bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonimmunoglobulin Crystal-Storing Histiocytosis (CSH): Case Report and Literature Review
Authors: Beltran Manuel , Khurana Sharad , Gil Yennifer , Lewis Jason T. , Kumar Rohit , Foran James M.
Published: October 2020

Crystal-storing histiocytosis (CSH) is an uncommon condition in which histiocytes accumulate a crystalline matter within their cytoplasm. Generally, those crystals are composed of either monoclonal or polyclonal immunoglobulin chains, which have a strong association with an underlying lymphoproliferative or plasma cell disorder (LP-PCD). Rarely, CSH has been reported as local or generalized manifestation of a variety of benign disorders. These cases are associated with crystals composed of nonimmunoglobulin substances. We are reporting an exceptional case of a local colonic CSH with Charcot–Leyden crystals. This patient underwent a screening colonoscopy that detected some polyps. The biopsy reported tubular adenomas, with a markedly dense, transmural inflammatory infiltrates, which were predominantly composed of eosinophils and crystal-storing histiocytes containing Charcot–Leyden crystals. The patient had a negative workup for LP-PCD and autoimmune conditions, including a normal skeletal survey and bone marrow aspirate/biopsy. The only positive laboratory workup was an elevated absolute eosinophil count and a positive IgG anti-Strongyloides antibody. Giving those findings, this parasitic infection is the most likely etiology of the CSH in our patient. Although there was an initial negative evaluation for LP-PCD, close monitoring of patients with either immunoglobulin or nonimmunoglobulin CSH is recommended.
Uterine Torsion in an Elderly Woman Associated with Leiomyoma and Continuously Elevating Muscle Enzymes: A Case Study and Review of Literature
Authors: Oda Hiroko , Yamada Youko , Uehara Yuriko , Ohno Tamami , Hoya Mari , Sassa Mariko , Mishima Misako
Published: October 2020

Uterine torsion is extremely rare in postmenopausal women. Total ischemia of the uterus may cause life-threatening conditions; hence, accurate diagnosis and surgical intervention are crucial. However, preoperative diagnosis is often challenging due to nonspecific clinical features and laboratory findings. We report a case of uterine torsion in a 73-year-old woman who presented with mild but gradually worsening intermittent abdominal pain. During a 5-day observation, repeated blood exams showed elevating serum muscle enzyme levels, lactate dehydrogenase (LDH), and creatinine kinase (CPK), in addition to nonspecific signs of inflammation. Computed tomography (CT) scans were obtained before and after the worsening of symptoms, which revealed changes in size and position of the enlarged uterus with a large leiomyoma, even within a 5-day interval. Based on these findings, the preoperative diagnosis was uterine torsion. Emergency surgery revealed a 540-degree torsion of the uterus at the cervix and uterine body junction. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Plasma muscle enzyme levels normalized after surgery, and the patient recovered without complications. In conclusion, uterine torsion should be considered during differential diagnosis in elderly women with large leiomyoma, even when symptoms are mild. Elevating plasma muscle enzymes may be an indication of uterine torsion; hence, repeated laboratory works and CT scanning should be performed when symptoms progress. Comparison of CT images, taken before and after the worsening of symptoms, may also be relevant for diagnosis. Since uterine torsion may cause rapid deterioration and become life-threatening, early diagnosis and surgical intervention are crucial to avoid serious complications.
Simultaneous Bilateral Rupture of the Patellar Tendon and Medial Collateral Ligament: A Case Report and Literature Review
Authors: Louka Jean G. , Pourre Damien
Published: October 2020

Bilateral rupture of the patellar tendon is considered an uncommon and rare musculoskeletal injury. The association of this lesion with medial collateral ligament tear appears to be exceedingly rare. We present the case of a combined rupture of the medial collateral ligament (MCL) and the patellar tendon of both knees in a 48-year-old man, after falling 2 meters down an embankment. While there are numerous publications concerning associated MCL tears and other knee ligaments, a combination of MCL tear with a patellar tendon rupture is very rare. In addition, our case presents the first case recorded in the literature, involving both knees of a patient. The clinical case is described and discussed following a review of the literature. The symmetrical knee injury was treated with a primary direct repair of the MCL tears and using a suture anchor fixation of the patellar tendon ruptures, which was reinforced by a stainless steel wire and an autograft of the ipsilateral quadriceps tendon.
Evaluating the Academic Performance of K-12 Students in the Philippines: A Standardized Evaluation Approach
Authors: Almerino Porferio M. , Ocampo Lanndon A. , Abellana Dharyll Prince M. , Almerino Jana Gloria F. , Mamites Irene O. , Pinili Lilibeth C. , Tenerife Janine Joy L. , Sitoy Regina E. , Abelgas Limuel J. , Peteros Emerson D.
Published: October 2020

With growing technological advancements, demands for the industry with skilled and equipped workforce are proportionately rising. While this match between curricular offerings in academia and needs in the industry has been addressed in many countries across the globe through initiatives such as the K-12 educational system, some countries like the Philippines have only started its adoption. In the Philippines’ early adoption of the K-12 educational system, several concerns have been raised regarding its implementation, mainly, the mismatch between coursework offered in Philippine K-12 educational institutions with industry demands. With such outcomes, it is necessary to determine the status of the K-12 educational system in the Philippines. This paper attempts to shed light on such concerns by evaluating the performance of the K-12 students using a standardized approach. The Scholastic Abilities Test for Adults, a standardized test for measuring the academic competence of adults, is used in this study to measure scholastic abilities. The descriptive analyses made in this paper may aid in the development of more robust strategy frameworks for positioning the current K-12 educational system to global and industry demands. Moreover, the results obtained in this study would aid stakeholders in overseeing strategies that would address current gaps in the K-12 educational system of the country.
Study on a New Rock Fracability Evaluation Model of Shale Gas Reservoir
Authors: Wang Fei , Zhang Yonghao , Li Xin , Han Xue
Published: October 2020

Shale gas is an important unconventional energy resource that needs large-scale fracturing to form industrial deliverability. The evaluation of reservoir fracability plays a key role in the optimization of the sweet spot, the design of multistage fracturing, and the prediction of economic benefit. Based on volumetric fracturing, the study proceeded from the fracture complexity of the fractured core, and the bursting pressure experiment technology using the constant strain rate method was established. After the core has fractured, the fracture morphology was extracted and the fracture parameters including fracture area ratio and fracture declination dispersion were calculated to construct the fracture complexity of the pressed core. Combined with the core strength, the fracability index of the core was determined to evaluate the reservoir fracability. This method can represent not only the fracturing effect but also the fracturing difficulty. Compared with the monitoring data of hydrofracture-induced microseism of the sample well, the core fracturing index was found to be in good agreement with the actual fracturing effect. This method is more reasonable than the traditional brittleness index method and rock mechanics parameter method.
Social Inequalities in Cancer Survival in Belgium: A Population-Based Cohort Study
Authors: Rosskamp Michael , Verbeeck Julie , Sass Victoria , Gadeyne Sylvie , Verdoodt Freija , De Schutter Harlinde
Published: October 2020

Background:

Socioeconomic status (SES) is an important factor in cancer survival; however, results are heterogeneous and linked to characteristics of the study population and health care system. This population-based cohort study evaluates the association between individual-level socioeconomic and demographic factors and cancer survival for the first time in Belgium.

Methods:

From the Belgian Cancer Registry, we identified 109,591 patients diagnosed between 2006 and 2013 with one of eight common cancer types. Information on treatment, socioeconomic parameters, and vital status were retrieved from multiple data sources and linked using a unique personal identification number. The outcome was 5-year observed survival. Associations between survival and socioeconomic and demographic factors were assessed using multivariable Cox proportional–hazard regression models.

Results:

Lower income, unemployment, and living alone were all associated with worse cancer survival. These associations were most pronounced for certain lifestyle-related cancer types (e.g., head and neck cancers) and those with good to moderate prognosis (e.g., colorectal and female breast cancer).

Conclusions:

These results indicate that, despite a comprehensive and nationwide health insurance program in which equity in rights and access to health care are pursued, SES is associated with disparities in cancer survival in Belgium.

Impact:

This population-based study with individual-level socioeconomic information of more than 100,000 patients with cancer identifies patient groups that may be at highest risk for socioeconomic disparities in cancer survival. Reasons behind the observed disparities are multiple and complex and should be further examined. Health policy interventions should consider the observed deprivation gap to plan targeted actions.
Lessons Learned from Setting Up a Prospective, Longitudinal, Multicenter Study with Women at High Risk for Breast Cancer
Authors: Patuleia Susana I.S. , Hagenaars Sophie C. , Moelans Cathy B. , Ausems Margreet G.E.M. , van Gils Carla H. , Tollenaar Rob A.E.M. , van Diest Paul J. , Mesker Wilma E. , van der Wall Elsken
Published: October 2020

Women identified with an increased risk of breast cancer due to mutations in cancer susceptibility genes or a familial history of breast cancer undergo tailored screening with the goal of detecting tumors earlier, when potential curative interventions are still possible. Ideally, screening would identify signs of carcinogenesis even before a tumor is detectable by imaging. This could be achieved by timely signaling of altered biomarker levels for precancerous processes in liquid biopsies. Currently, the Nipple Aspirate Fluid (NAF) and the Trial Early Serum Test BREAST cancer (TESTBREAST), both ongoing, prospective, multicenter studies, are investigating biomarkers in liquid biopsies to improve breast cancer screening in high-risk women. The NAF study focuses on changes over time in miRNA expression levels both in blood and NAF samples, whereas the TESTBREAST study analyzes changes in protein levels in blood samples at sequential interval timepoints. These within-subject changes are studied in relation to later occurrence of breast cancer using a nested case–control design. These longitudinal studies face their own challenges in execution, such as hindrances in logistics and in sample processing that were difficult to anticipate. This article offers insight into those challenges and concurrently aims to provide useful strategies for the set-up of similar studies.

See related commentary by Sauter, p. 429
Assessing Impact of HPV Vaccination on Cervical Cancer Incidence among Women Aged 15–29 Years in the United States, 1999–2017: An Ecologic Study
Authors: Mix Jacqueline M. , Van Dyne Elizabeth A. , Saraiya Mona , Hallowell Benjamin D. , Thomas Cheryll C.
Published: October 2020

Background:

To date, the impact of the human papillomavirus (HPV) vaccine on invasive cervical cancers in the United States has not been documented due, in part, to the time needed for cancer to develop and to recent changes to cervical cancer screening guidelines and recommendations, which complicate data interpretation.

Methods:

We examined incidence rates of cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) among women aged 15–29 years diagnosed during 1999–2017 using population-based cancer registry data covering 97.8% of the U.S. population. Trends were stratified by age and histology. The annual percent change in cervical cancer incidence per year was calculated using joinpoint regression.

Results:

During 1999–2017, SCC rates decreased 12.7% per year among women aged 15–20 years, 5.5% among women aged 21–24 years, and 2.3% among women aged 25–29 years. The declines in SCC rates were largest among women aged 15–20 years during 2010–2017, with a decrease of 22.5% per year. Overall, AC rates decreased 4.1% per year among women aged 15–20 years, 3.6% per year among women aged 21–24 years, and 1.6% per year among women aged 25–29 years. AC rates declined the most among women aged 15–20 years during 2006–2017, decreasing 9.4% per year.

Conclusions:

Since HPV vaccine introduction, both SCC and AC incidence rates declined among women aged 15–20 years, a group not typically screened for cervical cancer, which may suggest HPV vaccine impact.

Impact:

Timely vaccination and improved screening and follow-up among recommended age groups could result in further reductions in invasive cervical cancer.
Improved Assessment of Response Status in Patients with Pancreatic Cancer Treated with Neoadjuvant Therapy using Somatic Mutations and Liquid Biopsy Analysis
Authors: Yin Lingdi , Pu Ning , Thompson Elizabeth , Miao Yi , Wolfgang Christopher , Yu Jun
Published: October 2020

Purpose:

To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in patients with Pancreatic ductal adenocarcinoma (PDAC) with pathologic complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome.

Experimental Design:

Thirty-six patients with PDAC with pCR were identified from 2009 to 2017. Macrodissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, normal parenchyma, and undefined ductal cells (UDCs). Cell-free DNA and CTCs were also extracted. Next-generation sequencing was used to detect mutations of KRAS, CDKN2A, SMAD4, TP53, GNAS, and BRAF.

Results:

KRAS mutation was detected in UDCs and fibrosis while SMAD4, TP53, and GNAS were only seen in UDCs. Patients with TP53 mutation showed relatively worse overall survival (HR, 3.596, 95% CI, 0.855–15.130; P = 0.081). Five patients available for CTCs data were all positive for CTCs and seven of 16 patients with pCR were detected with ctDNA at surgery. We proposed a new concept of regression assessment combining genomic analysis of resected specimens and liquid biopsy data for PDAC, namely, molecular complete response (mCR). Three of six patients with mCR recurred as compared with six in 15 non-mCR patients. Seven of 15 non-mCR patients died during follow-up, while there was only one in six patients with mCR.

Conclusions:

This study first reports that somatic mutations, CTCs, and ctDNA existed even in patients with PDAC with pCR to NAT, which could possibly predict early recurrence and reduced survival. The current regression evaluation system of PDAC needs to be reassessed at a molecular level.
Early 3+3 Trial Dose-Escalation Phase I Clinical Trial Design and Suitability for Immune Checkpoint Inhibitors
Authors: Rahma Osama E. , Reuss Joshua E. , Giobbie-Hurder Anita , Shoja E Razavi Ghazaleh , Abu-Shawer Osama , Mehra Pooja , Gupta Seema , Simon Richard , Khleif Samir N.
Published: October 2020

Purpose:

Despite the expansion of immune checkpoint inhibitor (ICI) indications, the relationship between ICI dose and toxicity or response is not well established. To understand this correlation, we performed a meta-analysis of ICI trials that used dose escalation.

Experimental Design:

We searched PubMed and abstracts presented at (inter)national meetings for trials using FDA-approved ICIs. The reported rates of grade 3–5 adverse events (G3–5 AE), immune-related adverse events (irAE), and response were correlated with doses within each ICI using marginal exact generalized linear models.

Results:

A total of 74 trials (7,469 patients) published between January 2010 and January 2017 were included. For ipilimumab, the incidence of G3–5 AEs was 34% with a significant 27% reduced risk in lower doses (P = 0.002). However, no relationship was observed between dose and irAEs or response. For nivolumab, the incidence of G3–5 AEs was 20.1% which was lower in non–small cell lung cancer (NSCLC) compared with renal cell carcinoma (RCC) or melanoma (P ≤ 0.05) with no dose-toxicity relationship. In melanoma and NSCLC, a dose–response association was observed, which was not observed in RCC. For pembrolizumab, the incidence of G3–5 AEs was 13.3%, which was lower in melanoma compared with NSCLC (P = 0.03) with no dose-toxicity relationship. In melanoma, lower dose levels correlated with decreased odds of response (P = 0.01), a relationship that was not observed in NSCLC.

Conclusions:

Our analysis shows a lack of consistent dose-toxicity or dose–response correlation with ICIs. Therefore, dose escalation is not an appropriate design to conduct ICI studies. Here we present an innovative trial design for immune-modulating agents.
HLAPolymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Authors: Ureshino Hiroshi , Shindo Takero , Tanaka Hidenori , Saji Hiroh , Kimura Shinya
Published: October 2020

Treatment-free remission (TFR) is one of the therapeutic goals for patients with chronic phase chronic myeloid leukemia (CML-CP). Although previous reports indicated that antitumor immunity contributes to TFR, its determinants are still unclear. We previously reported that allelic polymorphisms of killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) are associated with achievement of deep molecular response (DMR) in patients with CML-CP. Here, we examined the association between TFR and polymorphisms of KIRs and HLAs in patients who discontinued tyrosine kinase inhibitors (TKI). Seventy-six patients were enrolled, and their KIR and HLA polymorphisms and natural killer (NK) cell activation status were investigated as previously described. Overall, 33 patients discontinued TKIs, and 21 of 33 achieved TFR [63.6%; 95% confidence interval (CI), 44.9%–77.5%] at 1 year. Multivariate analysis revealed that male sex (HR, 0.157; 95% CI, 0.031–0.804; P = 0.003) and HLA-A*02:01, *11:01, or *24:02 (HR, 6.386; 95% CI, 1.701–23.980; P = 0.006) were associated with TFR. Patients who achieved DMR and discontinued TKIs exhibited higher NK cell activation status than those who did not. By contrast, there were no significant differences in NK cell activation status between the patients who achieved TFR and those who experienced molecular relapse. These results suggest NK cell activation status contributes to achievement of DMR, whereas T-cell–mediated immunity contributes to TFR in patients with CML-CP.
The Relative Expression of ERα Isoforms ERα66 and ERα36 Controls the Cellular Response to 24R,25-Dihydroxyvitamin D3 in Breast Cancer
Authors: Verma Anjali , Cohen D. Joshua , Jacobs Thomas W. , Boyan Barbara D. , Schwartz Zvi
Published: October 2020

Vitamin D3 and its metabolites have antitumorigenic properties in vitro and in vivo; however, clinical trials and retrospective studies on the effectiveness of vitamin D3 oral supplementation against cancer have been inconclusive. One reason for this may be that clinical trials ignore the complex vitamin D metabolome and the many active vitamin D3 metabolites present in the body. Recent work by our lab showed that 24R,25(OH)2D3, a vitamin D3 metabolite that is active in chondrocyte proliferation and differentiation, has antitumorigenic properties in estrogen receptor alpha-66 (ERα66)–positive (ER+) breast cancer, but not in ERα66-negative (ER−) breast cancer. Here we show that 24R,25(OH)2D3 is protumorigenic in an in vivo mouse model (NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice) of ER− breast cancer, causing greater tumor growth than in mice treated with vehicle alone. In vitro results indicate that the effect of 24R,25(OH)2D3 is via a membrane-associated mechanism involving ERs and phospholipase D. 24R,25(OH)2D3 increased proliferation and reduced apoptosis in ERα66-negative HCC38 breast cancer cells, and stimulated expression of metastatic markers. Overexpressing ESRI, which encodes ERα66, ERα46, and ERα36, reduced the proapoptotic response of ERα66− cells to 24R,25(OH)2D3, possibly by upregulating ERα66. Silencing ESR1 in ERα66+ cells increased apoptosis. This suggests 24R,25(OH)2D3 is differentially tumorigenic in cancers with different ERα isoform profiles. Antiapoptotic actions of 24R,25(OH)2D3 require ERα36 and proapoptotic actions require ERα66.

Implications:

These results suggest that 24R,25(OH)2D3, which is a major circulating metabolite of vitamin D, is functionally active in breast cancer and that the regulatory properties of 24R,25(OH)2D3 are dependent upon the relative expression of ERα66 and ERα36.
Potentials and Limitations of Directional Deep Brain Stimulation: A Simulation Approach
Authors: Kramme Johanna , Dembek Till A. , Treuer Harald , Dafsari Haidar S. , Barbe Michael T. , Wirths Jochen , Visser-Vandewalle Veerle
Published: October 2020

Background: Directional leads are increasingly used in deep brain stimulation. They allow shaping the electrical field in the axial plane. These new possibilities increase the complexity of programming. Thus, optimized programming approaches are needed to assist clinical testing and to obtain full clinical benefit. Objectives: This simulation study investigates to what extent the electrical field can be shaped by directional steering to compensate for lead malposition. Method: Binary volumes of tissue activated (VTA) were simulated, by using a finite element method approach, for different amplitude distributions on the three directional electrodes. VTAs were shifted from 0 to 2 mm at different shift angles with respect to the lead orientation, to determine the best compensation of a target volume. Results: Malpositions of 1 mm can be compensated with the highest gain of overlap with directional leads. For larger shifts, an improvement of overlap of 10–30% is possible, depending on the stimulation amplitude and shift angle of the lead. Lead orientation and shift determine the amplitude distribution of the electrodes. Conclusion: To get full benefit from directional leads, both the shift angle as well as the shift to target volume are required to choose the correct amplitude distribution on the electrodes. Current directional leads have limitations when compensating malpositions >1 mm; however, they still outperform conventional leads in reducing overstimulation. Further, their main advantage probably lies in the reduction of side effects. Databases like the one from this simulation could serve for optimized lead programming algorithms in the future.
Clinical Performance of New Software to Automatically Detect Angioectasias in Small Bowel Capsule Endoscopy
Authors: Costa Dalila , Vieira Pedro , Pinto Catarina , Arroja Bruno , Leal Tiago , Mendes Sofia , Gonçalves Raquel , Lima Carlos , Rolanda Carla
Published: October 2020

Background: Video capsule endoscopy (VCE) revolutionized the diagnosis and management of obscure gastrointestinal bleeding, though the rate of detection of small bowel lesions by the physician is still disappointing. Our group developed a novel algorithm (CMEMS-Uminho) to automatically detect angioectasias which display greater accuracy in VCE static frames than other methods previously published. We aimed to evaluate the algorithm overall performance and assess its diagnostic yield and usability in clinical practice. Methods: Algorithm overall performance was determined using 54 full-length VCE recordings. To assess its diagnostic yield and usability in clinical practice, 38 VCE examinations with the clinical diagnosis of angioectasias consecutively performed (2017–2018) were evaluated by three physicians with different experiences. The CMEMS-Uminho algorithm was also applied. The performance of the CMEMS-Uminho algorithm was defined by a positive concordance between a frame automatically selected by the software and a study independent capsule endoscopist. Results: Overall performance in complete VCE recordings was 77.7%, and diagnostic yield was 94.7%. There were significant differences between physicians in regard to global detection rate (p < 0.001), detection rate per capsule (p < 0.001), diagnostic yield (p = 0.007), true positive rate (p < 0.001), time (p < 0.001), and speed viewing (p < 0.001). The application of CMEMS-Uminho algorithm significantly enhanced all readers’ global detection rate (p < 0.001) and the differences between them were no longer observed. Conclusion: The CMEMS-Uminho algorithm detained a good overall performance and was able to enhance physicians’ performance, suggesting a potential usability of this tool in clinical practice.
Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients
Authors: Zarrabi Maryam , Nazarinia Mohammadali , Rahimi Jaberi Abbas , Gholijani Nasser , Amirghofran Zahra
Published: October 2020

Objective: Interleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc). Subjects and Methods: A total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA. Results: Levels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls. Conclusion: The higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.
A Japanese Family with DICER1 Syndrome Found in Childhood-Onset Multinodular Goitre
Authors: Nagasaki Keisuke , Shibata Nao , Nyuzuki Hiromi , Sasaki Sunao , Ogawa Yohei , Soda Satoshi , Kogai Takahiko , Hishinuma Akira
Published: October 2020

Introduction: Germline DICER1 mutations have recently been identified in familial multinodular goitre (MNG). The natural history of thyroid nodules in DICER1 carriers in children is unclear. The purpose of this study was to describe the clinical and genetic findings of childhood-onset MNG with DICER1 carrier in a patient who underwent total thyroidectomy. Case Presentation: The 6-year-old proband had a thyroid nodule, and the number and size of nodules increased over 3 years. A total thyroidectomy was chosen because of the rapid rise in thyroglobulin levels, discomfort when swallowing, and the mother’s history of poorly differentiated thyroid cancer (PDTC). Histopathology revealed adenomatous goitre without malignant cells. Her mother, maternal aunt, and maternal grandmother also had thyroid nodules removed during adolescence. Also, her mother had PDTC with lung metastases, and her maternal aunt had an ovarian germ cell tumour. DICER1 mutation analysis identified a heterozygous novel nonsense mutation (c.4509C>G, p.Y1503X) for the patient, her mother, her maternal grandmother, and her asymptomatic elder brother. Y1503X was identified in all resected thyroid tissues, while heterozygous D1709G, D1810V, and E1813K mutations were identified in individual nodules. Discussion/Conclusion: A thyroid nodule was detected in chemotherapy- or radiotherapy-naïve patient with DICER1 carrier aged 6 years, and MNG developed over 3 years. This pedigree highlights the natural history of nodular disease in DICER1 carriers and identifies a possible association between DICER1 and more aggressive malignancies.
Sex Differences in Management and Outcomes of Critical Limb Ischemia in the Medicare Population
Authors: Mentias Amgad , Vaughan-Sarrazin Mary , Saad Marwan , Girotra Saket
Published: October 2020

Background:

Evidence about sex differences in management and outcomes of critical limb ischemia (CLI) is conflicting.

Methods:

We identified Fee-For-Service Medicare patients within the 5% enhanced sample file who were diagnosed with new incident CLI between 2015 and 2017. For each beneficiary, we identified all hospital admissions, outpatient encounters and procedures, and pharmacy prescriptions. Outcomes included 90-day mortality and major amputation.

Results:

Incidence of CLI declined from 2.80 (95% CI, 2.72–2.88) to 2.47 (95% CI, 2.40–2.54) per 1000 person from 2015 to 2017,
P
<0.01. Incidence was lower in women compared with men (2.19 versus 3.11 per 1000) but declined in both groups. Women had a lower prevalence of prescription of any statin (48.4% versus 52.9%,
P
<0.001) or high-intensity statins (15.3% versus 19.8%,
P
<0.01) compared with men. Overall, 90-day revascularization rate was 52%, and women were less likely to undergo revascularization (50.1% versus 53.6%,
P
<0.01) compared with men. Women had a similar unadjusted (9.9% versus 10.3%,
P
=0.5) and adjusted 90-day mortality (adjusted rate ratio, 0.98 [95% CI, 0.85–1.12],
P
=0.7) compared with men. Over the study period, unadjusted 90-day mortality remained unchanged for men (10.4% in 2015 to 9.9% in 2017,
P
for trend
=0.3), and women (9.5% in 2015 to 10.6% in 2017,
P
for trend
=0.2). Men had higher unadjusted (12.9% versus 8.9%,
P
<0.001) and adjusted risk of 90-day major amputation (adjusted rate ratio, 1.30 [95% CI, 1.14–1.48],
P
<0.001). One-third of patients with CLI underwent major amputation without a diagnostic angiogram or trial of revascularization in the preceding 90 days regardless of the sex.

Conclusions:

Women with new incident CLI are less likely to receive statin or undergo revascularization at 90 days compared with men. However, the differences were small. There was no difference in risk of 90-day mortality between both sexes.

Graphic Abstract:

A
graphic abstract
is available for this article.
Redox-Resistant SERCA [Sarco(endo)plasmic Reticulum Calcium ATPase] Attenuates Oxidant-Stimulated Mitochondrial Calcium and Apoptosis in Cardiac Myocytes and Pressure Overload–Induced Myocardial Failure in Mice
Authors: Goodman Jena B. , Qin Fuzhong , Morgan Robert J. , Chambers Jordan M. , Croteau Dominique , Siwik Deborah A. , Hobai Ion , Panagia Marcello , Luptak Ivan , Bachschmid Markus , Tong XiaoYong , Pimentel David R. , Cohen Richard A. , Colucci Wilson S.
Published: October 2020

Background:

SERCA [sarco(endo)plasmic reticulum calcium ATPase] is regulated by oxidative posttranslational modifications at cysteine 674 (C674). Because sarcoplasmic reticulum (SR) calcium has been shown to play a critical role in mediating mitochondrial dysfunction in response to reactive oxygen species, we hypothesized that SERCA oxidation at C674 would modulate the effects of reactive oxygen species on mitochondrial calcium and mitochondria-dependent apoptosis in cardiac myocytes.

Methods:

Adult rat ventricular myocytes expressing wild-type SERCA2b or a redox-insensitive mutant in which C674 is replaced by serine (C674S) were exposed to H
2
O
2
(100 µmol/Lμ). Free mitochondrial calcium concentration was measured in adult rat ventricular myocytes with a genetically targeted fluorescent probe, and SR calcium content was assessed by measuring caffeine-stimulated release. Mice with heterozygous knock-in of the SERCA C674S mutation were subjected to chronic ascending aortic constriction.

Results:

In adult rat ventricular myocytes expressing wild-type SERCA, H
2
O
2
caused a 25% increase in mitochondrial calcium concentration that was associated with a 50% decrease in SR calcium content, both of which were prevented by the ryanodine receptor inhibitor tetracaine. In cells expressing the C674S mutant, basal SR calcium content was decreased by 31% and the H
2
O
2
-stimulated rise in mitochondrial calcium concentration was attenuated by 40%. In wild-type cells, H
2
O
2
caused cytochrome c release and apoptosis, both of which were prevented in C674S-expressing cells. In myocytes from SERCA knock-in mice, basal SERCA activity and SR calcium content were decreased. To test the effect of C674 oxidation on apoptosis in vivo, SERCA knock-in mice were subjected to chronic ascending aortic constriction. In wild-type mice, ascending aortic constriction caused myocyte apoptosis, LV dilation, and systolic failure, all of which were inhibited in SERCA knock-in mice.

Conclusions:

Redox activation of SERCA C674 regulates basal SR calcium content, thereby mediating the pathologic reactive oxygen species–stimulated rise in mitochondrial calcium required for myocyte apoptosis and myocardial failure.
Efficient Outside Computation
Authors: Gildea Daniel
Published: October 2020

Weighted deduction systems provide a framework for describing parsing algorithms that can be used with a variety of operations for combining the values of partial derivations. For some operations, inside values can be computed efficiently, but outside values cannot. We view out-side values as functions from inside values to the total value of all derivations, and we analyze outside computation in terms of function composition. This viewpoint helps explain why efficient outside computation is possible in many settings, despite the lack of a general outside algorithm for semiring operations.
Sparse Transcription
Authors: Bird Steven
Published: October 2020

The transcription bottleneck is often cited as a major obstacle for efforts to document the world’s endangered languages and supply them with language technologies. One solution is to extend methods from automatic speech recognition and machine translation, and recruit linguists to provide narrow phonetic transcriptions and sentence-aligned translations. However, I believe that these approaches are not a good fit with the available data and skills, or with long-established practices that are essentially word-based. In seeking a more effective approach, I consider a century of transcription practice and a wide range of computational approaches, before proposing a computational model based on spoken term detection that I call “sparse transcription.” This represents a shift away from current assumptions that we transcribe phones, transcribe fully, and transcribe first. Instead, sparse transcription combines the older practice of word-level transcription with interpretive, iterative, and interactive processes that are amenable to wider participation and that open the way to new methods for processing oral languages.
Gender (Im)balance in Citation Practices in Cognitive Neuroscience
Authors: Fulvio Jacqueline M. , Akinnola Ileri , Postle Bradley R.
Published: October 2020

In the field of neuroscience, despite the fact that the proportion of peer-reviewed publications authored by women has increased in recent decades, the proportion of citations of women-led publications has not seen a commensurate increase: In five broad-scope journals, citations of papers first- and/or last-authored by women have been shown to be fewer than would be expected if gender was not a factor in citation decisions [Dworkin, J. D., Linn, K. A., Teich, E. G., Zurn, P., Shinohara, R. T., & Bassett, D. S. The extent and drivers of gender imbalance in neuroscience reference lists. Nature Neuroscience, 23, 918–926, 2020]. Given the important implications that such underrepresentation may have on the careers of women researchers, it is important to determine whether this same trend is true in subdisciplines of the field, where interventions might be more targeted. Here, we report the results of an extension of the analyses carried out by Dworkin et al. (2020) to citation patterns in the Journal of Cognitive Neuroscience. The results indicate that the underrepresentation of women-led publications in reference sections is also characteristic of papers published in Journal of Cognitive Neuroscience over the past decade. Furthermore, this pattern of citation imbalances is present regardless of author gender, implicating systemic factors. These results contribute to the growing body of evidence that intentional action is needed to address inequities in the way that we carry out and communicate our science.
Resonator Networks, 2: Factorization Performance and Capacity Compared to Optimization-Based Methods
Authors: Kent Spencer J. , Frady E. Paxon , Sommer Friedrich T. , Olshausen Bruno A.
Published: October 2020

We develop theoretical foundations of resonator networks, a new type of recurrent neural network introduced in Frady, Kent, Olshausen, and Sommer ( 2020 ), a companion article in this issue, to solve a high-dimensional vector factorization problem arising in Vector Symbolic Architectures. Given a composite vector formed by the Hadamard product between a discrete set of high-dimensional vectors, a resonator network can efficiently decompose the composite into these factors. We compare the performance of resonator networks against optimization-based methods, including Alternating Least Squares and several gradient-based algorithms, showing that resonator networks are superior in several important ways. This advantage is achieved by leveraging a combination of nonlinear dynamics and searching in superposition, by which estimates of the correct solution are formed from a weighted superposition of all possible solutions. While the alternative methods also search in superposition, the dynamics of resonator networks allow them to strike a more effective balance between exploring the solution space and exploiting local information to drive the network toward probable solutions. Resonator networks are not guaranteed to converge, but within a particular regime they almost always do. In exchange for relaxing the guarantee of global convergence, resonator networks are dramatically more effective at finding factorizations than all alternative approaches considered.
New Insights Into Learning With Correntropy-Based Regression
Authors: Feng Yunlong
Published: October 2020

Stemming from information-theoretic learning, the correntropy criterion and its applications to machine learning tasks have been extensively studied and explored. Its application to regression problems leads to the robustness-enhanced regression paradigm: correntropy-based regression. Having drawn a great variety of successful real-world applications, its theoretical properties have also been investigated recently in a series of studies from a statistical learning viewpoint. The resulting big picture is that correntropy-based regression regresses toward the conditional mode function or the conditional mean function robustly under certain conditions. Continuing this trend and going further, in this study, we report some new insights into this problem. First, we show that under the additive noise regression model, such a regression paradigm can be deduced from minimum distance estimation, implying that the resulting estimator is essentially a minimum distance estimator and thus possesses robustness properties. Second, we show that the regression paradigm in fact provides a unified approach to regression problems in that it approaches the conditional mean, the conditional mode, and the conditional median functions under certain conditions. Third, we present some new results when it is used to learn the conditional mean function by developing its error bounds and exponential convergence rates under conditional ([Formula: see text])-moment assumptions. The saturation effect on the established convergence rates, which was observed under ([Formula: see text])-moment assumptions, still occurs, indicating the inherent bias of the regression estimator. These novel insights deepen our understanding of correntropy-based regression, help cement the theoretic correntropy framework, and enable us to investigate learning schemes induced by general bounded nonconvex loss functions.
Information-Theoretic Representation Learning for Positive-Unlabeled Classification
Authors: Sakai Tomoya , Niu Gang , Sugiyama Masashi
Published: October 2020

Recent advances in weakly supervised classification allow us to train a classifier from only positive and unlabeled (PU) data. However, existing PU classification methods typically require an accurate estimate of the class-prior probability, a critical bottleneck particularly for high-dimensional data. This problem has been commonly addressed by applying principal component analysis in advance, but such unsupervised dimension reduction can collapse the underlying class structure. In this letter, we propose a novel representation learning method from PU data based on the information-maximization principle. Our method does not require class-prior estimation and thus can be used as a preprocessing method for PU classification. Through experiments, we demonstrate that our method, combined with deep neural networks, highly improves the accuracy of PU class-prior estimation, leading to state-of-the-art PU classification performance.
Empirical Analysis of Demand for Real Money Balances in Africa: Panel Evidence from Nigeria and Ghana
Authors: Nkalu Chigozie Nelson
Published: October 2020

This study investigates demand for real money balances in Africa using panel time-series data from Nigeria and Ghana between 1970 and 2014. The study employs Levin, Lin, Chu common unit root process and Pedroni Residual Cointegration Test which the results reveal that all the variables in the model are stationary and cointegrated respectively. Data sourced from the World Development Indicators (WDI) were analyzed using Panel Two-Stage Estimated Generalized Least Squares (cross-section Seemingly Unrelated Regression model (SURE)) with Instrumental Variables (IV). The results conform to the liquidity preference theory, with all the variables – inflation, real interest rates, and official exchange rates are statistically significant except real income. It is recommended that the monetary authorities in Africa especially the economies of Nigeria and Ghana should adopt appropriate monetary policies by placing interest rates, inflation and official exchange rates at acceptable levels to boost income through private sector investments.
Displaying Mythological Characters
Authors: Tsukahara Shinji , Pultz Jude
Published: October 2020

The large figures displayed atop the floats in the Sawara Grand Festival portray characters drawn from mythology and history that have been strongly associated with Japanese nationalism and imperialism. In order to investigate the meanings that these float figures hold for the participants and audience of the festival, this article acknowledges the close relations between folklore and politics and interprets the works themselves as agents that enact emotions and responses, rather than focusing on the creative intentions of the producers. The figure subjects were freely chosen by the people of Sawara, mostly during the prewar period, and were based on characters that were popular at the time—namely, the emperors and their mythological ancestors and historical champions. In the present, however, the figures are rarely seen in light of their nationalistic origins. Instead, they are appreciated more for their aesthetic beauty and as mascots of the various wards of Sawara.
Gion Matsuri in Kyoto
Authors: Porcu Elisabetta
Published: October 2020

In this paper, I analyze Gion Matsuri in Kyoto as a multilayered phenomenon, and explore its religious aspects in context, with particular attention to interactions between actors, such as its organizing bodies, residents of the neighborhoods that sponsor the yama and hoko floats, the local government, and Yasaka Shrine (Yasaka Jinja 八坂神社). Based on my extended fieldwork, I focus on the festival’s most recent transformations (esp. the reinstatement of ato matsuri in 2014) and the negotiation of religious and secular boundaries, both within and without the festival’s physical spaces. I also reflect on Gion Matsuri as a “contested zone,” an idea that contributes to opening up new perspectives for the study of this and other festivals. More broadly, my analysis aims to shed light not only on the multidimensional character of Gion Matsuri, but also on the interplay of religion with different arenas of contemporary society, including local communities and government, tourism, the economy, and cultural policies.
Primary Heptaic Melanoma or Melanoma of Unknown Primary?
Authors: Wright Jesse P. , Geevarghese Sunil K.
Published: October 2020

Melanoma is the deadliest malignancy of the skin with an estimated 91 000 new annual cases with 9300 deaths in 2018. Metastatic disease generally presents with identification of known primary lesion; however, in 3.2% of patients, metastatic disease is discovered with unknown primary lesion/site. Rarely, melanoma is diagnosed as a primary lesion in visceral organs. Suspected primary hepatic melanoma is exceedingly rare and described in only a few case reports. We present the case of a 69-year-old Caucasian male who was found to have a hepatic melanoma on final pathology after resection of suspected primary hepatic malignancy. After a thorough postoperative workup, a primary lesion was unable to be identified. As such, a visceral primary lesion is considered.