bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Evaluation and Prediction of Porous Implant Design and Flow Performance
Authors: Li Jian , Chen Diansheng , Luan Huiqin , Zhang Yingying , Fan Yubo
Published: June 2018

Porous structure has been widely acknowledged as important factor for mass transfer and tissue regeneration. This study investigates effect of aimed-control design on mass transfer and tissue regeneration of porous implant with regular unit cell. Two shapes of unit cells (Octet truss, and Rhombic dodecahedron) were selected, which have similar symmetrical structure and are commonly used in practice. Through parametric design, porous scaffolds with the strut sizes ofφ0.5, 0.7, 0.9, and 1.1mm were created, respectively. Then using fluid flow simulation method, flow velocity, permeability, and shear stress which could reflect the properties of mass transfer and tissue regeneration were compared and evaluated, and the relationships between porous structure’s physical parameters and flow performance were studied. Results demonstrated that unit cell shape and strut size greatly determine and influence other physical parameters and flow performances of porous implant. With the increasing of strut size, pore size and porosity linearly decrease, but the volume, surface area, and specific surface area increased. Importantly, implant with smaller strut size resulted in smaller flow velocity directly but greater permeability and more appropriate shear stress, which should be beneficial to cell attachment and proliferation. This study confirmed that porous implant with different unit cell shows different performances of mass transfer and tissue regeneration, and unit cell shape and strut size play vital roles in the control design. These findings could facilitate the quantitative assessment and optimization of the porous implant.
Safety and Accuracy of Core Needle Biopsy for Soft Tissue Masses in an Ambulatory Setting
Authors: Walker J. Brock , Stockwell Erin , Worhacz Kellen , Kang Paul , Decomas Amalia
Published: June 2018

Background. Percutaneous needle biopsy has been found to be a safe and accurate method for the initial investigation of soft tissue masses. The notion exists that needle biopsies should be performed in specialized sarcoma centers, which can place a financial burden on patients without a sarcoma center near their place of residence. There is no consensus in the current literature regarding the diagnostic accuracy and clinical utility of clinic-based percutaneous core needle biopsy performed by community orthopedic surgeons with fellowship training in musculoskeletal oncology.Questions/Purposes. Our primary goal was to determine if office-based core needle biopsy of soft tissue masses could safely yield accurate diagnoses when performed by a community orthopedic surgeon with fellowship training in musculoskeletal oncology.Patients and Methods. We retrospectively reviewed the charts of 105 patients who underwent percutaneous core needle biopsy of soft tissue masses in a community clinic. All procedures were performed by one fellowship-trained musculoskeletal oncologist. Accuracy of the initial clinic-based needle biopsy was determined through comparison to the results of pathological analysis of the surgically excised masses. Final data analysis included 69 patients who underwent both clinic-based biopsy and subsequent surgical excision of their masses.Results. We found clinic-based biopsies to be 87.0% accurate for exact diagnosis and 94.2% accurate in determining whether the mass was benign or malignant (p<0.0001). Minor complications related to the clinic-based biopsy occurred in 5.80% of cases, with no documentation of major complications.Conclusions. Our results provide evidence that office-based percutaneous biopsy can be administered safely and yield accurate, clinically useful results when performed by a fellowship-trained musculoskeletal oncologist.
Sclerotic Bone Metastasis in Pulmonary Adenocarcinoma
Authors: Ali Mohammed Hammamy Riyadh , Farooqui Khalid , Ghadban Wisam
Published: June 2018

Pulmonary adenocarcinoma is one of the major types of lung cancers in which metastasis is very common and it accounts approximately to one-third of all primary pulmonary cancers. Although a minority of patients with lung cancer are asymptomatic, which gets usually detected in routine chest radiography, most of the patients present with some symptoms. Lung cancer metastasis may occur virtually in every organ system. Patients with non-small-cell lung cancer commonly have extrathoracic metastases to the adrenal glands, liver, brain, bones, and lymph nodes at presentation. Approximately one-third of patients with lung cancer will present with symptoms related to extrathoracic spread. Metastasis to the bone is not uncommon in lung cancer; however, osteoblastic bone metastasis is very rare. Here we present a 30-year-old female diagnosed to have pulmonary adenocarcinoma with multiple sclerotic bony lesions in the vertebra.
Human Risk Assessment of Organochlorine Pesticide Residues in Vegetables from Kumasi, Ghana
Authors: Bolor Vincent Kwadwo , Boadi Nathaniel Owusu , Borquaye Lawrence Sheringham , Afful Samuel
Published: June 2018

The use of organochlorine pesticides has been banned worldwide due to their toxicities. However, some farmers use them illegally because of their potency. The aim of this study was to assess the level of organochlorine pesticide (OCP) residues and the potential health risk associated with vegetables, soil, and groundwater obtained from farms in Ayigya, Nsenie, Gyenyase, and Kentinkrono in Kumasi, Ghana. A total of 15 samples were analyzed using a gas chromatograph equipped with an electron capture detector. The highest mean concentration of 184.10 ± 12.11 µg/kg was recorded for methoxychlor in cabbage from Ayigya. Beta-hexachlorocyclohexane (beta-HCH) recorded the lowest mean concentration of 0.20 ± 0.00 µg/kg in cabbage from Ayigya. The combined risk index showed significant health risk to children than adults. The soil samples mainly contained methoxychlor followed by dichlorodiphenyltrichloroethane (DDT), aldrin, and other OCPs. Concentrations of total HCHs, total DDTs, and total OCPs in the soil samples ranged from <0.01 to 49.00, <0.01 to 165.81, and <0.01 to 174.91 µg/kg, respectively. Among all HCH and DDT isomers, only β-HCH and p,p′-DDT were detected in some of the water samples. Carcinogenic risk values for β-HCH, aldrin, and p,p′ DDT in the groundwater were found to be >10−6, posing a potentially serious cancer risk to consumers. Moreover, the hazard quotients (HQs) of aldrin exceeded the threshold value of one, indicating that daily exposure is a potential concern.
Biochemical and Histological Evaluation of Three Selected Medicinal Plant Extracts of Sri Lankan Origin on Dyslipidemia and Oxidative Stress in Alloxan Induced Diabetic Rats
Authors: Attanayake Anoja Priyadarshani , Jayatilaka Kamani Ayoma Perera Wijewardana , Mudduwa Lakmini Kumari Boralugoda , Pathirana Chitra
Published: June 2018

The objective of the present study was to investigate the effect of refluxed aqueous extracts ofGmelina arborea,Spondias pinnata, andCoccinia grandison atherogenicity and oxidative stress in rats with chemically induced type 1 diabetes mellitus. Alloxan monohydrate (150 mg/kg, intraperitoneal) was used to induce diabetes to Wistar rats. Thereafter, diabetic rats (n=6 per group) were treated with the three selected plant extracts at their optimum effective therapeutic doses and glibenclamide (0.50 mg/kg, positive control) for 30 days. Administration of the three extracts in diabetic rats exhibited antihyperglycemic, antiatherogenic, and antioxidant effects in diabetic rats on the 30th day of the study. The atherogenic and coronary risk indices were also reduced in support of the antiatherogenic effects. The results of the study revealed that the bark extracts ofG. arborea,S. pinnata, and leaf extract ofC. grandisexerted beneficial effects against dyslipidemia, atherogenicity, and oxidative stress in alloxan induced diabetic rats. The selected plant extracts would be beneficial for the development of food supplements targeting main complications associated with diabetes.
Nontyphi Salmonella Empyema with Bronchopleural Fistula in a Patient with Human Immunodeficiency Virus
Authors: Bretzing Douglas , Lat Tasnim , Shakespeare Andrew , Lee Mary , Surani Salim , Ghamande Shekhar
Published: June 2018

Patients with human immunodeficiency virus (HIV) have an increased risk of inoculation with nontyphoid Salmonella compared to the general population. While nontyphoid Salmonella commonly manifests as gastroenteritis, Salmonella bacteremia can be seen in patients with HIV. We present a case of disseminated Salmonellosis in a patient with HIV complicated by bronchopleural fistula and secondary empyema. Case Presentation. A 40-year-old African American male with HIV noncompliant with HAART therapy presented with complaints of generalized weakness, weight loss, cough, night sweats, and nonbloody, watery diarrhea of four weeks’ duration. A computed tomography (CT) scan demonstrated a bilobed large, thick-walled cavitary lesion in the right upper lobe communicating with the pleural space to form a bronchopleural fistula. Thoracentesis yielded growth of nontyphi Salmonella species consistent with empyema; he was treated with intravenous Ceftriaxone and underwent placement of chest tube for drainage of empyema with instillation of alteplase/dornase twice daily for three days. Repeat CT chest showed a hydropneumothorax. The patient subsequently underwent video-assisted thoracoscopy with decortication. The patient continued to improve and follow-up CT chest demonstrated improved loculated right pneumothorax with resolution of the right bronchopleural fistula and resolution of the cavitary lesions. Discussion. We describe one of the few cases of development of bronchopulmonary fistula and the formation of empyema in the setting of disseminated Salmonella. Empyema complicated by bronchopulmonary fistula likely led to failure of intrapleural fibrinolytic therapy and the patient ultimately required decortication in addition to antibiotics. While Salmonella bacteremia can be seen in immunocompromised patients, extraintestinal manifestations of Salmonella infection such as empyema and bronchopleural fistulas are uncommon. Bronchopleural fistulas most commonly occur as a postoperative complication of pulmonary resection. Conclusions. This case highlights the unusual pulmonary manifestations that can occur due to disseminated Salmonella in an immunocompromised patient as well as complex management decisions related to these complications.
Impact of Irrigation Ecology on Rice Production Efficiency in Ghana
Authors: Bidzakin John Kanburi , Fialor Simon C. , Awunyo-Vitor Dadson , Yahaya Iddrisu
Published: June 2018

Irrigation production is a means by which agricultural production can be increased to meet the growing food demands in the world. This study evaluated the effect of irrigation ecology on farm household technical, allocative, and economic efficiency of smallholder rice farmers. Cross-sectional data was obtained from 350 rice farmers across rain fed and irrigation ecologies. Stochastic frontier analyses are used to estimate the production efficiency and endogenous treatment effect regression model is used to estimate the impact of irrigation ecology on rice production efficiency. The impact of irrigation ecology on technical efficiency is about 0.05, which implies farmers producing under irrigation ecology are more technically efficient in their rice production than those in rain fed production. The impact of irrigation ecology on allocative efficiency is about 0.33, which shows that farmers participating in irrigation farming are more allocatively efficient in their rice production than those in rain fed production. The impact on economic efficiency is about 0.23, meaning that farmers participating in irrigation farming are more economically efficient in their rice production than those in rain fed production. Irrigation ecology has positive impact on production efficiency; hence farmers should be encouraged to produce more under irrigation for increased yield and profit.
Damping Identification with Acceleration Measurements Based on Sensitivity Enhancement Method
Authors: Wang Xusheng , Liu Kun , Liu Hongbo , He Yuhan
Published: June 2018

The damping is important for forward and inverse structural dynamic analysis, and damping identification has become a hot issue in structural health monitoring recently. The dynamic responses of the structure can be measured in practice, and the structural parameter usually can be identified by inverse response sensitivity analysis. To reduce the measurement noise effect and enhance the effectiveness of the response sensitivity method, an enhanced sensitivity analysis method was proposed to identify the structural damping based on the Principal Component Analysis (PCA) method. The measured acceleration responses were analyzed by PCA method, and the updated analytical responses and the response sensitivities were projected into the subspace determined by the first‐order principal component. The projection equations were adopted to identify the parameters of damping model. The proposed damping identification method was numerically validated with a planar truss structure at first, and then the experimental study was conducted with a steel planar frame structure. It shows that the proposed method is effective in identifying the parameters of damping model with better accuracy compared with the conventional acceleration response sensitivity method, and it is also robust to the sensor placement and measurement noise.
Synovial Fluid Aspiration Should Not Be Routinely Performed during the Two-Stage Exchange of the Knee
Authors: Boelch Sebastian P. , Roth Magnus , Arnholdt Joerg , Rudert Maximilian , Luedemann Martin
Published: June 2018

Purpose. Detection of infection persistence during the two-stage exchange of the knee for periprosthetic joint infection is challenging. Synovial fluid culture (SFC) and synovial white blood cell count (SWBCC) before joint reimplantation are widespread diagnostic means for this indication. The sensitivity and specificity of SFC and of SWBCC for infection persistence before planned reimplantation were evaluated. Methods. 94 two-stage exchanges of the knee with synovial fluid aspiration performed after a drug holiday of at least 14 days and before reimplantation or spacer exchange (planned reimplantation) were retrospectively analyzed. Only cases with at least 3 intraoperative samples at planned reimplantation were included. SFC and SWBCC were compared to pathogen detection (SFC(culture)/SWBCC(culture)) and to histopathological signs of infection persistence (SFC(histo)/SWBCC(histo)) from intraoperative samples at planned reimplantation. For SFC, the sensitivity and specificity were calculated. For SWBCC, the optimal cut-off value with its sensitivity and specificity was calculated with the Youden-Index. Results. Sensitivity and specificity of SFC(culture) were 0.0% and 98.9%. Sensitivity and specificity of SFC(histo) were 3.4% and 100%. The optimal cut-off value for SWBCC(culture) was 4450 cells/μl with a sensitivity of 50.0% and a specificity of 86.5%. The optimal cut-off value for SWBCC(histo) was 3250 cells/μl with a sensitivity of 35.7% and a specificity of 92.9%. Conclusion. The detection of infection persistence remains challenging and a consented approach is lacking. The results do not warrant the routine performance of SFC during the two-stage exchange at the knee. SWBCC can be used to confirm infection persistence at high cut-offs, but they only occur in few patients and are therefore inappropriate for the routine use.
On an Inverse Problem of Reconstructing a Heat Conduction Process from Nonlocal Data
Authors: Sadybekov Makhmud A. , Dildabek Gulnar , Ivanova Marina B.
Published: June 2018

We consider an inverse problem for a one-dimensional heat equation with involution and with periodic boundary conditions with respect to a space variable. This problem simulates the process of heat propagation in a thin closed wire wrapped around a weakly permeable insulation. The inverse problem consists in the restoration (simultaneously with the solution) of an unknown right-hand side of the equation, which depends only on the spatial variable. The conditions for redefinition are initial and final states. Existence and uniqueness results for the given problem are obtained via the method of separation of variables.
Dyslipidemia and Fatty Liver Disease in Overweight and Obese Children
Authors: Deeb Asma , Attia Salima , Mahmoud Samia , Elhaj Ghada , Elfatih Abubaker
Published: June 2018

Introduction. Obesity is a worldwide concern. It is associated with morbidity such as dyslipidemia and liver disease. Childhood obesity has dramatically increased, particularly in the Gulf region. We aim to assess the prevalence of dyslipidemia and fatty liver disease (FLD) in overweight and obese children and analyze the association between different anthropometric measures with dyslipidemia and fatty liver disease. Methods. A descriptive, cross-sectional study conducted on children referred with obesity. BMI percentiles were plotted and standardized waist circumference (WC) was generated. Family history of metabolic syndrome was recorded. Fasting lipid, liver transaminases, and ultrasound scans (US) for those with elevated enzymes were performed. Descriptive statistics were used for quantitative parameters. Results. 216 participants were recruited. Mean ± SD age was 10.58 ± 2.996 years. 55.3% had dyslipidemia; 11.7% had high cholesterol, 28.6% high triglyceride, 32.7% high LDL, and 18.0% low HDL. 51 (84%) had either elevated transaminases. All had liver US, and 43 had FLD. WC was strongly associated with dyslipidemia and FLD (P=0.04  and  0.003). Conclusion. Dyslipidemia is common in overweight, obese children. FLD is prevalent in those with elevated liver transaminases. WC is an easy tool that can be utilized to screen for dyslipidemia and FLD in overweight and obese children.
Resistant Gram-Negative Bacteria and Diagnostic Point-of-Care Options for the Field Setting during Military Operations
Authors: Frickmann Hagen , Podbielski Andreas , Kreikemeyer Bernd
Published: June 2018

The spread of multidrug-resistant bacteria in resource-poor settings affects the military medical service in case of deployments of soldiers to war and crisis zones. Patients with war injuries are prone to colonization or infection with multidrug-resistant bacteria. Resistant Gram-negative bacteria play a dominant role in military wound infections. Problematic hygiene conditions on deployment facilitate exposition of soldiers with subsequent colonization. Although colonizing strains are frequently cleared from their hosts after returning from deployment, transmission to close contacts of the soldiers in the home country cannot be excluded and therapeutic options are reduced if colonization progresses to invasive infection. Since sophisticated culture-based diagnostic approaches are typically not available in the field setting on deployment, molecular rapid diagnostic test systems are an option for transmission control if the locally prevalent molecular resistance mechanisms are known. Efforts for global resistance surveillance can contribute to better understanding of resistance distribution and spread at deployment sites. This review summarizes experience of the military medical services with multidrug resistance on deployment and with the influx of resistant strains to the home country and discusses potential use of available molecular rapid test systems as an option for the field setting.
A Rare Case of Large Schwannoma of the Parapharyngeal Space
Authors: Siupsinskiene Nora , Arechvo Irina , Lapinskaite Rimante , Padervinskis Evaldas , Ryskiene Silvija , Vaitkus Saulius
Published: June 2018

Schwannoma originating from the peripheral nerves is a rare lesion of the parapharyngeal space. The special traits of the presented case included the following: the patient presented with slowly progressing dysphagia, speech difficulties, jaw numbness, and taste dysfunction. A dislocated lateral pharyngeal wall with mild inflammatory changes of the oropharyngeal mucosa was observed during pharyngoscopy. The radiological and histological characteristics of the neoplasm are consequently presented. Special emphasis is placed on the surgical treatment of the tumor.
Integrative Genome-Wide Analysis of Long Noncoding RNAs in Diverse Immune Cell Types of Melanoma Patients
Authors: Wang Lei , Felts Sara J. , Van Keulen Virginia P. , Scheid Adam D. , Block Matthew S. , Markovic Svetomir N. , Pease Larry R. , Zhang Yuji
Published: June 2018

Genome-wide identification and characterization of long noncoding RNAs (lncRNA) in individual immune cell lineages helps us better understand the driving mechanisms behind melanoma and advance personalized patient treatment. To elucidate the transcriptional landscape in diverse immune cell types of peripheral blood cells (PBC) in stage IV melanoma, we used whole transcriptome RNA sequencing to profile lncRNAs in CD4+, CD8+, and CD14+ PBC from 132 patient samples. Our integrative computational approach identified 27,625 expressed lncRNAs, 2,744 of which were novel. Both T cells (i.e., CD4+ and CD8+ PBC) and monocytes (i.e., CD14+ PBC) exhibited differential transcriptional expression profiles between patients with melanoma and healthy subjects. Cis- and trans-level coexpression analysis suggested that lncRNAs are potentially involved in many important immune-related pathways and the programmed cell death receptor 1 checkpoint pathways. We also identified nine gene coexpression modules significantly associated with melanoma status, all of which were significantly enriched for three mRNA translation processes. Age and melanoma traits closely correlated with each other, implying that melanoma contains age-associated immune changes. Our computational prediction analysis suggests that many cis- and trans-regulatory lncRNAs could interact with multiple transcriptional and posttranscriptional regulatory elements in CD4+, CD8+, and CD14+ PBC, respectively. These results provide novel insights into the regulatory mechanisms involving lncRNAs in individual immune cell types in melanoma and can help expedite cell type-specific immunotherapy treatments for such diseases.

Significance: These findings elucidate melanoma-associated changes to the noncoding transcriptional landscape of distinct immune cell classes, thus providing cell type-specific guidance to targeted immunotherapy regimens. Cancer Res; 78(15); 4411–23. ©2018 AACR.
Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma
Authors: Chi Yihebali , Fang Zhiwei , Hong Xiaonan , Yao Yang , Sun Ping , Wang Guowen , Du Feng , Sun Yongkun , Wu Qiong , Qu Guofan , Wang Shusen , Song Jianmin , Yu Jianchun , Lu Yongkui , Zhu Xia , Niu Xiaohui , He Zhiyong , Wang Jinwan , Yu Hao , Cai Jianqiang
Published: June 2018

Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies.

Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks).

Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%–18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred.

Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233–8. ©2018 AACR.
Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile
Authors: Querfeld Christiane , Leung Samantha , Myskowski Patricia L. , Curran Shane A. , Goldman Debra A. , Heller Glenn , Wu Xiwei , Kil Sung Hee , Sharma Sneh , Finn Kathleen J. , Horwitz Steven , Moskowitz Alison , Mehrara Babak , Rosen Steven T. , Halpern Allan C. , Young James W.
Published: June 2018

Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T cells in a background of chronic inflammation. Although dendritic cells (DCs) stimulate T cells and are present in skin, cutaneous T cells in CTCL do not respond with effective antitumor immunity. We evaluated primary T-cell and DC émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3. CD8+ CTCL populations contained more T cells expressing CTLA-4 and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell costimulator (ICOS), a marker of T-cell activation. DC émigrés from healthy or CTCL skin biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1 expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA expression profiles corroborated that advanced T3/T4-stage samples expressed more checkpoint inhibition mRNA compared with T1/T2 stage patients or healthy controls. Exhaustion of activated T cells is therefore a hallmark of both CD4+ and CD8+ T cells isolated from the lesional skin of patients with CTCL, with increasing expression as the disease progresses. These results justify identification of antigens driving T-cell exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion earlier in the treatment of CTCL. Cancer Immunol Res; 6(8); 900–9. ©2018 AACR.
The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity
Authors: Danilova Ludmila , Anagnostou Valsamo , Caushi Justina X. , Sidhom John-William , Guo Haidan , Chan Hok Yee , Suri Prerna , Tam Ada , Zhang Jiajia , Asmar Margueritta El , Marrone Kristen A. , Naidoo Jarushka , Brahmer Julie R. , Forde Patrick M. , Baras Alexander S. , Cope Leslie , Velculescu Victor E. , Pardoll Drew M. , Housseau Franck , Smith Kellie N.
Published: June 2018

Mutation-associated neoantigens (MANA) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates T-cell receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications. This assay can be adapted for all types of antigens, including MANAs via tumor exome-guided prediction of MANAs. Following in vitro identification by the MANAFEST assay, the MANA-specific CDR3 sequence can be used as a molecular barcode to detect and monitor the dynamics of these clonotypes in blood, tumor, and normal tissue of patients receiving immunotherapy. MANAFEST is compatible with high-throughput routine clinical and lab practices. Cancer Immunol Res; 6(8); 888–99. ©2018 AACR.
Frequent and Rare HABP2 Variants Are Not Associated with Increased Susceptibility to Familial Nonmedullary Thyroid Carcinoma in the Spanish Population
Authors: de Randamie Rajdee , Martos-Moreno Gabriel Ángel , Lumbreras César , Chueca Maria , Donnay Sergio , Luque Manuel , Regojo Rita María , Mendiola Marta , Hardisson David , Argente Jesús , Moreno José C.
Published: June 2018

Background/Aims: A genomic HABP2 variant was proposed to be responsible for familial nonmedullary thyroid carcinoma (FNMTC). However, its involvement has been questioned in subsequent studies. We aimed to identify genetic HABP2 mutations in a series of FNMTC patients and investigate their involvement in the disease. Methods: HABP2 was sequenced from 6 index patients. Presence of the variants was investigated in all members of one family. Somatic BRAF and RAS “hotspot” mutations were investigated by the IdyllaTM BRAF Mutation Test and/or Sanger sequencing. Results: Two HABP2 variants (p.E393Q and p.G534E) were identified in the index patient from one family with papillary thyroid carcinoma (PTC) (follicular variant). The prevalence of p.E393Q in Spanish control alleles was 0.5% and that of p.G534E was 5.1%. However, neither change cosegregated with the phenotype in 3 affected members and 5 healthy members of the kindred. Interestingly, all 3 members affected by PTC harbored the p.V600E somatic mutation in BRAF. Conclusions: The variant G534E is prevalent in the Spanish population (5.1%); however, p.E393Q is rare (< 1%) and none cosegregated with the FNMTC phenotype. The presence of the noninheritable V600E BRAF mutation in this family supports Knudson’s “double-hit” hypothesis for cancer development and suggests the involvement of more than 1 gene in the clinical expression of FNMTC.
The Story of Imatinib in GIST - a Journey through the Development of a Targeted Therapy
Authors: Reichardt Peter
Published: June 2018

The introduction of the tyrosine kinase inhibitor (TKI) imatinib 15 years ago has radically changed the treatment of advanced/metastatic gastrointestinal stroma tumours (GIST). This review describes and discusses the development of this successful targeted therapy. It shows the evolution of imatinib to become the standard first-line treatment for advanced/metastatic GIST, starting from the first dose-finding trials to the pivotal trials. Other themes discussed are the detection of predictive factors, the results of discontinuing treatment and how long the treatment should last. The discoveries described in the development and research of imatinib now serve as models for treating many other cancers. However, there are still unanswered questions, so research into treating GIST with TKI or other compounds continues.
Overactive Bladder Symptoms after Transobturator Sling Surgery for Pure Stress Urinary Incontinence: A Cross-Sectional Comparative Study
Authors: Pereira e Silva Ricardo , Gomes Olival Vanessa , Ponte Carolina , Palma dos Reis José , Colaço João , Grilo Isabel , Nunes Filomena
Published: June 2018

Introduction: Transobturator tape (TOT) surgery has been associated with increased overactive bladder (OAB) although much controversy exists. Methods: In a cross-sectional study, women who underwent TOT surgery for pure stress incontinence (MonarcTM) answered the 6 questions of the symptom bother (SB) subscale of the OAB questionnaire – short form (OABq-SF) and an additional question regarding whether symptoms began after surgery. Women with SB score over the 4th quartile (≥30/100) were reassessed after a longer follow-up. Patients from primary care were recruited as controls. Results: We recruited 213 patients (135 in the TOT group and 78 age-adjusted controls). The mean age of operated patients was 58.7 ± 10.1 years with a mean follow-up of 25.9 ± 13.2 months. OABq-SF SB scores did not differ between the TOT group and controls (respectively, 18.5 ± 30 and 15.5 ± 6.7, p = 0.202). A total of 48% patients reported no relationship between symptoms and surgery. Highly symptomatic operated patients were reassessed after a longer follow-up (46.3 ± 10.6 months). The mean score in the second follow-up (n = 25) was not statistically different from the first assessment (46.4 ± 22.7 and 58.1 ± 19.8, p = 0.059). Conclusions: Women who underwent TOT surgery did not show increased OAB SB scores when compared to controls. Our study suggests that OAB symptoms may thus be present but overlooked during initial clinical assessment.
Stability of Cellular Immune Parameters over 12 Weeks in Patients with Major Depression or Somatoform Disorder and in Healthy Controls
Authors: Krause Daniela , Stapf Theresa M. , Kirnich Verena B. , Hennings Anika , Riemer Sabine , Chrobok Agnieszka , Fries Daniel R. , Pedrosa Gil Francisco  , Rief Winfried , Schwarz Markus J. , Schmidmaier Ralf
Published: June 2018

Objective: Cellular immune status in major depression (MD) patients differs from that in somatoform disorder (SFD) patients and healthy controls (HC). It is still questionable whether the patterns of immune parameters remain stable over time. Therefore, we studied lymphocyte and monocyte cell counts and neopterin levels in peripheral blood of MD and SFD patients and HC over 12 weeks and tested for correlations between biochemical and psychometric parameters. Methods: Thirty-nine patients with MD, 27 with SFD, and 51 HC were recruited. Peripheral blood was drawn at four visits, at 4-week intervals. We assessed the total cell count of B lymphocytes, natural killer (NK) cells, T lymphocyte subpopu­lations, and monocytes by flow cytometry, and neopterin serum levels by ELISA. Psychometric parameters were measured with questionnaires. Results: Counts of lymphocytes, monocytes, and neopterin were stable in the SFD and HC groups. In the MD group, total CD3+, CD3+CD8+, NK cells, and CD3+CD25+ T cells showed inhomogeneous variances in Friedman tests, particularly in females. Neopterin correlated with depressed mood in MD patients, and with body mass index in HC. Conclusions: Cellular immune parameters are stable in HC and SFD. Our results may indicate influences of MD and gender on some cellular immune parameters. This may need to be considered in future immunological studies.
Cognitive-Behavioral and Psychodynamic Therapy in Adolescents with Social Anxiety Disorder: A Multicenter Randomized Controlled Trial
Authors: Salzer Simone , Stefini Annette , Kronmüller Klaus-Thomas , Leibing Eric , Leichsenring Falk , Henningsen Peter , Peseschkian Hamid , Reich Günter , Rosner Rita , Ruhl Uwe , Schopf Yvonne , Steinert Christiane , Vonderlin Eva , Steil Regina
Published: June 2018

Background: Although social anxiety disorder (SAD) has an early onset and is frequently found in adolescence, evidence for psychotherapeutic treatments of SAD in adolescents is rather scarce. Within the Social Phobia Psychotherapy Research Network (SOPHO-NET), we examined the efficacy of cognitive-behavioral (CBT) and psychodynamic therapy (PDT) compared to a waiting list (WL) in these patients. Methods: In a multicenter randomized controlled superiority trial, 107 patients, aged 14–20 years, were randomized to CBT (n = 34), PDT (n = 34), or WL (n = 39). Assessments were made at baseline, at the end of treatment, and 6 and 12 months after termination. The Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA) applied by raters masked to the treatment condition was used as the primary outcome. As secondary outcomes, rates of response and remission and the Social Phobia Anxiety Inventory (SPAI) were used. Results: Both treatments were superior to WL in the LSAS-CA (CBT: p = 0.0112, d = 0.61, 95% CI 0.14–1.08; PDT: p = 0.0261, d = 0.53, 95% CI 0.06–1.00). At the end of treatment, response rates were 66, 54, and 20% for CBT, PDT, and WL. The corresponding remission rates were 47, 34, and 6%, respectively. CBT and PDT were significantly superior to WL regarding remission (CBT: p = 0.0009, h = 1.0; PDT: p = 0.0135, h = 0.74), response (CBT: p = 0.0004, h = 0.97; PDT: p = 0.0056, h = 0.72), and the SPAI (CBT: p = 0.0021, d = 0.75, 95% CI 0.27–1.22; PDT: p = 0.0060, d = 0.66, 95% CI 0.19–1.13). Treatment effects were stable at 6- and 12-month follow-ups. Conclusions: These results are comparable to the large SOPHO-NET trial in adults (n = 495). Early treatments for social anxiety are needed in order to prevent chronic manifestation of SAD.
Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients
Authors: Heneberg Petr , Kocková Lucie , Čecháková Marie , Daňková Pavlína , Černá Marie
Published: June 2018

Background: A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. Methods: We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. Results: We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.–1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). Conclusions: The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood.
Different Doses of Tripterygium Glycosides in the Treatment of Diabetic Nephropathy: Effects on Blood Lipids
Authors: Wang Wei
Published: June 2018

Background/Aims: The aim of this study was to investigate the therapeutic effect of different doses of tripterygium glycosides (TG) in the treatment of diabetic nephropathy (DN). The effect of TG on blood lipids and safety were also evaluated. Methods: Sixty patients with type 2 DN were randomly divided into three groups (n=20 per group): low-dose (30 mg/day TG), double-dose (60 mg/day TG) and control (placebo) groups, all three times daily for 6 months. The levels of triglycerides, total cholesterol, urinary protein, plasma albumin and serum tumour necrosis factor (TNF)-α were compared between the three groups. Results: After treatment, urinary protein and TNF-α level significantly decreased in patients in the treatment groups, compared with the control group. This decrease was significantly larger in the double-dose group than in the low-dose group. However, there was no significant decrease in triglycerides and total cholesterol in the two treatment groups. Furthermore, plasma albumin was lower in the treatment groups than in the control group. Conclusion: The double dose of TG has improved clinical efficacy, compared with the low dose, and the same safety profile.
ДОСВІД ПОЗААУДИТОРНОЇ РОБОТИ ЗІ СТУДЕНТАМИ НА КАФЕДРІ ТЕРАПЕВТИЧНОЇ СТОМАТОЛОГІЇ
Authors: Petrushanko T. O. , Nikolishуna E. V. , Ilenko N. M. , Popovich I. Yu. , Litovchenko I. Yu.
Published: June 2018

Мета роботи – проаналізувати сутність позааудиторної самостійної роботи студентів як складової професійної підготовки майбутніх лікарів-стоматологів, а також висвітлити досвід її організації та проведення на кафедрі терапевтичної стоматології ВДНЗУ “УМСА”.Основна частина. Для підвищення освітнього рівня підготовки висококваліфікованих спеціалістів та збагачення їх інтелектуального та творчого потенціалу слід постійно раціоналізовувати навчальний процес шляхом удосконалювання змісту, форм і методів навчально-пізнавальної діяльності студентів вищих навчальних закладів. При обмеженні навчального аудиторного часу виникає необхідність навчання в позааудиторний час. Заходами позааудиторної роботи з розвитку особистості майбутнього лікаря і підготовки професійно-орієнтованого фахівця є проведення відбіркового туру Всеукраїнського студентського конкурсу на кращу практичну роботу “Фахівець”, а також індивідуальні та групові фантомні заняття.Висновок. Практично спрямований вид позааудиторної роботи дозволяє кожному бажаючому студенту напрацювати мануальні навички, сприяє максимальному розвитку індивідуальних творчих здібностей і в кінцевому підсумку приводить до поліпшення якості та рівня підготовки майбутніх фахівців.
ОСОБЛИВОСТІ ВИКЛАДАННЯ МЕДИЧНОГО ПРАВА ДЛЯ СТУДЕНТІВ-МЕДИКІВ
Authors: Rohalskyy I. O. , Kalyniuk N. M.
Published: June 2018

Мета роботи – дослідження особливостей викладання дисципліни “Медичне право України” для студентів-медиків.Основна частина. У статті досліджено проблемні моменти викладання дисципліни “Медичне право України” для студентів неюридичних спеціальностей, зокрема для студентів-медиків. Проаналізовано окремі аспекти навчальної програми з медичногоправа. Обґрунтовано необхідність вдосконалення методів та технологій викладання медичного права для студентів-медиків. Визначено, що вітчизняна нормативно-правова база має положення, що регулюють права громадян у сфері охорони здоров’я. Однак євроінтеграційний вектор розвитку нашої країни, збільшення обсягів міждержавних обмінів, розвиток ринкових відносин, потребує вивчення та ревізії вітчизняного права, врахування кращого світового досвіду участі професійних і громадських організацій щодо захисту прав медичних працівників та пацієнтів, зобов’язує науковців і законодавчі органи удосконалювати нормативну базу в галузі охорони здоров’я. А впровадження та вивчення її у вищих навчальних закладах забезпечить імплементацію медичного права в систему права України.Висновки. Доведено, що навчальна дисципліна “Медичне право України” включає в себе норми інших галузей права, що регулюють суспільні відносини, учасниками яких є медичні працівники та пацієнти. Це надає змогу студентам-медикам вивчити та знати ази конституційного, цивільного, адміністративного, кримінального законодавства.
ДОСВІД ВИКОРИСТАННЯ КРОСВОРДІВ ПРИ ВИКЛАДАННІ ДИСЦИПЛІНИ “ПСИХІАТРІЯ. НАРКОЛОГІЯ”
Authors: Spirina I. D. , Shornikov A. V. , Tymofieiev R. M. , Fedenko E. S.
Published: June 2018

Мета роботи – пошук шляхів покращення засвоєння деяких тем при навчанні студентів дисципліни “Психіатрія. Наркологія”, зокрема за допомогою кросвордів.Основна частина. Дослідження базувалось на вивченні матеріалів, отриманих із відкритих джерел інформації, та використанні авторських кросвордів, створених на кафедрі психіатрії, загальної та медичної психології ДЗ “Дніпропетровська медична академія МОЗ України”. У дослідженні взяли участь 57 вітчизняних студентів 4 курсу спеціальності “Лікувальна справа”, яким замість вхідного тестового контролю необхідно було розв’язати кросворди за темою практичного заняття “Психічні та поведінкові розлади внаслідок вживання речовин, які не внесені в державний перелік наркотиків”. Також для визначення ефективності запропонованої форми оцінки знань студентів було розроблено опитувальник, що містить 4 питання. Отримані результати виявили як позитивне, так і негативне ставлення з боку студентів до ефективності даного способу.Висновки. Розв’язання кросвордів в якості контролю аудиторної роботи студентів стало позитивним досвідом практичного застосування нових способів навчання. Використання кросвордів у викладанні дисципліни може бути потужним стимулом для набуття нових знань. Однак більш доцільно застосовувати дану методику в якості самоконтролю або для контролю самостійної позааудиторної роботи, що поліпшить рівень навчання студентів та сформує заплановані навчальною програмою компетенції з дисципліни “Психіатрія. Наркологія”.
ОСОБЛИВОСТІ ЕМОЦІЙНОЇ СФЕРИ МЕДИЧНИХ ПРАЦІВНИКІВ
Authors: Tolokova T. I.
Published: June 2018

Мета роботи. Стаття присвячена вивченню особливостей емоційної сфери медичних працівників. Зміни в емоційній сфері медиків пов’язані з емоційними та етичними перевантаженнями в професійній діяльності. У медичній освіті необхідно акцентувати увагу на тренінгу адаптаційних можливостей емоційної сфери.Основна частина. У статті окреслена проблематика пов’язана з факторами ризику, сильною емоційною напругою, відсутністю достатніх умов для відновлення сил, недостатністю психологічного супроводу у практиці системи охорони здоров’я, що несприятливо впливають на медичних працівників. Однією з найважливіших якостей медичного працівника є емоційна стійкість. Ключовим виявом емоційного стану особистості є настрій. Емоційне відчуття або настрій – це своєрідний акумулятор всієї інформації, яка сприймається і переробляється індивідом за відповідний час. Внаслідок цього настрій стає тривалим емоційним станом, що створюється зовнішніми впливами на особистість залежно від її індивідуальних особливостей і темпераменту. Нестабільність настрою медичного працівника, як правило, пов’язана не лише безпосередньо з тією або іншою конкретною медичною ситуацією, а й з комплексом найрізноманітніших вражень від зовнішніх чинників, роздумів і переживань. На настрій будь-якої особистості впливають ті чи інші життєві турботи, занепокоєння, викликані певними надзвичайними обставинами, ображене самолюбство, докори сумління. Будь-яка з цих емоцій або їхнє поєднання можуть бути помітні пацієнтам і заважати нормальній діяльності фахівця. І якщо медичний працівник не в змозі подолати такий настрій, то це може спричинити прий­няття неправильного рішення, здійснення хибних медичних дій, створення напружених відносин iз пацієнтами.Висновки. Виникла необхідність сформувати у майбутніх медичних працівників готовність до емоційного співпереживання і співчуття стосовно проблем у сфері здоров’я пацієнтів. Розглянуто основні характеристики і встановлено чинники, які зумовлюють порушення емоційної сфери у медичних працівників. Вивчення емоційної сфери – важливе теоретичне і практичне завдання, що вимагає поглибленого дослідження, зорієнтованого на практику, що потребує подальшої розробки.
СТАН СФОРМОВАНОСТІ ПРОФЕСІЙНО-ЕТИЧНОЇ КУЛЬТУРИ МАЙБУТНЬОГО ЛІКАРЯ
Authors: Korolova T. V.
Published: June 2018

Мета робoти – розробка критеріально-показникової системи дослідження рівня сформованості професійно-етичної культури майбутніх лікарів та аналіз результатів сформованості професійно-етичної культури майбутніх лікарів у процесі гуманітарної підготовки.Основна частина. Стаття присвячена дослідженню стану сформованості професійно-етичної культури майбутніх лікарів. Автором представлено результати оцінювання рівня сформованості професійно-етичної культури, розроблено систему критеріїв, показників і рівнів сформованості професійно-етичної культури майбутніх лікарів. Також у статті зазначені використані методи дослідження.Висновок. Було доведено, що гуманітарні дисципліни відіграють значну роль у формуванні професійно-етичної культури майбутніх лікарів.