bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of low-confidence interactions on computational identification of protein complexes
Authors: Paul Madhusudan , Anand Ashish
Published: June 2020

Protein complexes are the cornerstones of most of the biological processes. Identifying protein complexes is crucial in understanding the principles of cellular organization with several important applications, including in disease diagnosis. Several computational techniques have been developed to identify protein complexes from protein–protein interaction (PPI) data (equivalently, from PPI networks). These PPI data have a significant amount of false positives, which is a bottleneck in identifying protein complexes correctly. Gene ontology (GO)-based semantic similarity measures can be used to assign a confidence score to PPIs. Consequently, low-confidence PPIs are highly likely to be false positives. In this paper, we systematically study the impact of low-confidence PPIs on the performance of complex detection methods using GO-based semantic similarity measures. We consider five state-of-the-art complex detection algorithms and nine GO-based similarity measures in the evaluation. We find that each complex detection algorithm significantly improves its performance after the filtration of low-similarity scored PPIs. It is also observed that the percentage improvement and the filtration percentage (of low-confidence PPIs) are highly correlated.
Effect of antibacterial photodynamic therapy on Streptococcus mutans plaque biofilm in vitro
Authors: Liang Xiaoyue , Zou Zhaohui , Zou Zheng , Li Changyi , Dong Xiaoxi , Yin Huijuan , Yan Guohui
Published: June 2020

The main objective of this study is to evaluate the antibacterial effect of antibacterial photodynamic therapy (aPDT) on Streptococcus mutans (S. mutans) biofilm model in vitro. The selection of photosensitizers is the key step for the efficacy of photodynamic therapy (PDT). However, no studies have been conducted in the oral field to compare the functional characteristics and application effects of PDT mediated by various photosensitizers. In this research, the antibacterial effect of Methylene blue (MB)/650[Formula: see text]nm laser and Hematoporphyrin monomethyl ether (HMME)/532[Formula: see text]nm laser on S. mutans biofilm was compared under different energy densities to provide experimental reference for the clinical application of the two PDT. The yield of lactic acid was analyzed by Colony forming unit (CFU) and spectrophotometry, and the complete biofilm activity was measured by Confocal Laser Scanning Microscopy (CLSM) to evaluate the bactericidal effect on each group. Based on the results of CFU, the bacterial colonies formed by 30.4[Formula: see text]J/cm2 532[Formula: see text]nm MB-aPDT group and 30.4[Formula: see text]J/cm2 532[Formula: see text]nm HMME-aPDT group were significantly less than those in other groups, and the bacterial colonies in HMME-aPDT group were less than those in HMME-aPDT group. Lactic acid production in all treatment groups except the photosensitizer group was statistically lower than that in the normal saline control group. The activity of bacterial plaque biofilm was significantly decreased in the two groups treated with 30.4[Formula: see text]J/cm2 aPDT. Therefore, aPDT suitable for energy measurement can kill S. mutans plaque biofilm, and MB-aPDT is better than HMME-aPDT.
A new upper bound for sorting permutations with prefix transpositions
Authors: Nair Pramod P. , Sundaravaradhan Rajan , Chitturi Bhadrachalam
Published: June 2020

Permutations are discrete structures that naturally model a genome where every gene occurs exactly once. In a permutation over the given alphabet [Formula: see text], each symbol of [Formula: see text] appears exactly once. A transposition operation on a given permutation [Formula: see text] exchanges two adjacent sublists of [Formula: see text]. If one of these sublists is restricted to be a prefix then one obtains a prefix transposition. The symmetric group of permutations with [Formula: see text] symbols derived from the alphabet [Formula: see text] is denoted by [Formula: see text]. The symmetric prefix transposition distance between [Formula: see text] and [Formula: see text] is the minimum number of prefix transpositions that are needed to transform [Formula: see text] into [Formula: see text]. It is known that transforming an arbitrary [Formula: see text] into an arbitrary [Formula: see text] is equivalent to sorting some [Formula: see text]. Thus, upper bound for transforming any [Formula: see text] into any [Formula: see text] with prefix transpositions is simply the upper bound to sort any permutation [Formula: see text]. The current upper bound is [Formula: see text] for prefix transposition distance over [Formula: see text]. In this paper, we improve the same to [Formula: see text].
Simulation and analysis on the ship energy efficiency operational indicator for bulk carriers by Monte Carlo simulation method
Authors: Tran Tien Anh
Published: June 2020

The ship energy efficiency management is an important topic in the field of the energy management onboard and the exhaust gases emission nowadays. The advanced model plays a vital role to improve the ship energy efficiency management when considering the variable factors. The establishment of the ship energy efficiency model through energy efficiency operational indicator (EEOI) index has been conducted through Monte Carlo simulation method along with using the operation data of a bulk carrier. A bulk carrier is chosen, namely, M/V NSU JUSTICE 250,000 DWT of VINIC Shipping Transportation Company in Vietnam. This research uses the real operational data to perform a statistical methodology which calculates the various factors used to calculate EEOI. This method is supported by Matlab program through the curve fitting tool. The normal distribution estimation and the kernel density estimation method are used for the parametric curve fitting and non-parametric curve fitting, respectively. The average weather condition (wind speed and wave height) and the fouling condition of hull have been investigated and compared with the research results. The validation of the proposed methods has been conducted through the study of the external factors influencing the research results. The research result shows the optimal operational data for the fuel consumption at each certain voyage. This paper is useful for the ship-owners and the ship-operators in the field of the ship energy efficiency management.
Repeated Nucleic Acid Tests Are Necessary for Early Diagnosis of Atypical COVID-19: A Case Report
Authors: Qu Lihong , Xiong Wujun , Fan Chenghui , Kang Sheng
Published: June 2020

In Wuhan, China, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported on December 8, 2019. The patient’s symptoms included fever, coughing and breathing difficulties. According to the sixth China version of 2019 coronavirus disease (COVID-19) diagnostic criteria, some patients with COVID-19 may present atypical symptoms and have negative nucleic acid tests (NATs), possibly leading to misdiagnosis and viral transmission.

Our patient was a 29-year-old woman who complained of a three-day history of nasal obstruction, and no fever, coughing or breathing difficulties were noted. Physical examination revealed no obvious signs of pneumonia. On January 16, 2020, the patient flew from Wuhan to Germany for a business trip and returned to Shanghai on January 28, a passenger on her flight was tested positive for SARS-CoV-2 later. Although two consecutive NATs performed at an interval of 24 h were negative, considering her direct contact with a SARS-CoV-2-infected individual, a 64-slice computed tomography (CT) scan showed a few scattered ground-glass nodules in the left lung, suggesting possible viral pneumonia. Given the clinical characteristics, epidemiological records, CT findings and a third positive NAT, our patient was diagnosed with COVID-19.

The combination of history of epidemiology, clinical symptom, lung CT scan and routine blood test will improve the clinical diagnosis of asymptomatic COVID-19, but the early diagnosis of COVID-19 can be confirmed only by the repeated NATs.
BDNF and Its Multirole Function in Neurogenesis, Synaptic Transmission and Neurodegenerative Diseases
Authors: Huang Ying-ying , Wang Yu-qi , Gao Yi-ming , Liu Qing-zhuo , Ye Fang-fei , Guo Bin , Wu Yi-chen , Xue Lei
Published: June 2020

Brain-derived neurotrophic factor (BDNF), a crucial member of the neurotrophic family, is most widely distributed and extensively studied in the mammalian central nervous system. Accumulating evidence from animal and human studies indicates that BDNF plays critical roles in regulating neurogenesis, synaptogenesis and plasticity, and neurological diseases. In this review, we summarize the synthesis and general signaling pathway of BDNF and review its pivotal roles in neurogenesis and the maintenance of axon and dendrites, synaptic transmission and plasticity, which are thought to be the cellular basis for learning and memory, and certain neurological diseases, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Future studies should focus on understanding the multifunctional roles of BDNF in different brain regions and tightly controlled clinical studies.
Dielectric dispersion, linear and nonlinear optical properties of Li2O–WO3–B2O3: V2O5 glasses
Authors: Srinivasa Rao Linganaboina , Thirmal Chinthakuntla , Raghavendra Rao Parchuri
Published: June 2020

40 Li2O–5 WO3–(55-[Formula: see text]) B2O3: [Formula: see text]V2O5 (mol%) for [Formula: see text] glasses were prepared by melt-quenching. Electric polarization was described in terms of the dielectric constant ([Formula: see text]) and loss ([Formula: see text]). Mixed conduction phenomenon was explained by redox pairs [Formula: see text] and [Formula: see text] at high temperatures. Electronic polarizability ([Formula: see text]) was determined over a range of frequencies (100[Formula: see text]Hz–100[Formula: see text]kHz) and temperatures (30–[Formula: see text]C). The change of boron coordination in the glass network was explained with the aid of temperature coefficient of polarizability ([Formula: see text]). Nonlinear susceptibility ([Formula: see text]) and optical band gap ([Formula: see text]) were studied as a function of concentration of V2O5. The highest values of [Formula: see text] and [Formula: see text] were obtained at [Formula: see text][Formula: see text]mol%. These glasses may find potential practical applications in the fields of solid-state ionics and nonlinear optics.
São Tomé and Príncipe: More than the Land of Cocoa and Coffee
Authors: Leandro Francisco B. S. José , Lobo Anthony
Published: June 2020

The Democratic Republic of São Tomé and Príncipe, a small and remote island state, located in the Gulf of Guinea, has long offered little geopolitical and geo-economic interest. This situation is however gradually changing. In fact, since 2016, interest in the country has begun to grow, after the country resumed diplomatic relations with People’s Republic of China (hereafter China) and recognized the “one-China policy”. While the island state and Cabo Verde have followed different development paths in the post-colonial era, both share common features and both have the potential to perform important geopolitical regional roles in the context of the Belt and Road initiative (BRI). This paper discusses São Tomé and Príncipe’s regional engagement in the Gulf of Guinea (GG), the Economic Community of Central African States (ECCAS), the Community of Portuguese-Speaking Countries (CPLP), and in multi-level cooperation in light of the Forum for Economic and Trade Cooperation between China and Portuguese-Speaking Countries (FM) as well as bilateral cooperation. We argue that São Tomé and Príncipe is of geopolitical value to China and that the island state will serve Chinese interests in extending the BRI in the Gulf of Guinea. The microstate of São Tomé and Príncipe has the potential to transform itself to function as the “Qatar of the Gulf of Guinea”, and contribute to regional stability by providing regional services for shipping, banking, finance, high-quality education, tourism and as an engaged partner. This paper presents a methodological theoretical-inductive and constructivist perspective, combining qualitative, quantitative and non-participant observation.
CryptoLesion
Authors: Tanwar Vishesh Kumar , Raman Balasubramanian , Rajput Amitesh Singh , Bhargava Rama
Published: June 2020

The low-cost, accessing flexibility, agility, and mobility of cloud infrastructures have attracted medical organizations to store their high-resolution data in encrypted form. Besides storage, these infrastructures provide various image processing services for plain (non-encrypted) images. Meanwhile, the privacy and security of uploaded data depend upon the reliability of the service provider(s). The enforcement of laws towards privacy policies in health-care organizations, for not disclosing their patient’s sensitive and private medical information, restrict them to utilize these services. To address these privacy concerns for melanoma detection, we propose
CryptoLesion
, a privacy-preserving model for segmenting lesion region using whale optimization algorithm (WOA) over the cloud in the encrypted domain (ED). The user’s image is encrypted using a permutation ordered binary number system and a random stumble matrix. The task of segmentation is accomplished by dividing an encrypted image into a pre-defined number of clusters whose optimal centroids are obtained by WOA in ED, followed by the assignment of each pixel of an encrypted image to the unique centroid. The qualitative and quantitative analysis of
CryptoLesion
is evaluated over publicly available datasets provided in
The International Skin Imaging Collaboration
Challenges in 2016, 2017, 2018, and PH
2
dataset. The segmented results obtained by
CryptoLesion
are found to be comparable with the winners of respective challenges.
CryptoLesion
is proved to be secure from a probabilistic viewpoint and various cryptographic attacks. To the best of our knowledge,
CryptoLesion
is first moving towards the direction of lesion segmentation in ED.
A history of Clojure
Authors: Hickey Rich
Published: June 2020

Clojure was designed to be a general-purpose, practical functional language, suitable for use by professionals wherever its host language, e.g., Java, would be. Initially designed in 2005 and released in 2007, Clojure is a dialect of Lisp, but is not a direct descendant of any prior Lisp. It complements programming with pure functions of immutable data with concurrency-safe state management constructs that support writing correct multithreaded programs without the complexity of mutex locks.

Clojure is intentionally hosted, in that it compiles to and runs on the runtime of another language, such as the JVM. This is more than an implementation strategy; numerous features ensure that programs written in Clojure can leverage and interoperate with the libraries of the host language directly and efficiently.

In spite of combining two (at the time) rather unpopular ideas, functional programming and Lisp, Clojure has since seen adoption in industries as diverse as finance, climate science, retail, databases, analytics, publishing, healthcare, advertising and genomics, and by consultancies and startups worldwide, much to the career-altering surprise of its author.

Most of the ideas in Clojure were not novel, but their combination puts Clojure in a unique spot in language design (functional, hosted, Lisp). This paper recounts the motivation behind the initial development of Clojure and the rationale for various design decisions and language constructs. It then covers its evolution subsequent to release and adoption.
The origins of Objective-C at PPI/Stepstone and its evolution at NeXT
Authors: Cox Brad J. , Naroff Steve , Hsu Hansen
Published: June 2020

The roots of Objective-C began at ITT in the early 1980s in a research group led by Tom Love investigating improving programmer productivity by an order of magnitude, a concern motivated by the perceived "software crisis" articulated in the late 1960s. In 1981, Brad Cox, a member of this group, began to investigate Smalltalk and object-oriented programming for this purpose, but needed a language compatible with the Unix and C environments used by ITT. That year, Cox quickly wrote up the Object-Oriented Pre-Compiler (OOPC) that would translate a Smalltalk-like syntax into C.

Love felt there was a market for object-oriented solutions that could coexist with legacy languages and platforms, and after a brief stint at Schlumberger-Doll, co-founded with Cox Productivity Products International (PPI), later renamed as Stepstone, to pursue this. At PPI, Cox developed OOPC into Objective-C. Cox saw Objective-C as a crucial link in his larger vision of creating a market for "pre-fabricated" software components ("software-ICs"), which could be bought off the shelf and which, Cox believed, would unleash a "software industrial revolution."

Steve Naroff joined Stepstone in 1986 as Steve Jobs' NeXT Computer became an important customer for Objective-C, as it was being used in its NeXTSTEP operating system. Naroff became the primary Stepstone developer addressing NeXT's issues with Objective-C, solving a key fragility problem preventing NeXT from deploying forwards-compatible object libraries. Impressed with NeXT, Naroff left Stepstone for NeXT in 1988, and once there, added Objective-C support to Richard Stallman's GNU GCC compiler, which NeXT was using as its C compiler, removing the need to use Stepstone's ObjC to C translator. Over the next several years, Naroff and others would add significant new features to Objective-C, such as "categories," "protocols," and the ability to mix in C++ code. When Stepstone folded in 1994, all rights to Objective-C were acquired by NeXT. This eventually transferred to Apple when NeXT was acquired by Apple in 1997. Objective-C became the basis for Apple's Mac OS X and then iOS platforms, and Naroff and others at Apple added additional features to the language in the late 2000s as the iPhone App Store greatly expanded Objective-C's user base.
A history of the Oz multiparadigm language
Authors: Van Roy Peter , Haridi Seif , Schulte Christian , Smolka Gert
Published: June 2020

Oz is a programming language designed to support multiple programming paradigms in a clean factored way that is easy to program despite its broad coverage. It started in 1991 as a collaborative effort by the DFKI (Germany) and SICS (Sweden) and led to an influential system, Mozart, that was released in 1999 and widely used in the 2000s for practical applications and education. We give the history of Oz as it developed from its origins in logic programming, starting with Prolog, followed by concurrent logic programming and constraint logic programming, and leading to its two direct precursors, the concurrent constraint model and the Andorra Kernel Language (AKL). We give the lessons learned from the Oz effort including successes and failures and we explain the principles underlying the Oz design. Oz is defined through a kernel language, which is a formal model similar to a foundational calculus, but that is designed to be directly useful to the programmer. The kernel language is organized in a layered structure, which makes it straightforward to write programs that use different paradigms in different parts. Oz is a key enabler for the bookConcepts, Techniques, and Models of Computer Programming(MIT Press, 2004). Based on the book and the implementation, Oz has been used successfully in university-level programming courses starting from 2001 to the present day.
The evolution of Smalltalk: from Smalltalk-72 through Squeak
Authors: Ingalls Daniel
Published: June 2020

This paper presents a personal view of the evolution of six generations of Smalltalk in which the author played a part, starting with Smalltalk-72 and progressing through Smalltalk-80 to Squeak and Etoys. It describes the forces that brought each generation into existence, the technical innovations that characterized it, and the growth in understanding of object-orientation and personal computing that emerged. It summarizes what that generation achieved and how it affected the future, both within the evolving group of developers and users, and in the outside world.

The early Smalltalks were not widely accessible because they ran only on proprietary Xerox hardware; because of this, few people have experience with these important historical artifacts. To make them accessible, the paper provides links to live simulations that can be run in present-day web browsers. These simulations offer the ability to run pre-defined scripts, but also allow the user to go off-script, browse the details of the implementation, and try anything that could be done in the original system. An appendix includes anecdotal and technical aspects of how examples of each generation of Smalltalk were recovered, and how order was teased out of chaos to the point that these old systems could be brought back to life.
Verilog HDL and its ancestors and descendants
Authors: Flake Peter , Moorby Phil , Golson Steve , Salz Arturo , Davidmann Simon
Published: June 2020

This paper describes the history of the Verilog hardware description language (HDL), including its influential predecessors and successors. Since its creation in 1984 and first sale in 1985, Verilog has completely revolutionized the design of hardware. Verilog enabled the development and wide acceptance of logic synthesis. For large-scale digital logic design, previous schematic-based techniques have transformed into textual register-transfer level (RTL) descriptions written in Verilog. As of 2018 about 80% of integrated circuit design teams worldwide use Verilog and its compatible descendant SystemVerilog.
Exploiting Errors for Efficiency
Authors: Stanley-Marbell Phillip , Alaghi Armin , Carbin Michael , Darulova Eva , Dolecek Lara , Gerstlauer Andreas , Gillani Ghayoor , Jevdjic Djordje , Moreau Thierry , Cacciotti Mattia , Daglis Alexandros , Jerger Natalie Enright , Falsafi Babak , Misailovic Sasa , Sampson Adrian , Zufferey Damien
Published: June 2020

When a computational task tolerates a relaxation of its specification or when an algorithm tolerates the effects of noise in its execution, hardware, system software, and programming language compilers or their runtime systems can trade deviations from correct behavior for lower resource usage. We present, for the first time, a synthesis of research results on computing systems that only make as many errors as their end-to-end applications can tolerate. The results span the disciplines of computer-aided design of circuits, digital system design, computer architecture, programming languages, operating systems, and information theory. Rather than over-provisioning the resources controlled by each of these layers of abstraction to avoid errors, it can be more efficient to exploit the masking of errors occurring at one layer and thereby prevent those errors from propagating to a higher layer.

We demonstrate the potential benefits of end-to-end approaches using two illustrative examples. We introduce a formalization of terminology that allows us to present a coherent view across the techniques traditionally used by different research communities in their individual layer of focus. Using this formalization, we survey tradeoffs for individual layers of computing systems at the circuit, architecture, operating system, and programming language levels as well as fundamental information-theoretic limits to tradeoffs between resource usage and correctness.
Acoustic Microfluidics
Authors: Zhang Peiran , Bachman Hunter , Ozcelik Adem , Huang Tony Jun
Published: June 2020

Acoustic microfluidic devices are powerful tools that use sound waves to manipulate micro- or nanoscale objects or fluids in analytical chemistry and biomedicine. Their simple device designs, biocompatible and contactless operation, and label-free nature are all characteristics that make acoustic microfluidic devices ideal platforms for fundamental research, diagnostics, and therapeutics. Herein, we summarize the physical principles underlying acoustic microfluidics and review their applications, with particular emphasis on the manipulation of macromolecules, cells, particles, model organisms, and fluidic flows. We also present future goals of this technology in analytical chemistry and biomedical research, as well as challenges and opportunities.
Nutritional Requirements for Sustaining Health and Performance During Exposure to Extreme Environments
Authors: Pasiakos Stefan M.
Published: June 2020

Dietary guidelines are formulated to meet minimum nutrient requirements, which prevent deficiencies and maintain health, growth, development, and function. These guidelines can be inadequate and contribute to disrupted homeostasis, lean body mass loss, and deteriorated performance in individuals who are working long, arduous hours with limited access to food in environmentally challenging locations. Environmental extremes can elicit physiological adjustments that alone alter nutrition requirements by upregulating energy expenditure, altering substrate metabolism, and accelerating body water and muscle protein loss. The mechanisms by which the environment, including high-altitude, heat, and cold exposure, alters nutrition requirements have been studied extensively. This contemporary review discusses physiological adjustments to environmental extremes, particularly when those adjustments alter dietary requirements.
A Multichannel fNIRS System for Prefrontal Mental Task Classification with Dual-level Excitation and Deep Forest Algorithm
Authors: Chen Cheng , Wen Yizhen , Cui Shaoyang , Qi Xiangao , Liu Zhenhong , Zhou Linfeng , Chen Mingyi , Zhao Jian , Wang Guoxing
Published: June 2020

This paper presents a multichannel functional continuous-wave near-infrared spectroscopy (fNIRS) system, which collects data under a dual-level light intensity mode to optimize SNR for channels with multiple source-detector separations. This system is applied to classify different cortical activation states of the prefrontal cortex (PFC). Mental arithmetic, digit span, semantic task, and rest state were selected as four mental tasks. A deep forest algorithm is employed to achieve high classification accuracy. By employing multigrained scanning to fNIRS data, this system can extract the structural features and result in higher performance. The proposed system with proper optimization can achieve 86.9% accuracy on the self-built dataset, which is the highest result compared to the existing systems.
Differentiation of Rat Adipose-Derived Stem Cells into Parathyroid-Like Cells
Authors: Zhang Ping , Zhang Hao , Dong Wenwu , Wang Zhihong , Qin Yuan , Wu Changhao , Dong Qi
Published: June 2020

Background. The current treatment for postoperative hypoparathyroidism has shortcomings, such as repeated blood monitoring for dosage adjustment, uncertain long-term efficacy, and the high price of recombinant parathyroid hormone therapy. Adipose-derived stem cells can undergo adipogenic and osteogenic differentiation in vitro and are considered a novel source of parathyroid-like cells, but the idea lacks theoretical basis and feasibility. We aimed at establishing a protocol for differentiating adipose-derived stem cells into parathyroid-like cells for treating hypoparathyroidism. Materials/Methods. Adipose-derived stem cells were isolated and purified from the inguinal adipose tissue of Sprague Dawley rats. Adipogenic differentiation and osteogenic differentiation of the cells were identified by oil red O and alizarin red S staining, respectively. The adipose-derived stem cells were stimulated by sonic hedgehog (SHH) and activin A. The differentiation of the adipose-derived stem cells to parathyroid-like cells was confirmed by the detection of parathyroid hormone and the related parathyroid markers. Results. Adipose-derived stem cells were successfully isolated and purified from the rat adipocytes. The adipogenic and osteogenic differentiation capabilities of the adipose-derived stem cells were determined. SHH and activin A stimulated parathyroid hormone secretion by the adipose-derived stem cells and significantly increased the expression of calcium-sensing receptor (CaSR), parathyroid hormone, and glial cells missing homolog 2 (GCM2) in the cells in a time- and concentration-dependent manner. Conclusion. We successfully differentiated rat adipose-derived stem cells into parathyroid-like cells, which will pave a new route to curing hypoparathyroidism.
Dysregulation of Circulating FGF19 and Bile Acids in Primary Biliary Cholangitis‐Autoimmune Hepatitis Overlap Syndrome
Authors: Li Zhanyi , Liu Yu , Yang Fangji , Pang Jiahui , Wu Yuankai , Chong Yutian , Li Xiangyong
Published: June 2020

Background. Primary biliary cholangitis‐autoimmune hepatitis overlap syndrome (PBC‐AIH OS), which exhibits features between autoimmune hepatitis and cholestasis, is a common condition and usually shows a progressive course toward cirrhosis and liver failure without adequate treatment. Synthesis of bile acids (BAs) plays an important role in liver injury in cholestasis, and the process is regulated by fibroblast growth factor 19 (FGF19). The overall role of circulating FGF19 in BA synthesis and PBC‐AIH OS requires further investigation. Methods. We analyzed BA synthesis and correlated clinical parameters with serum BAs and FGF19 in 35 patients with PBC‐AIH OS. Serum concentrations of 7alpha‐hydroxycholest‐4‐en‐3‐one (C4) were used to quantify the synthesis of BA directly. Results. Serum FGF19 levels were higher, while C4 levels were substantially lower in PBC‐AIH OS patients than those in healthy controls. Circulating FGF19 levels strongly correlated with C4 (r = −0.695, p < 0.0001), direct bilirubin (r = 0.598, p = 0.0001), and total bile acids (r = 0.595, p = 0.002). Moreover, circulating FGF19 levels strongly correlated with the model for end‐stage liver disease score (r = 0.574, p = 0.0005) and Mayo risk score (r = 0.578, p = 0.001). Conclusions. Serum FGF19 is significantly increased in patients with PBC‐AIH OS, while BA synthesis is suppressed. Circulating FGF19 primarily controls the regulation of BA synthesis in response to cholestasis and under cholestatic conditions. Therefore, modulation of circulating FGF19 could provide a promising targeted therapy for patients with PBC‐AIH OS.
Probabilistic Forecasting Method of Metro Station Environment Based on Autoregressive LSTM Network
Authors: Tian Qing , Li Bo , Qu Hongquan , Pang Liping , Zhao Weihang , Han Yue
Published: June 2020

With the increasing number of metros, the comfort and safety of crew and passengers in metro stations have been paid great attention. The environment forecasting has become very important for decision-making. The outputs of the traditional point prediction methods are some exact values in the future. However, it might be closer to the real conditions that the predicted variables are given a probability range with a different confidence rather than exact values. This paper proposes a probabilistic forecasting method of metro station environment based on autoregressive Long Short Term Memory (LSTM) network. It has a good performance to quantify the uncertainty of environment trend in a metro station. Seven-day field tests were carried out to obtain the measured data of 7 internal environmental parameters in a metro station and 8 external environment parameters. In order to ensure the prediction performance, the random forest algorithm is used to select the input variables for the proposed probabilistic forecasting method. The selected input variables and the previous predicted values are as the input variables to build the probabilistic forecasting model. The proposed method can realize to predict the probabilistic distribution of internal environmental parameters in a metro station. This work may contribute to prevent emergency events and regulate environment control system reasonably.
Heat Concentration around a Cylindrical Interface Crack in a Composite Tube
Authors: Fu J. W. , Qian L. F.
Published: June 2020

Cracks always form at the interface of discrepant materials in composite structures, which influence thermal performances of the structures under transient thermal loadings remarkably. The heat concentration around a cylindrical interface crack in a bilayered composite tube has not been resolved in literature and thus is investigated in this paper based on the singular integral equation method. The time variable in the two-dimensional temperature governing equation, derived from the non-Fourier theory, is eliminated using the Laplace transformation technique and then solved exactly in the Laplacian domain by the employment of a superposition method. The heat concentration degree caused by the interface crack is judged quantitatively with the employment of heat flux intensity factor. After restoring the results in the time domain using a numerical Laplace inversion technique, the effects of thermal resistance of crack, liner material, and crack length on the results are analyzed with a numerical case study. It is found that heat flux intensity factor is material-dependent, and steel is the best liner material among the three potential materials used for sustaining transiently high temperature loadings.
Patient Delay in Initiating Tuberculosis Treatment and Associated Factors in Oromia Special Zone, Amhara Region
Authors: Abdu Muhammed , Balchut Awraris , Girma Eshetu , Mebratu Wondwosen
Published: June 2020

Background. Tuberculosis (TB) is a major global public health problem. The disease is a leading cause of morbidity and mortality in Ethiopia. Early identification of cases and commencement of effective chemotherapy is an effective method to control the spread of tuberculosis. Delay in diagnosis and starting tuberculosis treatment increases severity, risk of mortality, and transmission of the disease in the community. Objective. The purpose of this study is to assess the magnitude of patient delay in initiating tuberculosis treatment and its associated factors among tuberculosis patients in health facilities of Oromia Special Zone, Ethiopia. Methods. A facility-based cross-sectional study was conducted in Oromia Special Zone. Data were collected using pretested questionnaires from patients with tuberculosis who are on treatment during the study period. The simple random sampling method was used to select health facilities and study participants. Data were entered using Epi Info version 7.2 and analyzed by SPSS version 23. Bivariate and multivariate logistic regression analyses were used to see the significance of association between the outcome and independent variables. A P value < 0.05 was considered statistically significant. Results. Three hundred and eighty-seven tuberculosis patients aged 18 years and above enrolled in the study. Among these, 223 (57.6%) were males, 194 (50.1%) were married, and 206 (53.2%) lived in rural areas. The mean age of respondents was 35 years. The median patient delay was 35 (IQR=30) days, and 54.4% of patients seek their first consultation after 21 days. Patients who have a basic schooling level (AOR=0.45, 95% CI: 0.23, 0.89) compared with the college/university level, long distance greater than 10 km (AOR=3.23, 95% CI: 1.97, 5.42), seeking treatment from informal source and private drug stores (AOR=3.01, 95% CI: 1.52, 5.95), extrapulmonary tuberculosis (AOR=2.30, 95% CI: 1.26, 4.23), and poor knowledge about tuberculosis (AOR=1.58, 95% CI: 1.01, 2.49) were associated factors that predict patient delay. Conclusion and Recommendation. A significant proportion of tuberculosis patients delayed to seek treatment. Health promotion and education involving different stake holders will make the community create awareness about tuberculosis that could help reduce delays in initiating tuberculosis treatment.
Selenium Level in Patients with Vitiligo: A Meta‐Analysis
Authors: Dai Ting , Xiaoying Sun , Li Xin , Hongjin Li , Yaqiong Zhou , Bo Liang
Published: June 2020

Background. It has been reported that deficiency of selenium can cause autoimmune disease. This meta‐analysis was aimed at evaluating whether there exits an association between selenium level and vitiligo. Methods. A comprehensive search was conducted on PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Med Online, and China VIP databases from the inception to February 12, 2019. The main outcome was the standardized mean difference (SMD) with 95% confidence interval (CI) in serum selenium level between vitiligo patients and healthy controls. Results. A total of 8 studies with 305 vitiligo patients and 6156 healthy controls were included in this meta‐analysis. The results showed that there was no significant difference in selenium level between vitiligo patients and healthy controls (SMD = 0.481, 95%CI = −0.642 to 1.604, Z = 0.840, P > 0.05). Further subgroup analysis stratified by area revealed that Asian vitiligo patients had decreased selenium level, while that finding was not observed in Caucasian patients (Asian: SMD = −0.303, 95%CI = −0.603 to −0.004, P < 0.05; Caucasian: SMD = 0.957, 95%CI = −0.752 to 2.665, P > 0.05). Conclusions. Although overall selenium level was similar between vitiligo patients and health controls, subgroup analysis showed decreased levels of selenium in Asian vitiligo patients. It may suggest a clinical tailored administration of selenium supplementation in Asian vitiligo patients.
Jurkat T Cell Detectability and Toxicity Evaluation of Low-Temperature Synthesized Cadmium Quantum Dots
Authors: Vo Ngoc Thuy , Vu Thi Bich , Diep Hong Tran Thi , Le Khanh Thien , Van Hieu Tran , Nguyen Thanh Binh , Vinh Lam Quang
Published: June 2020

Early and highly accurate detection of diverse diseases is in urgent demand than ever, especially for cancers and infectious ones. Among possibilities, biosensing by utilizing conjugated nanoparticles is still a method of choice. However, the toxicity of quantum dots remains a big matter of concern in those biooriented applications. In this study, mercaptosuccinic acid-coated cadmium selenide quantum dots of approximately 2.3 nm were synthesized with a simple green method at low temperature and cost-saving chemicals. The influence of synthesis factors was investigated with different spectroscopic methods. The toxicity issue was evaluated on the NIH-3T3 cell line (ATCC® CRL-1658™) and an MTT assay, revealing a secure threshold of 20 μg/ml. Consequently, successful conjugation to the CD3 antibody including an A/G protein bridge was implemented and verified with fluorescent methods. Finally, Jurkat T cell detectability of conjugated CdSe was successfully validated with fluorescent microscopy. The CdSe-based products are accessible for future biosensing applications.
Nivolumab in Patients with Advanced Platinum-resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-up from CheckMate 275
Authors: Galsky Matthew D. , Saci Abdel , Szabo Peter M. , Han G. Celine , Grossfeld Gary , Collette Sandra , Siefker-Radtke Arlene , Necchi Andrea , Sharma Padmanee
Published: June 2020

Purpose:

We report efficacy and safety with extended follow-up, and exploratory biomarker analyses from the phase II CheckMate 275 trial to identify biomarkers of response to nivolumab in platinum-resistant metastatic or unresectable urothelial carcinoma (mUC).

Patients and Methods:

Patients received nivolumab 3 mg/kg once every 2 weeks until disease progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was objective response rate (ORR) per blinded independent review committee (BIRC; using RECIST v1.1) in all treated patients and by tumor PD-L1 expression. Key secondary endpoints were progression-free survival (PFS) per BIRC using RECIST v1.1 and overall survival (OS) in all patients and by PD-L1 expression. Exploratory endpoints included safety and biomarker analyses of tumor mutational burden (TMB), PD-L1, and previously identified mutational signatures.

Results:

Of 270 treated patients, 139 had evaluable TMB. With 33.7 months' minimum follow-up, ORR per BIRC, median PFS, and median OS [95% confidence interval (CI)] in all treated patients were 20.7% (16.1–26.1), 1.9 months (1.9–2.3), and 8.6 months (6.1–11.3), respectively. No new safety signals were identified. Higher TMB was associated (P < 0.05) with improved ORR [OR (95% CI): 2.13 (1.26–3.60)], PFS [HR: 0.75 (0.61–0.92)], and OS [HR: 0.73 (0.58–0.91)]. TMB combined with PD-L1 better predicted ORR, PFS, and OS than PD-L1 alone. Higher mutational signature 2 score was associated with better OS but did not improve the predictive value of TMB.

Conclusions:

These results support the durable antitumor activity of nivolumab and suggest that TMB may enrich for better response in mUC. Future studies of TMB/PD-L1 as biomarkers for response to nivolumab in randomized trials are warranted.

See related commentary by Swami et al., p. 5059
A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408
Authors: Evens Andrew M. , Hong Fangxin , Habermann Thomas M. , Advani Ranjana H. , Gascoyne Randy D. , Witzig Thomas E. , Quon Andrew , Ranheim Erik A. , Ansell Stephen M. , Cheema Puneet Singh , Dy Philip A. , O'Brien Timothy E. , Winter Jane N. , Cescon Terrence P. , Chang Julie E. , Kahl Brad S.
Published: June 2020

Purpose:

We sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL).

Patients and Methods:

Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683).

Results:

For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P = 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P = 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3–4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs <1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3–4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P < 0.0001), and febrile neutropenia 10% versus 2%, respectively (P = 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P = 0.36) with OS rates of 87%, 90%, and 84%, respectively (P = 0.79). For prognostication, CR rate and POD-24 were associated with survival.

Conclusions:

Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.
Multifocal Stroke Complicating Anti-NMDA Receptor Encephalitis
Authors: Stavitsky Zina H. , Nguyen Colin H. , Johnston James Martin
Published: June 2020

Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is an autoimmune form of encephalitis, first described in 2005 and now recognized as among the more common causes of encephalitis. While NMDARE can result in permanent neurologic deficits or even mortality, the prognosis in children is generally more favorable; 75–85% of children and teenagers achieve a full or substantial recovery. We describe here a preadolescent female, whose course of NMDARE was complicated by a unilateral stroke, resulting in permanent deficits. The imaging characteristics suggest a vascular (thrombotic) etiology. To our knowledge, this is the first report of stroke in the setting of NMDARE.
Polymorphism of the Oxytocin Receptor (OXTR) Gene Affects the Circulating Oxytocin Receptor Levels in Late-Term Pregnancy in a Turkish Population
Authors: Akdemir Nermin , Cinemre Fatma Behice , Cinemre Hakan , Sevinc Leyla , Aydemir Birsen , Coban Betul , Cevrioglu Arif Serhan , Ozden Selcuk
Published: June 2020

Introduction: Postterm and late-term pregnancies still remain a serious health problem, and underlying exact mechanisms are not fully elucidated. These mechanisms are influenced by many factors. Objective: The aim of this study was to investigate the relationship between plasma oxytocin and oxytocin receptor levels and oxytocin receptor polymorphisms in term and late-term pregnant women. Methods: Sixty-eight singleton pregnant women with late-term pregnancy and 83 singleton pregnant women with term parturition were included in this study. A comparison was performed between pregnancies and neonates born at term (37 0/7 and 41 6/7 weeks’ gestation). Plasma oxytocin, oxytocin receptor, estradiol, and progesterone levels were measured by using enzyme-linked immunosorbent assay kits. TaqMan® SNP Genotyping Assays and qPCR ProbesMaster were used to investigate the polymorphisms of rs237911, rs2228485, rs53576, and rs2254298. Results: There was not any difference in gene distributions of 4 common single-nucleotide polymorphisms of oxytocin receptor of rs237911, rs2228485, rs53576, and rs2254298 between subjects in late-term and term pregnancy groups. With rs53576 of the GG genotype, serum oxytocin levels were 21.50 ± 10.69 (ng/L) in the late-term group and 62.71 ± 18.01 (ng/L) in the term group (p = 0.049). Oxytocin receptor levels in the late-term and term pregnancy groups of the GG genotype were 17.92 ± 8.15 (pg/mL) and 45.77 ± 11.66 (pg/mL), respectively (p = 0.046). Conclusion: Our findings suggest that the rs53576 oxytocin receptor single-nucleotide polymorphism is associated with late-term pregnancy through acting by direct modulation of oxytocin and oxytocin receptor levels.
Coronavirus Disease 2019 in Pregnancy: A Clinical Management Protocol and Considerations for Practice
Authors: López Marta , Gonce Anna , Meler Eva , Plaza Ana , Hernández Sandra , Martinez-Portilla Raigam J. , Cobo Teresa , García Felipe , Gómez Roig Maria Dolores , Gratacós Eduard , Palacio Montse , Figueras Francesc ,   on behalf of the COVID Collaborative Group
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of COVID-19 in pregnancy. We briefly contemplate all relevant aspects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth.