bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL in the DUO Crossover Extension Study
Authors: Davids Matthew S. , Kuss Bryone J. , Hillmen Peter , Montillo Marco , Moreno Carol , Essell James , Lamanna Nicole , Nagy Zsolt , Tam Constantine S. , Stilgenbauer Stephan , Ghia Paolo , Delgado Julio , Lustgarten Stephanie , Weaver David T. , Youssoufian Hagop , Jäger Ulrich
Published: January 2020

Purpose:

In the phase III DUO trial, duvelisib, an oral dual PI3K-δ,γ inhibitor, demonstrated significantly improved efficacy versus ofatumumab [median (m) progression-free survival (PFS), 13.3 vs. 9.9 months (HR, 0.52; P < 0.0001); overall response rate [ORR], 74% vs. 45% (P < 0.0001)], with a manageable safety profile in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report results from patients with progressive disease (PD) after ofatumumab who crossed over to duvelisib in the DUO trial.

Patients and Methods:

Patients with radiographically confirmed PD after ofatumumab received duvelisib 25 mg twice daily in 28-day cycles until PD, intolerance, death, or study withdrawal. The primary endpoint was ORR per investigator. Secondary endpoints included duration of response (DOR), PFS, and safety.

Results:

As of December 14, 2018, 90 ofatumumab-treated patients in the DUO trial prior to crossover had an ORR of 29%, mDOR of 10.4 months, and mPFS of 9.4 months. After crossover, 77% of patients (69/90) achieved a response, with an mDOR of 14.9 months and mPFS of 15.7 months. Patients with del(17p) and/or TP53 mutations had similar outcomes [ORR, 77% (20/26); mPFS, 14.7 months]. Notably, 73% of patients (47/64) with disease previously refractory to ofatumumab achieved a response. The most frequent any-grade/grade 3/4 treatment-emergent adverse events were diarrhea (47%/23%), neutropenia (26%/23%), pyrexia (24%/4%), cutaneous reactions (23%/4%), and thrombocytopenia (10%/6%).

Conclusions:

Duvelisib demonstrated high response rates with good durability and a manageable safety profile in patients with R/R CLL/SLL who progressed on ofatumumab, including patients with high-risk disease and disease previously refractory to ofatumumab.
CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies
Authors: Quayle Steven N. , Girgis Natasha , Thapa Dharma R. , Merazga Zohra , Kemp Melissa M. , Histed Alex , Zhao Fan , Moreta Miguel , Ruthardt Paige , Hulot Sandrine , Nelson Alyssa , Kraemer Lauren D. , Beal Dominic R. , Witt Luke , Ryabin Jessica , Soriano Jonathan , Haydock Mark , Spaulding Emily , Ross John F. , Kiener Peter A. , Almo Steven , Chaparro Rodolfo , Seidel Ronald , Suri Anish , Cemerski Saso , Pienta Kenneth J. , Simcox Mary Ellen
Published: January 2020

Purpose:

To assess the potential for CUE-101, a novel therapeutic fusion protein, to selectively activate and expand HPV16 E711-20-specific CD8+ T cells as an off-the shelf therapy for the treatment of HPV16-driven tumors, including head and neck squamous cell carcinoma (HNSCC), cervical, and anal cancers.

Experimental Design:

CUE-101 is an Fc fusion protein composed of a human leukocyte antigen (HLA) complex, an HPV16 E7 peptide epitope, reduced affinity human IL2 molecules, and an effector attenuated human IgG1 Fc domain. Human E7-specific T cells and human peripheral blood mononuclear cells (PBMC) were tested to demonstrate cellular activity and specificity of CUE-101, whereas in vivo activity of CUE-101 was assessed in HLA-A2 transgenic mice. Antitumor efficacy with a murine surrogate (mCUE-101) was tested in the TC-1 syngeneic tumor model.

Results:

CUE-101 demonstrates selective binding, activation, and expansion of HPV16 E711-20-specific CD8+ T cells from PBMCs relative to nontarget cells. Intravenous administration of CUE-101 induced selective expansion of HPV16 E711-20-specific CD8+ T cells in HLA-A2 (AAD) transgenic mice, and anticancer efficacy and immunologic memory was demonstrated in TC-1 tumor-bearing mice treated with mCUE-101. Combination therapy with anti-PD-1 checkpoint blockade further enhanced the observed efficacy.

Conclusions:

Consistent with its design, CUE-101 demonstrates selective expansion of an HPV16 E711-20-specific population of cytotoxic CD8+ T cells, a favorable safety profile, and in vitro and in vivo evidence supporting its potential for clinical efficacy in an ongoing phase I trial (NCT03978689).
Prospective Validation of First-Trimester Ultrasound Characteristics as Predictive Tools for Twin-Twin Transfusion Syndrome and Selective Intrauterine Growth Restriction in Monochorionic Diamniotic Twin Pregnancies
Authors: Mogra Ritu , Saaid Rahmah , Tooher Jane , Pedersen Lars , Kesby Greg , Hyett Jon
Published: January 2020

Objective: Monochorionic diamniotic (MCDA) twins are at increased risk of adverse outcome due to unequal placental sharing and placental vascular communications between the fetal circulations. Most centres perform ultrasound examination every 2–3 weeks to identify these complications. Identifying a high-risk cohort of MCDA twins in the first trimester would allow more efficient surveillance. We have attempted to validate first-trimester ultrasound characteristics as predictive tools for twin-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR) in MCDA twins. Material and Methods: This is a prospective cohort study including MCDA twins enrolled at the time of first-trimester combined screening. Differences in crown-rump length (CRL), nuchal translucency (NT) thickness, ductus venosus pulsatility index for veins (DV PIV), presence or absence of tricuspid regurgitation and right ventricular E/A ratio were assessed. Receiver operating characteristic (ROC) curves were used to assess the potential value of these measures as predictive tools for identifying a cohort of MCDA pregnancies at high risk of adverse pregnancy outcome. Results: Sixty-five MCDA pregnancies were included in the analysis. Nine (14%) developed TTTS, 17 (26%) developed sIUGR. The best predictive marker for TTTS was NT discordance of ≥20% (ROC AUC = 0.79; 95% CI 0.59–0.99). Combining measures did not improve performance (AUC = 0.80; 95% CI 0.62–0.99). Conclusion: NT discordance was the most effective characteristic at predicting TTTS but still had a relatively poor positive predictive value (36%). Intertwin differences in CRL, DV PIV and E/A ratio were not predictive of subsequent pregnancy complications. None of these characteristics have sufficient efficacy to be used to triage MCDA twin pregnancies ongoing obstetric surveillance.
Biomarkers for the Assessment of Fluoride Exposure in Children
Authors: Idowu Oladipo S. , Duckworth Ralph M. , Valentine Ruth A. , Zohoori Fatemeh Vida
Published: January 2020

Due to practical difficulties in quantifying fluoride exposure, the ability of various biomarkers to predict exposure has been investigated previously. However, the results are inadequate for validation of their application and usefulness. This study aimed to investigate the association between contemporary/recent biomarkers of fluoride exposure and total daily fluoride intake (TDFI) of children with large differences in fluoride exposure through drinking water. TDFI was assessed in 61 healthy 4- to 5-year-old children who provided at least 1 biomarker sample; 32 lived in a low-fluoride area (0.04 mg F/L) and 29 lived in a high-fluoride area (3.05 mg F/L). Validated questionnaires were administered to evaluate fluoride intake from diets (including water) and toothpaste ingestion. Daily urinary fluoride excretion (UFE) and fluoride concentrations in plasma, fasting whole saliva, hair, and nails (toenails/fingernails) were evaluated and related to total fluoride exposure. TDFI, UFE, and fluoride concentrations of biomarkers were statistically significantly higher in the high-fluoride area than in the low-fluoride area. There was a strong statistically significant positive correlation between TDFI and UFE (ρ = 0.756, p < 0.001); plasma fluoride concentration (ρ = 0.770, p < 0.001); and toenail fluoride concentration (ρ = 0.604, p < 0.001). The statistically significant positive correlation between TDFI and fingernail fluoride concentration (ρ = 470, p < 0.001) as well as between TDFI and fasting whole saliva fluoride concentration (ρ = 0.453, p = 0.001) was moderate, whereas it was weak between TDFI and hair fluoride concentration (ρ = 0.306, p = 0.027). In conclusion, the current study confirmed the suitability of 24-h urine samples for estimating fluoride exposure in children. The strong correlations between TDFI and fluoride in plasma and toenails also suggest these biomarkers may be considered for health risk assessments of fluoride in children who are susceptible to development of dental fluorosis.
Differences in the Natural Enamel Surface and Acquired Enamel Pellicle following Exposure to Citric or Hydrochloric Acid
Authors: Houghton Jack William , Yong Jing Teng , Carpenter Guy , Bartlett David , Moazzez Rebecca , O’Toole Saoirse
Published: January 2020

Objectives: The aim of this study was to investigate variations in the interaction between enamel, that is, the acquired enamel pellicle (AEP) and citric or hydrochloric acid. Materials and Methods: A 24-h AEP was formed on natural enamel specimens (n = 40) from pooled whole mouth human saliva. Samples were randomly allocated to citric (0.3%, pH 3.2) or hydrochloric (HCl) acid (0.01 M, pH 2.38) exposure for 30 or 300 s. The total protein concentration (TPC), and phosphorous and calcium concentrations of the pellicle were determined before and after acid exposure, and again after re-immersion in saliva. Surface roughness and tandem scanning confocal microscopy imaging were used to assess enamel changes. Results: After 300 s of citric acid exposure, the mean ± SD TPC reduced from 5.1 ± 1.1 to 3.5 ± 1.1 mg/mL (p < 0.05). In contrast, after 300 s of HCl exposure, the mean TPC did not reduce significantly from baseline (6.6 ± 1.1 to 5.7 ± 0.7 mg/mL) but was significantly reduced in the reformed pellicle to 4.9 ± 1.2 mg/mL (p < 0.001). This reduction occurred after significant release of calcium and phosphorous from the enamel surface (p < 0.001). Thirty seconds of exposure to either acid had no obvious effect on the AEP. The surface roughness of the enamel decreased after acid exposure but no differences between groups was observed. Conclusions: These findings indicate that citric acid interacted with proteins in the AEP upon contact, offering enamel protection. In contrast, HCl appeared to bypass the pellicle, and reduced protein was observed only after changes in the enamel chemical composition.
Impact of Clustering Oral Symptoms in the Pathogenesis of Radiation Caries: A Systematic Review
Authors: Gouvêa Vasconcellos Adriele Ferreira , Palmier Natália Rangel , Ribeiro Ana Carolina Prado , Normando Ana Gabriela Costa , Morais-Faria Karina , Gomes-Silva Wagner , Vechiato Filho Aljomar José , de Goes Mario Fernando , Paes Leme Adriana Franco , Brandão Thaís Bianca , Lopes Marcio Ajudarte , Marsh Philip D. , Santos-Silva Alan Roger
Published: January 2020

Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described “clustering of oral symptoms theory,” the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account.
Recovery of Dementia Syndrome following Treatment of Brain Inflammation
Authors: Lee Jong-hoon , Choi Su-hee , Lee Chul Joong , Oh Sang-suk
Published: January 2020

Aim/Background: This research aims to prevent progression from mild cognitive impairment (MCI) to Alzheimer’s disease. A Japanese study of leprosy patients revealed that the incidence of dementia in leprosy patients was lower than that in patients taking dapsone who had never been treated. But a similar study the following year refuted the finding of less dementia in leprosy patients taking dapsone. According to conflicting reports, Mycobacterium leprae was a factor in reducing the incidence of Alzheimer’s disease. Thus, we formed a hypothesis that if dapsone is administered to patients without leprosy but with MCI and the prophylactic effect of dementia syndrome is observed over a long period of time, we can determine whether dapsone can prevent the progression of MCI to dementia syndrome. If dementia does not occur after treating inflammation in brain cells while dementia develops after a certain long-term period (usually within 2–3 years), brain cell inflammation can be demonstrated as the cause of dementia. Methods: This is a prospective cohort research. We report on an elderly patient diagnosed with MCI from February 2008 to January 2019. The patient took dapsone 100 mg once a day from 2010 to 2015 for the treatment of MCI. Since 2016, the production of dapsone has ceased in Korea. In June 2018, the patient was diagnosed with Alzheimer’s disease. The patient took Aricept for the treatment of Alzheimer’s disease but complained of serious side effects. And dapsone was re-administered to the patient from November 2018. Results: The patient recovered to MCI and improved her daily life owing to the treatment with dapsone. The drug controls the inflammatory response in the brain, irrespective of whether proteins are deposited in neurons. Conclusions:This finding means that dementia syndrome is an inflammatory disease. This research suggests that diagnostic criteria for Alzheimer’s disease should be based on the presence or absence of inflammation in neurons. Because inflammation in neurons can occur in middle age due to various causes, we can treat inflammation in neurons and prevent and treat dementia syndrome, including Alzheimer’s disease.
Treatment Considerations for Patients with Unresectable Metastatic Melanoma Who Develop Pembrolizumab-Induced Guillain-Barré Toxicity: A Case Report
Authors: Muralikrishnan Sivraj , Ronan Lara K. , Coker Shodeinde , Rauschkolb Paula K. , Shirai Keisuke
Published: January 2020

Immunotherapy has improved outcomes in many malignancies, most notably in melanoma, lung cancer, and bladder cancer. Understanding the side effects associated with these medications is an important part of managing our patients. Although fatigue, rash, and diarrhea are commonly reported side effects, it is important to be cognizant of rarer ones, such as neuropathy. Amongst the different neurological toxicities that have been reported in the literature, Guillain-Barré-like neuropathies are quite rare. However, the occurrence of such neuropathies in a patient can be life threatening. The problem this poses in treating cancers such as melanoma is that it eliminates an effective class of medication available to the patient, which can ultimately affect their prognosis. We present a case of a 65-year-old female with unresectable metastatic melanoma who developed Guillain-Barré-like neuropathy after two doses of pembrolizumab. Her clinical course was complicated by three separate hospitalizations over 3 months due to recurring bouts of neuropathy, which resulted in a significant decline in performance status and delay in subsequent treatment of her melanoma. Her prolonged recovery eventually resulted in progression of her melanoma nearly 1 year later, while off therapy. Instead of discontinuing immunotherapy completely, she agreed to a re-challenge with ipilimumab. After one dose, her melanoma regressed and continues to show a sustained response nearly 1 year after treatment without any signs of relapse in her neuropathy. Guillain-Barré toxicity resulting from immune checkpoint inhibition poses a difficult challenge to an oncologist who is determining the next line of treatment for patients with unresectable metastatic melanoma that have progressed while off therapy and who have no targetable mutations. Our case raises the question of whether a re-challenge with a different class of immunotherapy agent is a reasonable option.
BRCA Mutation Association with Recurrence Score and Discordance in a Large Oncotype Database
Authors: Blanter Julia , Zimmerman Brittney , Tharakan Serena , Ru Meng , Cascetta Krystal , Tiersten Amy
Published: January 2020

Background: The Oncotype DX Breast Cancer Assay is a 21-gene assay used to predict the likelihood of distant recurrence and the benefit of chemotherapy in patients with node-negative, tamoxifen-treated breast cancer. Prior studies demonstrated 7–19% discordance, or a difference between the recurrence score (RS) and tumor grade (TG) in breast cancer patients. BRCA mutated tumors (BRCA+) have been shown to be associated with higher RS as compared to BRCA-negative patients (BRCA–). Objectives: We developed a large Oncotype RS database to determine if the BRCA mutation status is associated with discordance. Methods: We identified 723 patients (32 [4%] mutation-positive and 691 [96%] mutation-negative patients) with early-stage, hormone-positive breast cancer treated between 2006 and 2018, with tumor characteristics available for analysis. Discordance was defined as one- or two-step difference between RS (low, intermediate, high risk) and TG (well [WD], moderately [MD], and poorly [PD] differentiated). Mutation positive was defined as BRCA1 deleterious mutation, BRCA2 deleterious mutation, BRCA mutation of unknown type, BRCA variant of undetermined significance (VUS) or other mutation (classified as other VUS). Number (%) or median were used to describe patient characteristics between groups and were compared by the Kruskal-Wallis test at a significance level of 5%. Results: Among these patients, there were 32 (4% of total) who were identified as mutation-positive. Of those patients, 16% had a documented deleterious mutation in BRCA1, 22% in BRCA2, 6% had a BRCA mutation of unknown type (either 1 or 2), 25% were BRCA VUS, and 31% other VUS (most commonly CHEK2 and ATM). The median RS was 23.5 in patients with deleterious BRCA mutations (1, 2 or unknown) versus 16 in patients in the BRCA-negative database, which was statistically significant (p < 0.01). One- and two-step discordance was present in 46 and 8%, respectively, of patients with deleterious BRCA mutations versus 53 and 11%, respectively, in the BRCA-negative database. Conclusions: Patients with deleterious BRCA mutations demonstrated no difference in rates of discordance as compared to BRCA-negative patients. We further demonstrated that patients with BRCA-positive tumors display higher RS than patients with BRCA-negative tumors.
Self-Reported Changes in Cognition, Communication and Swallowing in Multiple Sclerosis: Data from the Swedish Multiple Sclerosis Registry and from a National Survey
Authors: Johansson Kerstin  , Schalling Ellika , Hartelius Lena
Published: January 2020

Purpose: The aim of this study was to investigate self-reported cognition, speech, communication and swallowing changes in a large sample of individuals with multiple sclerosis (MS) in Sweden. A second aim was to update information about speech and language pathology (SLP) services received by people with MS (pwMS). Method: Self-ratings of cognition, speech/communication and swallowing registered by pwMS between 2012 and 2018 were retrieved from the Swedish MS Registry. In addition, more detailed information about speech, communication, swallowing and provision of SLP services was collected using an online survey distributed via a national patient organization. Results: In total, entries from 5,289 pwMS were retrieved from the MS Registry. Nearly two thirds of the respondents reported that cognition was affected to some degree, whereas approximately one third perceived some difficulties with speech/communication. A smaller group reported swallowing problems. The majority of those who reported problems with speech/communication also reported problems with cognition. Among the 440 individuals who responded to the MS survey, word-finding difficulties were the most frequently self-reported problem related to communication, and the second most common problem was getting off topic. In all, close to four out of five respondents experienced at least one symptom related to speech and communication, such as speech-related fatigue or imprecise articulation. Swallowing difficulties were reported by one out of four respondents in the MS survey. As a result of their speech difficulties, up to one in three experienced changes in professional or social roles and participation. A limited number of respondents had received SLP services, the most common intervention being voice training. Conclusions: In MS, changes associated with cognition as well as speech/communication are frequent, cognitive-linguistic symptoms being the most common. Swallowing difficulties are also relatively prevalent. Access to SLP services seems to be insufficient compared to prevalence of perceived symptoms. Considering that the majority of pwMS are part of the working-age population, access to SLP services must be more highly prioritized and must address cognitive-linguistic problems as well as voice, speech and swallowing dysfunction.
General Anesthesia versus Local Anesthesia for Deep Brain Stimulation in Parkinson’s Disease: A Meta-Analysis
Authors: Liu Zhen , He Shuting , Li Liang
Published: January 2020

Background: Deep brain stimulation (DBS) implantation under general anesthesia (GA) is of great importance for patients with disabling off-medication symptoms or medical comorbidities. However, the relative advantages/disadvantages of routine local anesthesia (LA) surgery versus GA regarding clinical outcomes are controversial, and the safety of DBS implantation under GA is debatable. Summary: We systematically reviewed the literature to compare the efficacy and safety of awake and asleep DBS surgery. We identified cohort studies from the Cochrane library, MEDLINE, and EMBASE (January 1970 to August 2019) by using Review Manager 5.3 software to conduct a meta-analysis following the PRISMA guidelines. Fourteen cohort studies involving 1,523 patients were included. The meta-analysis results showed that there were no significant differences between the GA and LA groups in UPDRSIII score improvement (standard mean difference [SMD] 0.06; 95% CI –0.16 to 0.28; p = 0.60), postoperative LEDD requirement (SMD –0.17; 95% CI –0.44 to 0.12; p = 0.23), or operation time (SMD 0.18; 95% CI –0.31 to 0.67; p = 0.47). Additionally, there was no significant difference in the incidence of adverse events (OR 0.98; 95% CI 0.53–1.80; p = 0.94), including postoperative speech disturbance and intracranial hemorrhage. However, the volume of intracranial air was significantly lower in the GA group than that in the LA group. In a subgroup analysis, there was no significant difference in clinical efficacy between the microelectrode recording (MER) and non-MER groups. We demonstrated equivalent clinical outcomes of DBS surgery between GA and LA in terms of improvement of symptoms and the incidence of adverse events. Key Messages: MER might not be necessary for DBS implantation. For patients who cannot tolerate DBS surgery while being awake, GA should be an appropriate alternative.
Kikuchi-Fujimoto Disease-Like Inflammatory Reaction in a Silicone Breast Implant Seroma
Authors: Jiménez-Heffernan José A. , Muñoz-Hernández Patricia , Bárcena Carmen
Published: January 2020

Introduction: Kikuchi-Fujimoto disease (KFD) may have an autoimmune etiology and some cases have been associated with silicone breast implants. Cytomorphologic features of the disease have been well characterized by fine-needle aspiration of lymph nodes. They are so specific as to permit a precise cytologic diagnosis. Cytologic features have not been reported in fluid specimens. Case: A 33-year-old female presented with a unilateral periprosthetic silicone breast seroma. The fluid was drained, and cytological analysis revealed numerous lymphocytes with no neutrophils, karyorrhectic nuclear debris, and peculiar histiocytes with eccentrically located nuclei showing a crescentic shape. Many of those histiocytes showed intracellular apoptotic debris. Conclusion: A Kikuchi disease-like inflammatory reaction is possible not only in axillary and cervical lymph nodes of patients with silicone breast implants but also in breast seromas. There is still not enough evidence to establish if there is an association between KFD and breast implants. A detailed cytologic examination of periprosthetic silicone breast seromas may help answer this question. In any case, pathologists must be aware of this possibility. Cytologic features are characteristic enough to permit differentiation from breast implant-associated anaplastic large-cell lymphoma.
Conjunctival Melanoma Angiotropic Microsatellitosis: A Mechanism of Local Extravascular Migratory Metastasis
Authors: Echegaray Jose J. , Yeaney Gabrielle , Chen Rachel , Singh Arun D.
Published: January 2020

Purpose: To report a case of local metastasis of conjunctival melanoma, which may occur via extravascular migratory metastasis (EVMM), and discuss its clinical relevance in conjunctival melanoma tumor staging and possible management implications. Methods: Retrospective chart review of a single clinical case with clinicopathologic correlation. Results: A 65-year-old male referred due to local recurrence of conjunctival melanoma at the caruncle was successfully treated after two excisional procedures with negative sentinel lymph node biopsies. Forty-eight months after initial presentation, the patient developed a nodular lesion representing local recurrence in the ipsilateral upper tarsal conjunctiva, distant from the primary tumor site. Histopathology showed nodules in the substantia propria in the absence of primary acquired melanosis. The tumor cells were found along the extravascular surface without intralymphatic or intravascular tumor cells consistent with local metastasis. One possible mechanism is angiotropic microsatellitosis leading to local EVMM. Additional neck CT imaging showed no lymphadenopathy. Conclusion: EVMM via angiotropic microsatellitosis is another possible mechanism of noncontiguous local recurrence of conjunctival melanoma. Angiotropic microsatellitosis may represent a high-risk finding possibly related to increased melanoma-related mortality.
Cystatin C- Versus Creatinine-Based Assessment of Renal Function and Prediction of Early Outcomes Among Patients With a Left Ventricular Assist Device
Authors: Pinsino Alberto , Mondellini Giulio M. , Royzman Eugene A. , Hoffman Katherine L. , D’Angelo Debra , Mabasa Melissa , Gaudig Antonia , Zuver Amelia M. , Masoumi Amirali , Garan A. Reshad , Mohan Sumit , Husain Syed A. , Toma Katherine , Faillace Robert T. , Giles Jon T. , Takeda Koji , Takayama Hiroo , Naka Yoshifumi , Topkara Veli K. , Demmer Ryan T. , Radhakrishnan Jai , Colombo Paolo C. , Yuzefpolskaya Melana
Published: January 2020

Background:

Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies.

Methods:

A prospective cohort (n=116) with CysC and sCr concurrently measured at serial time points, and a retrospective cohort (n=91) with chest computed tomography performed within 40 days post-LVAD were studied. In the prospective cohort, the primary end point was a composite of in-hospital mortality, renal replacement therapy, or severe right ventricular failure. In the retrospective cohort, muscle mass was estimated using pectoralis muscle area indexed to body surface area (pectoralis muscle index).

Results:

In the prospective cohort, sCr-eGFR significantly improved early post-LVAD and subsequently declined, whereas CysC-eGFR remained stable. CysC-eGFR but not sCr-eGFR predicted the primary end point: odds ratio per 5 mL/(min·1.73 m
2
) decrease 1.16 (1.02–1.31) versus 0.99 (0.94–1.05). In retrospective cohort, for every 5 days post-LVAD, a 6% decrease in pectoralis muscle index was observed (95% CI, 2%–9%,
P
=0.003). After adjusting for time on LVAD, for every 1 cm
2
/m
2
decrease in pectoralis muscle index, there was a 4% decrease in 30-day post-LVAD sCr (95% CI, 1%–6%,
P
=0.004).

Conclusions:

Initial improvement in sCr-eGFR is likely due to muscle wasting following LVAD surgery. CysC may improve assessment of renal function and prediction of early postoperative outcomes in patients with an LVAD.
Typification of the Linnaean name Onoclea polypodioides, type of the fern genus Gleichenia (Gleicheniaceae, Polypodiopsida)

Authors: LIMA LUCAS VIEIRA , VIVEROS RAQUEL STAUFFER , SALINO ALEXANDRE
Published: January 2020

The fern family Gleicheniaceae was established by Presl (1825: 10) from the order Gleicheneae created by Brown (1810: 160) to accommodate two genera: Platyzoma Brown (1810: 160) and Gleichenia Smith (1793: 419). When the genus Gleichenia was established by Smith (1793), it included only G. polypodioides, but the genus concept was later used in a broader sense to include all Gleicheniaceae species known until the early 20th century (Diels 1900, Christensen 1905). The name proposed by Smith (1793) is a later homonym conserved against Gleichenia Necker (1790: 314) (Dryopteridaceae) (Nomenclature Committees 1954), and Gleichenia Smith is currently used with a narrow circumscription, with about 10 species (PPG I 2016). Nowadays, Gleicheniaceae is divided into six genera, although their monophyly is still questionable (PPG I 2016). The nomenclature of the family still needs attention due to the existence of few papers dealing with this subject as noted by Lima et al. (2018) and Lima & Salino (2018). While conducting taxonomic studies in Gleicheniaceae, we realized that the Linnaean name Onoclea polypodioides Linnaeus (1771: 306), the type species of Gleichenia, was not properly typified, as we explain in the next paragraphs.
1. The Hellenistic Merchantmen
Authors: Nantet Emmanuel
Published: January 2020

Although numerous scholars have explored the Mediterranean economy of the last centuries BCE, their research has included hardly any data about shipwrecks. This can be explained not only by the lack of such data, but likewise the lack of conferences dedicated to this issue. The impact of shipwrecks on the Hellenistic sea trade is therefore a gap in our collective knowledge. The purpose of this book is to suggest some approaches to the study of this issue.
5. The Rise of the Tonnage in the Hellenistic Period
Authors: Nantet Emmanuel
Published: January 2020

The available data on local boat-building techniques during the Late (664–332 BC) and Ptolemaic Periods (332–30 BC) of Ancient Egypt received a considerable boost from the more than sixty Ancient Egyptian ships that were found on the site of Thonis-Heracleion in 2000. Many of these ships seem to belong to the baris-type as described in Herodotus in his Historia. This chapter is an attempt to determine the space of navigation of these ships by examining the direct evidence derived from their construction, as well as indirect evidence drawn from the state of the ships’ timbers and the results of reconstruction of their hulls, and of their propulsion and steering systems.
6. A Note on the Navigation Space of the Baris-Type Ships from Thonis-Heracleion
Authors: Belov Alexander
Published: January 2020

‘Painting ships’ (naves pingere), as Pliny the Elder said about the activities of the painter Protogenes (‘until the age of fifty he was also a ship painter…’), may have two meanings: the first is to adorn ships; the second consists of representing ships in paintings. During Alexander’s funerals, the painter Apelles — or his workshop — may have produced four panels adorning the hearse of the Conqueror and celebrating the military power of the Macedonian. Among these depictions was his war fleet. However, this picture, linked to the event that defines the early Hellenistic period, is neither the first nor the only one to represent ships. This chapter will explore these two very different pictorial exercises over a long period of time.

Few artists are described as ‘ship painters’. As a prefect of the imperial war fleet in Misenum, Pliny knew ships very well. Therefore, in calling someone a ship painter, he might imply both artistic and technical expertise. We should therefore pay particular attention to the work of Protogenes. What precisely was a ship painter in the ancient Mediterranean?
Design of Rapid Bacterial Identification System Based on Scattering of Laser Light and Classification of Binned Plots
Authors: Hussain Mubashir , Lv Mu , Dong Xiaohan , Shen Han , Wang Wei , Li Song , Chen Zhu , Jin Lian , He Nongyue , Li Zhiyang , Liu Bin
Published: January 2020

The rapid detection and classification of bacterial pathogens have great medical utility, and widespread applications in clinical labs, intensive care units, and infectious disease departments. The Rapid Bacterial Identification System (RBIS) is based on the principle of variation in
light scattering when the laser beam passes through bacterial microbes. The use of laser light scattering and classification of binned plots algorithm gives a new dimension for real-time identification of different pathogens without any biochemical processing. Bacterium identification device
consists of an assembly of photodetectors surrounded by the bacterial sample at different angles. The photodetectors acquire the scattered light in form of peaks when the laser beam passes by the sample. The acquired peak values were used to create 3D histograms to evaluate the frequency of
occurrence. However, the identification is based on creating two dimensional binned plots with the help of the frequency of occurrence of peak values across two photodetectors. The algorithm of the system consists of two parts: Library files and the Comparator. Library files contain data of
bacterial species in form of binned plots, while comparator compares the data of test sample with library files. The classification of sample depends on the maximum resemblance of the number of binned plots with library files. The classification of Enterococcus faecalis, Staphylococcus
aureus, and Escherichia coli gives mean accuracies of 81.8%, 70.9%, and 71.4 %, respectively. The proposed system can be applied to future real-time intelligent theranostic systems for diagnosis and treatment of pathogenic diseases.
Reliability of Atmosphere Pressure-Plasma Enhanced Chemical Vapor Deposition Deposited Indium Gallium Zinc Oxide Resistive Random Access Memory Device with Microwave Annealing
Authors: Wu Chien-Hung , Kuo Song-Nian , Chang Kow-Ming , Chen Yi-Ming , Zhang Yu-Xin , Xu Ni , Liu Wu-Yang , Chin Albert
Published: January 2020

Recently resistive random access memory (RRAM) is considered to be the most promising one to become the next generation memory since its simple Metal/Insulator/Metal (MIM) structure, lower power consumption and fabrication cost (Meena, J.S., et al., 2014. Overview of emerging nonvolatile
memory technologies. Nanoscale Research Letters, 9(1), p.526). Due to some bottlenecks for current flash memory, such as high operation voltage, low operation speed, poor retention time and endurance, RRAM device is regarded as an alternative solution (Fuh, C.S., et al., 2011. Role
of environmental and annealing conditions on the passivation-free In–Ga–Zn–O TFT. Thin Solid Films, 520, pp.1489–1494). In this investigation, the memory layer of RRAM device is IGZO, and it is deposited with AP-PECVD technique which can operate under atmosphere,
reduce cost of the process. Microwave annealing (MWA) is used to enhance the RRAM device reliability (Fuh, C.S., et al., 2011. Role of environmental and annealing conditions on the passivation-free In–Ga–Zn–O TFT. Thin Solid Films, 520, pp.1489–1494). Experiment
shows that with appropriate MWA treatment, the IGZO RRAM device exhibits better electrical characteristics, reliability issues such as numbers of switching cycle and data retention time are also improved (Teng, L.F., et al., 2012. Effects of microwave annealing on electrical enhancement of
amorphous oxide semiconductor thin film transistor. Applied Physics Letters, 101, p.132901).
Investigation of Microwave Annealing on Resistive Random Access Memory Device with Atmospheric Pressure Plasma Enhanced Chemical Vapor Deposition Deposited IGZO Layer
Authors: Wu Chien-Hung , Kuo Song-Nian , Chang Kow-Ming , Chen Yi-Ming , Zhang Yu-Xin , Xu Ni , Liu Wu-Yang , Chin Albert
Published: January 2020

Non-volatile memory (NVM) is essential in almost every consumer electronic products. The most prevalent NVM used nowadays is flash memory (Meena, J.S., et al., 2014. Overview of emerging nonvolatile memory technologies. Nanoscale Res. Letters, 9(1), p.526). However, some bottlenecks
of flash memory have been identified, such as high operation voltage, low operation speed, and poor retention time. Resistive random access memory (RRAM) is considered to be the most promising one to become the next generation NVM device since its simple structure, fast program/erase speed,
and low power consumption. In this experiment, the RRAM device is fabricated, and its IGZO (memory) layer is deposited with AP-PECVD technique which can reduce cost of the process. Microwave annealing (MWA) is used to enhance electrical characteristics of the RRAM device (Fuh, C.S., et al.,
2011. Role of environmental and annealing conditions on the passivation-free In–Ga– Zn–O TFT. Thin Solid Films, 520, pp.1489–1494). Experiment results show that with appropriate MWA treatment, the IGZO RRAM device exhibits better electrical characteristics under
bipolar operation, all forming/set/reset voltage for RRAM device is simultaneously lowered.
Carrier Concentration and Threshold Voltage Variability of Amorphous Oxide Semiconductors Using Vacuum Rapid Thermal Annealing
Authors: Shin Joong-Won , Cho Won-Ju
Published: January 2020

This study evaluates the effect of rapid thermal annealing (RTA) in vacuum on the electrical properties of various amorphous oxide semiconductors (AOSs). We fabricated bottom-gate type TFTs using four types of a-IGZO (In2O3:Ga2O3:ZnO
= 1:1:1, 1:1:2, 4:2:3, 4:2:4.1), a-ZTO (ZnO:SnO2 = 1:1), a-ZnO, or two types of a-AZTO (Al2O3:ZnO:SnO2 = 3:67:30, 2:10:10) thin films on the active channel and performed vacuum RTA at various temperatures. Measurement of the
electrical characteristics of the thin film transistors (TFTs) revealed a unique behavior that the on-current of a-IGZO and a-ZnO TFTs increases with increasing vacuum RTA temperature, while threshold voltage (VTH) shifts significantly in the negative direction
and increases the leakage current. As a result of analyzing the resistivity and carrier concentration of the AOS thin films using the Hall measurement, it was verified that the electron concentration increases as the vacuum RTA temperature increases, resulting in a decrease in resistivity.
In addition, the increase in the carrier concentration of the IGZO and ZnO films is larger than that of the ZTO and AZTO films. In particular, the IGZO film with a composition of 4:2:3 showed the largest electron increase, while the AZTO film with a composition of 2:10:10 showed the smallest
electron increase. XPS analysis has demonstrated that a reduction in lattice oxygen concentration is observed in vacuum RTA-processed AOS thin films. The reduction of lattice oxygen in the IGZO film of 4:2:3 was the largest, but in AZTO film 2:10:10 was the smallest. The reduction of lattice
oxygen due to vacuum RTA results in an increase in oxygen vacancies, resulting in an increase in electron concentration, an increase in on-current, a negative shift in VTH, and an increase in leakage current. The loss of lattice oxygen in AOS thin films depends on the metal-oxygen
binding energy. Since Al and Sn in the ZTO and AZTO films have a large binding energy with oxygen, the oxygen hardly diffuses out of the film and little change in VTH occurs. In comparison, the binding energy of In, Ga, and Zn of IGZO and ZnO films are small. Therefore, the
higher the external diffusion of oxygen in IGZO and ZnO films by vacuum RTA, the variability of the carrier concentration and the VTH become larger.
Monolithic-3D (M3D) Complementary Metal-Oxide-Semiconductor-Nanoelectromechanical (CMOS-NEM) Hybrid Reconfigurable Logic (RL) Circuits
Authors: Ko Ji Wang , Choi Woo Young
Published: January 2020

Monolithic-three-dimensional (M3D) CMOS-nanoelectromechanical (CMOS-NEM) hybrid reconfigurable logic (RL) circuits are compared and analyzed with CMOS-only RL ones in the 130-nm CMOS technology node. M3D CMOS-NEM hybrid RL circuits are superior to CMOS-only ones in terms of power consumption
and signal transfer speed thanks to the NEM memory switches. As well as in the routing part, it has many advantages in the logic part following the switch.
Inter- and Intra-Rater Reliability of Laryngeal Sensation Testing with the Touch Method During Flexible Endoscopic Evaluations of Swallowing
Authors: Borders James C. , O’Dea Meredith B. , McNally Edel , Norberg Elizabeth , Kitila Merertu , Walsh Michael , Liu Rui , Pisegna Jessica M.
Published: January 2020

Objectives:

Sensation is an integral component of laryngeal control for breathing, swallowing, and vocalization. Laryngeal sensation is assessed by elicitation of the laryngeal adductor reflex (LAR), a brainstem-mediated adduction of the true vocal folds. During Flexible Endoscopic Evaluations of Swallowing (FEES), the touch method can be used to elicit the LAR to judge laryngeal sensation. Despite the prevalence of this method in clinical practice and research, prior studies have yet to examine inter- and intra-rater reliability.

Methods:

Four speech-language pathologists rated 125 randomized video clips for the presence, absence, or inability to rate the LAR. Fifty percent of video clips were re-randomized and re-rated 1 week later. Raters then created guidelines and participated in formal consensus training sessions on a separate set of videos. Ratings were repeated post-training.

Results:

Overall inter-rater reliability was fair (κ = 0.22) prior to training. Pre-training intra-rater reliability ranged from fair (κ = 0.35) to almost perfect (κ = 0.89). Inter-rater reliability significantly improved after training (κ = 0.42, P < .001), though agreement did not reach prespecified acceptable levels (κ ≥ 0.80). Post-training intra-rater reliability ranged from moderate (κ = 0.49) to almost perfect (κ = 0.85).

Conclusion:

Adequate inter-rater reliability was not achieved when rating isolated attempts to elicit the LAR. Acceptable within-rater reliability was observed in some raters 1 week after initial ratings, suggesting that ratings may remain consistent within raters over a short period of time. Limitations and considerations for future research using the touch method are discussed.
Building Credibility and Cooperation in Low-Trust Settings: Persuasion and Source Accountability in Liberia During the 2014–2015 Ebola Crisis
Authors: Tsai Lily L. , Morse Benjamin S. , Blair Robert A.
Published: January 2020

How can governments in low-trust settings overcome their credibility deficit when promoting public welfare? To answer this question, we evaluate the effectiveness of the Liberian government’s door-to-door canvassing campaign during the 2014–2015 Ebola epidemic, which aimed to persuade residents to voluntarily comply with policies for containing the disease. Combining data from an original representative survey of Monrovia during the crisis with variation in the campaign’s reach and using multiple identification strategies, we find that the informational campaign was remarkably effective at increasing adherence to safety precautions, support for contentious control policies, and general trust in government. To uncover the pathways through which the campaign proved so effective, we conducted over 80 in-depth qualitative interviews in 40 randomly sampled communities. This investigation suggests that local intermediaries were effective because their embeddedness in communities subjected them to monitoring and sanctioning, thereby assuring their fellow residents that they were accountable and thus credible.
The Pedagogical Frontiers of Urban Higher Education: Blended Learning and Co-Lecturing
Authors: Perera Corinne Jacqueline , Zainuddin Zamzami , Piaw Chua Yan , Cheah Kenny S. L. , Asirvatham David
Published: January 2020

Teachers of urban higher education institutions often explore new methods of teaching using innovative techno-pedagogical approaches. This study reports on postgraduate students’ perceptions of the blended learning mode of delivery, co-taught by two lecturers concurrently during the “Qualitative Research” elective course offered for the Master of Educational Leadership program, in a reputed Malaysian university. A qualitative action research methodology was adopted for this study with students’ comments captured through Padlet. Results indicate that students have very positive perceptions of their experiences gained through blended learning and co-lecturing. The findings of this action research study provide evidence of the meaningful and personalized learning experiences reported by students, gained through the collaborative blended mode of delivery. The results also provide more thoughtful reflections for teachers to draw on students’ feedback and possibly adapt their teaching practices to better accommodate students learning needs.
Using Differential Item Functioning to Test for Interrater Reliability in Constructed Response Items
Authors: Walker Cindy M. , Göçer Şahin Sakine
Published: January 2020

The purpose of this study was to investigate a new way of evaluating interrater reliability that can allow one to determine if two raters differ with respect to their rating on a polytomous rating scale or constructed response item. Specifically, differential item functioning (DIF) analyses were used to assess interrater reliability and compared with traditional interrater reliability measures. Three different procedures that can be used as measures of interrater reliability were compared: (1) intraclass correlation coefficient (ICC), (2) Cohen’s kappa statistic, and (3) DIF statistic obtained from Poly-SIBTEST. The results of this investigation indicated that DIF procedures appear to be a promising alternative to assess the interrater reliability of constructed response items, or other polytomous types of items, such as rating scales. Furthermore, using DIF to assess interrater reliability does not require a fully crossed design and allows one to determine if a rater is either more severe, or more lenient, in their scoring of each individual polytomous item on a test or rating scale.