bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of transthoracic echocardiography for pulmonary hypertension: a systematic review and meta-analysis
Authors: Ni Jin-Rong , Yan Pei-Jing , Liu Shi-Dong , Hu Yuan , Yang Ke-Hu , Song Bing , Lei Jun-Qiang
Published: December 2019

Objective

To evaluate the diagnostic accuracy of transthoracic echocardiography (TTE) in patients with pulmonary hypertension (PH).

Design

Systematic review and meta-analysis.

Data sources and eligibility criteria

Embase, Cochrane Library for clinical trials, PubMed and Web of Science were used to search studies from inception to 19 June, 2019. Studies using both TTE and right heart catheterisation (RHC) to diagnose PH were included.

Main results

A total of 27 studies involving 4386 subjects were considered as eligible for analysis. TTE had a pooled sensitivity of 85%, a pooled specificity of 74%, a pooled positive likelihood ratio of 3.2, a pooled negative likelihood ratio of 0.20, a pooled diagnostic OR of 16 and finally an area under the summary receiver operating characteristic curve of 0.88. The subgroup with the shortest time interval between TTE and RHC had the best diagnostic effect, with sensitivity, specificity and area under the curve (AUC) of 88%, 90% and 0.94, respectively. TTE had lower sensitivity (81%), specificity (61%) and AUC (0.73) in the subgroup of patients with definite lung diseases. Subgroup analysis also showed that different thresholds of TTE resulted in a different diagnostic performance in the diagnosis of PH.

Conclusion

TTE has a clinical value in diagnosing PH, although it cannot yet replace RHC considered as the gold standard. The accuracy of TTE may be improved by shortening the time interval between TTE and RHC and by developing an appropriate threshold. TTE may not be suitable to assess pulmonary arterial pressure in patients with pulmonary diseases.

PROSPERO registration number

PROSPERO CRD42019123289.
Real-time utilisation of administrative data in the ED to identify older patients at risk: development and validation of the Dynamic Silver Code
Authors: Balzi Daniela , Carreras Giulia , Tonarelli Francesco , Degli Esposti Luca , Michelozzi Paola , Ungar Andrea , Gabbani Luciano , Benvenuti Enrico , Landini Giancarlo , Bernabei Roberto , Marchionni Niccolò , Di Bari Mauro
Published: December 2019

Objective

Identification of older patients at risk, among those accessing the emergency department (ED), may support clinical decision-making. To this purpose, we developed and validated the Dynamic Silver Code (DSC), a score based on real-time linkage of administrative data.

Design and setting

The ‘Silver Code National Project (SCNP)’, a non-concurrent cohort study, was used for retrospective development and internal validation of the DSC. External validation was obtained in the ‘Anziani in DEA (AIDEA)’ concurrent cohort study, where the DSC was generated by the software routinely used in the ED.

Participants

The SCNP contained 281 321 records of 180 079 residents aged 75+ years from Tuscany and Lazio, Italy, admitted via the ED to Internal Medicine or Geriatrics units. The AIDEA study enrolled 4425 subjects aged 75+ years (5217 records) accessing two EDs in the area of Florence, Italy.

Interventions

None.

Outcome measures

Primary outcome: 1-year mortality. Secondary outcomes: 7 and 30-day mortality and 1-year recurrent ED visits.

Results

Advancing age, male gender, previous hospital admission, discharge diagnosis, time from discharge and polypharmacy predicted 1-year mortality and contributed to the DSC in the development subsample of the SCNP cohort. Based on score quartiles, participants were classified into low, medium, high and very high-risk classes. In the SCNP validation sample, mortality increased progressively from 144 to 367 per 1000 person-years, across DSC classes, with HR (95% CI) of 1.92 (1.85 to 1.99), 2.71 (2.61 to 2.81) and 5.40 (5.21 to 5.59) in class II, III and IV, respectively versus class I (p<0.001). Findings were similar in AIDEA, where the DSC predicted also recurrent ED visits in 1 year. In both databases, the DSC predicted 7 and 30-day mortality.

Conclusions

The DSC, based on administrative data available in real time, predicts prognosis of older patients and might improve their management in the ED.
Phase transition of the Sznajd model with anticonformity for two different agent configurations
Authors: Muslim Roni , Anugraha Rinto , Sholihun Sholihun , Rosyid Muhammad Farchani
Published: December 2019

In this work, we study the opinion dynamics of the Sznajd model with anticonformity on a fully-connected network. We consider four agents with two different configurations; three against one (3–1) and two against two (2–2). We consider two different individual behaviors, conformity and anticonformity, and observe the effect on the critical behavior of the model. We analyze the differences between the phase transitions that occur for both agent configurations. We find that both agent configurations have a different critical point. The critical point of the 3–1 agent is smaller than that of the 2–2 agent configuration. From the simulation and analytical result, we find that the critical point for the 3–1 occurs at [Formula: see text], and for the 2–2, at [Formula: see text]. From the social viewpoint, the consensus process in a population is faster with a larger influencer in the same number of small group of the population. In addition, we find the critical exponents for both configurations are the same, that are [Formula: see text] and [Formula: see text]. Our results suggest that both models are identical and in the mean-field Ising universality class.
Computing skew left braces of small orders
Authors: Bardakov Valeriy G. , Neshchadim Mikhail V. , Yadav Manoj K.
Published: December 2019

We improve Algorithm 5.1 of [Math. Comp. 86 (2017) 2519–2534] for computing all nonisomorphic skew left braces, and enumerate left braces and skew left braces of orders up to 868 with some exceptions. Using the enumerated data, we state some conjectures for further research.
Wilf’s conjecture in fixed multiplicity
Authors: Bruns Winfried , García-Sánchez Pedro , O’Neill Christopher , Wilburne Dane
Published: December 2019

We give an algorithm to determine whether Wilf’s conjecture holds for all numerical semigroups with a given multiplicity [Formula: see text], and use it to prove Wilf’s conjecture holds whenever [Formula: see text]. Our algorithm utilizes techniques from polyhedral geometry, and includes a parallelizable algorithm for enumerating the faces of any polyhedral cone up to orbits of an automorphism group. We also introduce a new method of verifying Wilf’s conjecture via a combinatorially flavored game played on the elements of a certain finite poset.
Learning-Based Analysis of a New Wearable 3D Force System Data to Classify the Underlying Surface of a Walking Robot
Authors: Almeida Luís , Santos Vítor , Ferreira João
Published: December 2019

Biped humanoid robots that operate in real-world environments need to be able to physically recognize different floors to best adapt their gait. In this work, we describe the preparation of a dataset of contact forces obtained with eight force tactile sensors for determining the underlying surface of a walking robot. The data is acquired for four floors with different coefficient of friction, and different robot gaits and speeds. To classify the different floors, the data is used as input for two common computational intelligence techniques (CITs): Artificial neural network (ANN) and extreme learning machine (ELM). After optimizing the parameters for both CITs, a good mapping between inputs and targets is achieved with classification accuracies of about 99%.
The Kasparov product on submersions of open manifolds
Authors: van den Dungen Koen
Published: December 2019

We study the Kasparov product on (possibly non-compact and incomplete) Riemannian manifolds. Specifically, we show on a submersion of Riemannian manifolds that the tensor sum of a regular vertically elliptic operator on the total space and an elliptic operator on the base space represents the Kasparov product of the corresponding classes in KK-theory. This construction works in general for symmetric operators (i.e. without assuming self-adjointness), and extends known results for submersions with compact fibers. The assumption of regularity for the vertically elliptic operator is not always satisfied, but depends on the topology and geometry of the submersion, and we give explicit examples of non-regular operators. We apply our main result to obtain a factorization in unbounded KK-theory of the fundamental class of a Riemannian submersion, as a Kasparov product of the shriek map of the submersion and the fundamental class of the base manifold.
A generalized Frattini subgroup
Authors: Borodich Ruslan V.
Published: December 2019

In the work of Beidleman and Smith [On Frattini-like subgroups, Glasgow Math. J. 35 (1993) 95–98], the following question was raised: “If [Formula: see text] is a subnormal subgroup of a finite group [Formula: see text] containing [Formula: see text], then whether the supersolvability of [Formula: see text] follows the supersolvability of [Formula: see text]”. This problem was considered in works of Selkin [Maximal Subgroups in the Theory of Classes of Finite Groups (Belaruskaya, Navuka, 1997)], Skiba [On the intersection of all maximal [Formula: see text]-subgroups of a finite group, Prob. Phys. Math. Tech. 3(4) (2010) 56–62], Ballester-Bolinches [On [Formula: see text]-subnormal subgroups and Frattini-like subgroups of a finite group, Glasgow Math. J. 36 (1994) 241–247] and many other authors (see monograph [Maximal Subgroups in the Theory of Classes of Finite Groups (Belaruskaya, Navuka, 1997)]).

In this paper, we give the answer to the more general question: “Let [Formula: see text] be a local formation. If [Formula: see text] is a subnormal subgroup of a group [Formula: see text], then in what case [Formula: see text] will follow from [Formula: see text]”.
Michael Franklin Speaks Out on Data Science
Authors: Winslett Marianne , Braganholo Vanessa
Published: December 2019

Welcome to ACM SIGMOD Record series of interviews with distinguished members of the database community. I'm Marianne Winslett, and today we're at the 2017 SIGMOD and PODS conference in Chicago. I have here with me Mike Franklin, who is the chair of the Computer Science department at the University of Chicago. Before that, for many years, Mike was a professor at Berkeley where he also served as a chair of the Computer Science division. Mike was a co-founder and director of the Algorithms, Machines, and People Lab, better known as the AMPLab. He is an ACM fellow, a two-time winner of the SIGMOD Ten Year Test of Time Award, and a founder of the successful startup, Truviso. Mike's Ph.D. is from the University of Wisconsin Madison. So, Mike, welcome!
Report on the First International Workshop on Semantic Web Technologies for Health Data Management (SWH 2018)
Authors: Kondylakis Haridimos , Stefanidis Kostas , Rao Praveen
Published: December 2019

Better information management is the key to a more intelligent health and social system. To this direction, many challenges must be first overcome, enabling seamless, effective and efficient access to various health data sets and novel methods for exploiting the available information. The First International Workshop on Semantic Web Technologies for Health Data Management aimed at bringing together an interdisciplinary audience interested in the fields of semantic web, data management and health informatics to discuss the challenges in health-care data management and to propose novel and practical solutions for the next generation data-driven health-care systems. In this paper, we summarize the outcomes of the first instance of the workshop, and we present interesting conclusions and key messages.
RYK, a receptor of noncanonical Wnt ligand Wnt5a, is positively correlated with gastric cancer tumorigenesis and potential of liver metastasis
Authors: Fu Yongan , Chen Yilin , Huang Jinghua , Cai Zongda , Wang Yangqiang
Published: December 2019

Gastric cancer (GC) is the most prevalent human cancer around the globe. In GC, Wnt signaling is deregulated, and receptor-like tyrosine kinase (RYK) coreceptors have been identified to interact with noncanonical Wnt ligand Wnt5a. We, therefore, aimed to evaluate the role of RYK in GC development and metastasis. GC tumor samples were collected from 250 GC patients. Expressions of RYK, as well as markers for the epithelial-mesenchymal transition (EMT), such as N-cadherin and E-cadherin, were subjected to correlation analysis with clinicopathological features. Endogenous RYK expression levels were compared in GC cell lines with ascending metastatic potentials followed by stable RYK knockdown. Effect of RYK knockdown on GC cell migration, invasion, and EMT phenotype were assessed in vitro, and on GC tumor growth in vivo in a xenograft rodent model. Particularly, liver metastasis potential of tail vein-injected GC cells was also analyzed following RYK knockdown. RYK was highly correlated with liver metastasis of GC tumors and the expression profiles of EMT markers toward the mesenchymal tendency. RYK expression was also positively correlated with the metastasis potential of GC cells. RYK knockdown not only inhibited migration, invasion, and EMT of GC cells in vitro, but also suppressed tumorigenesis and liver metastasis of GC cells in vivo using the mouse xenograft model. RYK is highly correlated with GC tumorigenesis and potential of liver metastasis, suggesting it may be a novel oncogenic factor of the noncanonical Wnt signaling pathway contributing to GC.

NEW & NOTEWORTHY RYK is highly correlated with gastric cancer tumorigenesis and the potential of liver metastasis, suggesting it may be a novel oncogenic factor of the noncanonical Wnt signaling pathway contributing to gastric cancer.
GLI1-mediated pulmonary artery smooth muscle cell pyroptosis contributes to hypoxia-induced pulmonary hypertension
Authors: He Siyu , Ma Cui , Zhang Lixin , Bai June , Wang Xiaoying , Zheng Xiaodong , Zhang Junting , Xin Wei , Li Yiying , Jiang Yuan , Wang Sen , Zhu Daling
Published: December 2019

Pulmonary hypertension (PH) is a clinically common malignant cardiovascular disease. Pyroptosis is a new form of inflammatory cell death that is involved in many disease processes. Glioma-associated oncogene family zinc finger 1 (GLI1) is a transcriptional activator that participates in many diseases, but its role has never been explored in inducing pyroptosis and the progress of PH. In this study, we used an animal model and cell molecular biology to determine the effect of GLI1 on chronic hypoxia-mediated PH progression and pulmonary artery smooth muscle cell (PASMC) pyroptosis. The major findings of the present study are as follows: Hypoxia induced aberrant expression of GLI1. The inhibition of GLI1 attenuated hypoxia-induced PH and PASMC pyroptosis. Meanwhile, GLI1 enhanced apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression by binding with its promoter. GLI1 may promote PASMC pyroptosis through ASC to affect the progression of PH. These findings may identify novel targets for molecular therapy of PH.
Distal Femoral Varus Osteotomy for the Valgus Knee after Distal Femoral Growth Plate Fractures in Children: A Case Report
Authors: Kanto Ryo , Nakayama Hiroshi , Yoshiya Shinichi
Published: December 2019

An 18-year-old male suffered a valgus injury to the right knee due to a fall during a bigfoot race he took part in when he was 15 years old. He visited a different hospital at the age of 15. No obvious ligament injury or fracture was noted on MRI and physical examination. However, he gradually became aware of the valgus deformity of the right knee. Finally, he could not take part in a sports activity because of right knee pain. X-ray images at the age of 18 at an initial visit to our department showed severe valgus deformity with mechanical lateral distal femoral angle (mLDFA) of 71 degrees in contrast to left mLDFA which was 87 degrees. We performed a biplane-cut distal femoral varus osteotomy (DFO). Postoperative X-ray images showed an improvement of 86 degrees in mLDFA. Bony fusion was achieved six months after surgery, and he could play several sports activity.
Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review
Authors: Lanza Michele , Benincasa Giuditta , Costa Dario , Napoli Claudio
Published: December 2019

Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373,∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy.
Screening of Pleural Mesothelioma Cell Lines for Kinase Activity May Identify New Mechanisms of Therapy Resistance in Patients Receiving Platin-Based Chemotherapy
Authors: Borchert Sabrina , Suckrau Pia-Maria , Wessolly Michael , Mairinger Elena , Hegedus Balazs , Hager Thomas , Herold Thomas , Eberhardt Wildfried E. E. , Wohlschlaeger Jeremias , Aigner Clemens , Bankfalvi Agnes , Schmid Kurt Werner , Walter Robert F. H. , Mairinger Fabian D.
Published: December 2019

Background. Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumor associated with a dismal prognosis. Multimodal therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons underlying the rather poor efficacy of platinum compounds remain largely unknown. Kinase activity might influence cellular response to these regimens.Materials and Methods. For this exploratory study, we screened MPM cell lines (NCI-H2452, NCI-H2052, and MSTO-211H) differing in response to cisplatin and benign control fibroblasts (MRC-5) for overall phosphorylation patterns as well as kinase activity with respect to cellular response to cisplatin-based therapeutics. We analysed the cell lines for cellular kinases in a high-throughput manner using the highly innovative technique PamGene. Cell state analysis including apoptosis, necrosis, and cell viability was performed by using enzyme activity and fluorescent-based assays.Results. Cisplatin alters cellular phosphorylation patterns affecting cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis. In cisplatin-responsive cell lines, phosphorylation of AKT1 and GSK3B was decreased but could not be influenced in cisplatin-resistant NCI-H2452 cells. Cisplatin-responsive cell lines showed increased phosphorylation levels of JNK1/2/3 but decreased phosphorylation in cisplatin-resistant NCI-H2452 cells.Conclusion. Kinase phosphorylation and activity might play a crucial role in cellular response to cytostatic agents. Cisplatin influences phosphorylation patterns with distinct features in cisplatin-resistant cells. These alterations exert a significant impact on cell cycle, migration, adhesion, signal transduction, immune modulation, and apoptosis of the respective tumor cells. Based on our results, the induction of p38 or JNK1/3, or inhibition of AKT1 by, for example, BIA-6, might offer a positive synergistic effect by induction of an apoptotic response to cisplatin-based treatment, thus potentially enhancing the clinical outcome of MPM patients.
Coordination of a Green Supply Chain with One Manufacturer and Two Competing Retailers under Different Power Structures
Authors: Wang Wei , Liu Xiujuan , Zhang Wensi , Gao Ge , Zhang Hui
Published: December 2019

The main objective of this research is to examine the role of power relationship in a two-level green supply chain which is made up of one shared manufacturer and two competitive retailers. We develop six game theory-based models to explore the members’ operational decisions in a supply chain taking into account three vertical power structures (Manufacturer Stackelberg, Retailer Stackelberg, and Vertical Nash) as well as two retailers’ horizontal power structure (Bertrand or Stackelberg competition). Then, we design a two-part tariff contract which can encourage the supply chain members to promote cooperation and eventually coordinate the decentralized green supply chain under each power structure. Lastly, to further discuss the impact of the green awareness of consumers and the greening cost on supply chain players’ operational decisions and profits, we employ some numerical examples to conduct sensitivity analysis. The main conclusions are as follows. Firstly, the impact of power structure on the supply chain players’ operational decisions and profits mainly depends on the substitutability of the green products, the green awareness of consumers, and the greening cost for the manufacturer. Secondly, the more power the manufacturer has, the lower product greenness will be set. Thirdly, the consumer’s environmental awareness (the greening cost) positively (negatively) influences the manufacturer’s product greenness and wholesale price, the retailers’ sales prices, and the player’s profits under each power structure. Finally, the developed two-part tariff contract is practicable and beneficial for both the manufacturer and the two retailers.
Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid
Authors: Wang Jing Yi , Huo Lei , Yu Ru Qing , Rao Nian Jing , Lu Weijia William , Zheng Li Wu
Published: December 2019

Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.
Familial Adenomatous Polyposis and Desmoid Tumor Treated with Multivisceral Transplantation and Kidney Autotransplantation: Case Report and Literature Review
Authors: Janousek Libor , Novotny Robert , Kudla Michal , Oliverius Martin , Wohl Petr , Minguet Joan , Martinek Jan , Hucl Tomas , Fronek Jiri
Published: December 2019

Introduction. Desmoid tumours (DT) are commonly associated with Gardener’s syndrome. Their surgical resection may be complicated by their close proximity to major vessels, multiple organ involvement, and frequent local recurrence. Multivisceral transplantation (MVTx) is an alternative treatment for patients with intestinal and liver failure. In patients with DT closely associated with renal structures but without end-stage kidney disease, concomitant excision of the patient’s own kidney, ex vivo tumour resection with nephron-sparing surgery, or autotransplantation has been proposed. Case Presentation. A 36-year-old Caucasian female weighing 60 kg with Gardener’s syndrome with a history of abdominal surgery was presented to our department with progressive abdominal distention associated with paroxysmal pain. With the use of CT, the patient was diagnosed with a mass arising from the mesenterial region. The patient had normal kidney function and nonalcoholic steatohepatitis. The patient was indicated for MVTx. Management and Outcome. After 16 months on the waiting list, the patient received a multivisceral graft from a deceased donor. Following the restoration of graft vascular flow, the patient’s right kidney was removed and the DT dissected ex vivo before autotransplantation into the right pelvic fossa. The patient received immunosuppressive, antithrombotic, and antibiotic treatment. There was no acute rejection, though the patient experienced pulmonary infection, dysphagia, and oesophageal reflux with fungal infection. The patient had required temporary dialysis for acute renal failure for 75 days. One year after the surgery, nausea and violent vomiting caused delayed gastric emptying caused by spastic pylorus. Clinical improvement was achieved using gastric peroral endoscopic myotomy (G-POEM). Conclusion. MVTx with kidney autotransplantation is a feasible treatment option in patients with familiar adenomatous polyposis complicated by an abdominal DT. Precise tumour dissection with nephron-sparing surgery was carried ex vivo. G-POEM was used to relieve MVTx-related gastroparesis. The patient had no disease reoccurrence after one-year follow-up.
Nose-Cone Conformal Substrate-Integrated Waveguide Slot Array Antenna for X-Band Radar Applications
Authors: Khalil Hisham , Ahmed M. Mansoor , Rafique Umair
Published: December 2019

This paper presents the design of nose-cone conformal substrate-integrated waveguide (SIW) slot array antenna for modern radar applications. Firstly, the wave propagation characteristics have been investigated in doubly curved SIW, and it has been observed that they are non-uniform along the longitudinal direction of nose-cone conformal SIW. To ensure the constant wave propagation along the length of conformal SIW, the conventional design of SIW is reformulated for nose-cone conformal SIW and circuit model modification has been demonstrated. Secondly, the procedure for designing a SIW-based array on curved surfaces has been developed. In the proposed design, rectangular waveguide (RWG) to SIW feeding structure has been used to avoid spurious radiations. Finally, 1 × 6 element-based nose-cone conformal slotted array has been designed and compared with planar and cylindrical conformal arrays. It has been observed from the results that the nose-cone conformal slot array offers low sidelobe levels (SLLs) and high gain. For the validation of the proposed design, the conformal slotted array has been fabricated and measured, which exhibited a reasonable agreement between the measured and the simulated data.
Intratesticular Angiolipoma: A Rare Case of Adipose Tissue Presence in the Testis
Authors: Kalyvas V. , Gkekas C. , Papadopoulos D. , Malioris A. , Milias S. , Papathanasiou M. , Kalinderis N. , Moysidis K. , Hatzimouratidis K.
Published: December 2019

Introduction. Solid, fat-containing tumors of the testes are extremely rare with only a few cases having been reported so far, contrary to the more frequent occurrence of paratesticular lipomatosis. Testicular angiomyolipomas and gonadal involvement in Cowden’s disease, although infrequently occurring, are known examples of fat-bearing testicular lesions. Hereby, we present an extremely rare case of intratesticular angiolipoma. Angiolipomas are benign tumors of the subcutaneous tissue commonly occurring in the trunk and the extremities. Histologically, they are characterized by ample vascularity and an excess of mature adipocytes. Definitive diagnosis is established by biopsy of the lesion. Presentation of the Case. A 35-year-old patient presented to our andrology outpatient clinic for fertility assessment. Physical examination of external genitalia revealed no significant pathology. Testicular ultrasound however depicted an isoechoic lesion on the upper pole of the right testis measuring 1.8 cm×0.8 cm×1 cm and exhibiting intense arterial flow. After sonographic and MRI investigation, the patient was referred for semen analysis and cryopreservation. Subsequently, the patient underwent testicular biopsy (frozen section biopsy) and right partial orchiectomy. Final histology reported a noninfiltrating testicular angiolipoma. No recurrences have been observed in the follow-up period. Discussion. Angiolipomas, which mainly occur in the trunk and extremities, are classified as infiltrating and noninfiltrating. The diagnosis is based on both clinical and histologic criteria, and the main method of treatment for both types is by surgical excision. The infiltrating type exhibits higher recurrence rates. Conclusion. Angiolipomas commonly occur in the subcutaneous tissue and have been invariably treated by radical excision. Hereby, we report the first case of an intratesticular, noninfiltrating type angiolipoma which was treated by partial orchiectomy.
Validity of Measurement for Trailing Limb Angle and Propulsion Force during Gait Using a Magnetic Inertial Measurement Unit
Authors: Miyazaki Takasuke , Kawada Masayuki , Nakai Yuki , Kiyama Ryoji , Yone Kazunori
Published: December 2019

Propulsion force and trailing limb angle (TLA) are meaningful indicators for evaluating quality of gait. This study examined the validity of measurement for TLA and propulsion force during various gait conditions using magnetic inertial measurement units (IMU), based on measurements using a three-dimensional motion analysis system and a force platform. Eighteen healthy males (mean age 25.2  ±  3.2 years, body height 1.70   ±  0.06 m) walked with and without trunk fluctuation at preferred, slow, and fast velocities. IMU were fixed on the thorax, lumbar spine, and right thigh and shank. IMU calculated the acceleration and tilt angles in a global coordinate system. TLA, consisting of a line connecting the hip joint with the ankle joint, and the laboratory’s vertical axis at late stance in the sagittal plane, was calculated from thigh and shank segment angles obtained by IMU, and coordinate data from the motion analysis system. Propulsion force was estimated by the increment of velocity calculated from anterior acceleration measured by IMU fixed on the thorax and lumbar spine, and normalized impulse of the anterior component of ground reaction force (AGRF) during late stance. Similarity of TLA measured by IMU and the motion analysis system was tested by the coefficient of multiple correlation (CMC), intraclass correlation coefficient (ICC), and root mean square (RMS) of measurement error. Relationships between normalized impulse of AGRF and increments of velocity, as measured by IMU, were tested using correlation analysis. CMC of TLA was 0.956–0.959. ICC between peak TLAs was 0.831–0.876 (p<0.001), and RMS of error was 1.42°–1.92°. Velocity increment calculated from acceleration on the lumbar region showed strong correlations with normalized impulse of AGRF (r=0.755–0.892, p<0.001). These results indicated a high validity of estimation of TLA and propulsion force by IMU during various gait conditions; these methods would be useful for best clinical practice.
Type of Preservation Solution, UW or HTK, Has an Impact on the Incidence of Biliary Stricture following Liver Transplantation: A Retrospective Study
Authors: Karakoyun Rojbin , Romano Antonio , Nordström Johan , Ericzon Bo-Göran , Nowak Greg
Published: December 2019

Organ preservation plays a crucial role in the outcome following solid organ transplantation. The aim of this study was to perform a retrospective outcome analysis following liver transplantation using histidine tryptophan ketoglutarate (HTK) or the University of Wisconsin (UW) solutions for liver graft preservation. We retrospectively reviewed data on adult patients who were liver-transplanted at Karolinska University Hospital between 2007 and 2015. There was evaluation of donor and recipient characteristics, pre- and post-transplant blood chemistry tests, biliary and vascular complications, graft dysfunction and nonfunction, and patient and graft survivals. A total of 433 patients were included in the analyses, with 230 and 203 patients having received livers preserved with HTK and UW, respectively. Mean follow-up was 45 ± 29 months for the HTK group and 42.4 ± 26 for the UW group. There was no difference between the two groups either in terms of patient and graft survival, or of results of postoperative blood chemistry, or incidence of arterial complications, early allograft dysfunction, or primary graft nonfunction. However, the incidence of biliary stricture was higher in the UW group (22.7%) versus the HTK group (13.5%; p=0.013). Use of UW and HTK preservation solution in liver transplantation has no impact on patient and graft survival. However, use of HTK solution results in a lower incidence of posttransplant biliary stricture.
AMPK Activation of Flavonoids from Psidium guajava Leaves in L6 Rat Myoblast Cells and L02 Human Hepatic Cells
Authors: Li Jiankuan , Zhao Yujing , Cao Lingya , Zheng Qinghong , Gao Jianping
Published: December 2019

Objective. To isolate the hypoglycemic bioactive components from leaves of Psidium guajava and evaluate their AMP-activated protein kinase (AMPK) activities. Methods. A variety of column chromatography was used for the isolation of compounds, and nuclear magnetic resonance (NMR) and mass spectrum (MS) were used for the structure identification of compounds. AMP-activated protein kinase (AMPK) activity of compounds obtained from leaves of Psidium guajava was evaluated in L6 rat myoblast cells and L02 human hepatic cells by western blot. Results. Six principal flavonoids largely present in the leaves of Psidium guajava, quercetin (1), quercetin-3-O-α-L-arabinofuranoside (2), quercetin-3-O-α-L-arabinopyranoside (3), quercetin-3-O-β-D-galactopyranoside (4), quercetin-3-O-β-D-glucopyranoside (5), and quercetin-3-O-β-D-xylopyranoside (6), were obtained and compound 1–6 exhibited significant activity on AMPK activation both in L6 cells and L02 cells (p<0.01) compared with Control. In particular, the effects of quercetin on AMPK activation were extremely significant compared with Control (p<0.001). Conclusions. These findings demonstrated that these flavonoids had potential for the activation of AMPK and hypoglycemic activity.
Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon
Authors: Adedokun Babatunde , Zheng Yonglan , Ndom Paul , Gakwaya Antony , Makumbi Timothy , Zhou Alicia Y. , Yoshimatsu Toshio F. , Rodriguez Alex , Madduri Ravi K. , Foster Ian T. , Sallam Aminah , Olopade Olufunmilayo I. , Huo Dezheng
Published: December 2019

Background:

Sub-Saharan Africa (SSA) has a high proportion of premenopausal hormone receptor negative breast cancer. Previous studies reported a strikingly high prevalence of germline mutations in BRCA1 and BRCA2 among Nigerian patients with breast cancer. It is unknown if this exists in other SSA countries.

Methods:

Breast cancer cases, unselected for age at diagnosis and family history, were recruited from tertiary hospitals in Kampala, Uganda and Yaoundé, Cameroon. Controls were women without breast cancer recruited from the same hospitals and age-matched to cases. A multigene sequencing panel was used to test for germline mutations.

Results:

There were 196 cases and 185 controls with a mean age of 46.2 and 46.6 years for cases and controls, respectively. Among cases, 15.8% carried a pathogenic or likely pathogenic mutation in a breast cancer susceptibility gene: 5.6% in BRCA1, 5.6% in BRCA2, 1.5% in ATM, 1% in PALB2, 0.5% in BARD1, 0.5% in CDH1, and 0.5% in TP53. Among controls, 1.6% carried a mutation in one of these genes. Cases were 11-fold more likely to carry a mutation compared with controls (OR = 11.34; 95% confidence interval, 3.44–59.06; P < 0.001). The mean age of cases with BRCA1 mutations was 38.3 years compared with 46.7 years among other cases without such mutations (P = 0.03).

Conclusions:

Our findings replicate the earlier report of a high proportion of mutations in BRCA1/2 among patients with symptomatic breast cancer in SSA.

Impact:

Given the high burden of inherited breast cancer in SSA countries, genetic risk assessment could be integrated into national cancer control plans.
Association between Concomitant Use of Hydrochlorothiazide and Adverse Chemotherapy-Related Events among Older Women with Breast Cancer Treated with Cyclophosphamide
Authors: Hsu Christine D. , Hinton Sharon Peacock , Reeder-Hayes Katherine E. , Sanoff Hanna K. , Lund Jennifer L.
Published: December 2019

Background:

The pharmacy reference database, Micromedex, lists concomitant hydrochlorothiazide and cyclophosphamide use as a potential, major drug–drug interaction (DDI), although only one small, single-center study supports this claim. Our objective was to estimate associations between this potential DDI and two adverse chemotherapy-related events, neutropenia-related hospitalizations and treatment regimen discontinuation, among a cohort of women with breast cancer initiating adjuvant chemotherapy containing cyclophosphamide.

Methods:

Using linked Surveillance, Epidemiology, and End Results Program (SEER)-Medicare data, we included women 66 years and older with breast cancer diagnosis between 2007 and 2011, who initiated a regimen containing cyclophosphamide. Risk ratios (RR) and 95% confidence intervals for adverse outcomes comparing women exposed versus unexposed to the potential DDI were assessed using modified multivariable Poisson regression adjusting for potential confounders.

Results:

In total, 27% of women receiving cyclophosphamide treatment were exposed to concomitant hydrochlorothiazide, of which 11% experienced a neutropenia-related hospitalization and 21% discontinued their chemotherapy regimen prior to completion. Adjusted risks of both adverse events were similar between those exposed and unexposed to the potential DDI [neutropenia-related hospitalization: adjusted RR (aRR) = 0.92 (0.70–1.21); treatment discontinuation: aRR = 1.00 (0.96–1.05)].

Conclusions:

Our results do not support an association between concomitant hydrochlorothiazide use and two clinically relevant adverse chemotherapy-related events.

Impact:

Our results support reassessing and potentially lowering severity of this potential interaction in drug reference databases.
High-Throughput Generation of Bispecific Binding Proteins by Sortase A–Mediated Coupling for Direct Functional Screening in Cell Culture
Authors: Andres Fabio , Schwill Martin , Boersma Ykelien L. , Plückthun Andreas
Published: December 2019

High-throughput construction of multivalent binders and subsequent screening for biological activity represent a fundamental challenge: A linear increase of monovalent components translates to the square of possible bivalent combinations. Even high-efficiency cloning and expression methods become limiting when thousands of bispecific binders need to be screened for activity. In this study, we present an in vitro method for the efficient production of flexibly linked bispecific binding agents from individually expressed and purified monovalent binders. We established a sortase A–mediated coupling reaction to generate bispecific designed ankyrin repeat proteins (DARPins), with an optimized reaction maximizing the bivalent coupling product with low levels of monovalent side-products. These one-pot reaction mixtures could be used directly, without further purification, in cell-based assays. We generated a matrix of 441 different bispecific DARPins against the extracellular domains of the cancer-associated receptors EGFR, ErbB2, ErbB3, ErbB4, EpCAM, and c-MET and screened on two different ErbB2-positive cancer cells lines for growth-inhibitory effects. We identified not only known but also novel biologically active biparatopic DARPins. Furthermore, we found that the cancer cell lines respond in a highly reproducible and defined manner to the treatment with the 441 different bivalent binding agents. The generated response profiles can thus be used for functional characterization of cell lines because they are strongly related to the cell line–specific surface receptor landscape. Thus, our method not only represents a robust tool for screening and lead identification of bispecific binding agents, but additionally offers an orthogonal approach for the functional characterization of cancer cell lines.
Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women
Authors: Jiang Ming-Yue , Wu Zeni , Li Tingyuan , Yu Lulu , Zhang Shao-Kai , Zhang Xun , Qu Pengpeng , Sun Peisong , Xi Ming-Rong , Liu Xin , Liao Guangdong , Sun Lixin , Zhang Yongzhen , Chen Wen , Qiao You-Lin
Published: December 2019

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (Ptrend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (Ptrend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8–42.4) and OR for dual stain− (ORDS−) of 3.87(1.89–7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05–21.0) and ORDS− of 1.27(0.38–4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.
Community-Based Upper Gastrointestinal Cancer Screening in a Randomized Controlled Trial: Baseline Results in a Non-high-incidence Area
Authors: Xiao Hai-Fan , Yan Shi-Peng , Chen Yan-fang , Shi Zhaohui , Zou Yan-Hua , Zhu Song-lin , Xu Ke-Kui , Song Ting , Liao Xian-Zhen
Published: December 2019

A cluster-randomized controlled trial (RCT) was conducted to evaluate to the effectiveness of reducing mortality of upper gastrointestinal cancer (UGC) and feasibility of screening through a questionnaire combined with endoscopy in non-high-incidence urban areas in China. The trial design, recruitment performance, and preliminary results from baseline endoscopy are reported. Seventy-five communities in two urban cities with a non-high-incidence of UGC were randomized to a screening endoscopy arm (n = 38) or a control arm (n = 37). In the screening arm, individuals at high risk of UGC underwent endoscopic screening. The primary outcome was the UGC mortality, and secondary outcomes included the UGC detection rate, incidence rate, survival rate, and clinical stage at the time of diagnosis. A total of 10,416 and 9,565 individuals were recruited into the screening and control arms, respectively. The participation rate was 74.3%. In the screening arm, 5,242 individuals (50.3%) were estimated to be high-risk. Among them, 2,388 (45.6%) underwent endoscopic screening. Age and household income were associated with undergoing endoscopy. Three early esophageal cancer (0.13%), one gastric cancer (0.04%), 29 precancerous esophageal lesions (1.21%), and 53 precancerous gastric lesions (2.22%) were detected. Age, sex, a family history of cancer, intake of meat–egg–milk frequently, superficial gastritis, and clinical symptoms of gastric cancer were associated with the presence of precancerous lesions. The detection rate was low using endoscopic screening in non-high-incidence area given the relatively low compliance rate. These findings provide a reference for designing effective community-based UGC screening strategies in non-high-incidence urban areas.