bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of time and harvest on genetic diversity of natural and restored oyster reefs
Authors: Arnaldi Kimberly G. , Walters Linda J. , Hoffman Eric A.
Published: January 2018

Oysters serve as keystone species and ecosystem engineers in estuaries due to their fundamental role of providing services to the surrounding environment and to humans. Globally, however, oysters have precipitously declined in numbers over the last century. To remedy this drastic decrease, many coastal areas have initiated oyster restoration projects. In the Indian River Lagoon (IRL) of Florida, where oyster loss was primarily the result of recreational boat wake dislodgment, researchers have put in place a unique method to supplement natural recruitment of oysters. This method consists of deploying stabilized shell attached to mesh mats. Larval oysters thus have substrate on which to settle and three‐dimensional reef habitats have been reestablished in historical footprints. This restoration project has proven to be successful, shown by 9 years of data collection on growth, recruitment, and survivability. In this study, we sought to determine the length of time required for newly restored oyster reefs to reach equivalent levels of genetic diversity as undisturbed, natural (reference) oyster reefs. Additionally, we determined if recreational harvesting impacted the genetic diversity of these reference reefs. Using nine microsatellite loci, we found that restored oyster reefs accumulated as much genetic diversity as natural reefs as quickly as 1 month after stabilized shells were deployed. We likewise found that harvesting did not impact genetic diversity in oyster reefs in the IRL. These results are encouraging, and are a valuable addition to understanding the importance of oyster reef restoration on the ecosystem.
Modeling the traffic disruption caused by pluvial flash flood on intra‐urban road network
Authors: Li Mengya , Huang Qingyu , Wang Lei , Yin Jie , Wang Jun
Published: January 2018

Pluvial flash flood (PFF) can cause serious traffic disruption in big cities. We conducted interdisciplinary research by integrating flood modeling and traffic analysis to reveal the spatiotemporal pattern of the interplay between these two processes. A simplified simulation tool, which is capable of building a road network model, assigning trip paths with the effect of road closures, and evaluating travel delay and vehicle volume redistribution in a given PFF scenario, was developed to capture the traffic disruption in the face of PFF events. Modeling outputs from a case study in the city center of Shanghai showed that the delay of vehicles diverted to dry links or trapped in flooded links may reach 0.5 to 8 times the travel time in no‐flood scenarios. Overall, approximately 1–7% of vehicle volumes on flooded links would be redistributed onto dry links (more likely major arterial roads). However, the vehicle volume variation during each time interval demonstrated evident disparity with the spatiotemporal change of flood inundations. Simulating and mapping the congestion can largely facilitate the identification of vulnerable links. Future research will test the method in other intra‐urban areas and try to bridge the gap between modeling outputs and smart city planning and management.
The Impact of Military Expenditures on Economic Growth of Pakistan
Authors: Ajmair Muhammad , Hussain Khadim , Abbassi Faisal Azeem , Gohar Misbah
Published: January 2018

The purpose of this research paper is to examine the long run relationship between military expenditure, number of persons in military and economic growth. To fulfill this, the study used ARDL approach for annual time series data from 1990 to 2015. The results show that Pakistan military expenditures are insignificant (military burden for the country is statically insignificant) and number of persons in military are positively and significantly related with GDP growth in long run. The error correction term is negative and significant which shows that short run relationship exists among economic growth, military expenditures and number of army persons. In short run military expenditure and number of persons in military are positively and significantly related with GDP growth but in long run only number of military persons affects economic growth positively and significantly.
Exploring the Social Link between Cerebral and Cerebellar Neural Ensembles through a Falsifiable Psychological Heuristics
Authors: Cassella Antonio
Published: January 2018

This article wields the logos psychological heuristics in proposing that the universe, the social brain, and subatomic ensembles sustain the journey of the Mesoamerican demigod Quetzalcoatl. Within quantum coherence, the going “coatl-quetzal” marries in the hyperspace of our 5000 microcomplexes the legitimacy (probability = p = 1) of the autistic “coatl” (“serpent”), guarded by the 2 000 000 cortical columns in the cerebral cortex, with the illegitimacy (p = 0) of the schizophrenic “quetzal” (“bird”) lodged in the cerebellar cortex. Within quantum decoherence, the return of “quetzal-coatl” to the cerebral coatl in spacetime reflects our escape from madness with a new piece of knowledge. At the turn of the 20th century, the author found that autistics’ strength in Performance IQ agrees with the victory of repetitive legitimacy over unexpected illegitimacy in the first attention. He concluded that autistics’ weakness in verbal IQ agrees with a damaged qubit |1› and |0› (ket one and ket zero) in the going journey of Quetzalcoatl with the second attention. At the turn of the first decade of the 21st century, the author researched the reciprocal empowerment of the first and the second attention in the Third Attention. Here he emphasizes that in spontaneous laughing, the coherence of long-term potentiation in cerebellar granule cells, parallel fibers, and Purkinje cells is followed by the decoherence of long-term depression in the fewer Purkinje cells that carry Quetzalcoatl and the Third Attention into the deep nuclei of the cerebellum, and then into the spacetime of a refreshed first attention.
The Electoral College: A Constitutional Needle in a Political Hay Stack
Authors: Cox Anna M.
Published: January 2018

In examination of the constitutional and political institution of the Electoral College the research shows that throughout American politics and history the Electoral College always had and has a role of great political and historical influence. Furthermore the Electoral College has also been a source of much political and constitutional debate. This is an intriguing constitutional needle in a political hay stack for the simple fact that something appears to be insignificant and inconsequential until its time for the national presidential election to roll around every four years. Thus the Electoral College takes front and center of the national political stage as the collective national eyes are all on the presidential race and the ever so magical number of 270. How the Electoral College factors into American politics has been the subject of much political discussion relevant to how the president is elected, how the American public’s voice is represented and how democratic of a political institution or representative system is the Electoral College. Through the sands of time of American history there has been camps of voices echoing concerns about the constitutional needle in a political hay stack of the Electoral College and its influential role in American politics.
Field Testing Improves Citrus Plant Biological Treatment
Authors: Ashby Jim , Sobkowicz Tony
Published: January 2018

Wastewater from citrus processing contains high levels of sugars, suspended solids, and caustic cleaning agents. Biological treatment is the only economical process for removing and neutralizing all of these contaminants, and the activated sludge process is the workhorse of the biological treatment stable. The biological treatment system must produce a treated effluent of the highest quality, regardless of the wild variation in flow and composition of the influent. Problems in the treatment process can almost always be traced to either a wastewater loading that is higher than the system can tolerate, or a failure to maintain and operate the treatment system to realize its treatment potential. A thorough review of the operational and loading characteristics of the system will determine whether excessive loading or inadequate treatment system is responsible for the system failure. When the problem has been identified, it can be resolved in one of three ways:

□ A new treatment system of greater capacity can be installed to replace the inadequate system.

□ The wastewater loading, hydraulic and organic, can be reduced through changes in fruit processing practices.

□ Changes in the existing treatment system (equipment or operational) can be identified to increase its capacity.

Paper published with permission.
Brazil: Citrus Benchmarking
Authors: Schuermans Alex
Published: January 2018

More and more, the Citrus Business is becoming a global operation, narrowing the technological opportunities gap between processors around the world. Most of the largest Brazilian processors already have process units or commercial partners in the United States, which makes any new technology available worldwide virtually instantaneously. However, there are several market and environmental differences that directly impact the best use of the available technology according to the individual market.

Paper published with permission.
Engineering Solutions for Lightning and Surge Protection
Authors: Gates Paul
Published: January 2018

The main objective of this work is to discuss the significant impacts associated with lightning and electrical surges in large, complex electrical power systems. Electrical systems have evolved significantly in the last 10 years resulting in high penetration of electronics for automation, control, and protection. A representative example of this can be readily observed in the migration from single speed motors to VFD or electro mechanical relays to microprocessor based, multifunction relays. These electronic devices are very sensitive to electrical surges, noise and the presence of harmonics caused by a multitude of sources. These sources, such as variable speed drives, computers, electronic light ballasts, and power supplies, are now embedded in our electrical systems and heighten the need for lightning and surge protection.

Paper published with permission.
Production Quality Improvements and Energy Cost Reductions Associated With Compressed Air
Authors: Krisa Mark , Voelker David
Published: January 2018

Compressed air is utilized throughout various production processes in the citrus industry and can influence production quality and operating costs. Within production equipment, compressed air is expanded from a higher pressure to perform various tasks. The pressure ahead of the final discharge location can have a direct impact on the operation of the specific process. Article pressure is the term used to describe the pressure located closest to the point where air is expanded to do work. Article pressure can be influenced by many variables that exist between supply equipment (compressors) and the point of use. Understanding the relationship between the supply pressure and the article pressure will facilitate the ability to maximize the repeatability and performance of production equipment and minimize the supply power required to operate the compressed air system.

This paper will discuss variables that influence the difference between the pressure supplied by the compressor station and the pressure utilized within the production equipment. Illustrations and field examples will be utilized to describe issues. Troubleshooting methods will be discussed along with a description of how to trend variables that influence production so problems can be corrected before they influence productivity.

Paper published with permission.
Aseptic Ingredient Addition: Meeting the Demand for Better-Tasting Orange Juice
Authors: Brocker Paul P.
Published: January 2018

Since the late 1970’s, Aseptic Not-From-Concentrate Orange Juice (NFCOJ) has been successfully stored in large refrigerated aseptic storage tanks. Aseptic tanks have evolved from 280,000 gallons in volume to now in excess of 1.8 million gallons each. The total bulk storage capacity in Florida has grown to approximately 280 millions of gallons and continues to grow with new installations occurring each year at some facilities. Worldwide, the market is expanding into Brazil, Spain, and markets that are beginning to receive juice shipped in bulk on snips. The aseptic storage methods have been accepted in Brazil and Europe, and aseptic transfer of the juice is occurring via specially outfitted aseptic tanker vessels from Brazil to the US and Europe.

The consumer’s demand for NFCOJ has grown steadily throughout these years, and the suppliers of consumer packaged orange juice have developed special processes and methods to maximize the quality and flavor of the juices sent to the market. Fresh juice, light pasteurization, and flavor enhanced products are just some of these methods resulting in very high quality juice availability. Also, cost and price are always under assault, and the juice suppliers are always looking for an edge. Recently, the flavor enhancement method has come under scrutiny by the FDA, and the industry is being reminded that all added flavors must be made from naturally occurring orange derivatives or must be labeled appropriately: such as “with natural (other fruit) flavors” or “with artificial flavors,” both of which may have an undesirable impact on the market perception of the juice quality.

At this same time, as the bulk storage technology of NFCOJ has matured in the past 25 years, some processors who package their own juice are investing in special aseptic transfer methods from the aseptic bulk storage tanks without the need to re-pasteurize the juice prior to packaging. Their goal is to provide the highest quality juice to the consumer, and to minimize or eliminate the need to add expensive and special flavor packs to the juice. This is being done commercially in Florida and Spain.

This paper explores these methods of aseptic juice transfer direct to packaging and the aseptic addition of natural or otherwise desired and labeled ingredients, and their potential impact on the quality of the juice.

Paper published with permission.
Crossflow Filtration (Ceramic and Hollow Fiber Membranes) in the Citrus Industry
Authors: Sondhi Rishi
Published: January 2018

Crossflow filtration is becoming a cost-effective and preferred method of separation in the food and beverage industry. This paper introduces the concept of crossflow filtration and describes the different membrane technologies and materials. Additionally, advances in ceramic tubular and polymeric hollow fiber membrane technology are presented. New membrane configurations and their practical impact in the industry are discussed. Typical filtration applications in the citrus industry such as fruit juice clarification, clean-in-place (CIP) solutions recovery, and water recovery applications are highlighted.

Paper published with permission.
Caustic Recovery Using Membrane Filtration
Authors: Grigus Mike
Published: January 2018

Food and beverage processors that use dilute caustic solutions for cleaning process equipment have shown increased interest in recovering the used caustic. The primary reason is that the price of caustic has increased significantly in the past year or so. Membrane filtration technology can be used to remove suspended solids (clarify with microfiltration) and/or dissolved solids (purify with nanofiltration) from these used caustic solutions. These treated caustic solutions are suitable for reuse within the processing plant as cleaning solutions. While an end-user’s specific process, performance, capital and operating cost parameters require pilot testing and process design evaluations to determine the economic viability of caustic recovery, the existing body of information from commercial and process development work allows for an evaluation of a “typical” caustic recovery application.

Paper published with permission.
Water Conservation and Wastewater Load Reduction in Citrus Processing
Authors: Ashby James
Published: January 2018

In the state of Florida, the vast majority of potable water comes from groundwater supplies. Salt water intrusion into groundwater aquifers coupled with variable rainfall and periodic droughts are affecting the availability of this supply. As the supply of potable groundwater in Florida becomes less and less available, it is crucial for municipalities and industry alike to take the initiative to protect diminishing water resources through conservation.

In addition, increased scrutiny from state and federal regulators on effluent wastewater discharges from industrial facilities such as citrus processing plants has resulted in tighter effluent discharge standards, limits to organic loadings on land application and increased wastewater pretreatment requirements. These trends are expected to continue and citrus processors are faced with the reality that these tightening requirements are making wastewater treatment an even more critical part of their operations.

Paper published with permission.
Draft Genome Sequences of 510
Listeria monocytogenes
Strains from Food Isolates and Human Listeriosis Cases from Northern Italy
Authors: Lomonaco Sara , Gallina Silvia , Filipello Virginia , Sanchez Leon Maria , Kastanis George John , Allard Marc , Brown Eric , Amato Ettore , Pontello Mirella , Decastelli Lucia
Published: January 2018

Listeriosis outbreaks are frequently multistate/multicountry outbreaks, underlining the importance of molecular typing data for several diverse and well-characterized isolates. Large-scale whole-genome sequencing studies on
Listeria monocytogenes
isolates from non-U.S. locations have been limited. Herein, we describe the draft genome sequences of 510
L. monocytogenes
isolates from northern Italy from different sources.
Draft Genome Sequences of Two
Vibrio parahaemolyticus
Strains Associated with Gastroenteritis after Raw Seafood Ingestion in Colorado
Authors: Trinh Sonya A. , Leyn Semen A. , Rodionov Ivan D. , Godzik Adam , Satchell Karla J. F.
Published: January 2018

Vibrio parahaemolyticus
is a Gram-negative pathogen associated with gastrointestinal and wound infections after exposure to raw seafood or contaminated waters. We report here the whole-genome sequences of two stool isolates (CDC-AM50933 and CDC-AM43539) from patients in Colorado presenting with gastroenteritis after ingesting raw seafood.
Draft Genome Sequence of
Escherichia coli
Strain SN137, a Bacterium with Extracellular Proteolytic Activity on Immunoglobulins and Persistence in Human Tissue Blood
Authors: Najera-Hernandez Salustio , Sanchez-Alonso Maria Patricia , Anastacio-Marcelino Estela , Negrete-Abascal Erasmo , Vazquez-Cruz Candelario
Published: January 2018

The draft genome sequence of
Escherichia coli
strain SN137 is reported here. The genome comprises 172 contigs, corresponding to 4.9 Mb with 50% G+C content, and contains several genes related to pathogenicity that explain its survival in human hematic tissue.
Draft Genome Sequence of
Bacillus velezensis
OSY-S3, a Producer of Potent Antimicrobial Agents Active against Bacteria and Fungi
Authors: Gerst Michelle M. , Yesil Mustafa , Yousef Ahmed E.
Published: January 2018

Bacillus velezensis
OSY-S3 produces anti-
Listeria
, anti-
Escherichia coli
, and antifungal compounds. Additionally, fermentate of
B. velezensis
OSY-S3 culture removes
Staphylococcus aureus
biofilms effectively. The draft genome sequence of
B. velezensis
OSY-S3 reported here had a genome size of ~3.90 Mb and a G+C content of 46.5%.
Complete Genome Sequence of
Lacinutrix venerupis
DOK2-8 Isolated from Marine Sediment from the East Sea, Republic of Korea
Authors: Lim Se Ra , Jeong Dae Gwin , Chi Won-Jae , Kim Ji Hyung
Published: January 2018

Lacinutrix venerupis
has recently been considered a potential fish pathogen. Here, we report the complete genome sequence of
L. venerupis
DOK2-8, which possesses several virulence-related genes. This strain may be potentially virulent to other marine organisms, and its genomic information will provide important insights into the biodiversity of the genus
Lacinutrix
.
Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP Receptor Protein Complex in Vibrio vulnificus
Authors: Kim Jeong-A , Lee Mi-Ae , Jung You-Chul , Jang Bo-Ram , Lee Kyu-Ho
Published: January 2018

Septicemia-causing
Vibrio vulnificus
produces at least three exoproteases, VvpE, VvpS, and VvpM, all of which participate in interactions with human cells. Expression of VvpE and VvpS is induced in the stationary phase by multiple transcription factors, including sigma factor S, SmcR, and the cAMP-cAMP receptor protein (cAMP-CRP) complex. Distinct roles of VvpM, such as induction of apoptosis, lead us to hypothesize VvpM expression is different from that of the other exoproteases. Its transcription, which was found to be independent of sigma S, is induced at the early exponential phase and then becomes negligible upon entry into the stationary phase. SmcR and CRP were studied regarding the control of
vvpM
expression. Transcription of
vvpM
was repressed by SmcR and cAMP-CRP complex individually, which specifically bound to the regions −2 to +20 and +6 to +27, respectively, relative to the
vvpM
transcription initiation site. Derepression of
vvpM
gene expression was 10- to 40-fold greater in an
smcR crp
double mutant than in single-gene mutants. Therefore, these results show that the expression of
V. vulnificus
exoproteases is differentially regulated, and in this way, distinct proteases can engage in specific interactions with a host.

IMPORTANCE
An opportunistic human pathogen,
Vibrio vulnificus
produces multiple extracellular proteases that are involved in diverse interactions with a host. The total exoproteolytic activity is detected mainly in the supernatants of the high-cell-density cultures. However, some proteolytic activity derived from a metalloprotease, VvpM, was present in the supernatants of the low-cell-density cultures sampled at the early growth period. In this study, we present the regulatory mechanism for VvpM expression via repression by at least two transcription factors. This type of transcriptional regulation is the exact opposite of those for expression of the other
V. vulnificus
exoproteases. Differential regulation of each exoprotease's production then facilitates the pathogen's participation in the distinct interactions with a host.
Climatic modulation of neurotransmitter release in amphibian neuromuscular junctions: role of dynorphin-A
Authors: Ge Dengyun , Lavidis Nickolas
Published: January 2018

Amphibian neuromuscular junctions (NMJs) become relatively more silent during the dry winter season in Australia. During the dry, calcium sensitivity is reduced, whereas calcium dependence remains unchanged. Endogenous opioid peptides play an important role in the regulation of the physiological functions of active and dormant vertebrates. Previous findings suggest that dynorphin-A is more potent than other opiates in decreasing evoked neurotransmission in amphibian NMJs. Dynorphin-A has been shown not to alter the amplitude or the frequency of miniature quantal neurotransmitter release. In the present study, we report that dynorphin-A exerted a more pronounced inhibitory effect on evoked neurotransmitter release during the dry (hibernating period) when compared with the wet (active period) season. Dynorphin-A increased the frequency and decreased the amplitude of miniature neurotransmitter release only at relatively high concentration during the dry season. In the present study, we propose that dynorphin-A suppresses evoked neurotransmitter release and thus contraction of skeletal muscles, while allowing subthreshold activation of the NMJ by miniature neurotransmission, thus preventing any significant neuromuscular remodeling. The inhibitory effect of dynorphin-A on evoked transmitter release is reduced by increasing the extracellular calcium concentration.
Optimal Cement Mixtures Containing Mineral Admixtures under Multiple and Conflicting Criteria
Authors: García Nitza M. , Soto-Toro Hildélix L. , Cabrera-Ríos Mauricio , Suárez Oscar Marcelo
Published: January 2018

In modern construction industry, fabrication of sustainable concrete has turned the decision‐making process into a challenging endeavor. One alternative is using fly ash and nanostructured silica as cement replacements. In these modern mixtures, proper concrete bulk density, percentage of voids, and compressive strength normally cannot be optimized individually. Hereby, a decision‐making strategy on the replacement of those components is presented while taking into account those three performance measurements. The relationships among those components upon concrete fabrication required a design of experiments of mixtures to characterize those mineral admixtures. This approach integrates different objective functions that are in conflict and obtains the best compromise mixtures for the performance measures being considered. This optimization strategy permitted to recommend the combined use of fly ash and nanosilica to improve the concrete properties at its early age.
Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome
Authors: Chaucer Benjamin , Stone Abriella , Demanes Augustus , Seibert Shawn M.
Published: January 2018

The treatment of cancer is a rapidly evolving field. As more chemotherapeutic agents become available, reporting the side effects of these agents in clinical practice becomes increasingly important. Nivolumab is one of the chemotherapeutic agents commonly used for treatment of renal cell carcinoma, metastatic melanoma, and metastatic non-small cell lung cancer. While common side effects are known and well documented, encephalitis is documented as an extremely rare side effect. We present the case of an extremely rare side effect to a common chemotherapeutic agent.
Current Strategies of Endocrine Therapy in Elderly Patients with Breast Cancer
Authors: Lee Suk-young , Seo Jae Hong
Published: January 2018

Currently, the growing population of the elderly is one of biggest problems in terms of increase in geriatric diseases. Lack of data from large prospective studies on geriatric breast cancer patients often makes it difficult for clinicians to make treatments decisions for them. Because both benefit and risk of treatment should be taken into account, treatment is usually determined considering life expectancy or comorbidities in elderly patients. Treatment of breast cancer is differentiated according to histologic classifications, and hormone therapy is even adopted for patients with metastatic breast cancer if tumor tissue expresses hormone receptors. Endocrine therapy can offer great benefit to elderly patients considering its equivalent efficacy to chemotherapy with fewer toxicities if it is appropriately used. Aromatase inhibitors are usually prescribed agents in hormone therapy for elderly breast cancer patients due to their physiology after menopause. Here, endocrine therapy for elderly patients with breast cancer in neoadjuvant, adjuvant, and palliative setting is reviewed along with predictive adverse events resulting from the use of hormone agents.
Heat Capacity and Thermodynamic Property of Lithium Pentaborate Pentahydrate
Authors: Cui Wanjing , Li Long , Guo Yafei , Zhang Sisi , Deng Tianlong
Published: January 2018

The heat capacity of lithium pentaborate pentahydrate has been measured using an adiabatic calorimeter at the temperature from 297 to 375 K. No phase transition and thermal anomalies were observed. The molar heat capacity of LiB5O8·5H2O can be expressed as Cp,m (J·mol−1·K−1) = 396.79376 + 35.87528 [T-(Tmax+Tmin)/2]/[(Tmax-Tmin)/2] + 0.16494[T-(Tmax+Tmin)/2]/[(Tmax-Tmin)/2]2 + 8.3083[T-(Tmax+Tmin)/2]/[(Tmax-Tmin)/2]3, where T is the temperature in Kelvin, Tmax=375 K, and Tmin=297 K. The thermodynamic functions of (HT-H298.15), (ST-S298.15), and (GT-G298.15) of LiB5O8·5H2O are obtained via the molar heat capacity at the temperature of 5 K intervals.
A Localized Surface Plasmon Resonance Sensing Method for Simultaneous Determination of Atenolol and Amiloride in Pharmaceutical Dosage Forms and Urine Samples
Authors: El-Zahry Marwa R.
Published: January 2018

This contribution describes a simple, fast, and sensitive application of localized surface plasmon resonance effect of silver nanoparticles for simultaneous determination of antihypertensive drugs’ mixture atenolol and amiloride in both pharmaceutical dosage forms and in biological samples (urine). Silver nanoparticles were prepared by chemical reduction of silver nitrate using hydroxylamine HCL in an alkaline medium. Application of silver-hydroxylamine nanoparticles (SH NPs) provides many advantages including reproducibility, sensitivity, and cost effective way of analyte determination. Amiloride has four amino groups which act as attachment points on the surface of silver nanoparticles resulting in a synergistic effect on the absorption intensity of atenolol, leading to increase the sensitivity of the determination of both compounds. This method shows excellent advantages comparing with the previously reported methods, including accuracy, precision, and selectivity. The linear range of atenolol is 1 × 10−5–1 × 10−4 mol·L−1 and of amiloride is 1 × 10−6–1 × 10−5 mol·L−1. The limit of detection (LOD) values of atenolol and amiloride are 0.89 × 10−5 and 0.42 × 10−6 mol·L−1, respectively.
RASA1/NF1-Mutant Lung Cancer: Racing to the Clinic?
Authors: Kitajima Shunsuke , Barbie David A.
Published: January 2018

Although mutation of NF1 has been described in non–small cell lung cancer (NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP), defines a novel genetically defined subclass of NSCLC. RASA1/NF1-mutant cell lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of MAPK inhibition in this subclass of patients. Clin Cancer Res; 24(6); 1243–5. ©2018 AACR.

See related article by Hayashi et al., p. 1436
Relative Target Affinities of T-Cell–Dependent Bispecific Antibodies Determine Biodistribution in a Solid Tumor Mouse Model
Authors: Mandikian Danielle , Takahashi Nene , Lo Amy A. , Li Ji , Eastham-Anderson Jeffrey , Slaga Dionysos , Ho Jason , Hristopoulos Maria , Clark Robyn , Totpal Klara , Lin Kedan , Joseph Sean B. , Dennis Mark S. , Prabhu Saileta , Junttila Teemu T. , Boswell C. Andrew
Published: January 2018

Anti-HER2/CD3, a T-cell–dependent bispecific antibody (TDB) construct, induces T-cell–mediated cell death in cancer cells expressing HER2 by cross-linking tumor HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic synapse. TDB design is a very challenging process that requires consideration of multiple parameters. Although therapeutic antibody design strategy is commonly driven by striving for the highest attainable antigen-binding affinity, little is known about how the affinity of each TDB arm can affect the targeting ability of the other arm and the consequent distribution and efficacy. To our knowledge, no distribution studies have been published using preclinical models wherein the T-cell–targeting arm of the TDB is actively bound to T cells. We used a combined approach involving radiochemistry, invasive biodistribution, and noninvasive single-photon emission tomographic (SPECT) imaging to measure TDB distribution and catabolism in transgenic mice with human CD3ϵ expression on T cells. Using CD3 affinity variants, we assessed the impact of CD3 affinity on short-term pharmacokinetics, tissue distribution, and cellular uptake. Our experimental approach determined the relative effects of (i) CD3 targeting to normal tissues, (ii) HER2 targeting to HER2-expressing tumors, and (iii) relative HER2/CD3 affinity, all as critical drivers for TDB distribution. We observed a strong correlation between CD3 affinity and distribution to T-cell–rich tissues, with higher CD3 affinity reducing systemic exposure and shifting TDB distribution away from tumor to T-cell–containing tissues. These observations have important implications for clinical translation of bispecific antibodies for cancer immunotherapy. Mol Cancer Ther; 17(4); 776–85. ©2018 AACR.
Tumor Immunity and Survival as a Function of Alternative Neopeptides in Human Cancer
Authors: Rech Andrew J. , Balli David , Mantero Alejandro , Ishwaran Hemant , Nathanson Katherine L. , Stanger Ben Z. , Vonderheide Robert H.
Published: January 2018

The immune system exerts antitumor activity via T cell–dependent recognition of tumor-specific antigens. Although the number of tumor neopeptides—peptides derived from somatic mutations—often correlates with immune activity and survival, most classically defined high-affinity neopeptides (CDNs) are not immunogenic, and only rare CDNs have been linked to tumor rejection. Thus, the rules of tumor antigen recognition remain incompletely understood. Here, we analyzed neopeptides, immune activity, and clinical outcome from 6,324 patients across 27 tumor types. We characterized a class of “alternatively defined neopeptides” (ADNs), which are mutant peptides predicted to bind MHC (class I or II) with improved affinity relative to their nonmutated counterpart. ADNs are abundant and molecularly distinct from CDNs. The load of ADNs correlated with intratumoral T-cell responses and immune suppression, and ADNs were also strong predictors of patient survival across tumor types. These results expand the spectrum of mutation-derived tumor antigens with potential clinical relevance. Cancer Immunol Res; 6(3); 276–87. ©2018 AACR.
Sensitive Detection of Atrial Fibrillation in Acute Stroke Patients by Short-Term Bedside Electrocardiography Monitoring Software Analysis
Authors: Ross Linda Sarah , Bettin Markus , Kochhäuser Simon , Ritter Martin , Minnerup Jens , Eckardt Lars , Reinke Florian , Dittrich Ralf
Published: January 2018

Background: Atrial fibrillation (AF) is an important cause of stroke. Continuous electrocardiography (ECG) monitoring with software-based analysis algorithms has been suggested to enhance the AF detection rate. We investigated the ability of stroke risk analysis (SRA) in the detection of AF in acute stroke patients. Methods: Consecutive stroke patients numbering 1,153 were screened. Patients with cardioembolic stroke related to AF (n = 296, paroxysmal n = 63, persistent n = 233) and patients with cryptogenic stroke (n = 309) after standard diagnostic work-up (bedside ECG monitoring, ultrasound, transesophageal echocardiography, 24 h Holter ECG) received SRA during their stay at the Stroke Unit. Determination of AF risk by SRA in the patients with AF and in the patient group with cryptogenic stroke was assessed and compared. Results: Median SRA monitoring analysis time was 16 h (range 2–206 h, interquartile range 10–36). In AF patients, SRA also detected a possible or definitive AF in 98%. The overall sensitivity of SRA to detect possible or definitive AF in patients with proven AF by standard diagnostic work up and cryptogenic stroke was 98%, specificity 27%, positive predictive value 56%, and the negative predictive value (NPV) was 92%. Area under ROC curve was 0.622. Conclusion: SRA was found to be highly sensitive to detect possible or definitive AF in clinical routine within a short monitoring time. However, low specificity and poor accuracy do not allow diagnosing AF by SRA alone, but with the high NPV compared to current diagnostic standard, it is a valid diagnostic tool to rule out AF. Thereby, SRA is a contribution to clarify stroke etiology.
Role of the Frontal Sinus in Mediating Ocular Vestibular-Evoked Myogenic Potentials by Bone Vibration Stimuli Applied to the Forehead
Authors: Lin Kuei-You , Yeh Te-Huei , Jaw Fu-Shan , Young Yi-Ho
Published: January 2018

This study investigated ocular vestibular-evoked myogenic potential (oVEMP) tests via Fpz and Fz taps to assess the role of the frontal sinus in mediating oVEMP elicitation. Forty healthy subjects and 80 patients with Ménière disease (MD) underwent a series of oVEMP tests via a minishaker tapping at the Fpz and Fz sites in a randomized order. Response rates of oVEMP test via various tapping sites were compared. Dimensions of the frontal sinus were measured via CT scan. A significantly negative correlation between the age and height of the frontal sinus was noted, and the cutoff age for discriminating present and absent Fpz oVEMPs in MD patients was 52 years. Additionally, oVEMPs by Fpz tapping were more efficiently presented in males than females, likely because of the greater resonance by the larger height of the frontal sinus in males (3.88 ± 0.68 cm) than females (3.42 ± 0.67 cm). In conclusion, the height of the frontal sinus plays a role in mediating the elicitation of oVEMPs. The oVEMPs could be easily elicited by the first-order bone vibration (Fpz/Fz tapping) coupled with the second-order resonance effect (with a high extent of the frontal sinus). Thus, initial tapping at the Fpz site is suggested. If it fails, try the Fz site for screening the oVEMPs.
Correlation between Resection Margin and Disease Recurrence with a Restricted Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma
Authors: Lee Woohyung , Han Ho-Seong , Ahn Soyeon , Yoon Yoo-Seok , Cho Jai Young , Choi YoungRok
Published: January 2018

Background: The relationship between resection margin (RM) and recurrence of resected hepatocellular carcinoma (HCC) is unclear. Methods: We reviewed clinical data for 419 patients with HCC. The oncologic outcomes were compared between 2 groups of patients classified according to the inflexion point of the restricted cubic spline plot. Results: The patients were divided according to an RM of <1 cm (n = 233; narrow RM group) or ≥1 cm (n = 186; wide RM group). The 5-year recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in the narrow RM group. Patients with multiple lesions, or prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from subgroup analyses. In patients with a 2–5 cm HCC, the 5-year RFS was greater in the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95% CI 1.029–2.976, p = 0.039) was independently associated with disease recurrence. Conclusion: In patients with a single 2–5 cm HCC without prior TACE/RFA, an RM of ≥1 cm was associated with lower risk of recurrence after liver resection.
Severe Hepatic and Pulmonary Involvement in Rendu-Osler-Weber Syndrome
Authors: Verhelst Xavier , Geerts Anja , Van Vlierberghe Hans , Smeets Peter , Lecluyse Clarisse
Published: January 2018

We report the case of a young woman with hereditary hemorrhagic telangiectasia (HHT) with severe liver involvement and pulmonary shunting. The medical imaging in this patient illustrates the severe shunting that can occur in these patients who often are asymptomatic. By showing this case, we want to highlight the role of liver transplantation in HHT with hepatic involvement.
Spontaneous Rupture of Hepatocellular Carcinoma in a Young Patient with Fatal Outcome
Authors: Pinal-García David F. , Nuño-Guzmán Carlos M. , Gómez-Abarca Audrey , Corona Jorge L. , Espejo Ismael
Published: January 2018

Spontaneous rupture of hepatocellular carcinoma (HCC) is a potentially life-threatening complication. Diagnosis may be difficult, particularly in the absence of known liver cirrhosis or tumor. A 20-year-old male patient presented with progressive abdominal pain and shock. His past medical history was uneventful. Anemia, acute renal failure, and abnormal liver function test were demonstrated. Mild hepatomegaly, perihepatic and flank fluid, and multiple hypodense liver lesions suggestive of intrahepatic metastases or multifocal HCC were revealed by computed tomography. Two actively bleeding liver tumors and multiple tumors in a noncirrhotic liver were found. Hemostatic suture and perihepatic packing were performed. The patient remained in critical condition, with a fatal outcome 48 h later. Histopathologic analysis reported HCC and absence of cirrhotic changes. HCC spontaneous rupture incidence is reported between 2.3 and 26%. Median age is 65 years. No liver cirrhosis is found in one-third of patients, with a median age of 51 years. Sudden onset of abdominal pain and shock is observed in the majority of cases. An accurate preoperative diagnosis improves to 75% with ultrasound and computed tomography. Besides hemodynamic stabilization, there is no general agreement on the best treatment option. Transarterial embolization, surgical perihepatic packing, suture plication, and hepatic artery ligation are useful methods of hemostasis in unstable patients. Mortality has been reported from 16.5 to 100%. The histopathologic finding of HCC in a noncirrhotic liver represents a less frequent presentation. A case of spontaneous rupture of HCC carcinoma and a noncirrhotic liver in a young patient is herein reported.
JUDICIALIZAÇÃO DA SAÚDE E INTERNAÇÕES COMPULSÓRIAS DE JOVENS USUÁRIOS DE DROGAS – UM ESTUDO EM ESPÍRITO SANTO DO PINHAL/SP
Authors: Bartolomei Josiara Rabello , Rezende Laura Ferreira de
Published: January 2018

O artigo tem por objetivo analisar processos de internação compulsória de jovens e adultos usuários de drogas relativos aos anos de 2009 a 2014 na cidade de Espírito Santo do Pinhal (SP). Tratou-se de um estudo longitudinal retrospectivo, de caráter exploratório documental. O presente trabalho revelou que, em 99 processos, as famílias buscam na Justiça a internação compulsória de seus familiares. As internações de adolescentes via ação judicial são feitas em clínicas particulares pagas pelo município, enquanto os adultos são internados pelo Sistema Único de Saúde. Não há transferência de recursos estaduais, e os recursos federais não cobrem os gastos. Não há políticas públicas para esse fim, e há necessidade de fortalecimento dos Centros de Atenção Psicossocial para promoção da sustentabilidade e do equilíbrio social.
Responsabilidade Civil do Residente em Medicina: Jurisprudência do Estado de São Paulo
Authors: Kurauchi Ana Tomie Nakayama , Piacsek Mônica Vieira da Motta , Motta Márcia Vieira da
Published: January 2018

O médico residente, por ser profissional já graduado, responde a ações de responsabilidade civil em conformidade à legislação civilista ou consumerista de acordo com o âmbito do serviço prestado, se público ou privado, respectivamente. Este trabalho levantou a jurisprudência do Tribunal de Justiça de São Paulo em que residentes atuaram no polo passivo de lides sobre erro médico no estado de São Paulo, entre janeiro de 1998 e dezembro de 2016. As decisões indicaram que nas ações em que o residente respondeu com superiores hierárquicos acadêmicos eles não tiveram sua culpa apreciada e, sim, a dos seus supervisores, exceto em casos de erro grosseiro. Quando participaram do feito junto à equipe do hospital, sem que houvesse vinculação acadêmica, foram condenados em todas as ações, mediante verificação de culpa pessoal sobre o dano. Nas lides em que responderam sozinhos apenas com o hospital, foram condenados em apenas 2 casos (14,3%). Muito embora várias das instituições privadas que compuseram a amostra fossem prestadoras de serviço público, tanto seus médicos quanto os residentes não deveriam ter participado das lides por terem atuado como agentes públicos, porém a ilegitimidade não foi suscitada nas ações tempestivamente. O dever do médico de prover informação aos pacientes mereceu destaque nos acórdãos, já que a conduta esclarece quais procedimentos serão realizados e seus possíveis efeitos adversos. A falta de documentação neste sentido pode suscitar o entendimento de que houve dano indenizável pelos magistrados.
Valoração Médico-Pericial do Dano Estético
Authors: Leal Lucas Pedroso Fernandes Ferreira , Silva Élcio Rodrigues da , Spina Viviam Paula Lucianelli , Borracini Jonas Aparecido , Panza Fábio Tadeu
Published: January 2018

O exame pericial de avaliação de danos constitui uma atividade técnica, à qual se aplicam as regras da Arte Médica, considerando-se o âmbito do Direito em que se insere. O laudo médico deve ser completo e fazer compreender a situação real do indivíduo. A avaliação do experto deve assegurar o esclarecimento do juízo, contribuindo para que se promova a Justiça. É fundamental que o dano pessoal seja identificado, descrito e valorado de acordo com rigoroso método científico. Este artigo discorre sobre o Dano Estético e reflete a experiência do Instituto de Medicina Social e de Criminologia do Estado de São Paulo (IMESC) tanto em seu diagnóstico quanto em sua valoração dentro do arcabouço legal brasileiro, de acordo com método de avaliação baseado em escala quantitativa-descritiva, buscando-se harmonização em sua ponderação, dentro do princípio geral da reparação integral dos danos, de modo contextualizado e fundamentado.
Memória e Palavra: as cidades submersas de Julio Ramón Ribeyro
Authors: Reis Ana Gabriela Petillo Faversani
Published: January 2018

O escritor Julio Ramón Ribeyro foi um dos principais cronistas da realidade urbana do Peru do século passado. Mais do que retratar as cidades de que falava, o autor opera, a partir de sua memória, um efeito de recriação destas cidades dentro do universo da ficção que, embora mantenha referências reconhecíveis, confere a cada uma destas cidades um outro lugar simbólico e cheio de novos significados. Este texto pretende explorar os mecanismos envolvidos neste efeito de justaposição entre real e imaginário nas narrativas breves de Ribeyro, amparado no conceito de heterotopia, de Foucault e nas premissas da Teoria Literária e da Análise do Discurso.
O gênero fantástico e a ficção como ponte em La vista desde el puente, de Ramiro Sanchiz
Authors: Borges Eulálio Marques , Chiappara Juan Pablo
Published: January 2018

Este trabalho apresenta os resultados de uma pesquisa de Iniciação Científica realizada no Departamento de Letras da Universidade Federal de Viçosa, Minas Gerais, e foca uma discussão sobre o romance uruguaio contemporâneo La vista desde el puente, de Ramiro Sanchiz. Neste artigo propomos uma leitura contextualizada no processo de renovação da literatura uruguaia, que busca romper com a tradição predominantemente realista no Uruguai. Deste modo, postulamos que a literatura fantástica, tal como a propõe Sanchiz e outros escritores uruguaios, engloba a ficção científica e se distancia de certas formas de não realismo precedentes dentro da América Latina. No caso concreto do romance analisado, Sanchiz desconstrói a figura mítica do herói nacional uruguaio Artigas e a ideia do Uruguai como a Suíça da América e propõe uma ficção que dialoga com a tradição borgeana de fantástico para desconstruir certos clichês da história nacional e das práticas literárias mais frequentadas em seu país.