bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random survival forests identify pathways with polymorphisms predictive of survival in KRAS mutant and KRAS wild-type metastatic colorectal cancer patients
Authors: Naseem Madiha , Cao Shu , Yang Dongyun , Millstein Joshua , Puccini Alberto , Loupakis Fotios , Stintzing Sebastian , Cremolini Chiara , Tokunaga Ryuma , Battaglin Francesca , Soni Shivani , Berger Martin D. , Barzi Afsaneh , Zhang Wu , Falcone Alfredo , Heinemann Volker , Lenz Heinz-Josef 
Published: June 2021

AbstractKRAS status serves as a predictive biomarker of response to treatment in metastatic colorectal cancer (mCRC). We hypothesize that complex interactions between multiple pathways contribute to prognostic differences between KRAS wild-type and KRAS mutant patients with mCRC, and aim to identify polymorphisms predictive of clinical outcomes in this subpopulation. Most pathway association studies are limited in assessing gene–gene interactions and are restricted to an individual pathway. In this study, we use a random survival forests (RSF) method for identifying predictive markers of overall survival (OS) and progression-free survival (PFS) in mCRC patients treated with FOLFIRI/bevacizumab. A total of 486 mCRC patients treated with FOLFIRI/bevacizumab from two randomized phase III trials, TRIBE and FIRE-3, were included in the current study. Two RSF approaches were used, namely variable importance and minimal depth. We discovered that Wnt/β-catenin and tumor associated macrophage pathway SNPs are strong predictors of OS and PFS in mCRC patients treated with FOLFIRI/bevacizumab independent of KRAS status, whereas a SNP in the sex-differentiation pathway gene, DMRT1, is strongly predictive of OS and PFS in KRAS mutant mCRC patients. Our results highlight RSF as a useful method for identifying predictive SNPs in multiple pathways.
Human U90926 orthologous long non-coding RNA as a novel biomarker for visual prognosis in herpes simplex virus type-1 induced acute retinal necrosis
Authors: Shirahama Shintaro , Taniue Kenzui , Mitsutomi Shuhei , Tanaka Rie , Kaburaki Toshikatsu , Sato Tomohito , Takeuchi Masaru , Kawashima Hidetoshi , Urade Yoshihiro , Aihara Makoto , Akimitsu Nobuyoshi 
Published: June 2021

AbstractAcute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.
Entangled radicals may explain lithium effects on hyperactivity
Authors: Zadeh-Haghighi Hadi , Simon Christoph 
Published: June 2021

AbstractIt is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithium’s effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brain’s cognitive processes.
Large-scale open-source three-dimensional growth curves for clinical facial assessment and objective description of facial dysmorphism
Authors: Matthews Harold S. , Palmer Richard L. , Baynam Gareth S. , Quarrell Oliver W. , Klein Ophir D. , Spritz Richard A. , Hennekam Raoul C. , Walsh Susan , Shriver Mark , Weinberg Seth M. , Hallgrimsson Benedikt , Hammond Peter , Penington Anthony J. , Peeters Hilde , Claes Peter D. 
Published: June 2021

AbstractCraniofacial dysmorphism is associated with thousands of genetic and environmental disorders. Delineation of salient facial characteristics can guide clinicians towards a correct clinical diagnosis and understanding the pathogenesis of the disorder. Abnormal facial shape might require craniofacial surgical intervention, with the restoration of normal shape an important surgical outcome. Facial anthropometric growth curves or standards of single inter-landmark measurements have traditionally supported assessments of normal and abnormal facial shape, for both clinical and research applications. However, these fail to capture the full complexity of facial shape. With the increasing availability of 3D photographs, methods of assessment that take advantage of the rich information contained in such images are needed. In this article we derive and present open-source three-dimensional (3D) growth curves of the human face. These are sequences of age and sex-specific expected 3D facial shapes and statistical models of the variation around the expected shape, derived from 5443 3D images. We demonstrate the use of these growth curves for assessing patients and show that they identify normal and abnormal facial morphology independent from age-specific facial features. 3D growth curves can facilitate use of state-of-the-art 3D facial shape assessment by the broader clinical and biomedical research community. This advance in phenotype description will support clinical diagnosis and the understanding of disease pathogenesis including genotype–phenotype relations.
Landscape condition influences energetics, reproduction, and stress biomarkers in grizzly bears
Authors: Wilson Abbey E. , Wismer Dan , Stenhouse Gordon , Coops Nicholas C. , Janz David M. 
Published: June 2021

AbstractEnvironmental change has been shown to influence mammalian distribution, habitat use, and behavior; however, few studies have investigated the impact on physiological function. This study aimed to determine the influence of landscape condition on the expression of target proteins related to energetics, reproduction, and stress in grizzly bears. We hypothesized that changes in landscape condition explains protein expression. Skin biopsies were collected from free-ranging grizzly bears in Alberta, Canada from 2013–2019 (n = 86 individuals). We used an information theoretic approach to develop 11 a priori candidate generalized linear mixed models to explain protein expression. We compared models using Akaike Information Criteria (AICc) weights and averaged models with ΔAICc < 2 for each protein. Food resources, represented by increased distance to coal mines and decreased crown closure, positively influenced energetic proteins (adiponectin and alpha-1-acid glycoprotein). Proteins related to reproduction (ceruloplasmin and serpin B5) were positively associated with increased wetland and upland food resources in addition to movement, but negatively associated with increased distance to roads. One stress related protein, complement C3, was positively influenced by increased percent conifer. Given the need to detect emerging threats to wildlife, we suggest the assessment of physiological function will lead to improved monitoring of species in rapidly changing landscapes.
The neural economics of brain aging
Authors: Kosyakovsky Jacob 
Published: June 2021

AbstractDespite remarkable advances, research into neurodegeneration and Alzheimer Disease (AD) has nonetheless been dominated by inconsistent and conflicting theory. Basic questions regarding how and why the brain changes over time remain unanswered. In this work, we lay novel foundations for a consistent, integrated view of the aging brain. We develop neural economics—the study of the brain’s infrastructure, brain capital. Using mathematical modeling, we create ABC (Aging Brain Capital), a simple linear simultaneous-equation model that unites aspects of neuroscience, economics, and thermodynamics to explain the rise and fall of brain capital, and thus function, over the human lifespan. Solving and simulating this model, we show that in each of us, the resource budget constraints of our finite brains cause brain capital to reach an upper limit. The thermodynamics of our working brains cause persistent pathologies to inevitably accumulate. With time, the brain becomes damaged causing brain capital to depreciate and decline. Using derivative models, we suggest that this endogenous aging process underpins the pathogenesis and spectrum of neurodegenerative disease. We develop amyloid–tau interaction theory, a paradigm that bridges the unnecessary conflict between amyloid- and tau-centered hypotheses of AD. Finally, we discuss profound implications for therapeutic strategy and development.
Association between PM10 and specific circulatory system diseases in China
Authors: Zhang Yifan , Ma Yuxia , Feng Fengliu , Cheng Bowen , Wang Hang , Shen Jiahui , Jiao Haoran 
Published: June 2021

AbstractParticulate matter (PM) has been proved to be a risk factor for the development of circulatory system diseases (CSDs) around the world. In this study, we collected daily air pollutants, emergency room (ER) visits for CSDs, and meteorological data from 2009 to 2012 in Beijing, China. After controlling for the long-term trend and eliminating the influence of confounding factors, the generalized additive model (GAM) was used to evaluate the short-term effects of PM10 on CSDs and cause-specific diseases. The results showed that for every 10 μg/m3 increase in PM10, the largest effect estimates in ER visits of total CSDs, arrhythmia, cerebrovascular diseases, high blood pressure, ischemic heart disease and other related diseases were 0.14% (95% CI: 0.06–0.23%), 0.37% (95% CI: − 0.23 to 0.97%), 0.20% (95% CI: 0.00–0.40%), 0.15% (95% CI: 0.02–0.27%), 0.18% (95% CI: 0.02–0.35%) and 0.35% (95% CI: − 0.04 to 0.79%), respectively. When NO2 or SO2 was added into the model, the effect estimates of PM10 were mostly attenuated, while in those models with PM2.5 added, the effect estimates of PM10 were mostly increased. Stratified analysis indicated that PM10 had a greater effect on males and the elderly.
Cord blood DNA methylation modifications in infants are associated with white matter microstructure in the context of prenatal maternal depression and anxiety
Authors: Dean Douglas C. , Madrid Andy , Planalp Elizabeth M. , Moody Jason F. , Papale Ligia A. , Knobel Karla M. , Wood Elizabeth K. , McAdams Ryan M. , Coe Christopher L. , Hill Goldsmith H. , Davidson Richard J. , Alisch Reid S. , Kling Pamela J. 
Published: June 2021

AbstractMaternal and environmental factors influence brain networks and architecture via both physiological pathways and epigenetic modifications. In particular, prenatal maternal depression and anxiety symptoms appear to impact infant white matter (WM) microstructure, leading us to investigate whether epigenetic modifications (i.e., DNA methylation) contribute to these WM differences. To determine if infants of women with depression and anxiety symptoms exhibit epigenetic modifications linked to neurodevelopmental changes, 52 umbilical cord bloods (CBs) were profiled. We observed 219 differentially methylated genomic positions (DMPs; FDR p < 0.05) in CB that were associated with magnetic resonance imaging measures of WM microstructure at 1 month of age and in regions previously described to be related to maternal depression and anxiety symptoms. Genomic characterization of these associated DMPs revealed 143 unique genes with significant relationships to processes involved in neurodevelopment, GTPase activity, or the canonical Wnt signaling pathway. Separate regression models for female (n = 24) and male (n = 28) infants found 142 associated DMPs in females and 116 associated DMPs in males (nominal p value < 0.001, R > 0.5), which were annotated to 98 and 81 genes, respectively. Together, these findings suggest that umbilical CB DNA methylation levels at birth are associated with 1-month WM microstructure.
Prognostic implications of regression of metastatic axillary lymph nodes after neoadjuvant chemotherapy in patients with breast cancer
Authors: Chung Yul Ri , Woo Ji Won , Ahn Soomin , Kang Eunyoung , Kim Eun-Kyu , Jang Mijung , Kim Sun Mi , Kim Se Hyun , Kim Jee Hyun , Park So Yeon 
Published: June 2021

AbstractPrognostic implications of therapeutic response of metastatic lymph nodes (LNs) to neoadjuvant chemotherapy (NAC) remain unclear in patients with breast cancer. We aimed to evaluate the prognostic value of axillary LN regression after NAC in locally-advanced breast cancer patients. Therapeutic response of the LNs was evaluated in 563 breast cancer patients and classified into four grades according to the regression pattern. Initial pathologic N stage was estimated from the sum of the metastatic LNs and those with complete regression. In survival analyses, LN regression grade, pathologic N stage after NAC, and presumed initial pathologic N stage stratified clinical outcome of the patients in the whole group, in both ER-positive and ER-negative subgroups, and in those with residual breast disease. On multivariate analysis, LN regression grade and presumed initial pathologic N stage were revealed as independent prognostic factors. The number of completely-responsive LNs and the ratio of non-responsive LNs also revealed a prognostic value. In conclusion, regression grade of axillary LNs and presumed initial pathologic N stage have prognostic values in breast cancer patients who receive NAC. Thus, regression of axillary LNs should be evaluated and included in pathologic reporting of post-NAC resection specimens.
Repurposing CPAP machines as stripped-down ventilators
Authors: Nguyen J. , Kesper K. , Kräling G. , Birk C. , Mross P. , Hofeditz N. , Höchst J. , Lampe P. , Penning A. , Leutenecker-Twelsiek B. , Schindler C. , Buchenauer H. , Geisel D. , Sommer C. , Henning R. , Wallot P. , Wiesmann T. , Beutel B. , Schneider G. , Castro-Camus E. , Koch M. 
Published: June 2021

AbstractThe worldwide shortage of medical-grade ventilators is a well-known issue, that has become one of the central topics during the COVID-19 pandemic. Given that these machines are expensive and have long lead times, one approach is to vacate them for patients in critical conditions while patients with mild to moderate symptoms are treated with stripped-down ventilators. We propose a mass-producible solution that can create such ventilators with minimum effort. The central part is a module that can be attached to CPAP machines and repurpose them as low-pressure ventilators. Here, we describe the concept and first measurements which underline the potential of our solution. Our approach may serve as a starting point for open-access ventilator technologies.
Understanding porosity and temperature induced variabilities in interface, mechanical characteristics and thermal conductivity of borophene membranes
Authors: Pham Van-Trung , Fang Te-Hua 
Published: June 2021

AbstractEvaluating the effect of porosity and ambient temperature on mechanical characteristics and thermal conductivity is vital for practical application and fundamental material property. Here we report that ambient temperature and porosity greatly influence fracture behavior and material properties. With the existence of the pore, the most significant stresses will be concentrated around the pore position during the uniaxial and biaxial processes, making fracture easier to occur than when tensing the perfect sheet. Ultimate strength and Young’s modulus degrade as porosity increases. The ultimate strength and Young's modulus in the zigzag direction is lower than the armchair one, proving that the borophene membrane has anisotropy characteristics. The deformation behavior of borophene sheets when stretching biaxial is more complicated and rough than that of uniaxial tension. In addition, the results show that the ultimate strength, failure strain, and Young’s modulus degrade with growing temperature. Besides the tensile test, this paper also uses the non-equilibrium molecular dynamics (NEMD) approach to investigate the effects of length size, porosity, and temperature on the thermal conductivity (κ) of borophene membranes. The result points out that κ increases as the length increases. As the ambient temperature increases, κ decreases. Interestingly, the more porosity increases, the more κ decreases. Moreover, the results also show that the borophene membrane is anisotropic in heat transfer.
Changes in ocular morphology after cataract surgery in open angle glaucoma patients
Authors: Pakuliene Giedre , Kuzmiene Loreta , Siesky Brent , Harris Alon , Januleviciene Ingrida 
Published: June 2021

AbstractThe purpose of this study was to evaluate intraocular pressure (IOP) pre- and postoperatively, together with anterior chamber angle (ACA) parameters and biometrical results in cataract patients with or without open angle glaucoma (OAG). The prospective observational case–control study included 15 eyes with cataract and OAG in the glaucoma group and 25 eyes with only cataract in control group. Examination included full ophthalmic evaluation, IOP, ocular biometry and anterior segment optical coherence tomography measuring ACA pre- and 6 months postoperatively.
OAG patients had a larger absolute IOP reduction compared to control group. Anterior chamber depth (ACD) and ACA width significantly increased in both groups. The OAG group had a tendency of narrower ACA preoperatively, but overall ACA parameters did not differ in either group pre- and postoperatively. The ACD change after surgery correlated with ACA parameters in the control group, but not in OAG group. Axial length was shorter postoperatively in the control group, but remained similar in the OAG group. Absolute IOP reduction was more pronounced in cataract patients with OAG than in cataract patients without glaucoma. ACD and ACA postoperatively increased in both groups and AL shortening was observed in non-OAG in cataract group.
BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression
Authors: Dong Miao , Kwok Shu Hin , Humble Joseph L. , Liang Yimin , Tang Sze Wing , Tang Kin Hung , Tse Man Kit , Lei Josh Haipeng , Ramalingam Rajkumar , Koohi-Moghadam Mohamad , Au Doris Wai Ting , Sun Hongyan , Lam Yun Wah 
Published: June 2021

AbstractAntimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target.
Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer
Authors: Tahkola Kyösti , Ahtiainen Maarit , Mecklin Jukka-Pekka , Kellokumpu Ilmo , Laukkarinen Johanna , Tammi Markku , Tammi Raija , Väyrynen Juha P. , Böhm Jan 
Published: June 2021

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.
Transient behavior of compressed magnetorheological brake excited by step currents
Authors: Wang Hongyun , Bi Cheng , Zhang Yongju , Ji Axiang , Qiu Pengyuan 
Published: June 2021

AbstractTransient behavior of a magnetorheological brake excited by step currents under compression-shear mode has been experimentally studied. The results show that the amplitude of the applied current had little effect on the rising time of transient torque, while the rising time was significantly affected by the rotational speed, the compressive speed and the compressive strain position. The falling time of transient torque was independent of the amplitude of the applied current, the compressive speed and the compressive strain position, and it was affected by the rotational speed. The falling time of the transient torque was much shorter than the rising time by a step current. The transient process of MR brake applied as a step current was different from a stable process pre-applied at constant current in different particle chain structure forming processes. In addition, the compressive processes applied in one step current and randomly on/off current were compared and experimentally verified: the particle chains in two processes both experienced the same evolutionary of transient torque. The results achieved in this study should be properly considered in the design and control of magnetorheological brake under compression-shear mode.