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Recognizing intolerance or resistance to hydroxyurea (HU), which is related to the high risk of a disease transformation and reduced survival in essential thrombocythemia (ET), is crucial to making a reasonable decision about second-line therapy. We assessed the prognostic impact of the modified European LeukemiaNet (mELN) criteria used in a recent MAJIC-ET trial by analyzing the incidence of resistance or intolerance to HU and the survival outcome compared with those of the ELN criteria.We retrospectively compared the development of HU resistance or intolerance according to the ELN and mELN criteria for 148 high-risk ET patients receiving HU between 2014 and 2018. The maximum tolerated dose for defining HU resistance was used in the mELN criteria.The median age of patients was 65 years (range, 36-87), with a median follow-up of 3.6 years (range, 1.1-6.4). Two thromboembolic events were observed during HU treatment. When applying the ELN criteria, 10 patients (6.9%) were resistant (n = 5 [3.4%]) or intolerant (n = 5 [3.4%]) to HU in comparison with 22 patients (15%, 14 [9.8%]) resistant and 8 [5.5%] intolerant when applying the mELN criteria. Transformation to myelofibrosis and acute myeloid leukemia occurred in 2 (1.4%) patients and 1 (0.7%) patient, respectively, as defined by the ELN criteria compared with 3 (2.1%) and 2 (1.4%) patients as defined by the mELN criteria. In multivariate analysis of transformation-free survival, HU resistance defined by the mELN criteria but not the ELN criteria was an independent prognostic factor. In addition, HU resistance as defined by both sets of criteria was an independent risk factor for inferior overall survival. Intolerance of HU did not have any prognostic impact on survival.The mELN criteria are useful for identifying high-risk ET patients who might be eligible for second-line therapy in practice, which should be validated in a prospective setting.

Recent technical innovation has driven the evolution of autonomous vehicles. To improve safety as well as on-road vehicular experience, vehicles should be connected with each other or to vehicular networks. Some specification groups, e.g., IEEE and 3GPP, have studied and released vehicular communication requirements and architecture. IEEE's Wireless Access in Vehicular Environment focuses on dedicated and short-range communication, while 3GPP's New Radio V2X supports not only sidelink but also uplink communication. The 3GPP Release 16, which supports 5G New Radio, offers evolved functionalities such as network slice, Network Function Virtualization, and Software-Defined Networking. In this paper, we define and design a vehicular network architecture compliant with 5G core networks to enable and support autonomous driving. As a validation example, a high-definition map needs to contain the context of trajectory for localization and planning of autonomous driving vehicles. We also propose new methods by which autonomous vehicles can push and pull map content efficiently, without causing bottlenecks on the network core. We evaluate the performance of the proposed method via network simulations and our autonomous driving vehicle on the road. Experimental results indicate that the proposed method improves the performance of vehicular content delivery in real-world road environments.

Fas-associated death domain (FADD) is an adapter molecule that bridges the interaction between receptor-interacting protein 1 (RIP1) and aspartate-specific cysteine protease-8 (caspase-8). As the primary mediator of apoptotic cell death, caspase-8 has two N-terminal death-effector domains (DEDs) and it interacts with other proteins in the DED subfamily through several conserved residues. In the tumor necrosis receptor-1 (TNFR-1)-dependent signaling pathway, apoptosis is triggered by the caspase-8/FADD complex by stimulating receptor internalization. However, the molecular mechanism of complex formation by the DED proteins remains poorly understood. Here, we found that direct DED-DED interaction between FADD and caspase-8 and the structure-based mutations (Y8D/I128A, E12A/I128A, E12R/I128A, K39A/I128A, K39D/I128A, F122A/I128A, and L123A/I128A) of caspase-8 disrupted formation of the stable DED complex with FADD. Moreover, the monomeric crystal structure of the caspase-8 DEDs (F122A/I128A) was solved at 1.7 Å. This study will provide new insight into the interaction mechanism and structural characteristics between FADD and caspase-8 DED subfamily proteins.

Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL).Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up.Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis.Conclusions: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

The purpose of this study is to evaluate choroidal hyperreflective foci (HRF) changes in central serous chorioretinopathy (CSC) on en-face optical coherence tomography (OCT). Retrospective analysis of 42 patients with unilateral CSC (84 eyes, including fellow eyes for controls) and 42 age- and sex-matched controls. With 4.5 × 4.5 mm macular scans, structural en-face OCT choriocapillaris (CC) slabs were used to calculate the density and number of HRF in acute CSC eyes with serous retinal detachment (SRD), resolved CSC eyes without SRD, unaffected fellow eyes, control eyes, and 1-year follow-up eyes. Based on the 2-disc diameter (3000 μm), the en-face OCT scan was divided into foveal and perifoveal lesion and analyzed to consider the impact of SRF in HRF measurement. Regression analyses were performed on the several factors with HRF number and density in the acute and resolved CSC eyes. The perifoveal density and number of CC HRF was significantly lower in the resolved CSC eyes when compared to the acute CSC eyes (P = 0.002, both), fellow eyes (P = 0.042/density, 0.028/number), and controls (P = 0.021/density, P = 0.003/number). There was no significant difference between the acute CSC eyes, fellow eyes, controls, and 1-year follow-up eyes. As subfoveal choroidal thickness decreased and choroidal vascularity (CVI) increased, the perifoveal density and number of HRF was measured higher with a significant correlation in univariate regression analysis of the acute and resolved CSC eyes (all, P

While the postoperative closure rate of idiopathic macular holes (IMH) is quite high, its success rate and visual prognosis differ depending on macular hole (MH) characteristics. This study investigated the IMH progression rate before vitrectomy.This retrospective study compared optical coherence tomography (OCT) taken at baseline and on operation day for patients with stage 2, 3 and 4 IMH to determine the changes in minimum linear diameter (MLD), base diameter (BD), height and MH index (MHI). The IMH progression rate was calculated by dividing each difference in OCT parameters by the time interval.A total of 224 eyes of 216 patients were included. The average time interval from baseline to operation was 35.59 ± 23.43 (7-137) days. Final visual acuity was related to preoperative MLD, BD, best-corrected visual acuity and time interval between baseline and operation (p = 0.005, p = 0.003, p 0.001 and p = 0.005 respectively). Between baseline and operation, the average MLD and BD increased significantly (all p 0.001). The average progression rates of MLD and BD assessed by simple regression analysis were 0.698 μm/day (RThe relatively smaller MHs in stage 2 progress faster than those in stages 3 and 4. Therefore, it would ultimately be beneficial to perform vitrectomy without delay in patients with stage 2 MH.

Mixed phenotype acute leukemia (MPAL) encompasses a rare group of acute leukemia with blasts expressing markers specific to several lineages, which accounts for 2-5% of all newly diagnosed cases of acute leukemia. At present, patients with MPAL are treated with acute lymphoblastic leukemia (ALL)-directed chemotherapy. However, the prognosis of MPAL, especially in cases of relapsed/refractory (R/R) disease, remains poor. Blinatumomab, a bispecific T cell-engaging antibody, has shown encouraging outcomes in R/R B cell ALL positive for CD19. Here, we report a patient with CD19+ MPAL who achieved complete remission after treatment with blinatumomab, which may be a therapeutic option for patients with relapsed CD19+ MPAL. To our knowledge, this is the first case report of MPAL treated with blinatumomab in Korea.

How functional genetics research can be applied to improving crop yields is a timely challenge. One of the most direct methods is to produce larger inflorescences with higher productivity, which should be accompanied by a balance between stem cell proliferation and lateral organ initiation in meristems. Unbalanced proliferation of stem cells causes the fasciated inflorescences, which reflect the abnormal proliferation of meristems, derived from the Latin word ‘fascis’, meaning ‘bundle’. Maize, a model system for grain crops, has shown tremendous yield improvements through the mysterious transformation of the female inflorescence during domestication. In this review, we focus on maize inflorescence architecture and highlight the patterns of fasciation, including recent progress.

E-commerce retailers are increasingly faced with challenges of finding ways to provide a seamless shopping experience to customers. The checkout process and its related touch points are especially critical in shaping the customer experience. We study the impact of adopting one-click buying, a feature that reduces the number of steps required to place a purchase order to a single click, on subsequent customer behavior. Using quasi-experimental data over a period of 35 months from an online retailer before and after the launch of one-click buying, we find adopting one-click buying is effective in lifting customer purchases and does so by making treated customers purchase more often and more items. The impact of adopting one-click buying on customer purchases after adoption is economically significant, persistent over time, and heterogeneous across customers. Analyzing clickstream data of customer activity online and purchases across product categories, we provide evidence that the increase in purchases is driven by richer engagement through both more visits to the website and more page views on visit and the expansion of purchases across categories. We discuss the implications of our findings for customer experience and targeting. This paper was accepted by Duncan Simester, marketing. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.4716 .

This retrospective study aimed to determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular hole (MH) decreases before vitrectomy. We investigated the difference in MLD and BD between baseline and operation days in 282 eyes of 269 patients with stages 2, 3, and 4 MH using optical coherence tomography (OCT). Each difference in the OCT parameters was divided by the time interval to calculate the MH progression rate. The average time from baseline to operation was 36.02 ± 24.69 (7–197) days. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p

To investigate the preoperative morphology of the foveal avascular zone (FAZ) for prediction of the postoperative visual function in advanced idiopathic epiretinal membrane (ERM). 21 patients (21 eyes) with unilateral idiopathic ERM who underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling were included. Superficial FAZ was measured preoperatively in both eyes using optical coherence tomography angiography (OCTA). Area, perimeter, and circularity of FAZ were achieved, and their rationes between the ERM eyes and the contralateral eyes were calculated to analyze the degree of FAZ distortion in diseased eyes. The best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were measured at baseline and more than 6 months after surgery. The correlations of the preoperative FAZ rationes with BCVA and CFT were assessed. The FAZ in the eyes with ERM was significantly reduced, and the BCVA was significantly correlated with the area ratio (P = 0.004) and the perimeter ratio (P = 0.005) of the FAZ before surgery. Decimal BCVA changed from 0.326 ± 0.139 to 0.450 ± 0.202 (P = 0.058), and CFT reduced significantly (P = 0.001) after surgery. The preoperative FAZ area and perimeter rationes were significantly correlated with letter score gain (P = 0.001, P < 0.001), and the latter showed significant correlations with the postoperative BCVA (P = 0.031) and CFT reduction ratio (P = 0.008). The preoperative FAZ perimeter ratio is the best predictor of functional and morphological prognosis after surgery in advanced idiopathic ERM.

Purpose: To report a follow up of early intravitreal anti-vascular endothelial growth factor (VEGF) antibody treatment in a patient with maculopathy after accidental exposure to a high-powered cosmetic Nd:YAG laser.Case summary: A 36-year-old female patient visited our clinic with decreased visual acuity in the right eye after accidental exposure to a high-powered cosmetic Nd:YAG laser. The best-corrected visual acuity of the right eye was 0.1 and subretinal hemorrhage on the foveal area was observed during fundus examination. Optical coherence tomography revealed serous retinal detachment with hyperreflective disruption of the ellipsoid zone and retinal pigment epithelium-Bruch’s membrane complex. Intravitreal bevacizumab (Avastin®, 1.25 mg/0.05 mL; Roche Korea, Seoul, Korea) injections were performed three times. Visual acuity was unchanged at 6 months after the first visit. However, complete resolution of the subretinal hemorrhage was observed and there were no signs of secondary choroidal neovascularization or recurrence of choroidal hemorrhage.Conclusions: Early anti-VEGF antibody treatment in a patient with subfoveal hemorrhage and choroidal rupture after high-powered cosmetic Nd:YAG laser exposure improved morphology and prevented secondary choroidal neovascularization.

Purpose: To clarify the long-term visual prognosis and prognostic factors for vision loss in patients with vitreoretinal lymphoma (VRL).Methods: This retrospective longitudinal study included 64 consecutive patients with VRL. We analyzed the best-corrected visual acuity (BCVA), optical coherence tomography findings, and clinical features at every visit. Significant vision loss was defined as a final BCVA ≥0.5 logMAR. Predictors of significant vision loss following treatment were evaluated using univariate and multivariate linear regression analyses. Results: We included 64 eyes of 64 patients (mean age, 64.2±10.9 years), and 49 patients (76.6%) showed bilateral ocular involvement. The mean follow-up duration was 35.4±25.8 months. At diagnosis, 36 (56.3%), 17 (26.6%), and 11 (17.2%) patients had primary, secondary, and concurrent VRL, respectively. All patients received intraocular methotrexate injections (mean, 16.3±5.9 injections). The mean BCVA improved from 0.46±0.33 at diagnosis to 0.39±0.32 1 month after treatment initiation. Vision improved significantly after treatment (final mean BCVA, 0.29±0.29). Univariate and multivariate analyses showed that baseline BCVA and retinal/subretinal infiltration were significantly correlated with vision loss.Conclusion: In this study, a good visual outcome was maintained for >35 months in patients with VRL. Baseline BCVA and retinal/subretinal infiltration were significant predictors of vision loss after treatment for VRL.

Purpose To evaluate the choriocapillaris (CC) flow changes in branched retinal vascular obstruction (BRVO) on optical coherence tomography angiography (OCTA). Methods Retrospective analysis of 29 patients with unilateral BRVO (58 eyes, including unaffected fellow eyes for controls). 4.5 x 4.5 mm macular scans were divided into 4 quadrants. Serial analyses were conducted on CC flow voids of the opposite quadrant to the active occluded area in BRVO eyes. Each of the quadrants were also compared to the occluded quadrant of resolved eyes and the contralateral quadrant of fellow eyes by matched data analysis. A regression analysis was performed on the several parameters (Choroidal thickness; CT, Choroidal vascularity index; CVI, Central macular thickness; CMT, The number of intravitreal injections) and CC flow voids. Results The CC flow void increased sequentially: The uninvolved quadrant of acute BRVO-affected eyes, that of resolved eyes after 3-month/1-year, the contralateral quadrant of fellow eye, the involved (occluded) quadrant of resolved eyes. There were significant correlations between initial CMT, the number of injections and the CC flow void of uninvolved quadrants (P = 0.025, 0.031, respectively), and between the involved (occluded) quadrants and fellow CT (P = 0.029). Conclusion CC flow void of uninvolved macular areas decreased significantly in eyes with acute BRVO, suggesting that CC changes were limited to the blocked area and a compensatory mechanism would work in surrounding areas.

Dwarfism in crops is a useful breeding trait. In this study, we aimed to identify a candidate gene controlling semi-dwarfism in watermelon (Citrullus lanatus) using a combination of genetic mapping and quantitative trait loci (QTL)-seq. We evaluated phenotypes using an F2 and F2:3 population derived from a cross between a “Bush Sugar Baby” (BSB, semi-dwarf type) and a PCL-J1 (normal type) cultivar. Results indicated that a single recessive gene confers semi-dwarfism in BSB. We constructed a genetic map using 180 F2 plants and 336 single-nucleotide polymorphisms (SNPs), detected using genotyping-by-sequencing, and mapped the semi-dwarfism locus, sdw-1, between the SNP markers linked by 9.6 cM (0.99 Mb) on Chr. 9. QTL analysis pointed to the same genomic location for sdw-1 using single-marker analysis. Further, based on the QTL-seq, we identified a significant genomic region for sdw-1 that matched with the sdw-1-flanking region in the genetic linkage map. This 1-Mb region was narrowed down by mapping three SNP markers developed from the QTL-seq data. The sdw-1 locus was mapped to the 0.44-Mb genomic region, which harbored 13 genes. One of the 13 genes, ClCG09G018320 (ATP-binding cassette (ABC) transporter B family member 19), showed the SNPs in its coding sequence, and cleaved amplified APS markers developed from those SNPs co-segregated with sdw-1 in fine mapping using 620 F2 plants. Our results implied that a frameshift mutation in the ABC transporter gene and the resulting alteration in auxin transportation are the most likely to be responsible for semi-dwarfism in BSB.

Using data from a field experiment, we find that mobile coupons lift revenue primarily by increasing visits to the website rather than through redemption.

The clinical therapy for retinal vascular diseases requires repeated intravitreal injections of drugs owing to their short half-life, which imposes health and economic burdens on patients. Therefore, it is necessary to develop an advanced drug delivery system that can prolong the drug activity and minimize secondary complications. In this study, we developed a core/shell drug-loaded rod (drug rod) to deliver two types of drugs (bevacizumab (BEV) and dexamethasone (DEX)) from a single implant. The coaxial printing technique allowed BEV and DEX to be released with different kinetics at the same site by using a polymeric shell and a hydrogel core, respectively. The suggested printing technique facilitates the production of drug rods with various dimensions and drug concentrations, and the multi-layered design allows to adjust the release profile of dual drug-delivery system. The rod was injected in rat vitreous less invasively using a small-gauge needle. Further, we validated the efficacy of the implanted drug rods in inhibiting inflammatory responses and long-term suppression of neovascularization compared to the conventional intravitreal injection of BEV in animal model, indicating that the drug rods can be an alternative therapeutic approach for the treatment of various types of retinal vascular diseases.

PURPOSE To identify the optical coherence tomography biomarkers that can collectively predict the probability of collapse or reduction of drusenoid pigment epithelium detachment (PED). METHODS This consecutive observational case series reviewed the clinical data of 24 eyes with non-neovascular drusenoid PED. Among the study population, 17 eyes showed collapse or reduction of drusenoid PED. The mean follow-up duration was 44.8 ± 24.6 months. Optical coherence tomography-derived parameters were analyzed at baseline, at the last available visit before reduction of PED, at the first available visit after reduction of PED, and at the final visit. RESULTS The mean subfoveal choroidal thickness showed a significant decrease after PED reduction and at the most recent visit (P = 0.015). Migration of retinal pigment epithelium cells was detected in 15 (88.2%) after PED reduction; however, there was no significance in the frequency of migration of retinal pigment epithelium cells at each time point (P = 0.392). Non-neovascular subretinal fluid was detected in 7 (41.2%) before PED reduction, 2 (11.8%) after PED reduction, and 2 (11.8%) at the final visit. Interestingly, subretinal fluid appeared more frequently just before reduction of PED (P = 0.029). CONCLUSION We found evidence of non-neovascular subretinal fluid and choroidal thinning before reduction in PED. This finding might be useful for detection and prediction of the progression of drusenoid PED.

Current nomenclature for the taxonomic classification of melon cultivars (Cucumis melo L.) at the horticultural group level relies on morphological variation in certain key characters. However, the reliability of current infraspecific classification scheme in considering horticultural groups as botanical taxa was not fully understood. In the present study, the information of horticultural group classification in melon was assessed at the molecular level using genome-wide single nucleotide polymorphisms (SNPs). A total of 143 melon accessions of 15 horticultural groups in two subspecies, subsp. melo and subsp. agresti were collected and genotyped by using Genotyping-By-Sequencing (GBS). From the filtering of resultant sequence variants, 10,949 SNPs were selected and used for downstream genetic analysis including population structure, principle component analysis, and hierarchical clustering of 143 melon accessions. Our genetic analyses indicated that the distribution of accessions at the molecular level generally matched the subspecies classification and no substantial contradictions existed between the division of accessions based on horticultural group information and genetic relatedness revealed by the GBS. However, the distinction between horticultural groups was not clear-cut, implying the limitation of considering horticultural groups as botanical taxa. To improve the resolution of horticultural group classification in melon, our SNP data may be useful as supporting information in conjunction with morphological characters.

The ripening pattern of strawberry (Fragaria × ananassa) is different from other fruits, primarily because plant hormones affect the fruit’s quality in a different way than in other fruits. However, most studies on strawberries have focused on cultivation methods, control of pests and diseases, and breeding, and considerably less research has been done on hormones that determine strawberry internal quality. Even though strawberries have good indicators for gauging external quality, there is not enough data to for it to be related to internal quality. As such, we sought to better understand quality as strawberry fruit in specific six progressive developmental stages: flower buds, flowering, green fruits (GF), white fruits, pink fruits, and red fruits (RF). The internal quality and hormonal changes of ‘Seolhyang’ and ‘Maehyang’ cultivars were investigated on the basis of these developmental stages. This report highlights the changes in plant hormones that affect fruit ripening of ‘Seolhyang’ and ‘Maehyang’ cultivars. ABA, cytokinin, JA, and SA content increased gradually with maturity from the GF to the RF stage, while auxin content decreased gradually from GF to RF. Meanwhile, cytokinin and GA3 content exhibited fluctuations and differences between ‘Seolhyang’ and ‘Maehyang’ cultivars. The quality of strawberries was highest at the sixth (RF) stage in the both cultivars. Our results reveal that plant hormones play a role in the maturation of strawberry fruits and provide a foundation for their agricultural use in controlling the maturity of fruits.

This study aimed to analyze the choroidal characteristics in eyes with polypoidal choroidal vasculopathy (PCV, affected eyes) and unaffected fellow eyes, and investigated the longitudinal changes in the choroidal structure of fellow eyes in patients with unilateral PCV. We retrospectively reviewed the medical records of 55 treatment-naive patients with unilateral PCV. The choroidal thickness and vascularity between PCV affected eyes, unaffected fellow eyes, and normal control eyes were compared. Structural changes in the choroid of the fellow eyes were reviewed during follow-up. PCV eyes had thicker subfoveal choroidal thickness (SFCT) (p

Warehouse robots have been widely used by manufacturers and online retailer to automate good delivery process. One of the fundamental components when designing a warehouse robot is path finding algorithm. In the past, many path finding algorithms had been proposed to identify the optimal path and improve the efficiency in different conditions. For example, A* path finding algorithm is developed to obtain the shortest path, while D* obtains a complete coverage path from source to destination. Although these algorithms improved the efficiency in path finding, dynamic obstacle that may exist in warehouse environment was not considered. This paper presents AD* algorithm, a path finding algorithm that works in dynamic environment for warehouse robot. AD* algorithm is able to detect not only static obstacle but also dynamic obstacles while operating in warehouse environment. In dynamic obstacle path prediction, image of the warehouse environment is processed to identify and track obstacles in the path. The image is pre-processed using perspective transformation, dilation and erosion. Once obstacle has been identified using background subtraction, the server will track and predict future path of the dynamic object to avoid the obstacle.

PURPOSE This study compared the visual outcome after pneumatic displacement of submacular hemorrhage among patients with different subtypes of age-related macular degeneration (AMD). METHODS We retrospectively reviewed the medical records of 67 patients (67 eyes) who underwent treatment for submacular hemorrhage associated with AMD. All the patients underwent pneumatic displacement. Demographic parameters, visual acuity, and anatomical features were analyzed among AMD subtypes: typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). RESULTS Among the eyes with submacular hemorrhage, 24, 30, and 13 eyes had typical AMD, PCV, and RAP, respectively. Post-treatment best-corrected visual acuity was best in the PCV group and worst in the RAP group (P < 0.001). The proportion of eyes with improved visual acuity was highest in the PCV subtype and lowest in the RAP subtype (P = 0.044). Logistic regression analysis showed that AMD subtype (P = 0.016) and time to treatment (

Purpose Silicone oil (SO) is commonly used for tamponade purposes in retinal detachment (RD) surgery, but the long-term visual prognosis after removal of the oil, and in particular, what is known about the recurrence of RD after SO removal, remains unclear. The purpose of this study is to evaluate the long-term vision prognosis after SO removal, and to understand the frequency and characteristics of RD recurrence. Methods We retrospectively reviewed the medical charts of 1017 eyes of patients with a diagnosis of RD who had a pars plana vitrectomy with SO tamponade between January 2009 and December 2018. Best-corrected visual acuity (BCVA) was obatained before and after vitrectomy and also at the last visit. After SO removal, the group who showed improvement in visual acuity and the group who did not were compared. The anatomical results were compared between the group in which the retina was detached again after SO removal and the group in which the retina was not detached. To determine whether the duration of SO tamponade affects RD recurrence, further analysis was performed by dividing subgroups according to SO tamponade duration. RD recurrence, visual acuity, SO tamponade period were investigated. Results Mean follow-up period was 56.65 ± 72.02 months. An average SO tamponade period was 6.68 ± 11.39 months. The average logMAR BCVA was 1.75 ± 0.91 before SO injection, 1.60 ± 0.75 before SO removal and 1.29 ± 0.96 after the removal. After SO removal, 926 of the 1017 (91.1%) patients had well attached retina without recurrence. There was no significant difference in visual acuity before SO removal in re-detachment group compared to no re-detachment group, but visual acuity of re-detachment group was worse than no re-detachment group after SO removal (p Conclusion The prognosis for final vision is generally good when performing surgery using SO in RD, but considering the complications that arise after surgery, long-term retention of SO is not recommended and the timing of SO removal should be considered.

The unwanted detachment of organs such as flowers, leaves, and fruits from the main body of a plant (abscission) has significant effects on agricultural practice. Both timely and precise regulation of organ abscission from a plant is crucial as it influences the agricultural yield. The tomato (Solanum lycopersicum) has become a model system for research on organ abscission. Here, we characterized four tomato natural abscission variants named jointless (j), functionally impaired jointless (fij), functionally impaired jointless like (fij like), and normal joint (NJ), based on their cellular features within the flower abscission zones (AZ). Using eight INFLORESCENCE DEFICIENT IN ABSCISSION (SlIDA) genes and eight HAESA genes (SlHAE) identified in the genome sequence of tomato, we analyzed the pattern of gene expression during flower abscission. The AZ-specific expression for three tomato abscission polygalacturonases (SlTAPGs) in the development of flower AZ, and the progression of abscission validated our natural abscission system. Compared to that of j, fij, and fij like variants, the AZ-specific expression for SlIDA, SlIDL2, SlIDL3, SlIDL4, and SlIDL5 in the NJ largely corelated and increased with the process of abscission. Of eight SlHAE genes examined, the expression for SlHSL6 and SlHSL7 were found to be AZ-specific and increased as abscission progressed in the NJ variant. Unlike the result of gene expression obtained from natural abscission system, an in silico analysis of transcriptional binding sites uncovered that SlIDA genes (SlIDA, SlIDL6, and SlIDL7) are predominantly under the control of environmental stress, while most of the SlHSL genes are affiliated with the broader context in developmental processes and stress responses. Our result presents the potential bimodal transcriptional regulation of the tomato IDA-HAE module associated with flower abscission in tomatoes.

Direct identification of the proteins targeted by small molecules can provide clues for disease diagnosis, prevention, and drug development. Despite concentrated attempts, there are still technical limitations associated with the elucidation of direct interactors. Herein, we report a target-ID system called proximity-based compound-binding protein identification (PROCID), which combines our direct analysis workflow of proximity-labeled proteins (Spot-ID) with the HaloTag system to efficiently identify the dynamic proteomic landscape of drug-binding proteins. We successfully identified well-known dasatinib-binding proteins (ABL1, ABL2) and confirmed the unapproved dasatinib-binding kinases (e.g., BTK and CSK) in a live chronic myeloid leukemia cell line. PROCID also identified the DNA helicase protein SMARCA2 as a dasatinib-binding protein, and the ATPase domain was confirmed to be the binding site of dasatinib using a proximity ligation assay (PLA) and in cellulo biotinylation assay. PROCID thus provides a robust method to identify unknown drug-interacting proteins in live cells that expedites the mode of action of the drug.

To evaluate the choriocapillaris (CC) flow in central serous chorioretinopathy (CSC) and determine the relationship between CC flow void with the choroidal thickness (CT) and choroidal vascularity index (CVI).Retrospective analysis of 20 patients with CSC (40 eyes, including unaffected fellow eyes) and 20 age- and sex-matched controls. After compensation with optical coherence tomography (OCT) en-face structural image, the CC flow void (%) was measured using the phansalkar threshold with a window radius of 3 and 15 pixels. The mean CC flow voids of acute CSC, recovered-acute CSC, unaffected fellow, and control eyes were compared by matched data analysis. A regression analysis was performed on the choroidal parameters (CT and CVI) and CC flow voids.The CC flow void had an increasing tendency in the following order: control, fellow, recovered-acute CSC, and acute CSC eyes. Acute/recovered comparison showed a significant P value (0.008) in the foveal lesion. Recovered/fellow and fellow/control presented significant P values regardless of location to fovea (all0.05). There were significant positive correlations between CT and CC flow void (P 0.05) in the acute CSC, recovered-acute CSC eyes.The CC flow on OCT angiography decreased in acute CSC eyes, especially in the foveal lesion, with a published compensation method. The findings suggest that unmodulated choroidal blood flow contributed to partially reversible diminished CC flow.

This study aimed to investigate the safety and tolerability of 90-min rapid infusion of rituximab, originator or biosimilar (Truxima), for rituximab-naïve patients with hematologic malignancy. We undertook a retrospective review of records of 118 patients (81 originator rituximab and 37 Truxima) with hematologic malignancy who had received rituximab rapid infusion from the first cycle of chemotherapy with corticosteroid premedication administration. Most patients had high Ann Arbor stage (80.9%), high International Prognostic Index risk (69.1%), favorable performance status (98.3%), and high lactate dehydrogenase level (78.8%). The patients received a collective total of 717 rapid rituximab infusions, with an average of 6 infusions per patient (range, 1-8). The incidence of infusion-related reactions (IRRs) of any grade and grade 3/4 during first infusion was 21.2% and 0.8%, respectively. No episode of grade 3/4 IRR was observed during the second and subsequent rituximab infusions. Severity and type of IRRs in Truxima administration were comparable to those of originator rituximab. This study suggests that 90-minute rituximab infusion with the first dose of chemotherapy was well tolerated. In terms of IRR, safety profiles of Truxima were comparable to that of originator rituximab, suggesting that Truxima might replace originator rituximab in a rapid infusion setting.

Kadsura coccinea (KC), a beneficial plant for human health, has been used for centuries in China, Thailand, and Korea in folk medicine and food. There is evidence supporting the biological effects of highly bioactive ingredients in KC such as lignans, triterpenoids, flavonoids, phenolic acids, steroids, and amino acids. In this study, we aimed to explore the effects, functions, and mechanisms of the extracts from KC root (KCR), stem (KCS), leaf (KCL), and fruit (KCF) in UVA and UVB-irradiated keratinocytes and α-melanocyte stimulating hormone (α-MSH)-stimulated melanocytes. First, the total polyphenol and flavonoid contents of KCR, KCS, KCL, and KCF and their radical scavenging activities were investigated. These parameters were found to be in the following order: KCL > KCR > KCS > KCF. UVA and UVB-irradiated keratinocytes were treated with KCR, KCS, KCL, and KCF, and keratinocyte viability, LDH release, intracellular ROS production, and apoptosis were examined. Our results demonstrated that KC extracts improved keratinocyte viability and reduced LDH release, intracellular ROS production, and apoptosis in the presence UVA and UVB irradiation. The overall photoprotective activity of the KC extracts was confirmed in the following order: KCL > KCR > KCS > KCF. Moreover, KC extracts significantly decreased the intracellular melanin content and tyrosinase activity in α-MSH-stimulated melanocytes. Mechanistically, KC extracts reduced the protein and mRNA expression levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated melanocytes. In addition, these extracts markedly downregulated myophthalmosis-related transcription factor expression and cAMP-related binding protein phosphorylation, which is upstream of the regulation of Tyrosinase, TRP-1, and TRP-2. The overall anti-melanogenic activity of the KC extracts was established in the following order. KCL > KCR > KCS > KCF. Overall, the KC extracts exert photoprotective and anti-melanogenic effects, providing a basis for developing potential skin-whitening and photoprotective agents.

To compare the effects of full-dose, half-dose, and half-dose-half-fluence photodynamic therapy (PDT) in central serous chorioretinopathy (CSC). This retrospective study enrolled patients with CSC who received full-dose (verteporfin 6 mg/m2), half-dose (verteporfin 3 mg/m2), and half-dose-half-fluence (verteporfin 3 mg/m2 and light energy reduced to 25 J/cm2) PDT. We measured visual acuity, subfoveal choroidal thickness (SFCT), subretinal fluid (SRF) thickness, and choroidal vascularity index (CVI) before and 3 months after PDT. Forty-three eyes (42 patients) were analyzed. Full-dose and half-dose groups showed improved vision (P = 0.023, 0.004, respectively), but half-dose-half-power group was not significantly improved (P = 0.254). SFCT in all three groups were significantly decreased (P = 0.005, 0.004, 0.002, respectively). SRF thicknesses in full-dose and half-dose groups showed significant decreases (P = 0.005