial burden on health care ecosystem comprising of hospitals, clinics, doctors and nurses. However, as of today, only a small number of studies have examined detailed hospitalization data from a planning perspective. The current study develops a comprehensive framework for understanding the critical factors associated with county level hospitalization and ICU usage rates across the US employing a host of independent variables. Drawing from the recently released Department of Health and Human Services weekly hospitalization data, we study the overall hospitalization and ICU usage—not only COVID-19 hospitalizations. Developing a framework that examines overall hospitalizations and ICU usage can better reflect the plausible hospital system recovery path to pre-COVID level hospitalization trends. The models are subsequently employed to generate predictions for county level hospitalization and ICU usage rates in the future under several COVID-19 transmission scenarios considering the emergence of new COVID-19 variants and vaccination rates. The exercise allows us to identify vulnerable counties and regions under stress with high hospitalization and ICU rates that can be assisted with remedial measures. Further, the model will allow hospitals to understand evolving displaced non-COVID hospital demand.
The characteristics of choriocapillaris flow void in the unilateral polypoidal choroidal vasculopathy fellow eyes
Authors: Wu Huajui , Sugano Yukinori , Itagaki Kanako , Kasai Akihito , Shintake Hiroaki , Sekiryu Tetsuju 
Published: November 2021

AbstractTo evaluate the morphological characteristics of flow void (FV) in the fellow eyes of the unilateral polypoidal choroidal vasculopathy (PCV). Fifty PCV fellow eyes (PCVF) and 31 age-matched normal ocular circulation controls were recruited in this retrospective study. The number of FV was analyzed according to the size in a centered 5 × 5 mm swept source optical coherence tomography angiography scans. We used indocyanine green angiography images to determine whether choroidal vascular hyperpermeability (CVH) has occurred. For the PCVF, the prevalence rate of CVH was 70% (35 of 50) The number of FVs was significantly lower in 400–25,000 μm2 (P = 0.005), 400–500 μm2 (P = 0.001), 525–625 μm2 (P = 0.001) and 650–750 μm2 (P = 0.018). compared to the controls. And showed no difference in size from 775 to 1125 μm2 between the two groups. The area under the receiver operating characteristic curve of PCVF with CVH and controls was 0.94 (95% CI 0.88–1.00) (P < 0.001). We found that the number of small FVs was significantly lower in the PCV fellow eyes than that in the eyes with control group.
Highly efficient TiO2-supported Co–Cu catalysts for conversion of glycerol to 1,2-propanediol
Authors: Mondach Wongsaphat , Chanklang Sarun , Somchuea Pooripong , Witoon Thongthai , Chareonpanich Metta , Faungnawakij Kajornsak , Sohn Hiesang , Seubsai Anusorn 
Published: November 2021

AbstractGlycerol is a low-cost byproduct of the biodiesel manufacturing process, which can be used to synthesize various value-added chemicals. Among them, 1,2-propanediol (1,2-PDO) is of great interest because it can be used as an intermediate and additive in many applications. This work investigated the hydrogenolysis of glycerol to 1,2-PDO over Co–Cu bimetallic catalysts supported on TiO2 (denoted as CoCu/TiO2) in aqueous media. The catalysts were prepared using the co-impregnation method and their physicochemical properties were characterized using several techniques. The addition of appropriate Cu increased the glycerol conversion and the 1,2-PDO yield. The highest 1,2-PDO yield was achieved over a 15Co0.5Cu/TiO2 catalyst at 69.5% (glycerol conversion of 95.2% and 1,2-PDO selectivity of 73.0%). In the study on the effects of operating conditions, increasing the reaction temperature, initial pressure, and reaction time increased the glycerol conversion but decreased the selectivity to 1,2-PDO due to the degradation of formed 1,2-PDO to lower alcohols (1-propanol and 2-propanol). The reaction conditions to obtain the maximum 1,2-PDO yield were a catalyst-to-glycerol ratio of 0.028, a reaction temperature of 250 °C, an initial H2 pressure of 4 MPa, and a reaction time of 4 h.
Evolutionary dynamics of HIV-1 subtype C in Brazil
Authors: Souto Bernardino , Triunfante Vera , Santos-Pereira Ana , Martins Joana , Araújo Pedro M. M. , Osório Nuno S. 
Published: November 2021

AbstractThe extensive genetic diversity of HIV-1 is a major challenge for the prevention and treatment of HIV-1 infections. Subtype C accounts for most of the HIV-1 infections in the world but has been mainly localized in Southern Africa, Ethiopia and India. For elusive reasons, South Brazil harbors the largest HIV-1 subtype C epidemic in the American continent that is elsewhere dominated by subtype B. To investigate this topic, we collected clinical data and viral sequences from 2611 treatment-naïve patients diagnosed with HIV-1 in Brazil. Molecular epidemiology analysis supported 35 well-delimited transmission clusters of subtype C highlighting transmission within South Brazil but also from the South to all other Brazilian regions and internationally. Individuals infected with subtype C had lower probability to be deficient in CD4+ T cells when compared to subtype B. The HIV-1 epidemics in the South was characterized by high female-to-male infection ratios and women-to-child transmission. Our results suggest that HIV-1 subtype C probably takes advantage of longer asymptomatic periods to maximize transmission and is unlikely to outcompete subtype B in settings where the infection of women is relatively less relevant. This study contributes to elucidate factors possibly underlying the geographical distribution and expansion patterns of the most spread HIV-1 subtypes.