bluuebunny/crossref_metadata_2025 huggingface dataset:
The integration of visual and target signals in V4 and IT during visual object search
Authors: Roth Noam , Rust Nicole C.
Published: October 2019

Searching for a specific visual object requires our brain to compare the items in view with a remembered representation of the sought target to determine whether a target match is present. This comparison is thought to be implemented, in part, via the combination of top-down modulations reflecting target identity with feed-forward visual representations. However, it remains unclear whether top-down signals are integrated at a single locus within the ventral visual pathway (e.g., V4) or at multiple stages [e.g., both V4 and inferotemporal cortex (IT)]. To investigate, we recorded neural responses in V4 and IT as rhesus monkeys performed a task that required them to identify when a target object appeared across variation in position, size, and background context. We found nonvisual, task-specific signals in both V4 and IT. To evaluate whether V4 was the only locus for the integration of top-down signals, we evaluated several feed-forward accounts of processing from V4 to IT, including a model in which IT preferentially sampled from the best V4 units and a model that allowed for nonlinear IT computation. IT task-specific modulation was not accounted for by any of these feed-forward descriptions, suggesting that during object search, top-down signals are integrated directly within IT.

NEW & NOTEWORTHY To find specific objects, the brain must integrate top-down, target-specific signals with visual information about objects in view. However, the exact route of this integration in the ventral visual pathway is unclear. In the first study to systematically compare V4 and inferotemporal cortex (IT) during an invariant object search task, we demonstrate that top-down signals found in IT cannot be described as being inherited from V4 but rather must be integrated directly within IT itself.
Neural and muscular determinants of maximal rate of force development
Authors: Dideriksen Jakob L. , Del Vecchio Alessandro , Farina Dario
Published: October 2019

The ability to produce rapid forces requires quick motor unit recruitment, high motor unit discharge rates, and fast motor unit force twitches. The relative importance of these parameters for maximum rate of force development (RFD), however, is poorly understood. In this study, we systematically investigated these relationships using a computational model of motor unit pool activity and force. Across simulations, neural and muscular properties were systematically varied in experimentally observed ranges. Motor units were recruited over an interval starting from contraction onset (range: 22–233 ms). Upon recruitment, discharge rates declined from an initial rate (range: 89–212 pulses per second), with varying likelihood of doublet (interspike interval of 3 ms; range: 0–50%). Finally, muscular adaptations were modeled by changing average twitch contraction time (range: 42–78 ms). Spectral analysis showed that the effective neural drive to the simulated muscle had smaller bandwidths than the average motor unit twitch, indicating that the bandwidth of the motor output, and thus the capacity for explosive force, was limited mainly by neural properties. The simulated RFD increased by 1,050 ± 281% maximal voluntary contraction force per second from the longest to the shortest recruitment interval. This effect was more than fourfold higher than the effect of increasing the initial discharge rate, more than fivefold higher than the effect of increasing the chance of doublets, and more than sixfold higher than the effect of decreasing twitch contraction times. The simulated results suggest that the physiological variation of the rate by which motor units are recruited during ballistic contractions is the main determinant for the variability in RFD across individuals.

NEW & NOTEWORTHY An important limitation of human performance is the ability to generate explosive movements by means of rapid development of muscle force. The physiological determinants of this ability, however, are poorly understood. In this study, we show using extensive simulations that the rate by which motor units are recruited is the main limiting factor for maximum rate of force development.
A Noninvasive Aid for Office-Based Gynecologists for the Diagnosis of Common External Genital Disorders
Authors: Giuffrida Giorgia , Lacarrubba Francesco , Boscaglia Simona , Nasca Maria Rita , Micali Giuseppe
Published: October 2019

Background. Gynecology and dermatology share the diagnosis and the management of some disorders of the female external genital area. In the last decade, clinical diagnosis in dermatology has dramatically improved, thanks to the introduction of dermatoscopy. Technique. Dermatoscopy is a noninvasive, rapid, and simple technique performed with an affordable handheld instrument called dermatoscope, endowed with a light source and a high-quality lens achieving 10 times magnification. Experience. The use of dermatoscopy for the diagnosis of some common external genital disorders, i.e., genital warts (GW), vestibular papillomatosis (VP), molluscum contagiosum (MC), angiokeratoma (AK), and pediculosis pubis (PP), is presented and discussed. Conclusion. The use of dermatoscopy in a gynecologic office may considerably help the specialist to enhance in selected cases the clinical diagnosis and to avoid unnecessary and cumbersome investigations which may be time and money consuming.
Tuberculosis at Farmer-Cattle Interface in the Rural Villages of South Gondar Zone of Northwest Ethiopia
Authors: Alelign Amir , Zewude Aboma , Petros Beyene , Ameni Gobena
Published: October 2019

Background. Tuberculosis (TB) has been an important public health concern in Ethiopia, particularly at areas of human-animal intersection. However, limited epidemiological information is available in this respect in the country. Therefore, the present study was conducted to investigate the transmission of TB at human-cattle interface, associated risk factors and public awareness about the disease at South Gondar Zone, northwest Ethiopia. Methods. A cross sectional study was conducted between March 2015 and April 2018 on 186 farmers and 476 cattle in South Gondar Zone, northwest Ethiopia. Bacteriological examination, region of difference (RD) 9-based polymerase chain reaction (PCR), single intradermal comparative tuberculin test (SICTT), and questionnaire were used for undertaking this study. Results. Culture positivity in farmers was 59.7% (111/186) and all the culture positive isolates were M. tuberculosis. About 68% (74/111) of culture positive respondents did not know about the transmission of TB from cattle to human or vice versa. The animal and herd prevalence of bovine TB were 1.5% (7/476) and 7.4% (7/95), respectively. Although the result was not statistically significant, the odds of bovine TB in cattle owned by TB positive households was slightly higher than those owned by TB free households (adjusted odds ratio, AOR = 1.39; 95% CI: 0.31–7.10; p=0.76). Conclusion. Although SIDCTT reactivity was slightly higher in cattle owned by TB positive households, all the human isolates were M. tuberculosis and no M. bovis was isolated from farmers, which could be due to the low prevalence of bovine TB in the area.
Regulation of Neural Stem Cell Proliferation and Differentiation by Graphene-Based Biomaterials
Authors: Xia Lin , Zhu Wenjuan , Wang Yunfeng , He Shuangba , Chai Renjie
Published: October 2019

The transplantation of neural stem cells (NSCs) has become an emerging treatment for neural degeneration. A key factor in such treatments is to manipulate NSC behaviors such as proliferation and differentiation, resulting in the eventual regulation of NSC fate. Novel bionanomaterials have shown usefulness in guiding the proliferation and differentiation of NSCs due to the materials’ unique morphological and topological properties. Among the nanomaterials, graphene has drawn increasing attention for neural regeneration applications based on the material’s excellent physicochemical properties, surface modifications, and biocompatibility. In this review, we summarize recent works on the use of graphene-based biomaterials for regulating NSC behaviors and the potential use of these materials in clinical treatment. We also discuss the limitations of graphene-based nanomaterials for use in clinical practice. Finally, we provide some future prospects for graphene-based biomaterial applications in neural regeneration.
An Isolated Hypogonadotropic Hypogonadism due to a L102P Inactivating Mutation of KISS1R/GPR54 in a Large Family
Authors: Alzahrani Ahmad J. , Ahmad Azzam , Alhazmi Tariq , Ahmad Lujin
Published: October 2019

KISS1R (GPR54) mutations have been reported in several patients with congenital normosmic idiopathic hypogonadotropic hypogonadism (nIHH). We aim to describe in detail nIHH patients with KISS1R (GPR54) mutations belonging to one related extended family and to review the literature. A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in three affected kindred (2 males and 1 female) from a consanguineous Saudi Arabian family. This residue is localized within the first exoloop of the receptor, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs its function. In the affected female, a combined gonadotropin administration restored regular period and ovulation and she conceived with a healthy baby boy after 4 years of marriage. We showed that a loss-of-function mutation (p.Tyr305C) in the KISS1R gene can cause (L102P) KISS1 receptor dysfunction and familial nIHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of periods and later on pregnancy by an exogenous gonadotropin administration further support, in humans, that the KISS1R mutation has no other harmful effects on the patients apart from the gonadotropin secretion impairment.
Formation of Incrustations during the Cocombustion of Biomass in Fluidised Bed Boilers
Authors: Buryan Petr
Published: October 2019

In this article, we focus on causes of formation of incrustations in fluidised bed boilers that result from combustion of biomass-containing energy-producing raw materials and can significantly limit the efficiency of the respective power equipment operation. We applied laboratory procedures followed for assessment of characteristic eutectics of mixtures of coal ashes, desulphurisation components (dolomite and limestone), and woodchip ashes. Our analysis proved that combustion of these (or similar) raw materials, accompanied by repeated heating and cooling of combustion and flue gas desulphurisation products, leads to the formation of unfavourable incrustations. These incrustations can grow up to several tens of centimetres in size, thereby significantly restricting the power equipment functionality. They arise due to incrust reheating that results in the formation of eutectics, which have lower melting temperatures than that during their first pass through the combustion process. The same holds for desulphuriation components themselves. Formation of these new eutectics can be attributed both to recycling of substances produced during the first pass through the furnace as well as to mixtures formed both from recycled materials and from components initially combusted in the boiler furnace.
Vibration Theoretical Analysis of Elastically Connected Multiple Beam System under the Moving Oscillator
Authors: He Binbin , Feng Yulin
Published: October 2019

To investigate the vibration analysis of elastically connected multiple beam system (ECMB) under the moving oscillator, finite sine‐Fourier transform has been applied to the dynamic partial differential equations of ECMB with respect to space coordinates. Then, the numerical integration has been used to solve the equations. Finally, the expression for vibration analysis of ECMB under the moving oscillator has been derived based on finite sine‐Fourier inverse transform. Using the method developed in this study and ANSYS numerical method, the vibration analysis of a four‐layer beam system under moving oscillator with different speeds has been calculated. The results show that the calculated results from the method developed in this study are in good agreement with the ANSYS numerical calculation results, and the differences between the two calculation results are all less than 2%, which verified the correctness of the method developed in this study. The method developed in this study has been applied to the beam‐rail system on a railway line in China. The effect of the train speed and interlayer stiffness on the vibration of beam‐rail system has been investigated. The results show that the maximum dynamic deflection of the rail under the train load is always near the midspan, while the maximum dynamic deflections of the track plate, base plate, and bridge occur after the train travel through the midspan. The interlayer stiffness has a larger impact on the vibration of the rail and the track plate and little impact on the vibration of the base plate and the bridge.
Stability Analysis and Monitoring Method for the Key Block Structure of the Basic Roof of Noncoal Pillar Mining with Automatically Formed Gob‐Side Entry
Authors: Liu Jianning , He Manchao , Wang Yajun , Huang Ruifeng , Yang Jun , Tian Xichun , Ming Can , Guo Shan
Published: October 2019

The key block of the basic roof is the main contributor to the structural stability of a roadway. Research on the stability of the key block structure is of great significance for the promotion of noncoal pillar mining with automatically formed gob‐side entry (GEFANM) technology. This paper is set in the engineering context of the GEFANM experiment at the Ningtiaota Coal Mine. The study fully considered the differences in the gob roof caving on the roof‐cutting‐line side, and the range of rotation angles to maintain a stable key block was determined. Based on this range of rotation angles, the range of safe bulking coefficients of gangue was calculated. The bulking coefficient of the gangue on the gravel side of the roadway was used as the metric in a new monitoring method and in the calculation of the field parameters. The range of safe bulking coefficients was determined to be 1.40–1.37. Field monitoring was conducted to obtain the gangue bulking coefficient on the gravel side. Combining the roof and floor convergence data, when the bulking coefficient fell within the safe range, the convergence was 95–113 mm. In this stage, the key block structure was stable. When the gangue bulking coefficient fell outside the safe range, the convergence was larger, and cracks were observed. The key block may be vulnerable to instability. The results affirmed that the gangue bulking coefficient can be used as a monitoring metric to study the stability of key block structures.
Airway Compromise due to Retropharyngeal Emphysema–A Rare Complication of an Extravasated Peripherally Inserted Central Venous Catheter
Authors: Licina Ana
Published: October 2019

A 48-year-old woman was scheduled for flexible bronchoscopy, video-assisted thoracoscopic surgery and mediastinal washout. She had developed voice changes, difficulty swallowing, shortness of breath with a fever and increased respiratory rate in intensive care unit 12 days after a double liver and kidney transplantation. Computerised tomography of neck and chest demonstrated extensive retropharyngeal and subcutaneous emphysema, laryngeal distortion and pneumo-mediastinum; however, the causative factors were not immediately obvious. Intraoperatively, an un-anticipated diagnosis of extravasated peripherally inserted central venous cannula (PICC) was made. Total parenteral nutrition had extravasated into the mediastinum and thorax. Subsequent inflammation and infection resulted in air pocket formation. The retropharyngeal air pockets were caused by mediastinal emphysema tracking through the tissue planes to the anterior and posterior larynx. Awareness of the tip position and accompanying clinical and radiological enquiry, must be performed prior to use of PICC lines in critically ill patients.
Prediction of Breast Cancer from Imbalance Respect Using Cluster-Based Undersampling Method
Authors: Zhang Jue , Chen Li , Abid Fazeel
Published: October 2019

To overcome the two-class imbalanced problem existing in the diagnosis of breast cancer, a hybrid of K-means and Boosted C5.0 (K-Boosted C5.0) is proposed which is based on undersampling. K-means is utilized to select the informative samples near the boundary. During the training phase, the K-means algorithm clusters the majority and minority instances and selects a similar number of instances from each cluster. Boosted C5.0 is then used as the classifier. As there is one different instance selection factor via clustering that encourages the diversity of the training subspace in K-Boosted C5.0, it would be a great advantage to get better performance. To test the performance of the new hybrid classifier, it is implemented on 12 small-scale and 2 large-scale datasets, which are the often used datasets in class imbalanced learning. The extensive experimental results show that our proposed hybrid method outperforms most of the competitive algorithms in terms of Matthews’ correlation coefficient (MCC) and accuracy indices. It can be a good alternative to the well-known machine learning methods.
A Novel Triangular Element with Continuous Nodal Acoustic Pressure Gradient for Acoustic Scattering Problems
Authors: Chai Yingbin , Li Wei , Zhang Yong-Ou
Published: October 2019

To improve the performance of the standard finite element (FE) method in acoustic simulation, a novel triangular element with continuous nodal acoustic pressure gradient (FEM‐T3‐CNG) is presented to solve two‐dimensional underwater acoustic scattering problems. In this FEM‐T3‐CNG model, the local approximation (LA) is represented by using the least‐squares (LS) scheme, and the standard FE shape functions are employed to satisfy the partition of unity (PU) concept. In order to possess the important delta Kronecker property, the constrained orthonormalized LS (CO‐LS) is utilized to construct the hybrid nodal shape functions. Incorporating the present FEM‐T3‐CNG element with the proper nonreflecting boundary condition, the two‐dimensional underwater acoustic scattering problems in the infinite domain could be solved ultimately. The numerical results show that the present FEM‐T3‐CNG element behaves much better than the standard FEM‐T3 element in terms of computation accuracy and can be regarded as a good alternative approach in exterior acoustic computation.
Adaptive Optimizing Control for Nonlinear Synchronous Generator System with Uncertain Disturbance
Authors: Deng Guiyang , Cheng Lianglun , Yang Baojian
Published: October 2019

In this paper, an adaptive optimizing control is proposed for nonlinear synchronous generator system with uncertain disturbance. Considering the issue of uncertain item, a low‐order Extended State Observer (ESO) is constructed to track each order states. Then, combining Backstepping technology and proposed ESO, a dynamic compensation control is designed to compensate the uncertainty disturbance in each state quantity. The proposed method demonstrated that stability of the system can be ensured, and tracking burden of ESO can be reduced. Finally, simulation results can show a good tracking performance and anti‐interference ability by the proposed control method.
Study on miRNAs in Pan-Cancer of the Digestive Tract Based on the Illumina HiSeq System Data Sequencing
Authors: Lai Chun-hui , Liang Xu-zhi , Liang Xiu-yun , Ma Sheng-jun , Li Jun-guo , Shi Ming-fang , Zhu Xu , Lan Hui-hua , Zeng Jiang-hui
Published: October 2019

Objective. miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ). Materials and Methods. After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs’ target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan–Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development. Results. Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway. Conclusion. The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.
Effect of 12-Month Resistance Training on Changes in Abdominal Adipose Tissue and Metabolic Variables in Patients with Prediabetes: A Randomized Controlled Trial
Authors: Yan Juan , Dai Xia , Feng Jitao , Yuan Xiaodan , Li Jianing , Yang Lihong , Zuo Panpan , Fang Zhaohui , Liu Chao , Hsue Cunyi , Zhu Junya , Miller Joshua D. , Lou Qingqing
Published: October 2019

Objective. To examine the effects of resistance training relative to aerobic training on abdominal adipose tissue and metabolic variables in adults with prediabetes. Methods. 105 participants with prediabetes were randomized into the resistance training group (RT, n=35), aerobic training group (AT, n=35), and control group (CG, n=35). The participants completed supervised 12-month exercise; the control group followed the primary lifestyle without exercise intervention. The primary outcomes were visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by computed tomography (CT). Secondary outcomes were body composition, lipid profile, and metabolic variables. Results. A total of 93 participants completed the study. There were nonsignificant differences between groups before intervention. After training, VAT decreased significantly in AT and RT compared with CG (P=0.001 and P=0.014, respectively). Although no significant difference in SAT was found across groups, SAT decreased significantly over time within each exercise group (all P=0.001). Increase in muscle mass was greater in RT than that in AT and CG (P=0.031 and P=0.045, respectively). Compared with CG, fasting plasma glucose (FPG) decreased significantly in RT and AT (P=0.003 and P=0.014, respectively). There was a significant difference in the number of prediabetes who converted to diabetes among AT and RT, as compared with the control group (P=0.031 and P=0.011, respectively). No significant differences were observed in lipid, waist-to-hip ratio (WHR), body mass index (BMI), fasting insulin (FI), 2-hour postprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), HOMA-IR, and HOMA-β across groups. Conclusion. Both aerobic training and resistance training are effective in reducing abdominal adipose tissue and fasting plasma glucose in adults with prediabetes. Importantly, resistance training but not aerobic training is effective in augmenting muscle mass. Trial Registration. The trial is registered with NCT02561377 (date of registration: 24/09/2015).
Effect of the Floor Level on the Probability of a Neurologically Favorable Discharge after Cardiac Arrest according to the Event Location
Authors: Choi Han Joo , Moon Hyung Jun , Jeong Won Jung , Kim Gi Woon , Woo Jae Hyug , Lee Kyoung Mi , Choi Hyuk Joong , Park Yong Jin , Lee Choung Ah
Published: October 2019

As the number of people living in high-rise buildings increases, so does the incidence of cardiac arrest in these locations. Changes in cardiac arrest location affect the recognition of patients and emergency medical service (EMS) activation and response. This study aimed to compare the EMS response times and probability of a neurologically favorable discharge among patients who suffered an out-of-hospital cardiac arrest (OHCA) event while on a high or low floor at home or in a public place. This retrospective analysis was based on Smart Advanced Life Support registry data from January 2016 to December 2017. We included patients older than 18 years who suffered an OHCA due to medical causes. A high floor was defined as ≥3rd floor above ground. We compared the probability of a neurologically favorable discharge according to floor level and location (home vs. public place) of the OHCA event. Of the 6,335 included OHCA cases, 4,154 (65.6%) events occurred in homes. Rapid call-to-scene times were reported for high-floor events in both homes and public places. A longer call-to-patient time was observed for home events. The probability of a neurologically favorable discharge after a high-floor OHCA was significantly lower than that after a low-floor OHCA if the event occurred in a public place (adjusted odds ratio (aOR), 0.58; 95% confidence intervals (CI), 0.37–0.89) but was higher if the event occurred at home (aOR, 1.40; 95% CI, 0.96–2.03). Both the EMS response times to OHCA events in high-rise buildings and the probability of a neurologically favorable discharge differed between homes and public places. The results suggest that the prognosis of an OHCA patient is more likely to be affected by the building structure and use rather than the floor height.
Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer
Authors: Li Lan , Yu Chaohui
Published: October 2019

The role of Helicobacter pylori (H. pylori) infection in patients following endoscopic resection of early gastric cancer (EGC) remains unclear. This article presents a review of literature published in the past 15 years. H. pylori‐mediated persistent methylation levels are associated with the development of metachronous gastric cancer. The methylation of certain specific genes can be used to identify patients with a high risk of metachronous gastric cancer even after H. pylori eradication. H. pylori eradication after endoscopic resection should be performed as early as possible for eradication success and prevention of metachronous precancerous lesions. Although whether the eradication of H. pylori could prevent the development of metachronous cancer after endoscopic resection is controversial, several meta‐analyses concluded that H. pylori eradication could reduce the incidence of metachronous gastric cancer significantly. In addition, H. pylori eradication in gastric cancer survivors after endoscopic resection could reduce healthcare cost and save lives in a cost‐effective way. Taken together, H. pylori eradication after endoscopic resection of EGC is recommended as prevention for metachronous precancerous lesions and metachronous gastric cancer.
Increased Risk of Chronic Myeloid Leukemia Following Gastric Conditions IndicatingHelicobacter pyloriInfection: A Case–Control Study
Authors: Larfors Gunnar , Richter Johan , Själander Anders , Stenke Leif , Höglund Martin
Published: October 2019

Background:

On the basis of a previous report of increased chronic myeloid leukemia (CML) risk following peptic ulcer, we hypothesized that chronic Helicobacter pylori infection could serve as a risk factor for CML.

Methods:

In a population-based, retrospective case–control study, we used Swedish registry data on 980 patients with CML and 4,960 age- and sex-matched controls to investigate associations between markers of previous infection with Helicobacter pylori and CML incidence.

Results:

Previous diagnoses of dyspepsia, gastritis or peptic ulcers, as well as previous proton pump inhibitor (PPI) medication, were all associated with a significantly increased risk of CML (RRs, 1.5–2.0; P = 0.0005–0.05). Meanwhile, neither inflammatory bowel disease nor intake of NSAIDs were associated with CML, indicating that it is not gastrointestinal ulcer or inflammation per se that influences risk.

Conclusions:

The consistent associations suggest a shared background between gastric conditions and CML, and strengthen the case that Helicobacter pylori could constitute this common risk factor.

Impact:

As the etiology of CML is practically unknown, and Helicobacter pylori could potentially be a therapeutic target, even this indirect evidence encourages further studies on the potential involvement of Helicobacter pylori in CML etiology.
Functional Genomic Screen in Mesothelioma Reveals that Loss of Function of BRCA1-Associated Protein 1 Induces Chemoresistance to Ribonucleotide Reductase Inhibition
Authors: Okonska Agata , Bühler Saskja , Rao Vasundhara , Ronner Manuel , Blijlevens Maxime , van der Meulen-Muileman Ida H. , de Menezes Renee X. , Wipplinger Martin , Oehl Kathrin , Smit Egbert F. , Weder Walter , Stahel Rolf A. , Penengo Lorenza , van Beusechem Victor W. , Felley-Bosco Emanuela
Published: October 2019

Loss of function of BRCA1-associated protein 1 (BAP1) is observed in about 50% of malignant pleural mesothelioma (MPM) cases. The aim of this study was to investigate whether this aspect could be exploited for targeted therapy. A genetically engineered model was established expressing either functional or nonfunctional BAP1, and whole-genome siRNA synthetic lethality screens were performed assessing differentially impaired survival between the two cell lines. The whole-genome siRNA screen unexpectedly revealed 11 hits (FDR < 0.05) that were more cytotoxic to BAP1-proficient cells. Two actionable targets, ribonucleotide reductase (RNR) catalytic subunit M1 (RRM1) and RNR regulatory subunit M2 (RRM2), were validated. In line with the screen results, primary mesothelioma (BAP1+/−) overexpressing BAP1 C91A (catalytically dead mutant) was more resistant to RNR inhibition, while BAP1 knockdown in the BAP1-proficient cell lines rescued the cells from their vulnerability to RNR depletion. Gemcitabine and hydroxyurea were more cytotoxic in BAP1-proficient cell line–derived spheroids compared with BAP1 deficient. Upregulation of RRM2 upon gemcitabine and hydroxyurea treatment was more profound in BAP1 mut/del cell lines. Increased lethality mediated by RNR inhibition was observed in NCI-H2452 cells reconstituted with BAP1-WT but not with BAP1 C91A. Upregulation of RRM2 in NCI-H2452-BAP1 WT spheroids was modest compared with control or C91A mutant. Together, we found that BAP1 is involved in the regulation of RNR levels during replication stress. Our observations reveal a potential clinical application where BAP1 status could serve as predictive or stratification biomarker for RNR inhibition-based therapy in MPM.
A TFAP2C Gene Signature Is Predictive of Outcome in HER2-Positive Breast Cancer
Authors: Wu Vincent T. , Kiriazov Boris , Koch Kelsey E. , Gu Vivian W. , Beck Anna C. , Borcherding Nicholas , Li Tiandao , Addo Peter , Wehrspan Zachary J. , Zhang Weizhou , Braun Terry A. , Brown Bartley J. , Band Vimla , Band Hamid , Kulak Mikhail V. , Weigel Ronald J.
Published: October 2019

The AP-2γ transcription factor, encoded by the TFAP2C gene, regulates the expression of estrogen receptor-alpha (ERα) and other genes associated with hormone response in luminal breast cancer. Little is known about the role of AP-2γ in other breast cancer subtypes. A subset of HER2+ breast cancers with amplification of the TFAP2C gene locus becomes addicted to AP-2γ. Herein, we sought to define AP-2γ gene targets in HER2+ breast cancer and identify genes accounting for physiologic effects of growth and invasiveness regulated by AP-2γ. Comparing HER2+ cell lines that demonstrated differential response to growth and invasiveness with knockdown of TFAP2C, we identified a set of 68 differentially expressed target genes. CDH5 and CDKN1A were among the genes differentially regulated by AP-2γ and that contributed to growth and invasiveness. Pathway analysis implicated the MAPK13/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses in different HER2+ cancer lines. To confirm the clinical relevance of the genes identified, the AP-2γ gene signature was found to be highly predictive of outcome in patients with HER2+ breast cancer. We conclude that AP-2γ regulates a set of genes in HER2+ breast cancer that drive cancer growth and invasiveness. The AP-2γ gene signature predicts outcome of patients with HER2+ breast cancer and pathway analysis predicts that subsets of patients will respond to drugs that target the MAPK or retinoic acid pathways.

Implications:

A set of genes regulated by AP-2γ in HER2+ breast cancer that drive proliferation and invasion were identified and provided a gene signature that is predictive of outcome in HER2+ breast cancer.
E-Cigarettes and Cancer Risk
Authors: Mravec Boris , Tibensky Miroslav , Horvathova Lubica , Babal Pavel
Published: October 2019

From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.
Anomalous Pigmentation in Invasive and Native Marmosets, Callithrix jacchus, Callithrix penicillata (Primates, Callitrichidae), and Their Hybrids in Brazil
Authors: Aximoff Izar , Zaluar Marina T. , Pissinatti Alcides , Bastos Paulo Alfredo , Morais Tatiania de Assis , da Rosa Clarissa Alves , Oliveira Leonardo C. , Teixeira Danilo Simonini , Vale Mariana M.
Published: October 2019

Leucism is the lack or reduction in pigmentation in the most or parts of the body, but not in the eyes and body extremities. It is extremely rare in primates and has never been reported for Callithrix, a genus endemic to Brazil. We searched for individuals of Callithrix jacchus and C. penicillata with pigmentation anomalies in a systematic survey of three protected areas in the Atlantic Forest, within museum collections in Brazil, and opportunistically during field studies. Since 2008, we have recorded 8 individuals with leucism in small urban and periurban forest patches. Four were from native populations of C. penicillata in Cerrado savannahs and of C. jacchus in the Caatinga xeric scrubland, and 4 were from populations of hybrids between C. jacchus and C. penicillata in invaded areas in the coastal Atlantic Forest. We found no pigmentation abnormalities in museum specimens. We hypothesize that the observed leucism may be linked to inbreeding within the native range, but to hybridization within the invaded range, and discuss the likely ecological consequences to leucistic individuals.
Efficacy of Desloratadine and Levocetirizine in Patients with Cedar Pollen-Induced Allergic Rhinitis: A Randomized, Double-Blind Study
Authors: Yonekura Syuji , Okamoto Yoshitaka , Sakurai Daiju , Iinuma Tomohisa , Sakurai Toshioki , Yoneda Riyo , Kurita Junya , Hanazawa Toyoyuki , Kawasaki Yohei
Published: October 2019

Background: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. Objective: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. Methods: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. Results: The difference in TNSS from placebo was –2.42 (p < 0.0001) with levocetirizine and –1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. Conclusion: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. Clinical Trial Registration number: UMIN ID: UMIN000029653.
Toxocara Optic Disc Granuloma: Deep Range Imaging Optical Coherence Tomography Findings
Authors: Karska-Basta Izabella , Kubicka-Trząska Agnieszka , Chrząszcz Michał , Pociej-Marciak Weronika , Romanowska-Dixon Bożena
Published: October 2019

We aimed to present a unique case of a child with an optic disc granuloma with exudative retinal detachment as a manifestation of ocular toxocariasis. The response to systemic therapy was assessed using deep range imaging optical coherence tomography. This imaging technique was the most accurate for identification of retinal, macular and vitreous changes associated with this intraocular pathology.
Mortality Risk among Cocaine Users before and after the Economic Recession: Results of a Longitudinal Study
Authors: Pavarin Raimondo Maria , Sanchini Samantha , Marani Silvia , Turino Elsa , Tadonio Leonardo , Cantarelli Barbara
Published: October 2019

Background: Studies have highlighted 2 different groups of cocaine users (CUs): “socially integrated” (stable living conditions, regular employment, use cocaine alone or in combination with other psychoactive substances) and “socially marginalized” (socioeconomic and health problems, former or current heroin users, many injecting cocaine). These differences are also found in the elevated mortality risk for CUs, higher among subjects with cocaine and heroin use. This study targeted residents in Northern Italy who turned to a public treatment center for drug addiction following problems caused by primary cocaine use between 1982 and 2016. Objectives: To estimate mortality risk for subjects who have never used heroin (CUs) compared to that of subjects who have used heroin (HCUs). Method: Retrospective cohort study. We selected 1,993 subjects; 18,015 Person Years (PY). Results: Over time, the quota of subjects injecting cocaine and using heroin decreased, while patients not using heroin increased. Both new patients and crude mortality rates (CMR) decreased during the years 2009–2012 and increased in the following period. CMRs were 5.55 per 1,000 PY, higher for HCUs, men and subjects aged over 44 years. Standardized mortality rates were 3.49, higher for women, injecting cocaine and HCUS. Among CUs, most of the deaths were from injury excluding drug related and tumors; among HCUs, from drug-related causes and diseases of the cardiovascular system. Conclusion: The study results show a change in the characteristics of SERD clients being treated for primary cocaine use, which are reflected both in mortality risk and causes of death. After a long period of a decrease, mortality risk increased in the period after the economic recession. Aspects concerning the effects of the economic recession on the problematic consumption of cocaine and on the risk of death are discussed.
Late Detection of Atrial Fibrillation after Stroke: Implications for the Secondary Prevention
Authors: Tanislav Christian , Kostev Karel
Published: October 2019

Background: This study is aimed at investigating the incidence of atrial fibrillation (AF) within 5 years after an acute cerebrovascular event in AF-naive patients and its relevance for secondary prevention. Methods: The current case-control study sample included patients who had received an initial ischemic stroke diagnosis documented in the Disease Analyzer database (IQVIA), which compiles data such as risk factors, drug prescriptions, and diagnoses obtained from 1,262 general practices in Germany. Results: After the selection procedure, the stroke and non-stroke groups each included 22,774 patients. In both groups, the mean age of the population was 68.0 years (SD ±12 years), and the proportion of male participants was 51.1%. Within 5 years of follow-up, we calculated a higher probability for detecting AF in stroke patients than in controls (hazard ratio 4.95; 95% CI 1.93–2.09, p < 0.001). In the stroke group, AF was detected in 2,369 individuals (10.4%), whereas AF was only evident in 1,101 patients (4.8%) in the non-stroke group. In 1,741 (73.5%) patients (out of 2,369), oral anticoagulants had been prescribed after the AF diagnosis. In stroke patients, factors like diabetes mellitus and ischemic heart disease were associated with restraint in prescribing oral anticoagulants; age did not influence the decision for or against oral anticoagulants (mean age 72.9 vs. 72.7 years). Conclusion: A recent stroke is a strong preconditioning factor for detecting AF within 5 years after an acute event. The majority of these patients are treated with oral anticoagulants, regardless of their age.
Морфологічні зміни в нирках за умов гострого поширеного перитоніту на тлі цукрового діабету
Authors: Dzubanovsky I. Ya. , Verveha B. M. , Pidruchna S. R. , Melnyk N. A.
Published: October 2019

Мета роботи: дослідити морфологічні зміни в нирках піддослідних тварин при змодельованому гострому поширеному перитоніті на тлі цукрового діабету порівняно із тваринами з експериментальним гострим поширеним перитонітом.

Матеріали і методи. В експерименті використано 56 білих щурів. Цукровий діабет моделювали шляхом внутрішньоочеревинного введення стрептозотоцину фірми “Sigmal” з розрахунку 7 мг на 100 г маси тварини, гострий поширений перитоніт – введенням 0,5 мл 10 % профільтрованої калової суспензії в черевну порожнину досліджуваних тварин. Досліджували тканину нирки 1, 3, 7 доби від початку моделювання перитоніту.

Результати досліджень та їх обговорення. У тварин із гострим поширеним перитонітом на тлі цукрового діабету патоморфологічні зміни були більш виражені: судини венозного русла дещо розширювались, були повнокровні, візуалізувались дрібні периваскулярні точкові крововиливи. Більшість вивідних канальців були розширені, проте їх просвіти були вільні від ексудату. В петлях Генле і прямих канальцях ми спостерігали виражений набряк епітелію. У тварин із гострим поширеним перитонітом на тлі цукрового діабету спостерігалися більш виражені патоморфологічні зміни у тканині нирок у всі терміни спостереження порівняно із групою тварин, яким не моделювали цукровий діабет, що характеризувалися периваскулярним набряком, збільшенням та розширенням судинного просвіту, наявністю серозного ексудату.
Активність каталази та супероксиддисмутази на тлі експериментальної ішемії-реперфузії кінцівки
Authors: Volotovska N. V. , Zarichna O. Yo. , Kuzmak I. P.
Published: October 2019

Мета роботи: встановити динаміку активності супероксиддисмутази та каталази нирок на тлі модифікацій ішемічнореперфузійного синдрому (ІРС).

Матеріали і методи. У експерименті використовували 210 нелінійних білих щурів-самців віком 5–5,5 місяця. Досліджено динаміку активності антиоксидних ферментів (каталаза (Кат), супероксиддисмутаза (СОД)) у тканині нирки в умовах моделювання модифікацій ішемічно-реперфузійного синдрому (ІРС). Забір зразків тканини здійснювали через 24 години, на 3, 7, 14 доби після травми. Щури виведені з експерименту методом тотального кровопускання з верхівки серця.

Результати досліджень та їх обговорення. У наших моделях ІРС рівень Кат в основному зменшувався в кожному періоді експерименту. Пік активності СОД спостерігався на 1, 3 добу або пригнічення (здебільшого на 3 добу) після експериментального ІРС – згідно з модифікаціями ступенів тяжкості травми. Таким чином, застосування кровоспинного джгута в поєднанні з втратою крові та механічною травмою спричиняли суттєві ураження антиоксидної системи нирок. При цьому навіть одноразове застосування джгута зумовлювало подібні хвилеподібні реакції. Загалом розвиток ІРС супроводжується сильним пригніченням антиоксидної системи нирки.
Гострі абсцеси легень та їх ускладнення: особливості перебігу та лікувальна тактика
Authors: Bedenyuk A. D. , Malovanyy V. V. , Viytovych L. E.
Published: October 2019

Мета роботи: підвищити ефективність комплексного лікування хворих на гострий абсцес легень.

Матеріали і методи. На базі відділення торакальної хірургії Тернопільської університетської лікарні за період 2014–2019 рр. проліковано 68 хворих із гострим абсцесом легень віком від 20 до 74 років.

Результати досліджень та їх обговорення. У лікуванні хворих використовували комплекс заходів, який включав антибактеріальну терапію, забезпечення дренажної функції бронхів, дезінтоксикацію та корекцію метаболічних порушень. За останні роки все частіше зустрічались тяжкі форми гнійних захворювань, які нерідко ускладнювались піопневмотораксом (у 18 хворих), емпіємою плеври (у 15 хворих), при яких проводилася пункція плевральної порожнини та дренування за Бюлау з подальшими санаціями антисептиками (діоксидин, хлоргексидин, декасан) тричі на день та активною аспірацією вмісту. При виникненні кровохаркання використовували препарати транексамової кислоти з гемостатичною метою. При арозивних кровотечах виконували ургентне операційне втручання (верхня лобектомія справа – у 2 пацієнтів). Тому перспективою подальших досліджень буде впровадження рентгенендоваскулярних методів зупинки арозивних кровотеч шляхом емболізації бронхіальних артерій, що надасть можливість стабілізувати стан хворого та підготувати до оперативного втручання, тим самим покращити прогноз лікування. Для покращення результатів лікування гострих абсцесів легень необхідний комплексний підхід з використанням сучасних консервативних та хірургічних методів.
Основи медичної статистики для науковців-початківців
Authors: Kashuba M. O.
Published: October 2019

Мета роботи: ознайомити науковців-початківців із можливостями медичної статистики. У статті викладено основні, базові терміни та поняття, необхідні для правильного планування статистичних досліджень.
Клінічний випадок складності діагностики та хірургічного лікування дивертикулу Меккеля
Authors: Kryzhevskyi V. V. , Znaievskyi M. I. , Bilyayeva O. O. , Kolomoitsev A. P.
Published: October 2019

У статті наведено випадок складності діагностики дивертикулу Меккеля, ускладненого некрозом та перфорацією дивертикулу, міжпетельним абсцесом, тонкокишковою декомпенсованою непрохідністю, загальним серозним перитонітом.