bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vision loss with pembrolizumab treatment: A report of two cases
Authors: Telfah Mohammad , Whittaker Thomas J. , C. Doolittle Gary 
Published: April 2019

Background Vision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembrolizumab treatment. Cases presentation Case 1 – A 58-year-old man was started on pembrolizumab for advanced melanoma. He was tolerating the treatment well. After receiving 14 cycles of pembrolizumab, he developed acute bilateral vision loss and occipital headaches. An emergent ophthalmologic evaluation revealed bilateral shallow choroidal effusion with bilateral focal exudative retinal detachment. After excluding other possible etiologies, inflammatory process secondary to pembrolizumab was suspected. Pembrolizumab was stopped, and the patient was started on a course of systemic and topical steroids. His vision improved within days and he recovered completely within two months. Calculated Naranjo Nomogram score was 7 indicating a “probable” correlation; Case 2 – A 57-year-old man with stage IIIC melanoma was started on adjuvant pembrolizumab. After a few weeks of treatments, he reported minor bilateral vision changes that progressively worsened over a period of six months. An ophthalmologic evaluation revealed bilateral posterior uveitis with right optic disc edema. Pembrolizumab-related inflammatory changes were suspected, and he was started on systemic and topical steroids. His symptoms improved within a few weeks and steroids were tapered. He was re-challenged with pembrolizumab and his symptoms quickly re-occurred. Pembrolizumab was stopped indefinitely and the patient again treated with systemic and topical steroids. His symptoms resolved and his vision returned to baseline within two months. The Naranjo Nomogram score was 9 indicating a “definite” correlation. Conclusions Vision loss is a serious complication that may occur at any point during treatment with PD-1 inhibitors. Vision loss is very distressing to the patients and their families. It is prudent for practitioners to recognize early vision abnormalities in patients receiving PD-1 antagonists to prevent permanent vision loss.
Effect of Acacia Honey on Transforming Growth Factor-Beta-1-Induced Myofibroblast Differentiation and Matrix Metalloproteinase-9 Production in Nasal Polyp Fibroblasts
Authors: Shin Seung-Heon , Ye Mi-Kyung , Lee Dong-Won , Che Mi-Hyun 
Published: April 2019

Background Acacia honey is known to have antioxidant, immune-modulatory, and antiproliferative properties. Nasal fibroblasts participate in local immune responses that control the recruitment of inflammatory cells and the production of extracellular matrix. Objectives The aim of this study was to determine the effect of acacia honey on myofibroblast differentiation and matrix metalloproteinase-9 (MMP-9) production in nasal polyp fibroblasts. Methods Primary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). Reverse transcription-polymerase chain reaction and Western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), tissue inhibitors of matrix metalloproteinase-1, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad ( pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase ( pAMPK) were then determined by Western blotting. Results TGF-β1 stimulation increased α-SMA and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Acacia honey effectively suppressed α-SMA and MMP-9 mRNA expression and protein production. It also prevented phosphorylation of Smad 2/3 and AMPK. Conclusion Acacia honey can inhibit TGF-β1-induced myofibroblast differentiation and MMP-9 production in nasal fibroblasts. These results suggest that acacia honey might be useful for inhibiting nasal polyp formation.
Comparative Assessment of the Magnitude of Hyperlipidemia in HIV-Infected Patients Receiving Lopinavir/r- and Atazanavir/r-Based Antiretroviral Drugs
Authors: Muya Esther , Kamuhabwa Appolinary 
Published: April 2019

Objective: To assess prevalence of hyperlipidemia in patients receiving lopinavir boosted with ritonavir (LPV/r) and atazanavir boosted with ritonavir (ATV/r) antiretroviral drugs. Methods: HIV-infected patients (300) were recruited in the study between December 2015 and April 2016. Lipid profile including triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were assessed. Results: Prevalence of derangement in TG was 71.0% in patients using LPV/r compared to 44% in those using ATV/r ( P = .01). Use of LPV/r was independently associated with increased total cholesterol (TC; P = .001) and TG ( P = .0003). Females had raised levels of TC compared to males ( P = .00008). Body mass index of ≥ 25 kg/m2 was also associated with raised TC ( P = .002) and LDL-C ( P = .006). Conclusion: LPV/r was significantly associated with lipid derangements, indicating the need to regularly monitor lipid profile in patients using LPV/r.
NAV-KIDS2 trial: protocol for a multi-centre, staggered randomised controlled trial of a patient navigator intervention in children with chronic kidney disease
Authors: van Zwieten Anita , Caldwell Patrina , Howard Kirsten , Tong Allison , Craig Jonathan C. , Alexander Stephen , Howell Martin , Armando Teixeira-Pinto , Hawley Carmel , Jesudason Shilpa , Walker Amanda , Mackie Fiona , Kennedy Sean , McTaggart Steve , McCarthy Hugh , Carter Simon , Kim Siah , Crafter Sam , Woodleigh Reginald , Guha Chandana , Wong Germaine 
Published: April 2019

Abstract
Background
Chronic kidney disease (CKD) is a devastating illness associated with increased mortality, reduced quality of life, impaired growth, neurocognitive impairment and psychosocial maladjustment in children. There is growing evidence of socioeconomic disparities in health outcomes among children with CKD. Patient navigators are trained non-medical personnel who assist patients with chronic conditions journey through the continuum of care and transit across different care settings. They help vulnerable and underserved populations to better understand their diagnosis, treatment options, and available resources, guide them through complex medical systems, and help them to overcome barriers to health care access. Given the complexity and chronicity of the disease process and concerns that current models of care may not adequately support the provision of high-level care in children with CKD from socioeconomically disadvantaged backgrounds, a patient navigator program may improve the provision of care and overall health of children with CKD.

Methods
The NAV-KIDS2 trial is a multi-centre, staggered entry, waitlisted randomised controlled trial assessing the health benefits and costs of a patient navigator program in children with CKD (stages 3–5, on dialysis, and with kidney transplants), who are of low socioeconomic backgrounds. Across 5 sites, 210 patients aged from 3 to 17 years will be randomised to immediate receipt of a patient navigator intervention for 24 weeks or waitlisting with standard care until receipt of a patient navigator at 24 weeks. The primary outcome is child self-rated health (SRH) 6-months after completion of the intervention. Other outcomes include utility-based quality of life, caregiver SRH, satisfaction with healthcare, progression of kidney dysfunction, other biomarkers, missed school days, hospitalisations and mortality. The trial also includes an economic evaluation and process evaluation, which will assess the cost-effectiveness, fidelity and barriers and enablers of implementing a patient navigator program in this setting.

Discussion
This study will provide clear evidence on the effectiveness and cost-effectiveness of a new intervention aiming to improve overall health and well-being for children with CKD from socioeconomically disadvantaged backgrounds, through a high quality, well-powered clinical trial.

Trial registration
Prospectively registered (12/07/2018) on the Australian New Zealand Clinical Trials Registry (ACTRN12618001152213).
Long-lasting insecticidal nets and indoor residual spraying may not be sufficient to eliminate malaria in a low malaria incidence area: results from a cluster randomized controlled trial in Ethiopia
Authors: Loha Eskindir , Deressa Wakgari , Gari Taye , Balkew Meshesha , Kenea Oljira , Solomon Tarekegn , Hailu Alemayehu , Robberstad Bjarne , Assegid Meselech , Overgaard Hans J. , Lindtjørn Bernt 
Published: April 2019

Abstract
Background
Conflicting results exist on the added benefit of combining long-lasting insecticidal nets (LLINs) with indoor residual spraying (IRS) to control malaria infection. The main study objective was to evaluate whether the combined use of LLINs and IRS with propoxur provides additional protection against Plasmodium falciparum and/or Plasmodium vivax among all age groups compared to LLINs or IRS alone.

Methods
This cluster-randomized, controlled trial was conducted in the Rift Valley area of Ethiopia from September 2014 to January 2017 (121 weeks); 44 villages were allocated to each of four study arms: LLIN + IRS, IRS, LLIN, and control. Each week, 6071 households with 34,548 persons were surveyed by active and passive case detection for clinical malaria. Primary endpoints were the incidence of clinical malaria and anaemia prevalence.

Results
During the study, 1183 malaria episodes were identified, of which 55.1% were P. falciparum and 25.3% were P. vivax, and 19.6% were mixed infections of P. falciparum and P. vivax. The overall malaria incidence was 16.5 per 1000 person-years of observation time (PYO), and similar in the four arms with 17.2 per 1000 PYO in the LLIN + IRS arm, 16.1 in LLIN, 17.0 in IRS, and 15.6 in the control arm. There was no significant difference in risk of anaemia among the trial arms.

Conclusions
The clinical malaria incidence and anaemia prevalence were similar in the four study groups. In areas with low malaria incidence, using LLINs and IRS in combination or alone may not eliminate malaria. Complementary interventions that reduce residual malaria transmission should be explored in addition to LLINs and IRS to further reduce malaria transmission in such settings.
Trial registration PACTR201411000882128 (08 September 2014)
High Detection Rate of MYD88 Mutations in Cerebrospinal Fluid From Patients With CNS Lymphomas
Authors: Watanabe Jun , Natsumeda Manabu , Okada Masayasu , Kobayashi Daiki , Kanemaru Yu , Tsukamoto Yoshihiro , Oishi Makoto , Kakita Akiyoshi , Fujii Yukihiko 
Published: April 2019

PURPOSE Biopsy is the gold standard for the diagnosis of primary CNS lymphoma (PCNSL). However, surgical biopsy has problems of morbidity related to hemorrhagic complications and false-negative findings, so safer and more reliable diagnostic methods are required. The aim of this study is to detect the MYD88 mutation, an important driver mutation, in the cerebrospinal fluid (CSF) of patients with CNS lymphoma. PATIENTS AND METHODS Twenty-six patients with CNS lymphoma (20 primary CNS lymphoma and six CNS relapse from systemic lymphoma) were studied. We extracted cell-free DNA (cfDNA) from CSF by lumbar puncture. cfDNA was extracted from 1 mL of CSF, and Sanger sequencing and droplet digital polymerase chain reaction (ddPCR) were performed. Furthermore, we performed DNA sequencing of MYD88 in 21 cases with available surgically obtained formalin-fixed paraffin-embedded (FFPE) tissue and compared the results. RESULTS The median cfDNA amount extracted from 1 mL CSF was 219 ng/mL (25th to 75th percentile, 129 to 333 ng/mL). MYD88 mutations were detected from CSF in 76.9% (20 of 26 cases), and L265P in exon 5 was the most frequent mutation in 19 out of 20 (95.0%) cases. S219C in exon 3 was detected in one case. In four patients, MYD88 mutation was confirmed by ddPCR but not by Sanger sequencing. In all 21 cases with sufficient FFPE tissue for DNA analysis, the detection of MYD88 mutation from cfDNA was consistent with those of tumor-derived DNA from FFPE tissue. CONCLUSION This pilot study provided evidence that the somatic driver mutation MYD88 can be reliably detected by combination of Sanger sequencing and ddPCR in the cfDNA taken from 1 mL of CSF in patients with CNS lymphomas.
Genomic Characterization of Prostatic Ductal Adenocarcinoma Identifies a High Prevalence of DNA Repair Gene Mutations
Authors: Schweizer Michael T. , Antonarakis Emmanuel S. , Bismar Tarek A. , Guedes Liana B. , Cheng Heather H. , Tretiakova Maria S. , Vakar-Lopez Funda , Klemfuss Nola , Konnick Eric Q. , Mostaghel Elahe A. , Hsieh Andrew C. , Nelson Peter S. , Yu Evan Y. , Montgomery R. Bruce , True Lawrence D. , Epstein Jonathan I. , Lotan Tamara L. , Pritchard Colin C. 
Published: April 2019

PURPOSE Ductal prostate cancer (dPC) is a rare variant of prostatic adenocarcinoma associated with poor outcomes. Although its histopathologic features are well characterized, the underlying molecular hallmarks of this aggressive subtype are not well described. We sought to provide a comprehensive overview of the spectrum of mutations associated with dPC. METHODS Three case series across multiple institutions were assembled. All patients had a diagnosis of dPC, and histopathologic classification was confirmed by an expert genitourinary pathologist. Case series 1 included men who were prospectively enrolled in a tumor sequencing study at the University of Washington (n = 22). Case series 2 and 3 included archival samples from men treated at Johns Hopkins Hospital (n = 21) and University of Calgary (n = 8), respectively. Tumor tissue was sequenced on a targeted next-generation sequencing assay, UW-OncoPlex, according to previously published methods. The frequency of pathogenic/likely pathogenic mutations are reported. RESULTS Overall, 25 patients (49%) had at least one DNA damage repair gene alteration, including seven (14%) with a mismatch repair gene mutation and 16 (31%) with a homologous repair mutation. Germline autosomal dominant mutations were confirmed or suspected in 10 patients (20%). Activating mutations in the PI3K pathway (n = 19; 37%), WNT pathway (n = 16; 31%), and MAPK pathway (n = 8; 16%) were common. CONCLUSION This study strongly suggests that dPCs are enriched for actionable mutations, with approximately 50% of patients demonstrating DNA damage repair pathway alteration(s). Patients with dPC should be offered next-generation sequencing to guide standard-of-care treatment (eg, immune checkpoint inhibitors) or triaged toward an appropriate clinical trial (eg, poly [ADP-ribose] polymerase inhibitors).
Snakes and Gutters
Authors: DeCaroli Robert 
Published: April 2019

AbstractVisitors to early (second century bce–fifth century ce) Buddhist monastic sites across South Asia encountered prominent figural images of nāgas, serpent-like beings who were believed to be closely connected to water and rainfall. Such images are commonly identified as guardians and occasionally have been linked to nearby water systems, such as ponds, tanks, and rivers. Yet, these images have not been studied as an aspect of water regulation within the monasteries themselves. This paper will first consider the water-related challenges that confronted the monks and architects at rock-cut monasteries. Then methods of hydraulic engineering designed to regulate the flow of water at the sites will be considered in relation to the role of nāga imagery. Their proximity to gutters and tanks reveals the Buddhist reliance on supernatural forces as an aspect of water control. The highly visible nature of this arrangement helps to explain the emergence of ritual texts, primarily after the fourth century ce, in which Buddhist ritualists adopt the role of rainmakers. These elaborate ceremonies promise to bring rain or end flooding for the benefit of the saṃgha and the wider community. The ritualists invariably invoke a special relationship with the nāgas, whom they enjoin to rectify undesirable conditions. This connection between image and text reveals a centuries-long process by which the monastic community developed an association with weather regulation that was contingent on a cultivated and highly public relationship with Buddhist-friendly nāgas.
Constructing the Afterlife, Reenvisioning Salvation
Authors: Chusid Miriam 
Published: April 2019

Abstract
By the thirteenth century in Japan, King Enma (Sanskrit: Yama-rāja) had become a familiar deity in the Buddhist pantheon. Largely understood as the judge of one's past deeds, Enma's position as one king in a series of ten was common knowledge, and offerings made to him, as well as to the other nine, served to ensure the petitioner a favorable rebirth in his or her next life. This article brings to light Enma's roles independent of this schema. It argues that far from serving solely as the judge of one's actions, Enma could be a figure to whom one petitioned for worldly benefits and even directed prayers for salvation. In addition, this essay shows that the architectural and spatial settings in which Enma was placed influenced the understanding of his varied functions, and ultimately enabled his refiguration as a salvific deity who had the power to grant birth in a Buddha land.
Small Intestinal Bacterial Overgrowth Is Common in Chronic Pancreatitis and Associates With Diabetes, Chronic Pancreatitis Severity, Low Zinc Levels, and Opiate Use
Authors: Lee Allen A. , Baker Jason R. , Wamsteker Erik J. , Saad Richard , DiMagno Matthew J. 
Published: April 2019

OBJECTIVES:Small intestinal bacterial overgrowth (SIBO) is often present in patients with chronic pancreatitis (CP) with persistent steatorrhea, despite pancreatic enzyme replacement therapy. Overall prevalence of SIBO, diagnosed by glucose breath test (GBT), varies between 0% and 40% but 0%–21% in those without upper gastrointestinal (GI) surgery. We investigated the prevalence and nonsurgical independent predictors of SIBO in CP without upper GI surgery.METHODS:Two hundred seventy-three patients ≥18 years old had a presumptive diagnosis of CP and a GBT between 1989 and 2017. We defined CP by Mayo score (0–16) ≥4 and a positive GBT for SIBO by Rome consensus criteria and retrospectively collected data for 5a priorivariables (age, opiates, alcohol use, diabetes mellitus (DM), gastroparesis) and 41 investigational variables (demographics, GI symptoms, comorbidities, CP etiologies and cofactors, CP symptom duration, Mayo score and nondiabetes components, and biochemical variables).RESULTS:Ninety-eight of 273 patients had definite CP and 40.8% had SIBO. Five of 46 variables predicted SIBO: opiates,P= 0.005; DM,P= 0.04; total Mayo score,P< 0.05; zinc,P= 0.005; and albumin,P< 0.05). Multivariable analysis of 3 noncorrelated variables identified zinc level (odds ratio = 0.0001;P= 0.03) as the sole independent predictor of SIBO (model C-statistic = 0.89;P< 0.001).DISCUSSION:SIBO, diagnosed by GBT, occurs in 40.8% of patients with CP without upper GI surgery. In patients with CP, markers of more severe CP (low zinc level, DM and increased Mayo score) and opiate use should raise clinical suspicion for SIBO, particularly in patients with persistent steatorrhea or weight loss despite pancreatic enzyme replacement therapy.
Harnack inequalities for curvature flows in Riemannian and Lorentzian manifolds
Authors: Bryan Paul , Ivaki Mohammad N. , Scheuer Julian 
Published: April 2019

Abstract
We obtain Harnack estimates for a class of curvature flows in Riemannian manifolds of constant nonnegative sectional curvature as well as in the Lorentzian Minkowski and de Sitter spaces. Furthermore, we prove a Harnack estimate with a bonus term for mean curvature flow in locally symmetric Riemannian Einstein manifolds of nonnegative sectional curvature. Using a concept of “duality” for strictly convex hypersurfaces, we
also obtain a new type of inequality, so-called “pseudo”-Harnack inequality, for expanding flows in the sphere and in the hyperbolic space.
Artinian bimodule with quasi-Frobenius bimodule of translations
Authors: Nechaev Aleksandr A. , Tsypyschev Vadim N. 
Published: April 2019

Abstract
The possibility to generalize the notion of a linear recurrent sequence (LRS) over a commutative ring to the case of a LRS over a non-commutative ring is discussed. In this context, an arbitrary bimodule AMB over left- and right-Artinian rings A and B, respectively, is associated with the equivalent bimodule of translations CMZ, where C is the multiplicative ring of the bimodule AMB and Z is its center, and the relation between the quasi-Frobenius conditions for the bimodules AMB and CMZ is studied. It is demonstrated that, in the general case, the fact that AMB is a quasi-Frobenius bimodule does not imply the validity of the quasi-Frobenius condition for the bimodule CMZ. However, under some additional assumptions it can be shown that if CMZ is a quasi-Frobenius bimodule, then the bimodule AMB is quasi-Frobenius as well.
A Wideband Polarization Reconfigurable Antenna Array Based on Mode Combination Method
Authors: Mu Zhuo , Wang Shen-Yun , Meng Wen-Ying 
Published: April 2019

Abstract
This paper reports a novel polarization-reconfigurable antenna array based on the theory of mode combination (MC), which can electronically alter its polarization states between left-hand circular polarization (LCP) mode, right-hand circular polarization (RCP) mode, and two combined linear polarization (LP) modes. The array element is adopted as the L-probes fed circularly-polarized antenna reported by Luk et al. [1]. To verify the concept, a prototype of 2×2 antenna array is manufactured and tested. By properly exciting the feeding probes, four polarization modes can be switchable. Measurement results show that the proposed antenna has an overlapped −10 dB impedance bandwidth around 34 % for both CP modes and LP(2) mode, and an overlapped 3 dB axial-ratio bandwidth around 22.0 % of the CP modes. The average realized gains are around 12.4 dB for CP modes and LP(1) mode, which remain stable in the axial-ratio bandwidth.
A Highly Accurate Collocation Method for Linear and Nonlinear Vibration Problems of Multi-Degree-Of-Freedom Systems Based on Barycentric Interpolation
Authors: Zhuang Meiling , Miao Changqing , Wan Caihong 
Published: April 2019

Abstract
A highly accurate collocation method based on barycentric interpolation (BICM) is proposed for solving linear and nonlinear vibration problems for multi-degree-of-freedom systems in this article. The mathematical model of the linear and nonlinear vibrations of multi-degree-of freedom systems is the initial value problem of the linear and nonlinear differential equations. The numerical solution of the linear differential equations can be directly solved by BICM. The numerical solution of nonlinear differential equations can be solved as following: Firstly, the nonlinear governing equation is converted to linear differential equation by assuming the initial function. Secondly, the linear differential equations are discretized into algebraic equations by using barycentric interpolation differential matrices. Thirdly, the numerical solution can be calculated by iteration method under given control precision. Finally, the numerical solution of calculation examples by using barycentric Lagrange interpolation iteration collocation method (BLIICM) and barycentric rational interpolation iteration collocation method (BRIICM) are compared with the analytical solution. Numerical results illustrate the advantages of proposed methodology are efficient, fast, simple formulations, and high precision. Comparing with BLIICM, BRIICM can still maintain its computational stability when dealing with a large number of nodes, especially the equidistant nodes.