bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 781: Methylation-based liquid biopsy of meningioma primary and recurrent samples
Authors: Sabedot Thais S. , Malta Tathiane M. , She Ruicong , Snyder James , Walbert Tobias , Lee Ian , Kalkanis Steven , Ewing James , Castro AnaValeria , Noushmehr Houtan
Published: September 2020

Meningiomas are mostly benign CNS tumors however, a subset of these tumors may become atypical or malignant. The standard of care to monitor patients after diagnosis requires serial MRI assessments, which have limited value in distinguishing malignant tumors from benign disease. Therefore the discovery of non-invasive methodologies that reflect meningioma tumor burden and its dynamic evolution in real-time is highly desirable. Liquid biopsy (LB) could be used to fine-tune surveillance and treatment with minimal risk to patients. Evidence of circulating tumor cells and cell-free (cf) tumor DNA in the blood has been shown in several tumor types however, limited progress has been made for brain tumors with known biomarkers; possibly due to the unlikelihood of capturing point mutations in circulating DNA fragments. On the other hand, DNA methylation signatures are maintained even in small DNA fragments, which suggests that DNA methylation is an attractive biomarker to be studied in liquid biopsy of brain cancers. In order to identify DNA methylation-based biomarkers using archival serum and tissue specimens, we generated and analyzed the epigenome (Illumina Human EPIC array) of patients with meningioma (including primary (n=6); recurrent (n=8)) and non-meningioma (including non-tumor patients (n=5), pituitary tumor (n=13), colorectal cancer (n=2) and other CNS diseases (n=6), such as inflammatory tissue and radiation necrosis). cfDNA fragment size distribution revealed peaks with 150~200bp on average. By randomly selecting 70% of our cohort as a discovery set, we identified 500 CpGs (FDR<0.05) differentially methylated between meningiomas and non-meningiomas, which show a DNA methylation profile similar to the matched meningioma tissue. Then, we trained a random-forest machine learning using the same signature and applied the model to the remaining 30% samples (validation set) from our cohort. The model was able to correctly classify samples into meningioma and non-meningiomas with a sensitivity of 100% and specificity of 100%. From this pilot data, we were able to investigate the LB methylome of meningioma patients and identify potential markers to detect tumor cells in the serum of these patients, which could eventually allow clinicians to monitor impending disease progression and recurrence.

Citation Format: Thais S. Sabedot, Tathiane M. Malta, Ruicong She, James Snyder, Tobias Walbert, Ian Lee, Steven Kalkanis, James Ewing, AnaValeria Castro, Houtan Noushmehr. Methylation-based liquid biopsy of meningioma primary and recurrent samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 781.
Abstract 848: Taming numerous information on variants for better treatment decisions
Authors: Glocker Katrin , Knurr Alexander , Al-Hmad Janine , Czogalla Dennis-Immanuel , Izzo Marvin , Koch Christian , Roth Benjamin , Ückert Frank
Published: September 2020

The developments in the field of genetic screening make high throughput sequencing of patient samples not only technically, but also financially feasible. However, this confronts physicians with a vast amount of information for one patient. Additionally, as more research is done on single variants, the knowledge about predictive biomarkers is also extensive and increasing steadily. To make information like the clinical relevance of single variants available to physicians, multiple databases are available. This adds to the enormous load of data physicians in a molecular Tumor Board (MTB) have to review on top of clinical data to find a suitable therapy for a specific patient.

To support a MTB in making informed therapy decisions based on genomic data, relevant clinical data like the diagnosis and previous therapies is extracted from the electronic health record used by the physicians to document the patients and their course of disease. After sequencing, the variants get pre-filtered by bioinformaticians and their characteristic features like the specific amino acid exchange for SNVs or total copy number for CNVs are presented. With these data, knowledge bases are queried in the background and relevant information is displayed in the Knowledge Connector. For each variant, information about effect of the mutation on the protein, an assessment of oncogeneity, drugs targeting the specific variation or the gene and pathways the gene is involved in, are summarized in one view to grasp all important facts at a glance. Furthermore, the tool offers the opportunity to manually assess the variants according to evidences and automatically generates a report upon this curation, which can be sent to treating physicians.

With this, physicians are supported in managing the huge amount of information referring to one patient in the whole process of a MTB. Additionally, the number of patients benefiting from this comprehensive analysis of specific characteristics can be increased by not only saving time of experienced specialists, but also by enabling physicians with less extensive knowledge about genetics to find therapies based on genetic variants.

Citation Format: Katrin Glocker, Alexander Knurr, Janine Al-Hmad, Dennis-Immanuel Czogalla, Marvin Izzo, Christian Koch, Benjamin Roth, Frank Ückert. Taming numerous information on variants for better treatment decisions [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 848.
Abstract 944: Quantitative cell-based reporter bioassays for functional characterization of immunotherapeutic biologics targeting co-stimulatory and co-inhibitory immune checkpoint receptors
Authors: Grailer Jamison , Gilden Julia , Stecha Pete , Garvin Denise , Wang Jun , Beck Michael , Hartnett Jim , Krishnan Gopal , Fan Frank , Cong Mei , Cheng Zhi-jie Jey
Published: September 2020

The human immune system is regulated by a complex network of inhibitory and stimulatory immune checkpoint receptors that regulate T Cell function. These receptors are promising new immunotherapy targets for the treatment of a variety of cancers and autoimmune disorders. Novel therapies employing a variety of strategies have been developed that rely on releasing the brakes on the immune system, with the aim of eliminating tumor cells even more efficiently. Immunotherapies designed to block co-inhibitory receptors (e.g. PD-1, CTLA-4) are showing unprecedented efficacy in the treatment of cancer. However, not all patients and tumor types respond to this approach. This has resulted in broadening of immunotherapy research programs to target additional co-inhibitory (e.g. LAG-3, TIM-3, TIGIT) and co-stimulatory (e.g. 4-1BB, GITR, OX40, ICOS) receptors, individually and in combination. A major challenge in the development of antibody-based biologics is access to quantitative and reproducible functional bioassays. Existing methods rely on primary cells and measurement of complex functional endpoints. These assays are cumbersome, highly variable and fail to yield data required for drug development in a quality-controlled environment. To address this need, we have developed a suite of cell-based functional bioassays to interrogate modulation of immune checkpoint receptors individually (e.g. PD-1, LAG-3, TIM-3, GITR, 4-1BB) and in combination (e.g. PD-1+CTLA-4, PD-1+LAG-3). These bioassays consist of stable cell lines that express luciferase reporters driven by response elements under the precise control of mechanistically relevant intracellular signals from TCR and immune checkpoint receptors. Thus, these bioassays reflect mechanisms of action for drug candidates designed for each immune checkpoint receptor and demonstrate high specificity, sensitivity and reproducibility. The bioassays are prequalified according to ICH guidelines and show the precision, accuracy and linearity required for routine use in potency and stability studies. Here we describe the application of MoA-based immune checkpoint receptor bioassays as tools for biologics drug discovery, development, potency and stability studies.

Citation Format: Jamison Grailer, Julia Gilden, Pete Stecha, Denise Garvin, Jun Wang, Michael Beck, Jim Hartnett, Gopal Krishnan, Frank Fan, Mei Cong, Zhi-jie Jey Cheng. Quantitative cell-based reporter bioassays for functional characterization of immunotherapeutic biologics targeting co-stimulatory and co-inhibitory immune checkpoint receptors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 944.
Abstract CT250: A Phase 1a/1b, open-label first-in-human study of the safety, tolerability, and feasibility of gene-edited autologous NeoTCR-T cells (NeoTCR-P1) administered to patients with locally advanced or metastatic solid tumors
Authors: Cristea Mihaela , Chmielowski Bartosz , Funke Roel , Stallings-Schmitt Todd , Denker Mitch , Frohlich Mark , Franzusoff Alex , Abedi Mehrdad , Ejadi Samuel
Published: September 2020

Introduction: Neoepitopes (neoE) derived from private tumor-exclusive mutations represent compelling targets for personalized TCR-T cell therapy. An ultra-sensitive and high-throughput process was developed to capture tumor mutation-targeted CD8 T cells from patient blood. NeoTCRs cloned from the captured CD8 T cells, when engineered into fresh CD8 and CD4 T cells, effected killing of patients' autologous tumor cells in vitro. These observations have been leveraged for the development of a fully personalized adoptive T cell therapy (NeoTCR-P1). A Phase 1 clinical trial testing NeoTCR-P1 in subjects with solid tumors is ongoing (NCT03970382). Study Design: During the initial trial phase, escalating doses of NeoTCR-P1 T cells administered without and with IL-2 in the regimen, and following conditioning chemotherapy, will be evaluated in subjects with advanced or metastatic solid tumors (melanoma, urothelial cancer, colorectal cancer, ovarian cancer, HR+ breast cancer, and prostate cancer). The objective of the Phase 1a study is to establish a recommended Phase 2 dose. Primary endpoints include the incidence and nature of DLTs and overall process feasibility. The proliferation, persistence, and trafficking of NeoTCR-T cells will be characterized. In the expansion trial phase, preliminary anti-tumor activity of NeoTCR-P1 will be assessed in selected tumors. The combination of NeoTCR-P1 dosing plus nivolumab will be tested in a Phase 1b study. Conclusion: This is the first clinical study of an autologous, fully personalized adoptive T cell therapy directed against private tumor-exclusive mutations, generated without using recombinant viral vectors.

Citation Format: Mihaela Cristea, Bartosz Chmielowski, Roel Funke, Todd Stallings-Schmitt, Mitch Denker, Mark Frohlich, Alex Franzusoff, Mehrdad Abedi, Samuel Ejadi. A Phase 1a/1b, open-label first-in-human study of the safety, tolerability, and feasibility of gene-edited autologous NeoTCR-T cells (NeoTCR-P1) administered to patients with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT250.
Abstract LB-100: Systematic target prioritization and validation from genome-scale loss-of-function screens in large panels of human cancer cell lines
Authors: Shibue Tsukasa , Krill-Burger John M. , Paolella Brenton R. , Gaeta Benjamin , Asfaw Adhana , Dempster Joshua M. , McFarland James M. , Root David E. , Boehm Jesse S. , Tsherniak Aviad , Hahn William C. , Vazquez Francisca
Published: September 2020

Despite its increasing success and revolutionary impact on clinical oncology, Precision Cancer Medicine still has major roadblocks before it becomes applicable to a large proportion of patients. One such roadblock is the limited number of therapeutic targets available. Indeed, for the vast majority of cancer patients, we either do not know what their specific vulnerabilities are or do not have strategies to precisely target their vulnerabilities. In the Cancer Dependency Map Project (DepMap) at the Broad Institute, we aim to overcome these limitations through the use of genome-scale loss-of-function screens in a large panel of cancer cell lines combined with systematic molecular characterization of these cell lines. To date, we have conducted viability screens with genome-wide RNAi and CRISPR/Cas9 libraries on > 800 cell lines, all of which have also been comprehensively profiled with various omics approaches. In order to systematically identify and prioritize potential therapeutic targets, we created an analytical framework that uses a multifaceted approach to score gene dependencies based on the information extracted from screening outcomes, predictive models of sensitivity from all the genetic and molecular information, and the use of priors. To reproducibly validate the nominated targets, we also developed a toolbox of standardized assays that include confirmation of cell viability effects with orthogonal reagents/read-outs and efficient testing for in vivo efficacy across multiple cancer models. Using this approach, we have identified and validated several promising targets, including the WRN DNA helicase that is selectively essential in cancers with microsatellite instability (MSI). The data, framework, and toolbox developed here can inform the nomination and advancement of promising targets for drug development for Precision Cancer Medicine.

Citation Format: Tsukasa Shibue, John M. Krill-Burger, Brenton R. Paolella, Benjamin Gaeta, Adhana Asfaw, Joshua M. Dempster, James M. McFarland, David E. Root, Jesse S. Boehm, Aviad Tsherniak, William C. Hahn, Francisca Vazquez. Systematic target prioritization and validation from genome-scale loss-of-function screens in large panels of human cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-100.
Lipid Loss Increases Stratum Corneum Stress and Drying Rates
Authors: Bow Jacob R. , Sonoki Yoshihiko , Uchiyama Masayuki , Shimizu Eri , Tanaka Kousei , Dauskardt Reinhold H.
Published: September 2020

Background: The lipid components and natural moisturizing factors (NMFs) of the stratum corneum (SC) are integral pieces of the self-regulating barrier strategy which comprises one of the most important functions of human skin and seems to be related to biomechanical responses of the SC. Objectives: This work presents the contributions of the lipid bilayers and NMFs to the barrier properties and mechanical responses of human SC. Methods: We performed 2 biomechanical experiments, substrate curvature testing and double cantilever beam cohesion measurements, on isolated human SC exposed to either water, a 1:1 mixture of acetone/ether, or a 1:1 mixture of chloroform/methanol for various durations. Results: We show that treating ex vivo SC with organic solvents results in lipid extraction which increases with duration of exposure. This extraction is tied to a remarkably linear increase in the levels and rates of biaxial stress development during drying/hydration cycles. This effect appears to be tied to the total amounts of lipids extracted. Furthermore, striking changes are seen in the intercellular cohesion properties of the tissue after solvent exposure. Interestingly, changes in drying stress profiles are not observed after treatment with water, which has been previously shown to remove NMFs from the tissue, and which therefore might be expected to induce changes in the drying behavior of the skin. However, changes in intercellular cohesion and the SC cohesion gradient are seen, suggesting impacts on the corneodesmosome protein binding junctions within the tissue. Conclusions: These results suggest that lipid loss causes marked increases in SC drying stresses, which may in turn contribute to changes in skin perception. NMF extraction may be important in vivo, but has remarkably little impact in isolated SC.
Atypical Teratoid/Rhabdoid Tumor of the Conus Medullaris
Authors: Kramer Dallas E. , Kerolus Mena G. , Nunna Ravi S. , Tan Lee A. , Jhaveri Miral , Nag Sukriti , Munoz Lorenzo F.
Published: September 2020

Introduction: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the central nervous system, especially when involving the spinal column or spinal cord. Case Presentation: We present a case of a 5-year-old girl with progressive bilateral lower extremity pain found to have a discrete nodular lesion of the conus with mild heterogeneous enhancement. Surgical decompression and resection demonstrated a pathologic tumor consistent with AT/RT with loss of INI1 protein on immunohistochemistry. Discussion and Conclusion: AT/RT lesions of the conus medullaris are exceedingly rare and associated with extensive disease. We report a rare case of AT/RT with selective involvement of the conus medullaris, as well as describe the surgical, radiographic, and pathologic findings of this tumor.
Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib
Authors: Ando Yuwa , Kawaoka Tomokazu , Suehiro Yosuke , Yamaoka Kenji , Kosaka Yumi , Uchikawa Shinsuke , Kodama Kenichiro , Morio Kei , Fujino Hatsue , Nakahara Takashi , Murakami Eisuke , Yamauchi Masami , Tsuge Masataka , Hiramatsu Akira , Fukuhara Takayuki , Mori Nami , Takaki Shintaro , Tsuji Keiji , Nonaka Michihiro , Hyogo Hideyuki , Aisaka Yasuyuki , Masaki Keiichi , Honda Yoji , Moriya Takashi , Naeshiro Noriaki , Azakami Takahiro , Takahashi Shoichi , Imamura Michio , Chayama Kazuaki , Aikata Hiroshi
Published: September 2020

Background: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. Methods: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. Results: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, p = 0.01) were significant prognostic factors. Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.
Exceptional Response to PD-1 Blockade as First-Line Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Kumai Takumi , Komatsuda Hiroki , Minami Yoshinori , Harabuchi Yasuaki
Published: September 2020

The effect of PD-1 blockade as a first-line therapy in nonmetastatic head and neck squamous cell carcinoma (HNSCC) remains unknown. We report a case of an exceptional response to PD-1 blockade as a first-line therapy in a patient with HNSCC and lung cancer. A 59-year-old man presented with cheek swelling and chest pain. He was diagnosed with maxillary sinus carcinoma (squamous cell carcinoma) and lung cancer (non-small-cell lung cancer, not otherwise specified). The maxillary sinus carcinoma was completely resolved after 8 cycles of pembrolizumab. Immune checkpoint blockade warrants further evaluation in previously untreated patients with HNSCC.
Reduction of Bladder Volume after BCG Immunotherapy
Authors: Yang Changzhao , Lv Zhengtong , Li Yuan
Published: September 2020

Bacillus Calmette-Guérin (BCG) immunotherapy is the most effective treatment for carcinoma in situ and high-risk non-muscle invasive bladder cancer (NMIBC). However, it can also provoke diverse side effects. We found 1 patient with a significantly and rapidly reduced bladder volume after the instillation of BCG. Few such cases and corresponding treatments have been reported. We speculated that the tuberculosis infection existed, so antitubercular therapy was given. After a 3-month oral intake of rifampicin, isoniazid, and ofloxacin, the volume of bladder returned to normal and the voiding symptoms disappeared. This case indicated that the reduction of bladder volume caused by BCG instillation could be treated with antitubercular therapy. Prompt and accurate diagnosis was important for the management.
Hybrid compensation of polarization-multiplexed QPSK optical format for high bit rate networks
Authors: Shabaan Omar Y. , Athab Omar A.
Published: September 2020

Transmitting the highest capacity throughput over the longest possible distance without any regeneration stage is an important goal of any long-haul optical network system. Accordingly, Polarization-Multiplexed Quadrature Phase-Shift-Keying (PM-QPSK) was introduced lately to achieve high bit-rate with relatively high spectral efficiency. Unfortunately, the required broad bandwidth of PM-QPSK increases the linear and nonlinear impairments in the physical layer of the optical fiber network. Increased attention has been spent to compensate for these impairments in the last years. In this paper, Single Mode Fiber (SMF), single channel, PM-QPSK transceiver was simulated, with a mix of optical and electrical (Digital Signal Processing (DSP)) compensation stages to minimize the impairments. The behaviour of the proposed system was investigated under four conditions: without compensation, with only optical compensator, with only DSP compensator and finally with both compensators. An evidence improvement was noticed in the case of hybrid compensation, where the transmission distance was multiplied from (720 km) to more than (3000 km) at 40 Gb/s.
Harmonic spectra of BLDC motor supplied by a solar PV multilevel inverter
Authors: Anwer Abbood Afaneen
Published: September 2020

The multilevel inverters have been used especially in renewable energy aspects in order to assess total harmonic distortion (THD).  THD is considered to produce a good quality of current signal of BLDC motor drive. In this paper, a solar PV inveter fed brushless DC (BLDC) motor drive is discussed considering two topologies of three phase multilevel inverters. These topologies are flying capacitor and clamped diode inverters. The inverter efficiency and output power have an effectiveness on THD values. A boost dc to dc converter using incremental conductance maximum power point tracking (INC-MPPT) is implemented with a solar PV. The mathematical model of the proposed systems ares tudied via simulation using Matlab/Simulink. The simulation results of a BLDC motor based on two multilevel inverters are compared with each other considering the  THD and the utilization of the dc-bus voltage, the comparition verified  that the clamped diode inverter has a better harmonic spectra.still the overshoot is a little bit high in the two types of inverter that are proposed. 
Implications of Genetic Testing in Dilated Cardiomyopathy
Authors: Verdonschot Job A.J. , Hazebroek Mark R. , Krapels Ingrid P.C. , Henkens Michiel T.H.M. , Raafs Anne , Wang Ping , Merken Jort J. , Claes Godelieve R.F. , Vanhoutte Els K. , van den Wijngaard Arthur , Heymans Stephane R.B. , Brunner Han G.
Published: September 2020

Background:

Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome.

Methods:

This study included 689 patients with DCM from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies, and Holter monitoring. Upon detection of a pathogenic variant in a patient with DCM, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization, and/or occurrence of life-threatening arrhythmias.

Results:

A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in nonfamilial DCM. Family segregation analysis showed familial disease in 46% of patients with DCM who were initially deemed nonfamilial by history. Overall, 18% of patients with a nongenetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block and inversely correlated with the presence of a left bundle branch block (
P
<0.01). After a median follow-up of 4 years, event-free survival was reduced in genetic versus patients with nongenetic DCM (
P
=0.01). This effect on outcome was mediated by the associated electrical phenotypes of genetic DCM (
P
<0.001).

Conclusions:

One in 5 patients with an established nongenetic risk factor or a nonfamilial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.
Economic Systems of Muslims in History
Authors: Çizakça Murat
Published: September 2020

During its long history, the Islamic world experienced three different economic systems. The original Islamic economy introduced by the Qurʾān and other classical sources of Islam, was a form of sui generis, commercial, pre-industrial and ethical capitalism. Evidence for this will be presented from the classical sources of Islam as well as from the history of Islamic economic thought. In later centuries it is possible to observe a transition from this unique capitalism towards more centralised structures, which reached its zenith with the Ottoman proto quasi-socialism. Most recently, after the Second World War, newly independent Muslims re-invented Islamic finance. Although an almost three trillion USD industry, so far this has been basically an imitation of conventional finance. Whether a truly modern and Islamic capitalism or another system will emerge from this, remains to be seen. Ample historical evidence across the Islamic world from West Africa to Indonesia is provided.
A species continuum exists between Pseudomallada prasinus and P. abdominalis (Neuroptera, Chrysopidae)
Authors: DUELLI PETER , HENRY CHARLES S.
Published: September 2020

It has recently been determined that Pseudomallada prasinus (Burmeister, 1839) is part of a complex of prasinoid species (Duelli & Obrist, 2019). Apart from P. prasinus s.s. and P. abdominalis s.s., each at the opposite end of the prasinoid spectrum, some populations in Switzerland and surrounding countries show consistently differing morphological and biological traits, while nevertheless living in the same habitats. To test whether they constitute reproductively isolated species, seven strains of three morphologically distinctive prasinoid morphs (Pp1, Pp2, Pp3) were reared and the virgin offspring (F1) paired with single partners of each of the six other strains. The four strains of morph Pp3 were unable to produce any viable offspring when paired with the two other morphs, suggesting that Pp3 is a distinct species. The Mediterranean morph Pp1 produced some offspring with the two strains of morph Pp2, but the crossed offspring (F2) of the hybrids yielded less than 2% viable larvae. Furthermore, in a cage experiment with free choice of partners between Pp1 and Pp2, all females produced offspring of their own morph; there were no hybrids. We conclude that north and south of the Alps there are at least three reproductively isolated prasinoid species in addition to P. prasinus and P. abdominalis. Their distinctiveness is principally based on live color traits, but also on the presence or absence of the “furwing” phenotype in males (double number of setae on wing veins). Therefore, many old museum specimens, especially females, cannot be identified with confidence. Because most of the dozens of synonymized type specimens of prasinoid species and varieties in museums are females, and all have lost their color, it is presently not possible to assign valid names to the three “new” species. We call them Pseudomallada prasinoid 1 (Pp1), P. prasinoid 2 (Pp2), and P. prasinoid 3 (Pp3). Using the distinctive traits given here, most specimens that have retained their original colors (live, recently pinned, or deep frozen) can be identified.
Four new species of the genus Novalena Chamberlin & Ivie, 1942 (Araneae: Agelenidae) from southeastern Mexican montane forests and first record of ocular anomaly in the genus
Authors: CAMPUZANO EMMANUEL F. , MONTAÑO-MORENO HÉCTOR , IBARRA-NÚÑEZ GUILLERMO
Published: September 2020

Four new species of the spider genus Novalena Chamberlin & Ivie, 1942 are described: N. bola sp. nov., N. mayae sp. nov., N. padillai sp. nov., and N. zootaxa sp. nov. All species were collected in montane forests in Chiapas, Mexico, and three of them occur in sympatry across their distribution range.
Comparative Analysis of Computed Tomography and Magnetic Resonance Imaging in Clinically Examining Sacroiliac Joint Complications of Ankylosing Spondylitis
Authors: Xu Bo , Bao Fuqin , Ma Juan , Li Zhiqi
Published: September 2020

Background: To analyze computed tomography (CT) and magnetic resonance Imaging (MRI) in examination diagnosis of sacroiliac joint disease of ankylosing spondylitis. Methods: Eighty patients with ankylosing spondylitis were randomly selected our experimental subjects, and
CT and MRI examinations were performed on them to observe and analyze the diagnosis results of the two examination methods. Results: The detection rates of I and II for ankylosing spondylitis sacroiliac joint disease were prominently higher than those of CT (P < 0.05). Note
that detection rates pertaining to MRI on ankylosing spondylitis, sacroiliac joint disease, erosion of the articular surface, and bone cysts under the articular surface were significantly higher than those of CT (P < 0.05). There exists no significant differences in the detection
rates of widening or narrowing and joint ankylosis (P > 0.05). Conclusions: The detection rate of MRI in clinical diagnosis of sacroiliac joint disease of ankylosing spondylitis is higher than that of CT. It possesses excellent clinical promotion and application.
Internal Tide Nonstationarity and Wave–Mesoscale Interactions in the Tasman Sea
Authors: Savage Anna C. , Waterhouse Amy F. , Kelly Samuel M.
Published: September 2020

Internal tides, generated by barotropic tides flowing over rough topography, are a primary source of energy into the internal wave field. As internal tides propagate away from generation sites, they can dephase from the equilibrium tide, becoming nonstationary. Here, we examine how low-frequency quasigeostrophic background flows scatter and dephase internal tides in the Tasman Sea. We demonstrate that a semi-idealized internal tide model [the Coupled-Mode Shallow Water model (CSW)] must include two background flow effects to replicate the in situ internal tide energy fluxes observed during the Tasmanian Internal Tide Beam Experiment (TBeam). The first effect is internal tide advection by the background flow, which strongly depends on the spatial scale of the background flow and is largest at the smaller scales resolved in the background flow model (i.e., 50–400 km). Internal tide advection is also shown to scatter internal tides from vertical mode-1 to mode-2 at a rate of about 1 mW m−2. The second effect is internal tide refraction due to background flow perturbations to the mode-1 eigenspeed. This effect primarily dephases the internal tide, attenuating stationary energy at a rate of up to 5 mW m−2. Detailed analysis of the stationary internal tide momentum and energy balances indicate that background flow effects on the stationary internal tide can be accurately parameterized using an eddy diffusivity derived from a 1D random walk model. In summary, the results identify an efficient way to model the stationary internal tide and quantify its loss of stationarity.
Global Calculations of Local and Remote Near-Inertial-Wave Dissipation
Authors: Alford Matthew H.
Published: September 2020

Global estimates are presented of the fraction q of wind-generated near-inertial wave power available for local turbulent dissipation under the assumption that modes 1–3 propagate “far” and the higher modes remain to eventually break. Using climatological stratification profiles and mixed layer depth, the modal distribution of near-inertial energy flux is computed following Gill's classic 1984 work by projecting a slab flow in the mixed layer onto the dynamical modes. Global maps and zonal-mean profiles are presented, which show a global-mean value of q = 0.63 and 0.75 for winter and summer profiles, respectively. The simplicity of the calculation makes it of potential use in parameterizations of near-inertial breaking in climate simulations.
Mechanical and thermal properties of carbon fiber reinforced composite with silanized graphene as nano-inclusions
Authors: Shagor RMR , Abedin F , Asmatulu R
Published: September 2020

The use of nanofillers to enhance the properties of fiber reinforced composites is limited due to the adverse effect on mechanical properties caused by agglomeration of these nanofillers in the matrix materials. In this study, graphene nanoflakes were functionalized with silane moiety to improve its dispersion, stability and bond strengths in the polymer matrices of the carbon fiber reinforced composites. Wet layup process was applied to incorporate graphene nanocomposites into the dry carbon fibers to make composite panels following the curing cycle of the epoxy and hardener. The impacts of the functionalized graphene on the mechanical and thermal properties of carbon reinforced composite were investigated in detail by tensile test, differential scanning calorimetry, dynamic mechanical analysis and scanning electron microscopy (SEM) analysis. It was observed that nanocomposites with 0.5 wt% silanized graphene exhibited maximum tensile strength and modulus of elasticity, indicating that 0.50 wt% silane functionalized graphene was the optimum nanofiller composition amongst the three different compositions investigated. The nanocomposites with 0.25 wt% and 0.50 wt% nanofillers showed improved ductility compared to the control sample. Based on the SEM studies on the crack zones, major morphological changes were observed after the salinization process. The interfacial interaction between epoxy and silane moiety of the graphene and reduction in the tendency to agglomerate could account for the improved properties of the nanocomposite observed here. Nanocomposites with silanized graphene showed overall higher glass transition temperature (Tg) and tensile strength than those with pristine graphene and control samples.
Endogenous Growth in a Spatial Economy: The Impact of Globalization on Innovations and Convergence
Authors: Broitman Dani , Czamanski Daniel
Published: September 2020

In this article we explore the claim that spatial interactions among cities are significant drivers of their growth. We assert that reallocation of ideas among cities is a source of improved allocation of resources. We propose a closed economy, agent-based model that is in constant flux. It is populated by autonomous agents that compete and adjust constantly their behavior in reaction to the conditions they perceive. The economy is a dynamic, self-organizing system. We focus on the intensity of globalization as the critical economic process that explains differences in convergence and divergence in the system. The means by which the extent of globalization affects the long-run performance of economies is the geographic reach of new ideas and their conversion into innovations. The question that plays out in our model is the relative influence of globalization and the localized entrepreneurial ecology on innovation. When the globalization is weak, new firms are limited by the market value of their own city. As the globalization strengthens, more and more new firms belong to the global playground. We demonstrate that in line with empirical literature, the gross domestic product of our urban system increases greatly with the increase in globalization level.
Trends in pneumonectomy for treatment of small-cell lung cancer
Authors: Zhao Jasmine , Nguyen Alexandra , Ding Li , David Elizabeth A , Atay Scott M , Wightman Sean C , McFadden P Michael , Kim Anthony W
Published: September 2020

Background

According to practice guidelines, patients with clinical stage T1–2 node-negative small-cell lung cancer are candidates for surgical resection. However, the role of pneumonectomy in small-cell lung cancer patients is not well understood. The objective of this study was to assess the extent to which pneumonectomy is used and to evaluate the survival implications for small-cell lung cancer patients who underwent pneumonectomy.

Methods

A total of 106 small-cell lung cancer patients who underwent pneumonectomy between 2006 and 2016 and met the study criteria were identified in the National Cancer Database. Demographics and treatment regimens are described, and overall survival was assessed using Kaplan-Meier and log-rank tests.

Results

The most common treatment was surgery with adjuvant chemotherapy, followed by surgery only and surgery with neoadjuvant therapy. The 5-year overall survival for the entire cohort after pneumonectomy was 23%. In subgroup analysis, the 5-year overall survival was 30% for guideline-concordant clinical stage I patients and 28% for clinical stage II/III patients who underwent pneumonectomy. There was no statistical difference in survival according to pathologic N disease. Patients with a right-sided pneumonectomy had higher mortality than patients with a left-sided pneumonectomy.

Conclusions

This study suggests a role for pneumonectomy in clinical stage I and potentially some clinical stage II and III small-cell lung cancer patients. Right-sided pneumonectomy is associated with higher mortality and should be approached with caution. Despite declining trends over the past decades, pneumonectomy is still an effective treatment that is able to achieve acceptable survival outcomes.
Prevalence of Gluteus Medius Pathology on Magnetic Resonance Imaging in Patients Undergoing Hip Arthroscopy for Femoroacetabular Impingement: Asymptomatic Tears Are Rare, Whereas Tendinosis Is Common
Authors: Meghpara Mitchell B. , Bheem Rishika , Shah Sapan , Shapira Jacob , Maldonado David R. , Rosinsky Philip J. , Lall Ajay C. , Domb Benjamin G.
Published: September 2020

Background:

There is a paucity of literature on asymptomatic gluteus medius pathology. Moreover, no studies have examined the prevalence of asymptomatic gluteus medius pathology.

Purpose:

To describe the prevalence of asymptomatic gluteus medius pathology in patients undergoing hip arthroscopy for femoroacetabular impingement.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

A database search of our institution was performed for patients undergoing hip arthroscopy for labral treatment between February 2008 and January 2019. Patients were included if they had gluteus medius pathology identified through magnetic resonance imaging (MRI). Patients were deemed to be asymptomatic if they lacked greater trochanteric hip tenderness, abductor weakness, a positive Trendelenburg sign, or a positive Trendelenburg gait on physical examination. Patients were excluded if they were unwilling to participate or did not have a documented physical examination or MRI read in the database.

Results:

A total of 2851 hips (2452 patients) met the inclusion/exclusion criteria. Gluteus medius pathology was found in 871 hips (30.6%) on MRI. Symptomatic gluteus medius pathology was observed in 414 (14.5%) hips, of which 305 (10.7%) had tendinosis, 99 (3.5%) had partial-thickness tears, and 10 (0.4%) had full-thickness tears. Asymptomatic gluteus medius pathology was observed in 457 (16.0%) hips, of which 408 (14.3%) had tendinosis and 49 (1.7%) had partial-thickness tears. No hips with full-thickness tears on MRI were asymptomatic. Patients with asymptomatic partial-thickness tears were significantly older than those with only tendinosis (45.3 vs 39.4 years, respectively; P = .001). Patients aged 40 years or older had a 2.11 (1.80-2.50) ( P < .001) relative risk of asymptomatic pathology compared with patients younger than 40 years.

Conclusion:

Although there is a meaningful prevalence of asymptomatic gluteus medius tendinosis, the prevalence of asymptomatic gluteus medius tears is low. Treatment of gluteus medius tendinosis should therefore be based not solely on MRI findings but rather on a complete clinical evaluation. In contrast, MRI findings of partial or full-thickness gluteus medius tears may be more likely to have clinical significance.
Sustained release of Zingerone from polymeric nanoparticles: An anti-virulence strategy against Pseudomonas aeruginosa
Authors: Sharma Karuna , Nirbhavane Pradip , Chhibber Sanjay , Harjai Kusum
Published: September 2020

Zingerone loaded chitosan nanoparticles (Z-NPs) were developed to deliver the Zingerone across cell membrane and to further enhance its anti-virulence property. The Z-NPs were characterized with respect to size, percentage entrapment efficiency (% EE), zeta potential and percentage drug release. Further the Z-NPs were evaluated for antioxidant DPPH assay, antibiofilm, anti-virulence activities, and gene expression profiles. The developed Z-NPs showed an average size of 390 nm, zeta potential of +56.6 mV, 67% drug entrapment efficiency, and exhibited pH dependent controlled release of Zingerone over a period of 5 days (up to 80%). The Z-NPs retained the antioxidant effect of Zingerone as assessed by DPPH scavenging assay. Evaluation of nanoformulation for anti-virulence potential against Pseudomonas aeruginosa depicted significant reduction in swimming, swarming, and twitching motilities along with quorum sensing inhibition and eradication of biofilms. Decrease in expression of quorum sensing (QS) genes was also observed in the presence of Z-NPs. The results of the present study revealed that Z-NPs could be exploited as a promising anti-virulence candidate against P. aeruginosa infections.
Gendered Places: The Dimensions of Local Gender Norms across the United States
Authors: Scarborough William J. , Sin Ray
Published: September 2020

In this study, we explore the dimensions of local gender norms across U.S. commuting zones. Applying hierarchical cluster analysis with four established indicators of gender norms, we find that these local cultural environments are best conceptualized with a multilevel framework. Commuting zones can be differentiated between those that are egalitarian and those that are traditional. Within these general categories, however, exist more complex dimensions. Gender-traditional areas may be distinguished between traditional-breadwinning and traditional-essentialist, while egalitarian areas are separated into those that are liberal-egalitarian and egalitarian-essentialist. Examining the factors sustaining this spatial variation, we test the role of compositional and contextual effects. We find limited support for compositional effects because commuting zone demographic makeup explains little variation in gender norm indicators. Instead, we find evidence that local gender norms are sustained through contextual effects where the experience of living in a particular environment shapes residents’ attitudes and behaviors. Contextual effects are exceptionally strong in areas with traditional gender norms, where residents who would otherwise hold gender-egalitarian perspectives (e.g., the highly educated) have more traditional outlooks than those who share the same characteristics but reside in places with egalitarian gender norms.
Non-Lactulose Medication Therapies for the Management of Hepatic Encephalopathy: A Literature Review
Authors: Reinert Justin P. , Burnham Kevin
Published: September 2020

Objective:

The most appropriate medication regimen to mitigate the consequences hepatic encephalopathy remains inconclusive. This review seeks to serve as a reference for clinicians to help guide therapy decisions with regard to hepatic encephalopathy.

Methods:

A comprehensive literature review between August 2018 and April 2019 was accomplished with the assistance of a medical librarian. Sources of literature review include PubMed, MEDLINE, SCOPUS, ProQuest Central, CINAHL, and ProQuest Dissertations. The authors selected randomized clinical and double-blind cross-over trials evaluating probiotics, zinc, polyethylene glycol, rifaximin, and flumazenil. Sixteen clinical trials are discussed in this review. Pertinent safety, efficacy, and statistical and clinical outcomes are summarized by the authors.

Conclusions:

The most appropriate regimen to mitigate the consequences of hepatic encephalopathy remains elusive; however, the agents discussed within this review offer alternative options for patients unresponsive to or intolerant of traditional lactulose therapy. This review seeks to serve as a repository for relevant clinical trials, and as a reference for clinicians to help guide therapy decisions.