bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous Intraoperative Rupture of a Large Interstitial Pregnancy: Laparoscopic Management
Authors: Koukoura Ourania , Dragoumis George , Gorila Georgia , Gkorezi-Ntavela Irontianta , Dafopoulos Konstantinos , Pistofidis George
Published: April 2020

We present a case of a large interstitial pregnancy which was intraoperatively ruptured, but was eventually laparoscopically treated. The patient experienced 9 weeks of amenorrhea, and a right cornual pregnancy measuring 6 cm was diagnosed. The patient consented on having a minimal surgical treatment, and a laparoscopic right cornuotomy was decided. During surgery, and prior to any manipulation to the uterus, there was a spontaneous rupture of the ectopic which resulted in excessive bleeding. Temporal pressure at the bleeding site and ligation of the superior branches of the right uterine artery allowed for a careful dissection of the right uterine cornua and achieved hemostasis. The surgery proceeded uneventfully thereafter. Although surgical intervention in such cases entails a high risk of hemorrhage, successful completion of the laparoscopy lies on the meticulous preoperative planning and the controlled precise surgical steps during the procedure.
Identification of Upper-Limb Movements Based on Muscle Shape Change Signals for Human-Robot Interaction
Authors: Huang Pingao , Wang Hui , Wang Yuan , Liu Zhiyuan , Samuel Oluwarotimi Williams , Yu Mei , Li Xiangxin , Chen Shixiong , Li Guanglin
Published: April 2020

Towards providing efficient human-robot interaction, surface electromyogram (EMG) signals have been widely adopted for the identification of different limb movement intentions. Since the available EMG signal sensors are highly susceptible to external interferences such as electromagnetic artifacts and muscle fatigues, the quality of EMG recordings would be mostly corrupted, which may decay the performance of EMG-based control systems. Given the fact that the muscle shape changes (MSC) would be different when doing various limb movements, the MSC signal would be nonsensitive to electromagnetic artifacts and muscle fatigues and maybe promising for movement intention recognition. In this study, a novel nanogold flexible and stretchable sensor was developed for the acquisition of MSC signals utilized for decoding multiple classes of limb movement intents. More precisely, four sensors were used to measure the MSC signals from the right forearm of each subject when they performed seven classes of movements. Also, six different features were extracted from the measured MSC signals, and a linear discriminant analysis- (LDA-) based classifier was built for movement classification tasks. The experimental results showed that using MSC signals could achieve an average recognition rate of about 96.06 ± 1.84% by properly placing the four flexible and stretchable sensors on the forearm. Additionally, when the MSC sampling rate was greater than 100 Hz and the analysis window length was greater than 20 ms, the movement recognition accuracy would be only slightly increased. These pilot results suggest that the MSC-based method should be feasible in movement identifications for human-robot interaction, and at the same time, they provide a systematic reference for the use of the flexible and stretchable sensors in human-robot interaction systems.
A Hybrid Wi-Fi Fingerprint-Based Localization Scheme Achieved by Combining Fisher Score and Stacked Sparse Autoencoder Algorithms
Authors: Wang Zhongyuan , Wang Zijian , Fan Li , Yu Zhihao
Published: April 2020

Along with the advancement of wireless technology, indoor localization technology based on Wi-Fi has received considerable attention from academia and industry. The fingerprint-based method is the mainstream approach for Wi-Fi indoor localization and can be easily implemented without additional hardware. However, signal fluctuations constitute a critical issue pertaining to the extraction of robust features to achieve the required localization performance. This study presents a fingerprint feature extraction method commonly referred to as the Fisher score–stacked sparse autoencoder (Fisher–SSAE) method. Some features with low Fisher scores were eliminated, and the representative features were then extracted by the SSAE. Furthermore, this study establishes a hybrid localization model constructed with the use of the global model and the submodel to avoid significant coordinate localization errors attributed to subregional localization errors. Combined with three accessible fingerprint-based positioning methods, namely, the support vector regression, random forest regression, and the multiplayer perceptron classification, the experimental results demonstrate that the proposed methods improve the localization accuracy and response time compared to other feature extraction methods and the single localization model. Compared with some state-of-the-art methods, the proposed methods have better localization performances when large number of features are used.
Hospital Prevalence of Colorectal Cancer among Colonoscopy Recipients Attending a Tertiary Hospital in Oman: A Cross-Sectional Study
Authors: Alsumait Alanoud F. , Al-Farsi Yahya M. , Waly Mostafa I. , Al-Qarshoobi Issa S. , Al-Adawi Samir , Albali Nawaf H. , Al-Moundhri Mansour S.
Published: April 2020

Purpose. Evidence from industrialized/developed countries showed that colorectal cancer (CRC) incidence rates have significantly dropped due to the widespread use of colonoscopy. In Arab countries, however, the CRC had been reported to have increased. Despite the concerted effort in the primary prevention and widespread use of colonoscopy, to our knowledge, there have been no reports of the prevalence rate of CRC among colonoscopy recipients from Oman. This study aims to explore the CRC prevalence estimates over selected sociodemographic characteristics among colonoscopy-recipients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. Methods. This hospital-based cross-sectional study reviewed reports of colonoscopies performed over 5-years of retrospective follow-up at a tertiary hospital in Oman. CRC prevalence estimates were calculated over age, gender, governorate, and time of follow-up. Results. A total of 442 CRC cases were enumerated among 3701 colonoscopies, with an overall CRC prevalence estimate of 11.9 per 100 colonoscopies (95% CI: 10.9, 13.0). Gender-specific CRC prevalence was higher among males compared with females (13.3 vs. 10.5). Age-specific CRC prevalence increased with advancing age, from 2.8 among those less than 40 years of age to 26.5 among aged 70 years or more. Regional CRC prevalence was highest among residents in Batinah Governorate. Over the 5-years of follow-up, there was a slow rise in CRC prevalence with an annual increment of 0.59%. Conclusion. The study provides supportive evidence for a steady increase in CRC prevalence over age categories and years of follow-up and depicted the variations of gender-specific CRC prevalence estimates over increasing age categories. The study calls for timely formulation and adoption of national CRC screening programs centered on the colonoscopy use as primary prevention and maximizing its utilization and efficiency.
Whole-Genome Sequencing of Mexican Strains of Anaplasma marginale: An Approach to the Causal Agent of Bovine Anaplasmosis
Authors: Martínez-Ocampo Fernando , Quiroz-Castañeda Rosa Estela , Amaro-Estrada Itzel , Dantán-González Edgar , de la Torre Jesús Francisco Preciado , Rodríguez-Camarillo Sergio
Published: April 2020

Anaplasma marginale is the main etiologic agent of bovine anaplasmosis, and it is extensively distributed worldwide. We have previously reported the first genome sequence of a Mexican strain of A. marginale (Mex-01-001-01). In this work, we report the genomic analysis of one strain from Hidalgo (MEX-14-010-01), one from Morelos (MEX-17-017-01), and two strains from Veracruz (MEX-30-184-02 and MEX-30-193-01). We found that the genome average size is 1.16-1.17 Mbp with a GC content close to 49.80%. The genomic comparison reveals that most of the A. marginale genomes are highly conserved and the phylogeny showed that Mexican strains cluster with Brazilian strains. The genomic information contained in the four draft genomes of A. marginale from Mexico will contribute to understanding the molecular landscape of this pathogen.
Effect of Ephedra Herb on Erlotinib Resistance in c‐Met‐Overexpressing Non‐Small‐Cell Lung Cancer Cell Line, H1993, through Promotion of Endocytosis and Degradation of c‐Met
Authors: Hyuga Sumiko , Hyuga Masashi , Amakura Yoshiaki , Yang Jinwei , Mori Eiko , Hakamatsuka Takashi , Goda Yukihiro , Odaguchi Hiroshi , Hanawa Toshihiko
Published: April 2020

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR‐TKIs) are used to treat non‐small‐cell lung cancer (NSCLC), harboring an EGFR‐activating mutation. However, acquired resistance to these treatments emerges after a few years. One of causes of resistance to EGFR‐TKIs is a high level of c‐Met amplification or c‐Met protein overexpression/hyperactivation. Therefore, combination therapy with EGFR‐TKIs and a c‐Met inhibitor is thought to be effective treatment for patients with NSCLC resistance carrying c‐Met amplification and/or protein hyperactivation. Ephedra Herb is a crude drug and is used in Japan as a component in many Kampo formulae. We previously reported that Ephedra Herb extract (EHE) inhibits HGF‐induced phosphorylation of c‐Met by preventing c‐Met tyrosine kinase activity. Thus, we investigated the combination effect of EHE and erlotinib, an EGFR‐TKI, on growth of H1993 cells, an erlotinib‐resistant NSCLC cell line with overexpression of c‐Met. The EHE and erlotinib combination proved to be effective in suppression of the growth of H1993 xenograft tumors and on inhibition of proliferation of H1993 cells, suggesting that EHE is effective in rescuing NSCLC cells from erlotinib resistance. Moreover, EHE not only inhibited the phosphorylation of c‐Met, but also downregulated the expression of c‐Met by facilitating clathrin‐mediated endocytosis and lysosomal degradation of c‐Met. EHE also promoted downregulation of the expression of EGFR and phosphorylation of EGFR. Ephedrine alkaloids‐free Ephedra Herb extract (EFE) had the same effects as EHE, and the 40% MeOH fraction from EFE, which mainly contained the high‐molecular mass condensed tannins, decreased the expression levels of c‐Met, pMet, EGFR, and pEGFR to almost the same level as EFE. These results suggest that recovery from resistance to erlotinib by EHE is derived from the high‐molecular mass condensed tannins and that EHE may be suitable for treatment of c‐Met‐overexpressing NSCLC with resistance to EGFR‐TKIs.
Phase Transition and Entropy Force between Two Horizons in (n+2)-Dimensional de Sitter Space
Authors: Zhang Yang , Wang Wen-qi , Ma Yu-bo , Wang Jun
Published: April 2020

In this paper, the effect of the space-time dimension on effective thermodynamic quantities in (n+2)-dimensional Reissner-Nordstrom-de Sitter space has been studied. Based on derived effective thermodynamic quantities, conditions for the phase transition are obtained. The result shows that the accelerating cosmic expansion can be attained by the entropy force arisen from the interaction between horizons of black holes and our universe, which provides a possible way to explain the physical mechanism for the accelerating cosmic expansion.
A Competitive Online Algorithm for Minimizing Total Weighted Completion Time on Uniform Machines
Authors: Chu Xuyang , Tao Jiping
Published: April 2020

We consider the classic online scheduling problem on m uniform machines in the online setting where jobs arrive over time. Preemption is not allowed. The objective is to minimize total weighted completion time. An online algorithm based on the directly waiting strategy is proposed. Its competitive performance is proved to be max2smax1−1/2∑si,2smax/1+smax2.5−1/2m by the idea of instance reduction, where sm is the fastest machine speed after being normalized by the slowest machine speed.
Nutrient Release Pattern and Greenhouse-Grown Swiss Chard Response to Biochar Inoculated with Vermicast
Authors: Abbey Lord , Cai Jinsheng , Gunupuru Lokanadha R. , Ijenyo Mercy , Esan Ebenezer O. , Lin Suwen
Published: April 2020

A study was performed to assess nutrient release from biochar inoculated with solid vermicast (SVB), vermicast tea (VTB), deionized water (DWB), uninoculated biochar (Bioc), and Promix-BX (Pro-BX). The growth response of Swiss chard (Beta vulgaris subsp. vulgaris) cv. Rhubarb chard was also assessed. Comparatively, nutrients were released slowly from treatments SVB and VTB compared to the other treatments. The rate of nutrient release determined by total dissolved solids and electric conductivity from the Pro-BX was the highest. The trend for the plant growth components, total leaf surface area and leaf fresh weight at first harvest, was Pro-BX > Bioc > DWB = SVB > VTB. The only treatment that increased total leaf area and leaf fresh weight at the second harvest by approximately 1.02- and 1.88-fold was VTB. Leaf fresh weight was significantly reduced by approximately 0.33-fold for DWB, 0.28-fold for Bioc, and 0.70-fold for Pro-BX but was not altered by SVB at the second harvest as compared to the first harvest. A 2-dimensional principal component analysis (PCA) biplot confirmed that treatment Pro-BX increased plant growth components at the first harvest only. The locations of SVB and VTB on the PCA biplot confirmed their efficacies, which led to increases in the plant growth components at the second harvest. Overall, the VTB adsorbed more nutrients onto its surface that were slowly released to enhance the Swiss chard cv. Rhubarb chard plant growth at the second harvest. Further studies should consider microbial activities.
Effectiveness of Various Final Irrigation Techniques on Sealer Penetration in Curved Roots: A Confocal Laser Scanning Microscopy Study
Authors: Yilmaz Ayca , Yalcin Turgut Y. , Helvacioglu-Yigit Dilek
Published: April 2020

Objective. To compare the efficacy of various techniques used for final irrigation on sealer penetration in the apical one‐third of curved root canals. Material and Methods. Sixty‐five freshly extracted maxillary first molar teeth with mesiobuccal roots having more than 20° of root curvature were used. The root canals were instrumented and randomly divided into four experimental groups and one control group. In the 4 experimental groups, 3 ml of 17% EDTA followed by 3 ml of 5.25% NaOCl was delivered with the use of the following protocols: Group 1: manual dynamic activation (MDA), Group 2: sonic irrigation (SI), Group 3: passive ultrasonic irrigation (PUI), and Group 4: conventional needle irrigation (CI). All teeth were obturated with gutta‐percha and AH Plus sealer labeled with fluorescent dye. Transverse sections at 2 mm and 4 mm distance from the root apex were examined with the aid of confocal laser scanning microscopy. Total percentage (%) and maximum depth (μm) of sealer penetration were measured. Results. All the experimental groups exhibited significantly higher penetration rates than the control group at both sections (p < 0.05). However, no significant differences were found in the penetration depth and percentage among the four experimental groups evaluated at both sections (p > 0.05). Conclusion. PUI, SI, and MDA did not significantly improve sealer penetration in the apical portion of curved root canals when compared to conventional needle irrigation.
Microbial‐Induced Carbonate Precipitation for Strengthening Soft Clay
Authors: Xiao J. Z. , Wei Y. Q. , Cai H. , Wang Z. W. , Yang T. , Wang Q. H. , Wu S. F.
Published: April 2020

Currently, calcite produced in sediments by microbial‐induced carbonate precipitation (MICP) is mainly used as a strengthening binder in sand because sands are porous and have good permeability. Conventional wisdom does not consider MICP to be suitable for use in soft clay because of the clay particles’ small size and its minimal porosity. Because of the clay’s high water content and complex chemical composition, very little research has been done and not much is known about the use of MICP in soft clay for strength enhancement. For this paper, soft clay specimens were prepared by mixing a solution containing Sporosarcina pasteurii bacteria, solutions with different concentrations of nutrient salts, and soft clay. Unconfined compressive strength tests were carried out on these specimens after they had cured for 28 days in a moisture‐controlled environment. These laboratory tests were used to study the chemical reactions, the clay’s strength, and other influencing factors. The results are as follows: (1) directly mixing a S. pasteurii solution, nutrient salts, and soft clay considerably improves the uniformity of the spatial distribution of the bacteria and the nutrients in the soft clay. Directly mixing these constituents promotes the formation of calcium carbonate and greatly simplifies soft clay sample preparation. (2) It is feasible to use MICP to increase the strength of soft clay. Compared to control specimens cured under the same conditions but without introduced nutrients and bacteria solution, the unconfined compressive strength of MICP‐treated specimens can be increased by as much as 2.42 times to an unconfined compressive strength of 43.31 kPa. The water content in MICP‐treated specimens was significantly reduced by the MICP reactions and in one case decreased from 40% to 30.73%. (3) The strength enhancement of microbially solidified soft clay is the result of two processes: urea hydration catalyzed by enzymes consumes water in the clay and the bacterially precipitated calcite forms in the sediment’s pores. (4) The micro‐organism‐produced calcite in the soft clay increases the calcite abundance from 0% to as much as 3.5%. (5) The MICP‐treated strength of soft clay varies with the concentration of the nutrients provided. For the experimental conditions used for this paper, the optimum concentration of the CaCl2·2H2O and CH4N2O nutrients is 0.5 mol/L.
Diabetes and Risk of Post-Fragility Hip Fracture Outcomes in Elderly Patients
Authors: Tian Wenqing , Wu Jueli , Tong Tao , Zhang Lu , Zhou Aiguo , Hu Ning , Huang Wei , Zhou Bo
Published: April 2020

Objective. To explore the effect of diabetes on short-term (30 days after fracture) and 1-year outcomes for fragility hip fracture patients. Methods. We conducted a retrospective cohort study involving 161 diabetic hip fracture patients (older than 60 years) and 483 nondiabetic hip fracture patients. Patients were followed up on day 30 and 1 year after fracture. The short-term outcome was complications that occurred within 30 days after hip fracture and length of stay. The 1-year outcomes were postfracture functional outcomes and reduced activity level and mortality rate within 1 year after fracture. The clinical characteristics and outcomes of patients were analyzed. Results. Compared with nondiabetic patients, diabetic patients had a longer length of awaiting surgery (6.0 vs. 5.0 days, P=0.031) and a longer length of total hospital stay (17 vs. 15 days, P<0.001). Furthermore, compared with nondiabetic patients, diabetic patients have higher costs (P=0.011), in addition to being more prone to developing urinary tract infections (6.2% vs. 1.7%, P=0.002) and deep vein thrombosis (4.3% vs. 1.4%, P=0.029) complications. However, at one-year follow-up, no differences in recovery of function and mortality were observed between the two groups. Conclusions. Diabetic patients are at an increased risk of urinary tract infections and deep vein thrombosis complications but have similar recovery of function and 1-year mortality compared to nondiabetic patients.
Periodic Solution of a Neutral Delay Leslie Predator-Prey Model and the Effect of Random Perturbation on the Smith Growth Model
Authors: Li Tongtong , Zhao Wencai
Published: April 2020

This paper puts forward a class of ratio-dependent Leslie predator-prey models. Firstly, a neutral delay predator-prey model with ratio dependence and impulse control is established and the existence of positive periodic solutions is proved by the coincidence degree theory. Secondly, a stochastic disturbance Leslie model of Smith growth is obtained when the interference of white noise is taken into consideration and the impact of delay is ignored. Applying Ito^’s formula, we get the conditions of system persistence and extinction. Finally we verify the correctness of theoretical analysis with numerical simulations.
Hydrogen Sulfide and β-Synuclein Are Involved and Interlinked in the Aging Glaucomatous Retina
Authors: Liu Hanhan , Mercieca Karl , Anders Fabian , Prokosch Verena
Published: April 2020

Purpose. Glaucoma, one of the leading causes of irreversible blindness worldwide, is a group of disorders characterized by progressive retinal ganglion cell (RGC) loss. Synucleins, a family of small proteins, have been of interest in studies of neurodegeneration and CNS. However, their roles and functions in glaucoma are still not completely understood and remain to be explored. Our previous studies showed that α-synuclein and H2S play a pivotal role in glaucoma. This study aims to (1) elucidate the potential roles and functions of synucleins in glaucoma throughout aging, (2) investigate the interaction between the synucleins and H2S, and better understand the mechanism of H2S in neuroprotection. Methods. The chronic IOP elevation model was carried out in 12 animals at different ages (3 months and 14 months), and RGCs were quantified by Brn3a staining. Mass spectrometric-assisted proteomics analysis was employed to measure synuclein levels and H2S producing proteins in retina. Secondly, the acute IOP elevation model was carried out in 12 juvenile animals, with or without intravitreal injection of GYY4137 (a H2S donor). RGCs were quantified along with the abundancy of synucleins. Results. RGCs and β-synuclein (SNCB) are significantly changed in old animals. Under chronic IOP elevation, there is a significant RGC loss in old animals, whereas no significant change in young animals; SNCB is significantly downregulated and 3MST is significantly upregulated in young animals due to IOP, while no significant changes in old ones are notable. Under acute IOP elevation (approx. 55 mmHg), a significant RGC loss is observed; exogenous H2S significantly reduced RGC loss and downregulated SNCB levels. Conclusion. The present study indicates a strong link between ageing and SNCB regulation. In young animals SNCB is downregulated going along with less RGC loss. Furthermore, increasing endogenous H2S is effective to downregulate SNCB and is neuroprotective against acute IOP elevation.
Nisin Z Production by Wild Strains ofLactococcus lactisIsolated from Brazilian (Italian Type) Fermented Sausage
Authors: Saraiva Margarete Alice Fontes , Birri Dagim Jirata , Brede Dag Anders , Baracat-Pereira Maria Cristina , Queiroz Marisa Vieira de , Nes Ingolf F , Moraes Célia Alencar de
Published: April 2020

In this study, five bacteriocin-producingLactococcus lactisstrains were identified from different naturally fermented Brazilian sausages. Ion exchange and reversed-phase chromatographies were used to purify the bacteriocins from culture supernatant of the five strains. Mass spectrometry (MALDI-TOF/TOF) showed that the molecular masses of the bactericoins fromL. lactisID1.5, ID3.1, ID8.5, PD4.7, and PR3.1 were 3330.567 Da, 3330.514 Da, 3329.985 Da, 3329.561 Da, and 3329.591 Da, respectively. PCR product sequence analysis confirmed that the structural genes of bacteriocins produced by the five isolates are identical to the lantibiotic nisin Z. Optimal nisin Z production was achieved in tryptone and casein peptone, at pH 6.0 or 6.5. The most favorable temperatures for nisin Z production were 25°C and 30°C, and its production was better under aerobic than anaerobic condition. The type of carbon source appeared to be an important factor for nisin Z production. While sucrose was found to be the most efficient carbon source for nisin Z production by fourL. lactisisolates, fructose was the best for one isolate. Lactose was also a good energy source for nisin Z production. Surprisingly, glucose was clearly the poorest carbon source for nisin Z production. The five isolates produced different amounts of the bacteriocin,L. lactisID1.5 and ID8.5 isolates being the best nisin Z producers. DNA sequence analysis did not reveal any sequence differences in thenisZandnisFpromoter regions that could explain the differences in nisin Z production, suggesting that there should be other factors responsible for differential nisin Z production by the isolates.
Targeting p63 Upregulation Abrogates Resistance to MAPK Inhibitors in Melanoma
Authors: Patel Ankit , Garcia Lucia Fraile , Mannella Viviana , Gammon Luke , Borg Tiffanie-Marie , Maffucci Tania , Scatolini Maria , Chiorino Giovanna , Vergani Elisabetta , Rodolfo Monica , Maurichi Andrea , Posch Christian , Matin Rubeta N. , Harwood Catherine A. , Bergamaschi Daniele
Published: April 2020

Targeting the MAPK pathway by combined inhibition of BRAF and MEK has increased overall survival in advanced BRAF-mutant melanoma in both therapeutic and adjuvant clinical settings. However, a significant proportion of tumors develop acquired resistance, leading to treatment failure. We have previously shown p63 to be an important inhibitor of p53-induced apoptosis in melanoma following genotoxic drug exposure. Here, we investigated the role of p63 in acquired resistance to MAPK inhibition and show that p63 isoforms are upregulated in melanoma cell lines chronically exposed to BRAF and MEK inhibition, with consequent increased resistance to apoptosis. This p63 upregulation was the result of its reduced degradation by the E3 ubiquitin ligase FBXW7. FBXW7 was itself regulated by MDM2, and in therapy-resistant melanoma cell lines, nuclear accumulation of MDM2 caused downregulation of FBXW7 and consequent upregulation of p63. Consistent with this, both FBXW7-inactivating mutations and MDM2 upregulation were found in melanoma clinical samples. Treatment of MAPK inhibitor–resistant melanoma cells with MDM2 inhibitor Nutlin-3A restored FBXW7 expression and p63 degradation in a dose-dependent manner and sensitized these cells to apoptosis. Collectively, these data provide a compelling rationale for future investigation of Nutlin-3A as an approach to abrogate acquired resistance of melanoma to MAPK inhibitor targeted therapy.

Significance:

Upregulation of p63, an unreported mechanism of MAPK inhibitor resistance in melanoma, can be abrogated by treatment with the MDM2 inhibitor Nutlin-3A, which may serve as a strategy to overcome resistance.
Diagnostic Capability and Influence Factors for a New Electrocardiogram Criterion in the Diagnosis of Left Ventricular Hypertrophy in a Chinese Population
Authors: Xia Yu , Li Xiaofeng , Zhang Hao , Liu Li , Fu Lijuan , Yan Wei , Li Qingxia , Zhang Yukun , Yu Miao , Liu Jun , Fang Pihua
Published: April 2020

Introduction: Based on a small sample of patients with hypertension, a few studies have reported that the newly proposed SD + SV4 criterion for left ventricular hypertrophy (LVH) is better than traditional criteria. This study aimed to verify the diagnostic capability of the SD + SV4 criterion in a Chinese population with or without hypertension and to analyze the factors affecting the diagnostic accuracy of LVH. Methods: A total of 248 patients with LVH or paroxysmal supraventricular tachycardia (PSVT) discharged from Fuwai Hospital from January 2010 to July 2018 were enrolled. Patients with LVH were diagnosed according to the left ventricular mass index calculated by the echocardiogram parameter as the gold standard in this study. The receiver operating curve (ROC) curve was performed to assess the diagnostic capability and cut-off values of the SD + SV4, RavL + SV3, and SV1 + RV5/RV6 criteria for LVH. Then, multivariate logistic regression analyses were performed to in­vestigate the factors affecting the accuracy of the SD + SV4 criterion. Results: There were 170 (68.5%) patients with hypertension and 110 (44.4%) with PSVT. According to echocardiography, 107 (43.1%) patients were diagnosed with LVH. The area under the curve (AUC) of the SD + SV4 criterion was the largest compared with that of the RavL + SV3 and SV1 + RV5/RV6 criteria (AUC 0.765 vs. 0.718 vs. 0.713, respectively). The sex-specific SD + SV4 criterion had the highest consistency with the gold standard (r = 0.532 ± 0.054, p < 0.01), accompanied by the highest sensitivity (70.1%) and specificity (85.8%). The cut-off values of the sex-specific SD + SV4 criterion for LVH were ≥2.65 mV (male)/2.15 mV (female). The left ventricular ejection fraction (LVEF; OR 0.920, 95% CI 0.882–0.959, p < 0.001) was significantly different between the SD + SV4 criterion and the gold standard for LVH after adjusting for hypertension, PSVT history, body surface area, interventricular septum thickness, posterior wall thickness, and left ventricular internal diameter. Conclusion: The newly proposed SD + SV4 criterion provides improved sensitivity and accuracy for the diagnosis of LVH in the Chinese population. A decrease in LVEF is an independent factor affecting the diagnostic accuracy of LVH.
Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias
Authors: Maiti Abhishek , Franquiz Miguel J. , Ravandi Farhad , Cortes Jorge E. , Jabbour Elias J. , Sasaki Koji , Marx Kayleigh , Daver Naval G. , Kadia Tapan M. , Konopleva Marina Y. , Masarova Lucia , Borthakur Gautam , DiNardo Courtney D. , Naqvi Kiran , Pierce Sherry , Kantarjian Hagop M. , Short Nicholas J.
Published: April 2020

Background: Philadelphia chromosome-positive (Ph+) advanced leukemias, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) in myeloid blast phase (MBP), have poor outcomes. Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKI) in preclinical studies. However, clinical activity of venetoclax and TKI-based regimens is unknown. Methods: We conducted a retrospective study on patients with Ph+ AML (n = 7) and CML-MBP (n = 9) who received venetoclax combined with TKI-based regimens at our institution. Results: Median patient age was 42 years, and the median number of prior therapy cycles was 5 (range 2–8). Nine patients received decitabine-based, and 7 received intensive chemotherapy-based regimens. Ten patients (63%) received ponatinib. The overall response rate (ORR) in 15 evaluable patients was 60% (1 complete remission [CR], 6 CR with incomplete hematologic recovery [CRi], 1 morphologic leukemia-free state, and 1 partial response). The ORR was 43% in Ph+ AML and 75% in CML-MBP. The median overall survival (OS) for all patients was 3.6 months, for AML OS was 2.0 months, and for CML-MBP OS was 10.9 months. The median relapse-free survival for AML and CML-MBP was 3.6 and 3.9 months, respectively. Compared to nonresponders, patients achieving CR/CRi had higher baseline Ph+ metaphases and BCR-ABL1 PCR. Conclusions: Combination therapy of venetoclax with TKI-based regimens shows encouraging activity in very heavily pretreated, advanced Ph+ leukemias, particularly CML-MBP.
Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis
Authors: Snast Igor , Sharon Eran , Kaftory Ran , Noyman Yehonatan , Oren-Shabtai Meital , Lapidoth Moshe , Hodak Emmilia , Mimouni Daniel , Mazor Sigal , Levi Assi
Published: April 2020

Introduction: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. Objectives: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. Methods: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. Results: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2–56 weeks demonstrated CR of 54% (95% CI, 40–67%; I2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22–53%; I2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. Conclusions: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.
Modulation of Airway Epithelial Innate Immunity and Wound Repair by M(GM-CSF) and M(M-CSF) Macrophages
Authors: van Riet Sander , van Schadewijk Annemarie , de Vos Steve , Vandeghinste Nick , Rottier Robbert J. , Stolk Jan , Hiemstra Pieter S. , Khedoe Padmini
Published: April 2020

Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and polarized primary monocyte-derived macrophages. Using this coculture, we studied the contribution of macrophages to epithelial innate immunity, wound healing capacity, and epithelial exposure to whole cigarette smoke (WCS). Coculture of ALI-PBEC with lipopolysaccharide (LPS)-activated M(GM-CSF) macrophages increased the expression of DEFB4A, CXCL8, and IL6 at 24 h in the ALI-PBEC, whereas LPS-activated M(M-CSF) macrophages only increased epithelial IL6 expression. Furthermore, wound repair was accelerated by coculture with both activated M(GM-CSF) and M(M-CSF) macrophages, also following WCS exposure. Coculture of ALI-PBEC and M(GM-CSF) macrophages resulted in increased CAMP expression in M(GM-CSF) macrophages, which was absent in M(M-CSF) macrophages. CAMP encodes LL-37, an antimicrobial peptide with immune-modulating and repair-enhancing activities. In conclusion, dynamic crosstalk between ALI-PBEC and macrophages enhances epithelial innate immunity and wound repair, even upon concomitant cigarette smoke exposure.
The Hamilton Rating Scales for Depression: A Critical Review of Clinimetric Properties of Different Versions
Authors: Carrozzino Danilo , Patierno Chiara , Fava Giovanni A. , Guidi Jenny
Published: April 2020

The format of the original Hamilton Rating Scale for Depression (HAM-D) was unstructured: only general instructions were provided for rating individual items. Over the years, a number of modified versions of the HAM-D have been proposed. They differ not only in the number of items, but also in modalities of administration. Structured versions, including item definitions, anchor points and semi-structured or structured interview questions, were developed. This comprehensive review was conducted to examine the clinimetric properties of the different versions of the HAM-D. The aim was to identify the HAM-D versions that best display the clinimetric properties of reliability, validity, and sensitivity to change. The search was conducted on MEDLINE, Scopus, Web of Science, and PubMed, and yielded a total of 35,473 citations, but only the most representative studies were included. The structured versions of the HAM-D were found to display the highest inter-rater and test-retest reliability. The Clinical Interview for Depression and the 6-item HAM-D showed the highest sensitivity in differentiating active treatment from placebo. The findings indicate that the HAM-D is a valid and sensitive clinimetric index, which should not be discarded in view of obsolete and not clinically relevant psychometric criteria. The HAM-D, however, requires an informed use: unstructured forms should be avoided and the type of HAM-D version that is selected should be specified in the registration of the study protocol and in the methods of the trial.
Neuropsychiatric Symptoms in Mild Cognitive Impairment: A Literature Review
Authors: Martin Evangelia , Velayudhan Latha
Published: April 2020

Background: Neuropsychiatric symptoms (NPS) in dementia have received much attention due to their high prevalence and their significant implications. NPS in mild cognitive impairment (MCI), a clinical concept proposed as an intermediate state between normal aging and dementia, is now gradually gaining in interest. We aimed to conduct a selective review to examine the prevalence rate of NPS in MCI and associations of NPS symptoms with disease progression. Summary: We searched the PubMed database for articles on NPS in MCI and included articles that fulfilled the inclusion criteria. NPS was present in 35–85% of MCI patients. The most common symptoms were depression, irritability, apathy, anxiety, agitation, and sleep problems. Although the associated risk for disease progression of some symptoms, such as apathy and anxiety, was more consistent across studies, evidence was conflicting for symptoms like depression and sleep problems. NPS tend to co-occur, and certain combinations of NPS had a mutual or cumulative effect on disease progression. Late-onset NPS, even in a mild form (mild behavioural impairment) were found to be associated with an increased risk of dementia, even in the absence of cognitive impairment. Key Messages: NPS are highly prevalent in MCI patients and associated with subsequent cognitive deterioration. Late-onset NPS should raise suspicions of neurodegeneration. Future studies with improvised methodology are required to understand the interrelations of NPS and the role they play in the prognosis for patients with MCI.
Clinical Usefulness of Serial Duplex Ultrasound in Cervical Artery Dissection Patients
Authors: Traenka Christopher , Streifler Jonathan , Lyrer Philippe , Engelter Stefan T.
Published: April 2020

Purpose: To study the clinical usefulness of serial color-coded duplex ultrasound (DUS) examinations in cervical artery dissection (CeAD) patients. Methods: Single-center, CeAD registry-based re-review of serial, routine DUS exams in consecutive CeAD patients treated at the Stroke Center Basel, Switzerland (2009–2015). Two experienced raters reassessed all DUS for the occurrence of new arterial findings during follow-up, that is. (i) recanalization of the dissected artery (if occluded at baseline), (ii) delayed occlusion of a patent dissected artery, and (iii) recurrent CeAD. We studied whether these new arterial findings were associated with clinical symptoms. Results: In 94 CeAD patients (n = 40 female [42.6%], median age 46 years [interquartile range (IQR) 36.2–53]), 506 DUS examinations were reviewed covering a median length of follow-up of 54.1 weeks (IQR 30.5–100.5). In total, 105 dissected arteries were detected, of which 27 (25.7%) were occluded. In 28/94 patients (29.8%), 31 new arterial findings were recorded, which were associated with clinical symptoms in 9/31 (30%) patients. Recanalization of occluded CeAD was observed in 22/27 (81.5%) arteries and occurred in 20/22 arteries within 3 months. In 4/22 patients (18.2%), recanalization was associated with clinical symptoms (ischemic events [n = 2], pure local symptoms [n = 2]). Delayed occlusions were observed in 4/78 (5.1%) dissected arteries patent at baseline. All were clinically asymptomatic and occurred within 14 days from baseline. Recurrent CeAD (all symptomatic) occurred in 5 previously non-dissected arteries. Conclusion: In CeAD patients, follow-up DUS identified new arterial findings, of which several were associated with clinical symptoms: we found that about 1 of 5 recanalizations were associated with clinical symptoms, of whom half were ischemic symptoms. Further, delayed occlusions occurred in patients with no or mild stenosis at baseline and were asymptomatic. This study emphasizes the potential importance of repeated DUS in CeAD particularly in the early phase of up to 4 weeks.
A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology
Authors: de Leon Jose , Ruan Can-Jun , Schoretsanitis Georgios , De las Cuevas Carlos
Published: April 2020

Using Richardson and Davidson’s model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level.
Rivaroxaban Versus Apixaban for Stroke Prevention in Atrial Fibrillation
Authors: Bonde Anders N. , Martinussen Torben , Lee Christina J.-Y. , Lip Gregory Y.H. , Staerk Laila , Bang Casper N. , Bhattacharya Jay , Gislason Gunnar , Torp-Pedersen Christian , Olesen Jonas Bjerring , Hlatky Mark A.
Published: April 2020

Background:

The comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) is uncertain, as they have not been compared directly in randomized trials. Previous observational comparisons of NOACs are likely to be biased by unmeasured confounders. We sought to compare the efficacy and safety of rivaroxaban and apixaban for stroke prevention in patients with atrial fibrillation (AF), using practice variation in preference for NOAC as an instrumental variable.

Methods and Results:

Patients started on apixaban or rivaroxaban after newly diagnosed AF were identified using Danish nationwide registries. Patients were categorized according to facility preferences for type of NOAC, independent of actual treatment, measured as fraction of the prior 20 patients with AF initiated on rivaroxaban in the same facility. Facility preference for NOAC was used as an instrumental variable. The occurrence of stroke/thromboembolism, major bleeding, myocardial infarction, and all-cause mortality over 2 years of follow-up were investigated using adjusted Cox regressions. We analyzed 6264 patients with AF initiated on rivaroxaban or apixaban. NOAC preference was strongly related to actual choice of treatment but not associated with any other measured baseline characteristics. Patients treated in facilities that had preference for rivaroxaban had more major bleeding: compared with patients treated in facilities that used rivaroxaban in 0% to 20% of cases, the adjusted hazard ratio for bleeding was 1.06 when treated in a facility with 25% to 40% use; 1.41 with 45% to 60% use; 1.51 with 65% to 80% use; and 1.81 with 0% to 100% use (
P
trend
=0.01). Higher facility preference for rivaroxaban was not significantly associated with increased risk of stroke/thromboembolism (
P
trend
=0.06), myocardial infarction (
P
trend
=0.65), or all-cause mortality (
P
trend
=0.89). When we used the instrumental variable to model the causal relationship between choice of NOAC and major bleeding, relative risk with rivaroxaban was 1.89 (95% CI, 1.06–2.72) compared with apixaban.

Conclusions:

Using instrumental variable estimation in a cohort of patients with AF, rivaroxaban was associated with higher risk of major bleeding compared with apixaban. No significant associations to other outcomes were found in main analyses.
Conjunctive and Elemental Representations of a Context in Humans
Authors: Genheimer Hannah , Andreatta Marta , Pauli Paul
Published: April 2020

The dual-process theory assumes that contexts are encoded in an elemental and in a conjunctive representation. However, this theory was developed from animal studies, and we still have to explore if and how elemental and conjunctive representations contribute to, for example, contextual anxiety in humans. Therefore, 28 participants underwent differential context conditioning in a newly developed flip-book paradigm. Virtual rooms were presented similar to a flip-book, that is, as a stream of 49 consecutive screenshots creating the impression of walking through the rooms. This allowed registration of event-related brain potentials triggered by specific screenshots. During two acquisition phases, two rooms were shown in this way for six times each. In one room, the anxiety context (CTX+), mildly painful electric stimuli (unconditioned stimuli [USs]) were administered unpredictably after 12 distinct screenshots, which became threat elements, whereas 12 selected comparable screenshots became nonthreat elements (elemental representation); all screenshots represented the anxiety context (conjunctive representation). In the second room, the safety context (CTX−), no USs were applied; thus, all screenshots created the safety context whereby 12 preselected screenshots represented safety elements. Increased US expectancy ratings for threat versus nonthreat or safety elements reflected elemental representation. Conjunctive representation was evident in differential ratings (arousal and contingency) and increased P100 and early posterior negativity amplitudes for threat and nonthreat CTX+ versus safety CTX− screenshots. These differences disappeared during two test phases without US delivery indicating successful extinction. In summary, we revealed the first piece of evidence for the simultaneous contributions of elemental and conjunctive representation during context conditioning in humans.