bluuebunny/crossref_metadata_2025_split huggingface dataset:
MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions
Authors: Wang Geng , Kim Tae-Hwan , Li Zhixiu , Cortes Adrian , Kim Kwangwoo , Bang So-Young , Leo Paul , Brown Matthew A. , Xu Huji 
Published: April 2020

Abstract
Background
The association of HLA-B*27 with AS is amongst the strongest of any known association of a common variant with any human disease. Nonetheless, there is strong evidence indicating that other HLA-B alleles are involved in the disease. European ethnicity studies have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, HLA-A, and HLA class II alleles, and demonstrated that in that ethnic group, the amino acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS. A recent study in Korean AS cases and controls additionally identified association at HLA-C*15:02. In the current study, we examined the MHC associations of AS in an expanded East Asian cohort.

Methods
A total of 1637 Chinese, Taiwanese, and Korean AS cases meeting the modified New York Criteria for AS, and 1589 ethnically matched controls, were genotyped with the Illumina Immunochip, including a dense coverage of the MHC region. HLA genotypes and amino acid composition were imputed using the SNP2HLA programme using the Han-MHC reference panel based on the data of Han Chinese subjects (n = 9689), and association tested using logistic regression controlling for population stratification effects.

Results
A strong association was seen with HLA-B*27 (odds ratio (OR) = 205.3, P = 5.76 × 10−244). Controlling for this association, the strongest risk association is seen with HLA-C*15 at genome-wide significant level (OR = 7.62, P = 9.30 × 10−19), and confirmed association is also seen with HLA-B*40 at suggestive level (OR = 1.65, P = 2.54 × 10−4). At amino acid level, the strongest association seen in uncontrolled analysis was with histidine at position 114 in HLA-B (P = 7.24 × 10−241), but conditional analyses suggest that the primary amino acid associations are with lysine at position 70 and asparagine at position 97. Restriction of the ERAP1 association with HLA-B27-positive AS, previously reported in European subjects, was confirmed in East Asians.

Conclusions
This study confirms in East Asians that the HLA associations of AS are multiple, including previously reported associations at HLA-B*27, HLA-B*40, and HLA-C*15, as well as novel association with HLA-DQB1*04. The HLA-B associations are driven by the amino acids at positions 70 and 97, in the B pocket of HLA-B.
MicroRNA-761 suppresses remodeling of nasal mucosa and epithelial–mesenchymal transition in mice with chronic rhinosinusitis through LCN2
Authors: Cheng Jinzhang , Chen Junjun , Zhao Yin , Yang Jingpu , Xue Kai , Wang Zonggui 
Published: April 2020

Abstract
Background
Chronic rhinosinusitis (CRS) is characterized by persistent symptomatic inflammation of the nasal passage and sinus mucosa. Various microRNAs (miRs) have been implicated in CRS. Hence, the current study was conducted to explore the effect of microRNA-761 (miR-761) on remodeling of nasal mucosa and epithelial–mesenchymal transition (EMT).

Methods
Bioinformatics analysis was initially performed to predict the differentially expressed genes (DEGs) associated with CRS. Gene targeting relationship between miR-761 and lipocalin 2 (LCN2) was analyzed by bioinformatics analysis and verified using dual-luciferase reporter gene assay. Histopathological analyses of the nasal mucosa tissues were conducted via hematoxylin–eosin (HE) and alcian blue (AB)-periodic acid Schiff (PAS) staining. ELISA was employed to determine the IL-8 and MMP-9 levels. To define downstream pathway of miR-761, levels of proteins related to LCN2/Twist1 signaling pathway were assessed. Additionally, the effects of miR-761 on EMT, proliferation, and apoptosis were determined.

Results
LCN2 was highly expressed in CRS. LCN2 was a target of miR-761. miR-761 overexpression or LCN2 silencing decreased IL-8 and MMP-9 levels and morphological changes in nasal epithelial tissue from CRS mice. Overexpressed miR-761 or silenced LCN2 decreased the expression of LCN2 and Twist1, indicating LCN2/Twist1 signaling pathway was inactivated. Moreover, miR-761 overexpression or LCN2 silencing reduced the expression of N-cadherin and vimentin, while increased that of E-cadherin, suggesting inhibition of EMT. Furthermore, miR-761 overexpression or LCN2 silencing promoted cell proliferation and inhibited cell apoptosis in CRS.

Conclusion
Taken together, miR-761 suppressed the remodeling of nasal mucosa through inhibition of LCN2 and the LCN2/Twist1 signaling pathway.
Invasive sphenoid sinus aspergillosis mimicking sellar tumor: a report of 4 cases and systematic literature review
Authors: Zhang Hanwen , Jiang Nian , Lin Xuelei , Wanggou Siyi , Olson Jeffrey J. , Li Xuejun 
Published: April 2020

AbstractBackgroundInvasive sphenoid sinus aspergillosis is a rare but life-threatening condition usually found in immunocompromised patients. When involving cavernous sinus and surrounding structures, patients are frequently misdiagnosed with a neoplasm or sellar abscess. Timely diagnosis and intervention are crucial to patients’ outcomes. The objective of this study is to review cases of invasive sphenoid sinus aspergillosis to describe disease manifestations, imaging features, treatment, and outcome.Case presentationWe describe four patients with invasive sphenoid sinus aspergillosis misdiagnosed as sellar tumors preoperatively. The mass was completely removed in three patients and partially removed in one patient microscopically. Pathological examinations confirmedAspergillusin all cases. All four patients received anti-fungal agents postoperatively. There was no recurrence at the time of each patient’s follow-up date. One patient with complete resection was lost to follow-up while the other three patients’ neurologic function improved. Additionally, we performed a systematic review regarding invasive sphenoid sinus aspergillosis of existing English literature.ConclusionWith regard to clinical symptoms, headache, vision impairment, and ophthalmoplegia were observed in over half of the patients in the literature. A sellar mass with bone destruction on CT and involvement of cavernous sinus is highly suggestive of invasive fungal sphenoid sinusitis. Immediate surgical removal of the lesion is recommended for invasive sphenoid sinus aspergillosis to preserve nerve function and increase the likelihood of survival.
Why does peer instruction benefit student learning?
Authors: Tullis Jonathan G. , Goldstone Robert L. 
Published: April 2020

AbstractIn peer instruction, instructors pose a challenging question to students, students answer the question individually, students work with a partner in the class to discuss their answers, and finally students answer the question again. A large body of evidence shows that peer instruction benefits student learning. To determine the mechanism for these benefits, we collected semester-long data from six classes, involving a total of 208 undergraduate students being asked a total of 86 different questions related to their course content. For each question, students chose their answer individually, reported their confidence, discussed their answers with their partner, and then indicated their possibly revised answer and confidence again. Overall, students were more accurate and confident after discussion than before. Initially correct students were more likely to keep their answers than initially incorrect students, and this tendency was partially but not completely attributable to differences in confidence. We discuss the benefits of peer instruction in terms of differences in the coherence of explanations, social learning, and the contextual factors that influence confidence and accuracy.
Spatial localization of hotspots in Fano-resonant plasmonic oligomers for surface-enhanced coherent anti-Stokes Raman scattering
Authors: Dutta Arpan , Vartiainen Erik M. 
Published: April 2020

AbstractRealization of Fano resonance in plasmonic oligomers is often exploited to design efficient plasmonic substrates for surface-enhanced coherent anti-Stokes Raman scattering. Disk-type Fano-resonant plasmonic oligomers are widely used to enhance the Raman signal of the probe material. Generally, hot spots are generated in those oligomers at different spatial locations at different wavelengths and only a few spatially overlapping hot spots at multiple wavelengths can be achieved with oblique incidence of excitation light. In this work, we proposed hexagonal gold nanoparticle based Fano-resonant plasmonic oligomers that can yield higher number of spatially overlapped hot spots compared to the disk type oligomers even with the normal incidence of excitation light. The oligomers were numerically modelled and optimized for surface-enhanced coherent anti-Stokes Raman scattering with 780 nm pumping and 500–1800 cm− 1 Raman signature region. The Fano lineshape was engineered to ensure near-field energy coupling at pump while enhancing the coherent anti-Stokes Raman signal at the far field. Our computational studies explored the purely electric origin of Fano resonance in those oligomers and provided maximum Raman enhancements of 1012–1013 from them to enable single-molecular level applications. Our findings provide a way to realize fabrication-friendly nanostructures with higher number of spatially localized hotspots for improving the Raman detection sensitivity.
Treatment concerns for psychiatric symptoms in patients with COVID-19 with or without psychiatric disorders
Authors: Zhang Kai , Zhou Xiaoqin , Liu Huanzhong , Hashimoto Kenji 
Published: April 2020

SummaryMany psychiatric patients have been infected with COVID-19, and patients with COVID-19 may develop psychiatric symptoms after treatment with antiviral drugs. Given the tolerability and minimal P450 interactions, antidepressants (i.e., citalopram, escitalopram etc.), antipsychotics (i.e., olanzapine) and valproate can be considered to be safe in combination with antiviral drugs.
Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH
Authors: Su H Irene , Kwan Brian , Whitcomb Brian W , Shliakhsitsava Ksenya , Dietz Andrew C , Stark Shaylyn S , Martinez Elena , Sluss Patrick M , Sammel Mary D , Natarajan Loki 
Published: April 2020

Abstract

Context
Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown.

Objective
To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age.

Design
In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis.

Results
763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P &lt; 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction &lt; 0.001).

Conclusions
In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.
Plasma Metabolomics Identifies Markers of Impaired Renal Function: A Meta-analysis of 3089 Persons with Type 2 Diabetes
Authors: Tofte Nete , Vogelzangs Nicole , Mook-Kanamori Dennis , Brahimaj Adela , Nano Jana , Ahmadizar Fariba , van Dijk Ko Willems , Frimodt-Møller Marie , Arts Ilja , Beulens Joline W J , Rutters Femke , van der Heijden Amber A , Kavousi Maryam , Stehouwer Coen D A , Nijpels Giel , van Greevenbroek Marleen M J , van der Kallen Carla J H , Rossing Peter , Ahluwalia Tarunveer S , ’t Hart Leen M 
Published: April 2020

Abstract

Context
There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease.

Objective
To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D).

Design
3089 samples from individuals with T2D, collected between 1999 and 2015, from 5 independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1100 individuals from 2 of the cohorts.

Main outcome measures
Plasma metabolites (n = 149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing.

Results
In total, 125 metabolites were significantly associated (PFDR = 1.5×10–32 − 0.046; β = −11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids (AAAs), glycoprotein acetyls, triglycerides (TGs), lipids in very low-density lipoproteins (VLDL) subclasses, and fatty acids (PFDR &lt; 0.03). We observed positive associations with cholesterol and phospholipids in high-density lipoproteins (HDL) and apolipoprotein A1 (PFDR &lt; 0.05). Albeit some metabolites were associated with UACR levels (P &lt; 0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr = 0.003; PHDLrelated &lt; 0.05), but not after.

Conclusions
This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation.
Murine FSH Production Depends on the Activin Type II Receptors ACVR2A and ACVR2B
Authors: Schang Gauthier , Ongaro Luisina , Schultz Hailey , Wang Ying , Zhou Xiang , Brûlé Emilie , Boehm Ulrich , Lee Se-Jin , Bernard Daniel J 
Published: April 2020

Abstract
Activins are selective regulators of FSH production by pituitary gonadotrope cells. In a gonadotrope-like cell line, LβT2, activins stimulate FSH via the activin type IIA receptor (ACVR2A) and/or bone morphogenetic protein type II receptor (BMPR2). Consistent with these observations, FSH is greatly reduced, though still present, in global Acvr2a knockout mice. In contrast, FSH production is unaltered in gonadotrope-specific Bmpr2 knockout mice. In light of these results, we questioned whether an additional type II receptor might mediate the actions of activins or related TGF-β ligands in gonadotropes. We focused on the activin type IIB receptor (ACVR2B), even though it does not mediate activin actions in LβT2 cells. Using a Cre-lox strategy, we ablated Acvr2a and/or Acvr2b in murine gonadotropes. The resulting conditional knockout (cKO) animals were compared with littermate controls. Acvr2a cKO (cKO-A) females were subfertile (~70% reduced litter size), cKO-A males were hypogonadal, and both sexes showed marked decreases in serum FSH levels compared with controls. Acvr2b cKO (cKO-B) females were subfertile (~20% reduced litter size), cKO-B males had a moderate decrease in testicular weight, but only males showed a significant decrease in serum FSH levels relative to controls. Simultaneous deletion of both Acvr2a and Acvr2b in gonadotropes led to profound hypogonadism and FSH deficiency in both sexes; females were acyclic and sterile. Collectively, these data demonstrate that ACVR2A and ACVR2B are the critical type II receptors through which activins or related TGF-β ligands induce FSH production in mice in vivo.
Identification, tracking, and sizing of nano-sized particles using dual-view polarization-resolved digital holography and T-matrix modeling
Authors: Öhman Johan , Sjödahl Mikael 
Published: April 2020

In this paper, we demonstrate how polarization-resolved holography can be used to determine if a particle is spherical or not and to estimate the size information of nanoparticles. The T-matrix method is used to model the scattered light from both spheres and spheroids. A dual-view polarization-resolved imaging system is used in order to obtain polarization ratio angles

(

β
1

,

β
2

)

. From the obtained

β
1

and

β
2

, it is possible to estimate whether or not a particle is spherical. It is found that nonsphericity only has a minor effect up to around sizes of 120 nm, and for that range, a spherical approximation is valid. For larger particles, the orientation influences the polarization response greatly. The size of a nonspherical particle can be estimated from the polarization ratio angles. The upper limit we can estimate unambiguously is around 200 nm. Finally, the model is applied to experimental measurements of naturally occurring particles in purified water. From the measurements, it is possible to separate spherical from nonspherical particles and also give a rough estimate of the size.
Broadly tunable Tm/Ho-codoped fiber lasers based on temperature-sensitive single-mode–multimode–single-mode fiber structures
Authors: Sakata Hajime , Kosaka Fuma , Hayakawa Kohei 
Published: April 2020

We present all-fiber tunable lasers using single-mode–multimode–single-mode (SMS) structures involving a liquid cladding in the multimode section. We make use of large thermooptic coefficients of the refractive-index liquids to tune the laser oscillation wavelength. The oscillation wavelength is changed over a range of 100 nm from 1858 nm to 1958 nm by controlling the temperature of the SMS structures in the Tm/Ho-codoped fiber ring resonators.
The Correlation of Neuronal Signals with Behavior at Different Levels of Visual Cortex and Their Relative Reliability for Behavioral Decisions
Authors: Kang Incheol , Maunsell John H.R. 
Published: April 2020

Behavior can be guided by neuronal activity in visual, auditory, or somatosensory cerebral cortex, depending on task requirements. In contrast to this flexible access of cortical signals, several observations suggest that behaviors depend more on neurons in later areas of visual cortex than those in earlier areas, although neurons in earlier areas would provide more reliable signals for many tasks. We recorded from neurons in different levels of visual cortex of 2 male rhesus monkeys while the animals did a visual discrimination task and examined trial-to-trial correlations between neuronal and behavioral responses. These correlations became stronger in primary visual cortex as neuronal signals in that area became more reliable relative to the other areas. The results suggest that the mechanisms that read signals from cortex might access any cortical area depending on the relative value of those signals for the task at hand.SIGNIFICANCE STATEMENTInformation is encoded by the action potentials of neurons in various cortical areas in a hierarchical manner such that increasingly complex stimulus features are encoded in successive stages. The brain must extract information from the response of appropriate neurons to drive optimal behavior. A widely held view of this decoding process is that the brain relies on the output of later cortical areas to make decisions, although neurons in earlier areas can provide more reliable signals. We examined correlations between perceptual decisions and the responses of neurons in different levels of monkey visual cortex. The results suggest that the brain may access signals in any cortical area depending on the relative value of those signals for the task at hand.
A Multicenter Phase II Study of Second-Line Axitinib for Patients with Advanced Hepatocellular Carcinoma Failing First-Line Sorafenib Monotherapy
Authors: Lin Zhong-Zhe , Chen Bang-Bin , Hung Yi-Ping , Huang Po-Hsiang , Shen Ying-Chun , Shao Yu-Yun , Hsu Chih-Hung , Cheng Ann-Lii , Lee Rheun-Chuan , Chao Yee , Hsu Chiun 
Published: April 2020

Abstract

Lessons Learned
For patients with advanced hepatocellular carcinoma after failure of first-line sorafenib monotherapy, second-line axitinib provides modest efficacy with tolerable toxicity. The discrepant tumor responses and survival outcomes in trials using axitinib as salvage therapy highlight the importance of optimal patient selection with the aid of clinical biomarkers.

Background
Multikinase inhibitors have been effective treatment for hepatocellular carcinoma (HCC). This multicenter phase II study explored the efficacy and safety of second-line axitinib for advanced HCC.

Methods
Patients with advanced HCC and Child-Pugh A liver function, experiencing progression on first-line sorafenib monotherapy, were eligible. Axitinib 5 mg twice daily was given continuously with allowed dose escalation. Tumor assessment was performed according to RECIST version 1.1. The primary endpoint was rate of disease control.

Results
From April 2011 to March 2016, 45 patients were enrolled. Thirty-seven patients (82%) tested positive for hepatitis B surface antigen. The disease control rate was 62.2%, and the response rate was 6.7%, according to RECIST criteria. Median progression-free survival (PFS) and overall survival (OS) were 2.2 months and 10.1 months, respectively. Treatment-related adverse events were compatible with previous reports of axitinib.

Conclusion
Second-line axitinib has moderate activity and acceptable toxicity for patients with advanced HCC after failing the first-line sorafenib monotherapy.