bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence and Structural Characterization of Toll‐Like Receptor 6 from Human and Related Species
Authors: Mustafa Ghulam , Mahrosh Hafiza Salaha , Arif Rawaba
Published: April 2021

Toll‐like receptors (TLRs) play an important role in the innate immune response against various pathogens. They serve as expected targets of natural selection in those species which are adapted to habitats with contrasting pathogen burdens. Till date, sufficient literature about TLRs especially TLR6 is not available. The current study was therefore planned to show evolutionary patterns of human TLRs generally and TLR6 specifically along with their conservation and diversity. The study also deals with characteristic polymorphic patterns of TLR6 in humans which are involved in serious clinical consequences. The sequence analysis of TLR6 from different mammals revealed conserved regions in the protein sequence. With respect to TLR6 evolution, human showed a close evolutionary relationship with chimpanzee and orangutans, while monkeys were appeared in a separate clade showing a distant evolutionary relationship. Old World monkeys and New World monkeys made their separate clades but both have evolved from a common ancestor. The C‐terminal of human TLRs (TLR1 to TLR10) exhibited more conservation as compared to other regions. The phylogram of human TLRs showed that TLR6 is closely related to TLR1 and both TLRs shared a common ancestor with TLR10. The domain analysis has revealed that TLR1 and TLR10 have least (i.e., 4) number of leucine‐rich repeat (LRR) while TLR6 contains five LRRs. Three single nucleotide polymorphisms were found in TLR6 which were found to be associated with benign. Conclusively, the current comparative sequence analyses and phylogenetic analyses provided informative insights into the process of TLR evolution in mammals. Furthermore, the polymorphism analysis would serve as a useful marker in the early detection of susceptibility and resistance against cancers and other diseases in humans.
A Vision‐Based Target Detection, Tracking, and Positioning Algorithm for Unmanned Aerial Vehicle
Authors: Liu Xin , Zhang Zhanyue
Published: April 2021

Unmanned aerial vehicles (UAV) play a pivotal role in the field of security owing to their flexibility, efficiency, and low cost. The realization of vehicle target detection, tracking, and positioning from the perspective of a UAV can effectively improve the efficiency of urban intelligent traffic monitoring. In this work, by fusing the target detection network, YOLO v4, with the detection‐based multitarget tracking algorithm, DeepSORT, a method based on deep learning for automatic vehicle detection and tracking in urban environments, has been designed. With the aim of addressing the problem of UAV positioning a vehicle target, the state equation and measurement equation of the system have been constructed, and a particle filter based on interactive multimodel has been employed for realizing the state estimation of the maneuvering target in the nonlinear system. Results of the simulation show that the algorithm proposed in this work can detect and track vehicles automatically in urban environments. In addition, the particle filter algorithm based on an interactive multimodel significantly improves the performance of the UAV in terms of positioning the maneuvering targets, and this has good engineering application value.
Shenxian-Shengmai Oral Liquid Improves Sinoatrial Node Dysfunction through the PKC/NOX-2 Signaling Pathway
Authors: Zhang Heng , Hao Miao , Li Lingkang , Chen Keyan , Qi Jing , Chen Wei , Cai Xintong , Chen Chen , Liu Zhuang , Hou Ping
Published: April 2021

Sick sinus syndrome (SSS) is one of the common causes of cardiac syncope and sudden death; the occurrence of SSS is associated with the accumulation of ROS in the sinoatrial node (SAN). Shenxian-shengmai (SXSM) is a traditional Chinese medicine available as oral liquid that causes a significant increase in heart rate. The objective of this study is to observe the improvement of SXSM on SAN function in SSS mice and explore its potential mechanism. In the current study, SSS was simulated in mice by inducing SAN dysfunction using a micro-osmotic pump to inject angiotensin II (Ang II). The mouse model with SSS was used to determine the effect of SXSM on SAN function and to explore its potential mechanism. Furthermore, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells. Our results indicated that SXSM significantly increased the heart rate of SSS mice by reducing the AngII-induced accumulation of ROS in the SAN and by inhibiting the expression of HDAC4, thereby reducing the loss of HCN4, a critical component of the cardiac conduction system. MASSON staining revealed a reduction of SAN damage in SSS mice that were treated with SXSM compared with controls. In vitro experiments showed that AngII treatment caused an upregulation of the PKC/NOX-2 signaling pathway in HL-1 cells which could be prevented by pretreatment with SXSM. The protective effect of SXSM was attenuated upon treatment with the PCK agonist PMA. In conclusion, SXSM reduced the AngII-induced accumulation of ROS in the SAN through the PKC/NOX2 signaling pathway, improving the functioning of the SAN and preventing the decrease of heart rate in SSS mice.
Design of a Model Predictive Trajectory Tracking Controller for Mobile Robot Based on the Event-Triggering Mechanism
Authors: He Ning , Qi Lipeng , Li Ruoxia , Liu Yuesheng
Published: April 2021

A novel model predictive control- (MPC-) based trajectory tracking controller for mobile robot is proposed using the event-triggering mechanism, and the aim is to solve the problem that the MPC optimization problem requires a large amount of online computation and communication resources. This method includes two different event-triggering strategies, namely, the event-triggering based on threshold curve and the event-triggering based on threshold band. The selection of the triggering threshold is achieved by applying the statistical method to the historical data of the trajectory tracking of the mobile robot under the classic MPC method. Simulation and experimental tests illustrate that the proposed approach is able to significantly reduce the computation and communication burdens without affecting the control performance. Furthermore, the experimental results show that compared with the classic MPC-based tracking method, the proposed two event-triggering strategies can reduce 28.1% and 75.7% of the computation load and 0.886 s and 2.385 s communication time.
Green, Cost-Effective Simultaneous Assay of Chloramphenicol, Methylparaben, and Propylparaben in Eye-Drops by Capillary Zone Electrophoresis
Authors: Tong Thi Thanh Vuong , Cao Thi Thoa , Tran Nguyen Ha , Le Thi Kim Van , Le Dinh Chi
Published: April 2021

A green, cost-effective, and simple capillary zone electrophoresis (CZE) method was developed and validated for simultaneous determination of chloramphenicol, methylparaben, and propylparaben in eye-drops. With sodium tetraborate as background electrolyte (BGE), the apparent mobilities of chloramphenicol, methylparaben, and propylparaben increased and analysis time reduced when pH of BGE increased from 8.5 to 10.0 and concentration of BGE decreased from 40 mM to 15 mM, but complete separation of chloramphenicol from other matrix components was achieved only with sodium tetraborate concentration at 30 mM or higher and at pH = 9.3 or lower. The most suitable electrophoretic conditions for the intended application were a 30 mM sodium tetraborate solution, pH 9.3 as BGE, working voltage set at 25 kV, and UV detection at 280 nm at the cathodic extremity of the capillary. The final method was validated and proved to be reliable for assay of chloramphenicol, methylparaben, and propylparaben in eye-drops.
Mathematical Modelling and Dynamic Analysis of a Direct‐Acting Relief Valve Based on Fluid‐Structure Coupling Analysis
Authors: Song Wen , Yang Chenshi , Zhang Xiaoyi , Li Yongdong
Published: April 2021

To explain the sudden jump of pressure as the variation of water depth for a direct‐acting relief valve used by torpedo pump as the variation of water depth, a 2‐DOF fluid‐structure coupling dynamic model is developed. A nonlinear differential pressure model at valve port is applied to model the axial vibration of fluid, and a nonlinear wake oscillator model is used to excite the valve element in the vertical direction; meanwhile, the contact nonlinearity between the valve element and valve seat is also taken into consideration. Based on the developed dynamical model, the water depths for the sudden jumps of pressure can be located precisely when compared with the experimental signals, and the corresponding vibration conditions of the valve element in both the axial and vertical directions are explored. Subsequently, in order to eliminate the sudden jumps of pressure, different pump inlet pressure was tested experimentally; when it was decreased to 0.4 MPa, the pressure jumps ever appeared during the dropping and lifting processes were removed, and the numerical simulation based on the developed mathematical model also verified the experimental measurements.
Appling an Improved Method Based on ARIMA Model to Predict the Short‐Term Electricity Consumption Transmitted by the Internet of Things (IoT)
Authors: Guo Ni , Chen Wei , Wang Manli , Tian Zijian , Jin Haoyue
Published: April 2021

The rapid development of the Internet of Things (IoT) has brought a data explosion and a new set of challenges. It has been an emergency to construct a more robust and precise model to predict the electricity consumption data collected from the Internet of Things (IoT). Accurately forecasting the electricity consumption is a crucial technology for the planning of the energy resource which could lead to remarkable conservation of the building electricity consumption. This paper is focused on the electricity consumption forecasting of an office building with a small‐scale dataset, and 117 daily electricity consumption of the building are involved in the dataset, among which 89 values are selected as the training dataset and the remaining 28 values as the testing dataset. The hybrid model ARIMA (autoregression integrated moving average)‐SVR (support vector regression) is proposed to predict the electricity consumption with different prediction horizons ranging from 1 day to 28 days. The model performances are assessed by three evaluation indicators, respectively, are the mean squared error (MSE), the root mean square error (RMSE), and the mean absolute percentage error (MAPE). The proposed model ARIMA‐SVR is compared with the other four models, respectively, are the ARIMA, ARIMA‐GBR (gradient boosting regression), LSTM (long short‐term memory), and GRU (gated recurrent unit) models. The experiment result shows that the ARIMA‐SVR model has lower prediction errors when the prediction horizon is within 20 days, and the ARIMA model is better when the prediction horizon is in the interval of 20 to 28 days. The provided method ARIMA‐SVR has higher flexibility, and it is a great choice for electricity consumption prediction with more accurate results.
Investigation on the Characteristics of a Combination Microflow Control Valve
Authors: Wang Yuqi , Liu Xinhui , Chen Jinshi , Han Yafang , Liu Siyuan , Huo Dongyang
Published: April 2021

Flow control valves have broad application prospects in aviation hydraulic systems. This paper proposes a combination microflow control valve (CMCV) instead of the traditional valve to optimize the performance. Influences of structural parameters of CMCV on its characteristics are numerically investigated to determine the static and dynamic characteristics of CMCV. The calculation results indicate that there is a negative feedback control between stages of the flow regulator, the orifice pressure drop is compensated, and the flow regulation deviation is reduced. The orifice area and the flow regulator valve port area have significant effects on flow characteristics. The diameter of orifice, the spring stiffness, the number of throttle holes, and the ultimate displacement of sleeve are positively correlated with the flow rate stability value of the valve. The valve port flow area gradient and initial overlap of the flow regulator affect the flow rate fluctuation range and response time of CMCV.
Strain Accumulation in Soft Marine Clay due to One‐Way Cyclic Load with Variable Confining Pressure
Authors: Sun Lei
Published: April 2021

The effect of variable confining pressure on the strain accumulation in soft marine clay was investigated to gain a better understanding of the deformation characteristic in the subgrade of pavements due to traffic loading. A series of variable confining pressure (VCP) experiments and corresponding constant confining pressure (CCP) experiments were conducted on Wenzhou soft clay using an advanced cyclic triaxial apparatus. A wide range of deviatoric stress amplitudes (qampl), combined with different isotropic stress amplitudes (pampl), and partially drained conditions are simulated in the experiments. The test results indicate that the variable confining pressure significantly influences the permanent axial strain and might exacerbate the potential of subgrade invalidation in soft marine clay area. The normalized permanent axial strain () after 1000 cycles is logarithmic with the normalized stress path length (L/LCCP), and one‐unit increment in the amplitude of cyclic confining pressure will induce an increment of 0.0213% in the permanent axial strain regardless of the CSR values. Based on the data from the CCP tests, a cyclic deviatoric stress ratio threshold is determined to be about 0.7, which may suggest that the upper bound of criterion will limit the cyclic traffic loadings on soft marine clayey deposit. Finally, the effect of variable confining pressure on the permanent axial strain is quantified and incorporated in a logarithmic model for the subsoil deformation prediction under traffic loading.
Drought Analysis in East Nusa Tenggara (Indonesia) Using Regional Frequency Analysis
Authors: Kuswanto Heri , Puspa Anggi Wahyu , Ahmad Imam Safawi , Hibatullah Fausania
Published: April 2021

Drought is a condition of a shortage of water that has an impact on economic activity. This research studies the severe drought area in Indonesia using Regional Frequency Analysis (RFA), based on daily precipitation data recorded at nine stations. The analysis reveals five homogeneous regions, based on discordancy and heterogeneity tests. Furthermore, the L-moment approach is applied to investigate the regional distribution and suggests that the Pearson type III distribution is the distribution that best fits the five regions. This distribution is also used to calculate the regional growth curve that is employed in the drought analysis. The drought return period analysis, for conditions of 40% of normal rainfall, concludes that the region containing the Fransiskus Xaverius, Gewayantana, and Mali stations has the highest drought risk, indicated by the fastest return period estimate of 2 years and 4 months. Moreover, the extreme drought analysis shows that two of the regions have the potential to experience the return of extreme drought, with less than 20% of normal rainfall, in less than four years.
Predictive Performances of Blood Parameter Ratios for Liver Inflammation and Advanced Liver Fibrosis in Chronic Hepatitis B Infection
Authors: Ding Rongrong , Zhou Xinlan , Huang Dan , Wang Yanbing , Li Xiufen , Yan Li , Lu Wei , Yang Zongguo , Zhang Zhanqing
Published: April 2021

Objective. Blood parameter ratios, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), have been reported that they are correlated to the progression of liver disease. This study is aimed at evaluating the predictive value of PLR, NLR, and MLR for liver inflammation and fibrosis in patients with chronic hepatitis B (CHB). Methods. We recruited 457 patients with CHB who underwent a liver biopsy and routine laboratory tests. Liver histology was assessed according to the Scheuer scoring system. The predictive accuracy for liver inflammation and fibrosis was assessed by receiver operating characteristics (ROC) analysis. Results. PLR and NLR presented significantly reverse correlation to liver inflammation and fibrosis. However, these correlations were not observed for MLR and liver histology. The AUROCs of PLR for assessing G2‐3 and G3 were 0.676 and 0.705 with cutoffs 74.27 and 68.75, respectively. The AUROCs of NLR in predicting inflammatory scores G2‐3 and G3 were 0.616 and 0.569 with cutoffs 1.36 and 1.85, respectively. The AUROCs of PLR for evaluating fibrosis stages S3‐4 and S4 were 0.723 and 0.757 with cutoffs 79.67 and 74.27, respectively. The AUROCs of NLR for evaluating fibrosis stages S3‐4 and S4 were 0.590 with cutoff 1.14. Conclusion. Although PLR has similar predictive power of progressive liver fibrosis compared with APRI, FIB‐4, and GPR in CHB patients, it has the advantage of less cost and easy application with the potential to be widely used in clinical practice.
Revealing Topography Evolution of Glass Surface under Air Pollution by Atomic Force Microscope
Authors: Huaicheng Zhou , Lei Wu , Bingjun Yu , Na Qin
Published: April 2021

Air pollution has become a matter of close concern to people with the continuous development of human society. However, the knowledge of air pollution mechanisms remains insufficient, and there is a lack of evaluation methods for actual pollution. In this paper, air pollution in Internet cafe was studied by detecting surface topography of glass slides after different exposure time by an atomic force microscope (AFM). It is found that the adsorption of air pollutants on glass surface undergoes initial aggregation, particle growth and interparticle deposition, and final full coverage. The chemical composition of contaminated glass surface was further analyzed by an X-ray photoelectron spectrometer, showing that the pollution was mainly composed of hydrocarbons regardless of exposure time. Cleaning experiments show that NaHCO3 solution can be the most effective one with saponification reaction and hydrolysis to remove the adsorbed contaminations. This study provides an alternative way for investigating air pollution and a reference for cleaning polluted material surfaces.
Compound Fault Diagnosis for Gearbox Based Using of Euclidean Matrix Sample Entropy and One‐Dimensional Convolutional Neural Network
Authors: Zhang Decai , Ren Xueping , Zuo Hanyue
Published: April 2021

Vibration signals of gearbox under different loads are sensitive to the existence of the fault and composite fault vibration signals are complex. Traditional fault diagnosis methods mostly rely on signal processing methods. It is difficult for signal processing methods to separate effective information from those fault signals. Therefore, traditional fault diagnosis methods are difficult to accurately identify those faults. In this paper, a one‐dimensional convolutional neural network (1‐D CNN) intelligent diagnosis method with improved SoftMax function is proposed. Local mean decomposition (LMD) decomposes the signals into different physical fictions (PF). PFs are input into the matrix sample entropy based on Euclidean distance (MESE), and the PFs which best reflect fault characteristics are selected. Finally, the PFs by MESE are used to train the CNN to identify the faults of parallel‐shaft gearbox. Experiment shows that MESE can quickly and accurately select the PFs with the most significant fault features. 1‐D CNN can get nearly 100% recognition rate with less time and the CNN of SoftMax improved can effectively eliminate LMD endpoint effect. This method can successfully identify single faults, combination faults, and faults under different loads of the gearbox. Compared with other methods, this method has the characteristics of high efficiency, accuracy, and strong anti‐interference. Therefore, it can effectively solve the problem of complex fault signal decomposition of gearbox and can diagnose the gearbox fault under different load operation. It has great significance for gearbox fault diagnosis in actual production.
Skin Lesion Classification Using Additional Patient Information
Authors: Sun Qilin , Huang Chao , Chen Minjie , Xu Hui , Yang Yali
Published: April 2021

In this paper, we describe our method for skin lesion classification. The goal is to classify skin lesions based on dermoscopic images to several diagnoses’ classes presented in the HAM (Human Against Machine) dataset: melanoma (MEL), melanocytic nevus (NV), basal cell carcinoma (BCC), actinic keratosis (AK), benign keratosis (BKL), dermatofibroma (DF), and vascular lesion (VASC). We propose a simplified solution which has a better accuracy than previous methods, but only predicted on a single model that is practical for a real‐world scenario. Our results show that using a network with additional metadata as input achieves a better classification performance. This metadata includes both the patient information and the extra information during the data augmentation process. On the international skin imaging collaboration (ISIC) 2018 skin lesion classification challenge test set, our algorithm yields a balanced multiclass accuracy of 88.7% on a single model and 89.5% for the embedding solution, which makes it the currently first ranked algorithm on the live leaderboard. To improve the inference accuracy. Test time augmentation (TTA) is applied. We also demonstrate how Grad‐CAM is applied in TTA. Therefore, TTA and Grad‐CAM can be integrated in heat map generation, which can be very helpful to assist the clinician for diagnosis.
Complex System Analysis of Blumeria graminis f.sp. tritici Isolates Collected in Central Hebei Province, China
Authors: Zhou Qingping , Li Lingli , Wang Long
Published: April 2021

Wheat powdery mildew (WPM), caused by Blumeria graminis f.sp. tritici, is a significant disease of wheat throughout the world and has resulted in substantial yield and economic losses in wheat production. It is particularly important to understand the population distribution and genetic resistance of B. graminis f.sp. tritici. In 2019, the cumulative incidence of wheat powdery mildew in China was nearly 8.7 million hm2, which seriously affected the safe production of wheat in China. However, the proportion of disease-resistant wheat varieties in actual production was relatively low, and effective disease-resistant genes were lacking. As one of the main wheat-producing provinces in China, it is of great significance for normal wheat production to understand powdery mildew resistance in Hebei province. In this study, using wheat seedling culture in vitro, the physiological races of wheat powdery mildew in central Hebei province were identified, and the population toxicity frequency was analyzed. The results were as follows: (1) 36 strains were purified and 20 physiological races were identified. Among them, the dominant race is 015, and the distribution frequency is 16.7%. Race 077 is the second dominant race. (2) The frequency of virulence genes VEra, V8, V1, V3c, and V3f in population toxicity frequency analysis was more than 70%, while the frequency of virulence genes V2, MID, V20, V21, V4b, and V4 was less than 16.7%, and 46% of virulence genes of powdery mildew were higher than 40%. It shows that the virulence gene frequency of powdery mildew in Hebei province is high, and the varieties containing Pm2 + MID, Pm20, Pm21, Pm1b, Pm1, and other disease resistance genes have a certain value inbreeding.
Effect of Dexamethasone Implant on Subfoveal Choroidal Thickness in Early Period in Vitrectomized Eyes with Diabetic Macular Edema
Authors: Altun A. , Hacimustafaoglu A. M.
Published: April 2021

Aim. To investigate the change in subfoveal choroidal thickness (SFCT) in vitrectomized eyes with intravitreal dexamethasone (IVD) implant injection for the treatment of diabetic macular edema (DME). Method. In this prospective and controlled study, the vitrectomized eyes of diabetic patients were included. The study group (Group 1) was formed by diabetic vitrectomized eyes with DME. The control group (Group 2) was formed by diabetic vitrectomized eyes without DME. Only one intravitreal IVD implant was injected into the eyes in Group 1. In the first, second, and fourth months, choroidal layers were measured by optical coherence tomography and complete ophthalmologic examinations were performed for all cases. Results. Ninety-six eyes of 96 cases were included in the study. There were 48 eyes of 48 different patients in each group. After IVD injection, statistically significant improvement was observed in the best corrected visual acuity in Group 1. The mean SFCT in eyes with DME was statistically significantly thinner (

p

 < 0.01) and thinness became more pronounced during the four-month follow-up period after IVD implant injection (

p

 < 0.01). Conclusion. In the presence of DME in vitrectomized eyes, the thinness of the SFCT may become evident after dexamethasone implant injection.
An Elegant Solution to a Ruptured Right Aberrant Subclavian Artery after Oesophageal Stent Removal
Authors: Thompson Daniel , Cerutti Sophie , Peerbux Muhammad , Ikponmwosa Anna , Bookun Hansraj , Lahham Yahya
Published: April 2021

Arterioenteric or arteriotracheal fistula is a known complication of an aberrant right subclavian artery (ARSA) and is often associated with prolonged nasogastric or endotracheal intubation or oesophageal stenting. Fistula formation from the ARSA can present unexpectedly with rapid exsanguination with massive haemoptysis or haematemesis, and unless promptly recognised and treated is rapidly fatal. We present a novel endovascular method for treating a fistula between the oesophagus, trachea and an ARSA in an unstable patient following oesophageal stent removal, utilising a covered iliac limb stent, eliminating the need for an open surgical approach.
Effects of Message Framing on Cervical Cancer Screening Knowledge and Intentions Related to Primary HPV Testing
Authors: Ogden Shannon N. , Leskinen Emily A. , Sarma Elizabeth A. , Wainwright Jocelyn V. , Rendle Katharine A.
Published: April 2021

Numerous national guidelines now include primary human papillomavirus (HPV) testing as a recommended screening option for cervical cancer in the United States yet little is known regarding screening intentions for this specific screening strategy or interventions that may increase uptake. Gain- and loss-framed messaging can positively impact health behaviors; however, there is mixed evidence on which is more effective for cervical cancer screening, with no published evidence examining HPV testing. To help address this gap, this study compared the effects of message framing on screening knowledge and intentions related to primary HPV testing. We randomized females aged 21–65 (n = 365) to receive brief messaging about cervical cancer screening with either gain- or loss-framing. In January–February 2020, participants completed pretest and posttest measures evaluating cervical cancer knowledge, beliefs, and intentions to be screened using HPV testing. We used generalized estimating equations to model message and framing effects on screening outcomes, controlling for age, education, race, and baseline measures. In comparison to pretest, messaging significantly increased HPV-related screening intentions [adjusted OR (aOR): 2.4 (1–3.5)] and knowledge [aOR: 1.7 (1.2–2.4)], perceived effectiveness of HPV testing [aOR: 4.3 (2.8–6.5)], and preference for primary HPV screening [aOR: 3.2 (1.2–8.5)], regardless of message framing. For all outcomes, no significant interaction by message framing was observed. Brief public health messaging positively impacted HPV-related screening intentions, knowledge, and beliefs, independent of message framing. In conjunction with other strategies, these results suggest that messaging could be an effective tool to increase uptake of primary HPV testing.

Prevention Relevance:

Primary HPV tests are more sensitive and offer greater reassurance than Pap tests alone yet use for routine cervical cancer screening remains low. Brief public health messaging can positively impact awareness, knowledge, and screening intention regarding primary HPV testing. Messaging campaigns paired with other strategies can increase uptake across populations.

See related Spotlight, p. 823
Determinants of Response and Intrinsic Resistance to PD-1 Blockade in Microsatellite Instability–High Gastric Cancer
Authors: Kwon Minsuk , An Minae , Klempner Samuel J. , Lee Hyuk , Kim Kyoung-Mee , Sa Jason K. , Cho Hee Jin , Hong Jung Yong , Lee Taehyang , Min Yang Won , Kim Tae Jun , Min Byung-Hoon , Park Woong-Yang , Kang Won Ki , Kim Kyu-Tae , Kim Seung Tae , Lee Jeeyun
Published: April 2021

Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers and associated with clinical response to anti–PD-1 antibodies. However, 50% of microsatellite instability–high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. The number of whole-exome sequencing (WES)–derived nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS). Coupling WES to single-cell RNA sequencing, we identified dynamic tumor evolution with greater on-treatment collapse of mutational architecture in responders. Diverse T-cell receptor repertoire was associated with longer PFS to pembrolizumab. In addition, an increase in PD-1+ CD8+ T cells correlated with durable clinical benefit. Our findings highlight the genomic, immunologic, and clinical outcome heterogeneity within MSI-H gastric cancer and may inform development of strategies to enhance responsiveness.

Significance:

This study highlights response heterogeneity within MSI-H gastric cancer treated with pembrolizumab monotherapy and underscores the potential for extended baseline and early on-treatment biomarker analyses to identify responders. The observed markers of intrinsic resistance have implications for patient stratification to inform novel combinations among patients with intrinsically resistant features.

See related commentary by Fontana and Smyth, p. 2126.

This article is highlighted in the In This Issue feature, p. 2113
Vitiligo with Progressive Repigmentation during Secukinumab Treatment in a Patient with Psoriatic Arthritis: A Case Report
Authors: Giordano Domenico , Magri Francesca , Persechino Flavia , Lepore Alejandra , Verde Romina , Capalbo Alessandro , Persechino Severino
Published: April 2021

The proposed role of interleukin (IL)-17 in vitiligo pathogenesis, as well as the possible action of anti-IL-17A drugs on vitiligo, are not fully understood. The appearance of vitiligo as a paradoxical effect of treatment with anti-tumor necrosis factor-α drugs is an event well known in the literature, but is rarely described with anti-IL-17A drugs. In this case report, we describe a 42-year-old woman who developed new-onset vitiligo with repigmentation during successful secukinumab therapy for psoriatic arthritis. After 1 year of secukinumab therapy, vitiligo affecting >85% of the skin was evident on clinical and dermatoscopic examination, together with small, repigmented lesions. In depigmented lesions, reflectance confocal microscopy (RCM) showed disappearance of the bright dermal papillary rings normally seen at the dermo-epidermal junction. In repigmented lesions, activated dendritic melanocytes were observed on RCM. The patient continued to receive secukinumab, and continued to experience a slow and progressive repigmentation. Our case shows that anti-IL-17A biological agents for chronic inflammatory diseases may be associated with the development of new-onset vitiligo that improves over time with ongoing therapy. Therefore, physicians should be aware of the possibility of this rare paradoxical skin reaction in patients receiving secukinumab, and that it may not be necessary to discontinue secukinumab to achieve repigmentation.
Foveal-Sparing ILM Peeling in a Case with Vitreomacular Traction and Foveal Detachment
Authors: Leisser Christoph , Findl Oliver
Published: April 2021

A pseudophakic female patient, 80 years of age, presented with a vitreomacular traction and foveal detachment at her right eye. To avoid development of a full-thickness macular hole during surgery, foveal-sparing ILM peeling was performed. After surgery, distance-corrected visual acuity increased from 0.3 to 0.6 (Snellen) 3 months after surgery and fovea was re-attached again with restoration of the retinal layers.
Primary Orbital Chondromyxoid Fibroma: A Cause of Monosymptomatic Periocular Pain
Authors: Hildestad Louise , Heegaard Steffen , Toft Peter Bjerre
Published: April 2021

Chondromyxoid fibroma (CMF) is a very rare entity, accounting for <1% of all bone tumours. So far, only 4 cases have been reported with the orbit as primary location. Here, we present a case of orbital CMF with periocular pain as the presenting symptom and as the only symptom when the tumour recurred after surgery. A 41-year-old man underwent a CT scan and later an MRI as part of evaluation for left periocular pain that had persisted for a year. Clinical examination was normal. CT and MRI revealed an irregular mass in the lateral part of the left orbital roof. The tumour was removed by curettage, and histopathological examination showed a CMF. The pain was absent for 3 months. A second MRI 5 months postoperatively revealed a recurrence, which was removed surgically, resulting in pain alleviation. In conclusion, CMF is a potential cause of periocular pain, and persistent periocular pain with normal clinical findings should warrant a CT or MRI scan.
Four Cases of Rhegmatogenous Retinal Detachment That Recurred More than 10 Years after Initial Reattachment by Pars Plana Vitrectomy
Authors: Baba Takayuki , Tatsumi Tomoaki , Oshitari Toshiyuki , Yamamoto Shuichi
Published: April 2021

Purpose: The purpose of this report was to present our findings in 4 cases of rhegmatogenous retinal detachment (RRD) that recurred 10, 11, 12, and 17 years after a reattachment surgery by pars plana vitrectomy (PPV). Methods: Four cases of a recurrent RRD had undergone scleral buckling surgery and vitrectomy. Patients: The recurrence of the RRD was observed 10–17 years after the successful attachment by PPV. The macula was detached in all cases, and none of the eyes had severe proliferative vitreoretinopathy. The cause of the recurrence was a new retinal break in 3 eyes and a reopening of an old retinal break in the other eye. The new breaks had a punched-out shape and had neither a horseshoe tear nor an atrophic hole associated with lattice degeneration. PPV combined with scleral buckling was performed, and a reattachment was achieved in all cases. The best-corrected visual acuity (BCVA) at the last visit ranged from 20/30 to 20/25, but the BCVA in 1 eye was 20/200 because of amblyopia. Conclusions: We experienced 4 rare cases of a recurrent retinal detachment 10–17 years after the primary RRD. PPV and scleral buckling were effective and the anatomical and the functional outcomes were good.
Combined Bacterial and Herpes Simplex Virus Keratitis following Small-Incision Lenticule Extraction for the Correction of Myopia
Authors: Ramirez-Miranda Arturo , Mangwani-Mordani Simran , Quiroz-Casian Natalia , Oliva-Bienzobas Valeria , Cabral-Macias Jesus , Navas Alejandro , Graue-Hernandez Enrique O.
Published: April 2021

A 28-year-old male presented unilateral visual loss, intense ocular pain, redness and intraocular hypertension in his right eye 2 days after undergoing small-incision lenticule extraction (SMILE) in both eyes. Initial examination of the affected eye revealed the presence of white infiltrates within the corneal interface, as well as a central epithelial defect. The patient was diagnosed with infectious keratitis, posteriorly the eye was irrigated with balanced saline solution and treatment was initiated with hourly moxifloxacin 0.5%. Since this approach failed to resolve symptoms, a sample from the interface was obtained for PCR assay, which revealed the presence of herpes simplex virus DNA, confirming the cause of the infection. The patient was prescribed a regimen of oral acyclovir, topical ganciclovir and prednisolone. Clinical improvement following resolution of the epithelial defect was observed. Although rare, herpetic keratitis following SMILE is best managed via early diagnosis and initiation of appropriate anti-herpetic treatment.
Recalcitrant Pseudomonas Aeruginosa Keratitis with Hyphaema
Authors: Chan Amy , Oo Hnin Hnin , Stanley Philip , Chang Benjamin
Published: April 2021

Purpose: To report a case of recalcitrant pseudomonas keratitis with a rare presentation of hyphaema. Observation: A 45-year-old female was noted to have contact lens-related pseudomonas keratitis with hyphaema. The organism was refractory to multiple antibiotics and only responded to Tazocin eye drops. Conclusion and Importance: Hyphaema is a rare presentation in bacterial keratitis and could represent infection with an especially virulent organism. Use of Aspirin could precipitate hyphaema in infective keratitis. Alternative antibiotic choices such as Tazocin, colistin, meropenem, and imipenem can be considered when standard therapy is ineffective for multidrug-resistant Pseudomonas keratitis.
Iatrogenic Retinal Penetration from Intravitreal Injections
Authors: Kishore Kamal , McGowan Daniel S. , Hanebrink Kurt A.
Published: April 2021

We present 2 cases of iatrogenic retinal penetration from intravitreal (IVT) injections in a retrospective noncomparative case series of 2 patients. The first patient, an 81-year-old Caucasian male, developed dense vitreous hemorrhage soon after receiving an IVT bevacizumab injection for macular edema from central retinal vein occlusion. A 25-g vitrectomy 1 week later showed a retinal hole surrounded by fresh hemorrhages in the same quadrant as the IVT injection. The second patient, an 87-years-old male, developed a retinal detachment after 28 injections of anti-VEGF medications for neovascular AMD. A peripheral round hole was observed during vitrectomy without any lattice degeneration in the same quadrant as prior IVT injections. Both eyes were pseudophakic, had normal axial lengths, and received injections without measuring the injection site. Retinal penetration from IVT injections can result in serious sight-threatening complications. Measuring the injection site from the limbus should be part of safe IVT injection technique.
Near-Infrared Reflectance Imaging to Detect an Incipient Retinal Arterial Macroaneurysm
Authors: Zienkiewicz Anastasia , Francone Anibal , Cirillo Maria Paz , Zompa Tamara , Charles Martin
Published: April 2021

Retinal arterial macroaneurysms (RAM) are characterized by a saccular or fusiform dilation of the retinal artery wall. An 84-year-old Caucasian woman with a medical history of poorly controlled hypertension was diagnosed with RAM in the left eye. Previous macular spectral-domain optical coherence tomography images from the patient were available for comparison. Near-infrared reflectance imaging (NIR-R), taken 3 years before, demonstrated a cuff-type thickening of the arteriolar vessel wall at the site of the current complicated RAM that had gone completely unnoticed. These findings suggest that NIR-R may contribute to the detection of early damage of the arterial wall that may predict arterial aneurysm formation in hypertensive patients.
Iridotrabecular and Iridocorneal Contact Changes after Cataract Surgery and Endothelial Keratoplasty in Bilateral Iridoschisis
Authors: Omoto Takashi , Agata Chisato , Akiyama Reina , Kitamoto Kohdai , Toyono Tetsuya , Yoshida Junko , Yamagami Satoru , Usui Tomohiko , Miyai Takashi
Published: April 2021

We report a case of bilateral iridoschisis with corneal oedema and a quantitative evaluation of the changes in iridotrabecular and iridocorneal contact before and after cataract surgery and after Descemet stripping automated endothelial keratoplasty (DSAEK). A 76-year-old woman with iridoschisis and cataracts, previously managed with laser iridotomy, experienced progressive vision loss. The preoperative iridotrabecular contact (ITC) index measured by anterior segment optical coherence tomography was 23.6% in the right eye and 24.4% in the left eye. Preoperative corneal oedema in the right eye was more severe than that in the left eye. Cataract surgery, followed by DSAEK, was performed in the right eye and subsequently in the left eye. Her visual acuity improved postoperatively, and the corneal oedema of both eyes was treated successfully. Moreover, the ITC index improved in both eyes, to 4.7 and 6.9% after cataract surgery and to 0 and 0% after DSAEK in the right and left eyes, respectively. Staged cataract surgery and DSAEK were effective for endothelial decompensation caused by iridoschisis. Additionally, we confirm that iridotrabecular and iridocorneal contacts improved after both surgical procedures not only after cataract surgery but also after DSAEK. This case report showed the clinical usefulness of the ITC index in the detection of changes after different surgical procedures.
Ibuprofen-Induced Aseptic Meningitis in a Male Adolescent with Intracranial Hypertension and Visual Impairment: A Case Report
Authors: Mousavi Mirzaei Seyed Mohammad , Ahmadi Zahra
Published: April 2021

Drug-induced aseptic meningitis (DIAM) is a rare complication of certain drugs, most commonly reported with ibuprofen use. The present study reports on a male adolescent with intracranial hypertension and visual impairment accompanied by DIAM. We present a 16-year-old male patient who after ibuprofen consumption displayed headache, fever, photophobia, and blurred vision following heavy exercises. Examination of cerebrospinal fluid showed a mononuclear pleocytosis and an increase in protein concentration. Other examinations had normal results. The development of common clinical signs following ibuprofen use reflected DIAM. The patient’s vision was found to improve with supportive care and stopping of the drug during follow-up. Given the widespread use of nonsteroidal anti-inflammatory drugs and the fact that these drugs are the most common cause of DIAM, the probability of occurrence of this event should be always kept in mind, and screening for autoimmune diseases in these patients is of great importance.
Atypical Evolution of Secondary Hemolytic Uremic Syndrome Defined as Paraneoplastic Syndrome under Eculizumab and Palbociclib Therapies
Authors: Perrier Quentin , Noble Johan , Grangé Steven , Bedouch Pierrick , Tetaz Rachel , Rostaing Lionel
Published: April 2021

Thrombotic microangiopathy (TMA) is most of the time caused by thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. A 60-year-old female was diagnosed in 2014 with mammary breast adenocarcinoma treated by several-line therapy: mastectomy, docetaxel, cyclophosphamide, radiotherapy, doxorubicine, and capecitabine. By mid-November, the patient was admitted to the hospital with regenerative, mechanical, and hemolytic anemia, schistocytes at 3%, and thrombopenia (99 G/L), associated with high blood transfusion requirement. After 9 sessions of plasmapheresis, there was no significant improvement in the biological parameters, nor after 2 cycles of paclitaxel. The patient was then treated with eculizumab during 4 weeks, with a slight reduction in blood requirement, and simultaneously with palbociclib. Since being treated with palpociclib, she had a great reduction in blood requirement and a good clinical condition. To conclude, we reported an initial moderate improvement of paraneoplasm-related TMA syndrome under eculizumab therapy with a slight reduction in red blood cell requirement; however, palbociclib therapy achieved a very good response with a dramatic reduction in red blood cell requirement.
Stroke due to Left Atrial Appendage Thrombus after Pulmonary Vein Isolation despite Novel Oral Anticoagulant: A Case Report
Authors: Chae Woon Hyung , Wieneke Heinrich , Dykun Iryna , Deuschl Cornelius , Köhrmann Martin , Frank Benedikt
Published: April 2021

In patients with atrial fibrillation, catheter ablation is suggested to reduce the mortality rate and is thus frequently performed. However, peri- and postprocedural thromboembolic complications as well as high recurrence rates of atrial fibrillation limit its advantages and require concomitant anticoagulation. With the advent of novel oral anticoagulants (NOACs), fixed dosing without routine laboratory monitoring became feasible. Nevertheless, several factors are associated with either an overdose or an insufficient drug activity of NOACs. We report on a patient with atrial fibrillation undergoing catheter ablation and cardioversion suffering from ischemic stroke despite being under oral anticoagulation. It turned out that the drug activity of the NOACs used was repeatedly insufficient in spite of regular intake and adequate dosing. In sum, drug activity controls should be taken into consideration in patients with thrombotic events despite oral anticoagulation with NOACs.
Efficacy and Safety of Cone-Beam Computed Tomography-Derived Augmented Fluoroscopy Combined with Endobronchial Ultrasound in Peripheral Pulmonary Lesions
Authors: Yu Kai-Lun , Yang Shun-Mao , Ko Huan-Jang , Tsai Hui-Yu , Ko Jen-Chung , Lin Ching-Kai , Ho Chao-Chi , Shih Jin-Yuan
Published: April 2021

Background: The diagnostic yield of peripheral pulmonary lesions (PPLs) using radial endobronchial ultrasound (EBUS) remains challenging without navigation systems. Cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) represents a recently developed technique, and its clinical utility remains to be investigated. Objectives: The aim of this study was to investigate the diagnostic yield of transbronchial biopsy (TBB) using a combination of CBCT-AF and radial EBUS. Methods: We recruited consecutive patients with PPLs who underwent radial EBUS-guided TBB, with or without AF, between October 2018 and July 2019. Following propensity score 1:1 matching, we recorded the procedure-related data and measured their efficacy and safety. Results: While 72 patients received EBUS-plus-AF, 235 patients received EBUS only. We included 53 paired patients following propensity score matching. The median size of lesions was 2.8 and 2.9 cm in the EBUS-plus-AF group and EBUS-only group, respectively. Diagnostic yield was higher in the former group (75.5 vs. 52.8%; p = 0.015). The diagnostic yield for the EBUS-plus-AF group was significantly higher for lesions ≤30 mm (73.5 vs. 36.1%; p = 0.002). Moreover, there was no significant difference in the complication rates (3.8 vs. 5.7%; p = 1.000). Twenty-four nodules (45.3%) were invisible by fluoroscopy in the EBUS-plus-AF group. All of them were identifiable on CBCT images and successfully annotated for AF. The mean radiation dose of total procedure, CBCT, and fluoroscopy was 19.59, 16.4, and 3.17 Gy cm2, respectively. Conclusions: TBB using a combination of CBCT-AF and EBUS resulted in a satisfactory diagnostic yield and safety.