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In coastal video monitoring, the direct linear transform (DLT) method with ground control points (GCPs) is commonly used for geo-rectification. However, current practices often overlook the impact of GCP quantity, arrangement, and the geographical characteristics of beaches. To address this, we designed scenarios at Chuam Beach to evaluate how factors such as the distance from the camera to GCPs, the number of GCPs, and the height of each point affect the DLT method. Accuracy was assessed by calculating the root mean square error of the distance errors between the actual GCP coordinates and the image coordinates for each setting. This analysis aims to propose an optimal GCP placement method. Our results show that placing GCPs within 200 m of the camera ensures high accuracy with few points, whereas positioning them at strategic heights enhances shoreline extraction. However, since only fixed cameras were used in this study, factors like varying heights, orientations, and resolutions could not be considered. Based on data from a single location, we propose an optimal method for GCP placement that takes into account distance, number, and height using the DLT method.

Abstract Neuromorphic computing research is being actively pursued to address the challenges posed by the need for energy-efficient processing of big data. One of the promising approaches to tackle the challenges is the hardware implementation of spiking neural networks (SNNs) with bio-plausible learning rules. Numerous research works have been done to implement the SNN hardware with different synaptic plasticity rules to emulate human brain operations. While a standard spike-timing-dependent-plasticity (STDP) rule is emulated in many SNN hardware, the various STDP rules found in the biological brain have rarely been implemented in hardware. This study proposes a CMOS-memristor hybrid synapse circuit for the hardware implementation of a Ca ion-based plasticity model to emulate the various STDP curves. The memristor was adopted as a memory device in the CMOS synapse circuit because memristors have been identified as promising candidates for analog non-volatile memory devices in terms of energy efficiency and scalability. The circuit design was divided into four sub-blocks based on biological behavior, exploiting the non-volatile and analog state properties of memristors. The circuit was designed to vary weights using an H-bridge circuit structure and PWM modulation. The various STDP curves have been emulated in one CMOS-memristor hybrid circuit, and furthermore a simple neural network operation was demonstrated for associative learning such as Pavlovian conditioning. The proposed circuit is expected to facilitate large-scale operations for neuromorphic computing through its scale-up.

Abstract This study aimed to assess the efficacy of dual T-cell suppression using individually tailored doses of antithymocyte globulin (ATG) and attenuated dose of post-transplant cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We conducted a retrospective analysis of 78 adults with acute leukemia or myelodysplastic syndrome who underwent haplo-HSCT using intravenous busulfan and fludarabine conditioning. Thirty-two patients received attenuated ATG/PTCy, while 46 patients received ATG (7.5 mg/kg) as GVHD prophylaxis. The 100-day cumulative incidence of grade III-IV (9.7% vs. 32.4%, P = 0.018) acute GVHD, as well as 2-year moderate-severe chronic GVHD (13.9% vs. 43.9%, P = 0.018) in the ATG/PTCy group were significantly lower than those in the ATG group. The 2-year overall survival was comparable between the two groups. However, 2-year GVHD-free, relapse-free survival in the ATG/PTCy group was significantly higher compared to that in the ATG group (38.9% vs. 21.7%, P = 0.021). Moreover, during post-engraftment period, the ATG/PTCy group exhibited lower incidences of life-threatening bacterial (12.5% vs. 37%, P = 0.033) and viral infection (0% vs. 17.4%, P = 0.035) than the ATG group. In conclusion, the combination of individually tailored ATG and low-dose PTCy appears to be a promising strategy in haplo-HSCT.

Abstract Background Lysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background. Methods Genotyping of the LD background was performed in a cohort of MPN patients (n = 190) and healthy controls (n = 461). Logistic regression modeling, utilizing genotype data, was employed to estimate the correlation between LD and MPN. Whole transcriptome sequencing (WTS) (LD carriers = 8, non‐carriers = 6) and single‐cell RNA sequencing data (LD carriers = 2, non‐carriers = 2, healthy controls = 2) were generated and analyzed. Results A higher variant frequency of LD was observed in MPN compared to healthy controls (healthy, 4.9%; MPN, 7.8%), with the highest frequency seen in polycythemia vera (PV) (odds ratio = 2.33, p = 0.03). WTS revealed that LD carriers exhibited upregulated inflammatory cytokine ligand–receptor genes, pathways, and network modules in MPNs compared to non‐carriers. At the single‐cell level, there was monocyte expansion and elevation of cytokine ligand–receptor interactions, inflammatory transcription factors, and network modules centered on monocytes. Notably, Oncostatin‐M (OSM) consistently emerged as a candidate molecule involved in the pathogenesis of LD‐related PV. Conclusions In summary, an LD background is prevalent in MPN patients and leads to increased cytokine dysregulation and inflammation. OSM, as one of the potential molecules, plays a crucial role in PV pathogenesis by impairing lysosomal function.

Abstract Objectives To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients. Methods Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT. Results In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed. Conclusions Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT. Trial registrations This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).

Abstract Anemia is a common condition, but its causes are often unclear, especially in elderly adults. Erythropoietin (EPO) levels are known to be elevated in myelodysplastic syndrome and hematologic malignancies, but decreased in chronic benign anemia. This study aimed to investigate whether EPO levels could be used to identify underlying bone marrow diseases including malignancies, among elderly anemic patients with unclear etiology. This single centered retrospective study included patients presented with isolated anemia and had their EPO levels measured at their first visit. Patients were divided into two groups: bone marrow disease and benign etiologic anemia, based on observation and bone marrow test results. Out of 1180 patients reviewed, 81 patients with anemia of unclear etiology were identified, including 67 with benign anemia and 14 with bone marrow disease. Statistically significant difference in EPO levels between these two groups (P

Abstract Various memristive devices have been proposed for use in neuromorphic computing systems as artificial synapses. Analog synaptic devices with linear conductance updates during training are efficiently essential to train neural networks. Although many different analog memristors have been proposed, a more reliable approach to implement analog synaptic devices is needed. In this study, we propose the memristor of a Cu/SiOx/implanted a-SiGex/p++ c-Si structure containing an a-Si layer with properly controlled conductance through Ge implantation. The a-SiGex layer plays a multifunctional role in device operation by limiting the current overshoot, confining the heat generated during operation and preventing the silicide formation reaction between the active metal (Cu) and the Si bottom electrode. Thus, the a-SiGex interface layer enables the formation of multi-weak filaments and induces analog switching behaviors. The TEM observation shows that the insertion of the a-SiGex layer between SiOx and c-Si remarkably suppresses the formation of copper silicide, and reliable set/reset operations are secured. The origin of the analog switching behaviors is discussed by analyzing current-voltage characteristics and electron microscopy images. Finally, the memristive-neural network simulations show that our developed memristive devices provide high learning accuracy and are promising in future neuromorphic computing hardware.

Background/Aims We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). Methods Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. Results In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. Conclusions The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials.gov NCT01429610).

Abstract The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) and dual SGLT1/2 inhibitor sotagliflozin (SOTA) are emerging as heart failure (HF) medications in addition to having glucose-lowering effects in diabetes mellitus (DM). However, the precise mechanism underlying this cardioprotective effect has not yet been elucidated. Here, we evaluated the effects of EMPA and SOTA in a zebrafish model of DM combined with HF with reduced ejection fraction (DM-HFrEF). To compare the effects of the two drugs, survival, locomotion, and myocardial contractile function were evaluated. The structural binding and modulating effects of the two medications on sodium-hydrogen exchanger 1 (NHE1) were evaluated in silico and in vitro. DM-HFrEF zebrafish showed impaired cardiac contractility and decreased locomotion and survival, all of which were improved by 0.2–5 μM EMPA or SOTA treatment. However, the 25 μM SOTA treatment group had worse survival rates and less locomotion preservation than the EMPA treatment group at the same concentration, and pericardial edema and an uninflated swim bladder were observed. SOTA, EMPA and cariporide (CARI) showed similar structural binding affinities to NHE1 in a molecular docking analysis and drug response affinity target stability assay. In addition, EMPA, SOTA, and CARI effectively reduced intracellular Na+ and Ca2+ changes through the inhibition of NHE1 activity. These findings suggest that both EMPA and SOTA exert cardioprotective effects in the DM-HFrEF zebrafish model by inhibiting NHE1 activity. In addition, despite the similar cardioprotective effects of the two drugs, SOTA may be less effective than EMPA at high concentrations.

Even though submerged breakwater reduces incident wave energy, it redistributes the coastal area's wave-induced current, sediment transport, and morphological change. This study examines the coastal hydrodynamics and the morphological response of a wave-dominated beach with submerged breakwaters installed through field observation and quasi-3D numerical modeling. The pre-and post-storm bathymetry, water level, and offshore wave under storm forcing were collected in Bongpo Beach on the East coast of Korea and used to analyze the coastal hydrodynamic response. Four vertically equidistant layers were used in the numerical simulation, and the wave-induced current was examined using quasi-3D numerical modeling. The shore normal incident wave (east-northeast) generated strong cross-shore and longshore currents toward the hinterland of the submerged breakwater. However, the oblique incident wave (east-southeast) induced the southeastward longshore current and the sedimentation in the northeast area of the beach. The results suggested that the incident wave direction is a significant factor in determining the current and sediment transport patterns in the presence of the submerged breakwaters. Moreover, the quasi-3D numerical modeling is more appropriate for estimating the wave transformation, current, and sediment transport pattern in the coastal area with the submerged breakwater.

Abstract Few studies have investigated the changes in patient state index (PSI) and bispectral index (BIS) in response to abrupt increase in electromyographic (EMG) activity. These were performed using intravenous anesthetics or reversal agents for neuromuscular blockade (NMB) other than sugammadex. We compared the changes in BIS and PSI values caused by the sugammadex reversal of NMB during steady-state sevoflurane anesthesia. We enrolled 50 patients with American Society of Anesthesiologists physical status 1 and 2. At the end of the surgery, we administered 2 mg kg−1 sugammadex while maintaining sevoflurane for a 10-min study period. The changes in BIS and PSI from baseline (T0) to train of four ratio of 90% were not significantly different (median difference 0; 95% CI − 3 to 2; P = 0.83), neither were the changes in BIS and PSI values from T0 to their maximum values (median difference 1; 95% CI − 1 to 4; P = 0.53). Maximum BIS and PSI were significantly higher than their baseline values (median difference 6; 95% CI 4–9; P

Background: Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement. Objectives: We conducted this study to identify the prognostic factors for successful treatment-free remission in patients with chronic-phase chronic myeloid leukemia who discontinued tyrosine kinase inhibitors (TKIs). We also aimed to validate ddPCR for predicting molecular relapse. Design: This is a prospective, multicenter study. Methods: We enrolled patients treated with TKIs for at least 3 years with a confirmed sustained deep molecular response (DMR) for at least 1 year. TKI was re-administered in patients who experienced the loss of major molecular response (MMR). Results: A total of 66 patients from five institutions in South Korea were enrolled. During a median follow-up period of 16.5 months, 29/66 (43.9%) patients experienced molecular relapse; the probability of molecular relapse-free survival (RFS) at 6 or 12 months after TKI discontinuation was 65.6% or 57.8%, respectively, with most molecular relapses occurring within the first 7 months. All patients who lost MMR were re-treated with TKI, and all re-achieved MMR at a median of 2.8 months. E14a2 transcript type ( p = 0.005) and longer DMR duration (⩾48 months) prior to TKI discontinuation ( p = 0.002) were associated with prolonged molecular RFS and with sustained DMR. Patients with both e13a2 transcript type and detectable BCR::ABL1 (⩾MR 5.0 ) by ddPCR at the time of TKI discontinuation showed shorter duration of molecular RFS ( p = 0.015). Conclusion: Our data suggest that transcript type and BCR::ABL1 transcript levels on ddPCR should be taken into consideration when deciding whether to discontinue TKI therapy.

Chemotherapy-induced cachexia causes severe metabolic abnormalities independently of cancer and reduces the therapeutic efficacy of chemotherapy. The underlying mechanism of chemotherapy-induced cachexia remains unclear. Here we investigated the cytarabine (CYT)-induced alteration in energy balance and its underlying mechanisms in mice. We compared energy balance-associated parameters among the three groups of mice: CON, CYT, and PF (pair-fed mice with the CYT group) that were intravenously administered vehicle or CYT. Weight gain, fat mass, skeletal muscle mass, grip strength, and nocturnal energy expenditure were significantly lowered in the CYT group than in the CON and PF groups. The CYT group demonstrated less energy intake than the CON group and higher respiratory quotient than the PF group, indicating that CYT induced cachexia independently from the anorexia-induced weight loss. Serum triglyceride was significantly lower in the CYT group than in the CON group, whereas the intestinal mucosal triglyceride levels and the lipid content within the small intestine enterocyte were higher after lipid loading in the CYT group than in the CON and PF groups, suggesting that CYT inhibited lipid uptake in the intestine. This was not associated with obvious intestinal damage. The CYT group showed increased zipper-like junctions of lymphatic endothelial vessel in duodenal villi compared to that in the CON and CYT groups, suggesting their imperative role in the CYT-induced inhibition of lipid uptake. CYT worsens cachexia independently of anorexia by inhibiting the intestinal lipid uptake, via the increased zipper-like junctions of lymphatic endothelial vessel.

The by-products obtained after the extraction of vitamin B2 from fermented soybean (VBP), primarily consisting of soybean meal, soybean oil, vitamin B2, and Bacillus subtilis, may serve as a cost-effective and recycled resource in animal feed. This research aimed to assess the impact of VBP on the growth performance, nutrient utilization, blood parameters, and meat quality of pigs in the growing–finishing phase. In this 16-week feeding experiment, 140 pigs of mixed breed [Duroc × (Landrace × Yorkshire)] were used, with an initial average body weight of 26.05 ± 1.32 kg. The pigs were assigned randomly to one of four dietary groups, each consisting of five pigs, with two gilts and three barrows per pen, and a total of seven repetitions per treatment. The animals were fed different levels of by-products after vitamin B2 extraction (0, 10, 20, and 30 g/kg as the CON, VBP10, VBP20, and VBP30 dietary groups, respectively) in a three-phase feeding trial (wk. 0–4, 4–8, and 8–13). When higher levels of VBP were added as supplements, the outcomes indicated that there were no notable variations (p > 0.05) in growth performance and nutrient digestibility among the treatment groups throughout the trial. In phase II (4–8 weeks), the inclusion of VBP in the diets showed a reduction (p = 0.011; with linear and quadratic effects, p = 0.003) in serum norepinephrine concentration. The sensory evaluation of meat color was linearly improved (p = 0.043) in pigs fed with graded levels of VBP supplementation. The percentage of lean meat showed a significant improvement (p = 0.016) with the gradual levels of VBP supplementation. The addition of 30 g/kg (on an as-fed basis) of vitamin B2 by-products in the diet can simultaneously mitigate the negative impacts of acute stress without compromising growth performance and enhance the percentage of lean meat. These findings suggest that VBP could be a viable and economical alternative to corn and soybean meal and partially replace it in pig feed.

The process-based XBeach model has numerous empirical parameters because of insufficient understanding of hydrodynamics and sediment transport on the nearshore; hence, it is necessary to calibrate parameters to apply to various study areas and wave conditions. Therefore, the calibration process of parameters is essential for the improvement of model performance. Generally, the trial-and-error method is widely used; however, this method is passive and limited to various and comprehensive parameter ranges. In this study, the Generalized Likelihood Uncertainty Estimation (GLUE) method was used to estimate the optimal range of three parameters (gamma, facua, and gamma2) using morphological field data collected in Maengbang beach during the four typhoons that struck from September to October 2019. The model performance and optimal range of empirical parameters were evaluated using Brier Skill Score (BSS) along with the baseline profiles, sensitivity, and likelihood density analysis of BSS in the GLUE tools. Accordingly, the optimal parameter combinations were derived when facua was less than 0.15 and simulated well the shifting shape, from crescentic sand bar to alongshore uniform sand bars in the surf zone of Maengbang beach after storm impact. However, the erosion and accretion patterns nearby in the surf zone and shoreline remain challenges in the XBeach model.

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.

Conventional filamentary memristors are limited in dynamics by the high electric-field dependence of the conductive filament. Here, Jeong et al. presents a method which creates a cluster-type memristor, enabling large conductance range and long data retention.

Abstract Water discharges at hydroelectric dams on the Imjin River, which flows through North and South Korea, generate abrupt water level increases downstream. We assessed infrasound signals from water discharges using an infrasound array located ∼32 km from the source and applied infrasound detection in a flash flood alert system. Using infrasound signals, there was a 79% detection rate for 48 water level increase events occurring in the river downstream during a 14‐year period (2008–2021). The detected signals had a low amplitude, long duration, and broad frequency range (0.5–15 Hz). The energy curves of the detected infrasound signals for selected events showed good correlations with the onset times and water level variations in water level records. These results demonstrate that infrasound monitoring can serve as a practical early warning system for impending flash floods resulting from unnoticed water discharges or sudden debris flows in mountainous regions.

Abstract Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL (P = 0.066) and fatigue (P = 0.189), and significantly longer TTD in PF (P = 0.028) and HS-VAS (P MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.

Feed enzymes have been extensively used in livestock diets to enhance nutrient digestion and promote their growth performance. Indeed, recent research has indicated that feed enzymes, notably phytase, protease, and xylanase, function as catalysts, facilitating the breakdown of phytic acid, proteins, and β-1,4-xylan bonds and offering prospective advantages linked to the intestinal well-being and microbiota of young pigs and chickens. Various feed enzymes are currently being added to the diets of swine and broiler chickens. The potential enzymes used in the feed industry include cellulase, β-mannanase, β-glucanases, xylanases, phytases, proteases, lipases, and galactosidases. Though significant research has been conducted on phytase, protease, and xylanase, consistent findings, particularly in terms of improving nutrient digestibility and promoting growth performance of monogastric animals, are still limited. Also, the outcome of recent studies raises the question whether phytase and xylanase could play functional roles beyond increasing nutrient digestibility and intestinal health, such as positively modulating the intestinal microbiota and reducing environmental problems. Therefore, in this review we aimed to address the functional roles of exogenous enzyme activities in monogastric animal diets. Also, we sought to explore the advantages of these enzymes in enhancing the nutritional value of both alternative and conventional feedstuffs.

Neuromorphic hardware is a system with massive potential to enable efficient computing by mimicking the human brain. The novel system processes information using neuron spikes (Action Potentials) and the synaptic connections between neurons are trained using biologically plausible methods like spike-timing-dependent plasticity (STDP). Memristor is one of the promising candidates to implement such neuromorphic hardware. Two types of memristors, diffusive and drift, have been proposed to form a synapse showing faithful emulation of STDP, where the diffusion effect is used to trace the spike timing history crucial for STDP and the drift memristor keeps the weight information in a longer time scale. The purpose of this paper is to systematically investigate STDP characteristics in such a synapse with serially connected two memristors using SPICE models. The results show that STDP properties are strongly dependent on device parameters and even the shape of STDP curves is modified. Different shapes of the STDP curve were identified. The results and analysis could support the design of emerging device-based synapses, which can faithfully mimic biological STDP characteristics for future neuromorphic systems.

Abstract The incidence of invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) has decreased with the introduction of antimold prophylaxis. Although acute lymphoblastic leukemia (ALL) has a lower risk of IFI than does AML, the incidences of IFI in both AML and ALL in the era of antimold prophylaxis should be re-evaluated. We analyzed adults with AML or ALL who had undergone induction, re-induction, or consolidation chemotherapy from January 2017 to December 2019 at Seoul National University Hospital. Their clinical characteristics during each chemotherapy episode were reviewed, and cases with proven or probable diagnoses were regarded as positive for IFI. Of 552 episodes (393 in AML and 159 in ALL), 40 (7.2%) were IFI events. Of the IFI episodes, 8.1% (12/148) and 5.9% (13/220) (P = 0.856) occurred in cases of ALL without antimold prophylaxis and AML with antimold prophylaxis, respectively. After adjusting for clinical factors, a lack of antimold prophylaxis (adjusted odds ratio [aOR], 3.52; 95% confidence interval [CI], 1.35–9.22; P = 0.010) and a longer duration of neutropenia (per one day, aOR, 1.02; 95% CI, 1.01–1.04; P = 0.001) were independently associated with IFI. In conclusion, the incidence of IFI in ALL without antimold prophylaxis was not lower than that in AML. A lack of antimold prophylaxis and prolonged neutropenia were independent risk factors for IFI. Clinicians should be on guard for detecting IFI in patients with ALL, especially those with risk factors.

Abstract VIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months. Here, we present an additional 6-months of follow-up of VIALE-C (median follow-up 17.5 months; range 0.1–23.5). Median OS was (venetoclax +LDAC vs. placebo +LDAC) 8.4 vs. 4.1 months (HR = 0.70, 95% CI 0.50,0.99; P = 0.040); a 30% reduction in the risk of death with venetoclax. Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were 48.3% vs. 13.2%. Transfusion independence rates (RBC) were 43% vs.19% and median event-free survival was 4.9 vs. 2.1 months (HR = 0.61; 95% CI 0.44,0.84; P = 0.002). These results represent improved efficacy over the primary analysis. Incidence of grade ≥3 adverse events were similar between study arms and overall safety profiles were comparable to the primary analysis. These data support venetoclax +LDAC as a frontline treatment option for patients with AML ineligible for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

Abstract The vascular complications have been a major cause of morbidity and mortality among all subtypes of BCR-ABL1 negative myeloproliferative neoplasms (MPN), but the ethnicity-specific data was limited. We therefore conducted a multi-center retrospective, longitudinal cohort study to evaluate the incidence, characteristics and risk factors of thromboembolic events of MPN patients. Of 256 patients, 27.3% experienced thromboembolic events, majority of which occurred before or within 12 months of MPN diagnosis. The multivariable Cox proportional analyses identified leukocytosis (HR 2.67, 95% CI 1.36–5.24, q = 0.004) and history of thrombosis (HR 9.68, 95% CI 2.00–46.88, q = 0.005) as the risk factors for thromboembolism. In subgroup analysis of polycythemia vera and hemoglobin concentration (HR 1.97, 95% CI 1.28–3.04, q = 0.002) appeared to be a significant risk factor of thrombosis, along with age and thrombosis history. In essential thrombocythemia, severity of the established IPSET score was closely correlated with the frequency of thromboembolic events. In primary myelofibrosis, history of thrombosis was associated with thrombosis events (HR 13.85, 95% CI 1.2–159.5, q = 0.035). Overall survival was worse in patients who experienced thromboembolic events. Our study highlighted the importance of recognizing high risk patients and implementing personalized intervention.

Continuous monitoring of the varying topographical characteristics of shorelines is important for effective coastal management. Closed-circuit television (CCTV) cameras are installed to accumulate photographic data on coastal topographical changes. The overall change in the coastal waters can be intuitively understood from the images. However, the amount of three-dimensional (3D) changes that can be grasped is limited. To address this, studies have employed aerial photogrammetry, which is the use of unmanned aerial vehicles (UAVs) to capture aerial pictures, construct 3D models of target areas, and perform analysis through scale-invariant feature transform and structure from motion technologies. Although highly efficient, this technique requires several ground-control points (GCPs), which could corrupt the overall imagery. This study designs real-time kinematics—global navigation satellite system (RTK–GNSS) UAV, which requires few GCPs. To evaluate the positional accuracy of the captured UAV orthographic images and digital surface models (DSMs) used for precise coastal terrain measurements, a virtual reference service survey was performed to determine the vertical errors. The R-squared was 0.985, which is close to 1.0. Short-term and one-year topographic changes before and after a storm were investigated using time-series UAV image data after a coastal maintenance project. Analysis of the coefficient of variation in the beach volume for one year revealed that submerged breakwater reduced erosion during high wave resistance. The submerged breakwater located in the center exhibited variability similar to the opening. Hence, this method is more suitable for periodically monitoring coastal areas.

Abstract Mid-infrared wavelengths are called the molecular fingerprint region because it contains the fundamental vibrational modes inherent to the substances of interest. Since the mid-infrared spectrum can provide non-destructive identification and quantitative analysis of unknown substances, miniaturized mid-infrared spectrometers for on-site diagnosis have attained great concern. Filter-array based on-chip spectrometer has been regarded as a promising alternative. In this study, we explore a way of applying a pillar-type plasmonic nanodiscs array, which is advantageous not only for excellent tunability of resonance wavelength but also for 2-dimensional integration through a single layer process, to the multispectral filter array for the on-chip spectrometer. We theoretically and experimentally investigated the optical properties of multi-periodic triangular lattices of metal nanodiscs array that act as stopband filters in the mid-infrared region. Soft-mold reverse nanoimprint lithography with a subsequent lift-off process was employed to fabricate the multispectral filter array and its filter function was successfully extracted using a Fourier transform infrared microscope. With the measured filter function, we tested the feasibility of target spectrum reconstruction using a Tikhonov regularization method for an ill-posed linear problem and evaluated its applicability to the infrared spectroscopic sensor that monitors an oil condition. These results not only verify that the multispectral filter array composed of stopband filters based on the metal nanodiscs array when combined with the spectrum reconstruction technique, has great potential for use to a miniaturized mid-infrared on-chip spectrometer, but also provide effective guidance for the filter design.

This study investigates the triple-level cell (TLC) memory retention of a MoS2-channel based charge trap flash (CTF) device. A top-gated CTF device with a high-κ gate dielectric is found to have a high coupling ratio, which enhances the tunneling efficiency for programming. The fabricated devices show the long memory retention performance for each state, demonstrating the feasibility of a robust TLC CTF memory device based on a CVD grown 2D material.

Background/Aims Understanding leukemic stem cell (LSC) is important for acute myeloid leukemia (AML) treatment. However, association of LSC with patient prognosis and genetic information in AML patients is unclear. Methods Here we investigated the associations between genetic information and the various LSC phenotypes, namely multipotent progenitor (MPP)-like, lymphoid primed multipotent progenitor (LMPP)-like and granulocyte-macrophage progenitors (GMP)-like LSC in 52 AML patients. Results In secondary AML patients, MPP-like LSC was significantly higher than de novo AML (p = 0.0037). The proportion of MPP-like LSC was especially high in post-myeloproliferative neoplasm AML (p = 0.0485). There was no correlation between age and LSC phenotype. Mutations of KRAS and NRAS were observed in MPP-like LSC dominant patients, TP53 and ASXL1 mutations in LMPP-like LSC dominant patients, and CEBPA, DNMT3A and IDH1 mutations in GMP-like LSC dominant patients. Furthermore, KRAS mutation was significantly associated with MPP-like LSC expression (p = 0.0540), and TP53 mutation with LMPP-like LSC expression (p = 0.0276). When the patients were separated according to the combined risk including next generation sequencing data, the poorer the prognosis, the higher the LMPP-like LSC expression (p = 0.0052). This suggests that the dominant phenotype of LSC is one of the important factors in predicting the prognosis and treatment of AML. Conclusions LSC phenotype in AML is closely associated with the recurrent mutations which has prognostic implication. Further research to confirm the meaning of LSC phenotype in the context of genetic aberration is warranted.

Artificial Coral Reefs (ACRs) have been introduced to help solve coastal erosion problems, but their feasibility has not been assessed with field data. This study conducted a feasibility analysis of ACRs on their erosion mitigation effects by performing a case study of Cheonjin-Bongpo beach, South Korea. A numerical-physical combined analysis was carried out using a SWAN model simulation and physical model test with a scale of 1/25 based on field observations of Cheonjin-Bongpo beach. Both Dean’s parameter and the surf-scaling parameter were applied to comparative analysis between the absence and presence conditions of the ACR. The results for this combined method indicate that ACR attenuates the wave height significantly (59~71%). Furthermore, ACR helps decrease the mass flux (~50%), undertow (~80%), and maximum wave set up (~61%). The decreases in Dean’s parameter (~66%) and the surf-scaling parameter suggest that the wave properties changed from the dissipative type to the reflective type even under high wave conditions. Consequently, an ACR can enhance shoreline stability.

Abstract Background Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination. Methods Live HZ vaccine was administered to patients 2–5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored. Results Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2–5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96–5.07] vs 5.05, 95% CI [2.50–10.20] vs 2.97, 95% CI [2.30–3.83] vs 1.42, 95% CI [1.08–1.86]). The GMFR of cellular immune responses was highest in the HSCT 2–5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period. Conclusion Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.

Background/Aims Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. Methods We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. Results Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). Conclusions Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Background/Aims A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged ≥ 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the 2nd, 3rd, and 4th weeks. Results Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.

Abstract Background Carbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy. Methods We reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital. Results Among 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3–284.1; P

Objectives This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the Korea Centers for Disease Control and Prevention (KCDC), from the point of detection to the provision of basic information to the relevant public health authorities. Methods To estimate the overall risk of specific public health events, probability, and impact at the country-level were evaluated using available information. To determine the probability of particular public health events, the risk of importation and risk of transmission were taken into consideration. KCDC used 5 levels (“very low,” “low,” “moderate,” “high,” and “very high”) for each category and overall risk was eventually decided. Results A total of 8 risk assessments were performed on 8 separate occasions between January 8th to February 28th, 2020, depending on the detection and report of COVID-19 cases in other countries. The overall risk of the situation in each assessment increased in severity over this period: “low” (first), “moderate” (second), “high” (third), “high” (fourth), “high” (fifth), “high” (sixth), “high” (seventh), and “very high” (eighth). Conclusion The KCDC’s 8 risk assessments were utilized to activate national emergency response mechanisms and eventually prepare for the pandemic to ensure the containment and mitigation of COVID-19 with non-pharmaceutical public health measures.

Abstract Objective The objective of this study was to prospectively evaluate the clinical features of chemotherapy‐induced oral mucositis (CIOM) in adult patients with acute leukemia and the aggravating factors for such symptoms. Subjects Thirty‐seven prospective patients aged ≥19 years with acute leukemia undergoing chemotherapy were enrolled. Oral and clinical investigations were performed at baseline and on Day 14 after starting chemotherapy. The presence and severity of cancer‐induced oral mucositis were demonstrated using the World Health Organization (WHO) scoring system. Results On Day 14, we found that oral mucositis had developed in eight patients (21.6%). Hematopoietic stem cell transplantation (HSCT) in patients was a predictor of increased WHO scores (β = 1.937, p < .001). Regarding oral sites, ventral tongue (β = 1.670), soft palate (β = 1.242), and buccal mucosa (β = 0.593) were predictors for increased scores. In addition, the increase in WHO scores was positively correlated with the number of oral lesions (r = .521), the difficulty in eating (r = .250), and the overall oral health (r = .534; all p < .05). Conclusion The main factors affecting the severity of CIOM symptoms were the treatment with HSCT and the location of oral lesions. The incidence of CIOM and WHO scores were not significantly different between the subgroups of disease. Our findings will help clinicians investigate the oral findings after chemotherapy in adult patients with acute leukemia.

Abstract The aim of this study was to evaluate the effects of Enterococcus faecium DSM 7,134 supplementation on the performance of sows and their litters. A total of 15 primiparous sows (Landrace × Yorkshire) were randomly divided into three treatments with five replicates. Dietary treatments were: CON, basal diet; E1, CON + 0.025% E. faecium; E2, CON + 0.05% E. faecium. No significant differences were observed on body weight and feed intake of lactating sows with E. faecium supplementation, but linearly increased the sow apparent total tract digestibility (ATTD) of dry matter (DM), nitrogen (N) and gross energy (GE; p

In the backdrop of rapidly changing relapsed/refractory (RR) multiple myeloma (MM) treatment schema that mainly evolves around immunotherapies, it is easy to disregard more traditional drugs. Finding the best partner for pomalidomide, a potent third-generation immunomodulatory drug, is an important agenda we face as a community and cyclophosphamide addition has been used for outcomes augmentation. We carried out this real-world study to identify patients who will show durable response to pomalidomide and those who will benefit from cyclophosphamide addition. A total of 103 patients (57 in pomalidomide-dexamethasone [Pd] group versus 46 in pomalidomide-cyclophosphamide-dexamethasone [PCd]) were studied. They were previously treated with bortezomib (98.1%) or lenalidomide (100%) and previous lines of therapy were median 3 lines. Significantly better overall response rate (ORR) was seen in the PCd (75.6%) than Pd (41.7%) group (p = 0.001), but no differences in survival outcomes. Subgroup analysis revealed that high-risk myeloma features, poor response to lenalidomide or bortezomib had superior ORRs when cyclophosphamide was added. Also, long-term responders for pomalidomide were associated with excellent response to previous IMiD treatments. Pomalidomide-based therapy was discontinued in five patients due to intolerance or adverse events, but there was no mortality during treatment. In conclusion, we showed that pomalidomide-based treatment is still relevant and can ensure durable response in RRMM setting, especially for patients who responded well to previous lenalidomide. Addition of cyclophosphamide to Pd is associated with better ORR, and can be positively considered in fit patients with high-risk MM, extramedullary disease, and less-than-satisfactory response to previous lenalidomide treatment.

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus -host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC

Given the recent success of artificial intelligence (AI) in computer vision applications, many pathologists anticipate that AI will be able to assist them in a variety of digital pathology tasks. Simultaneously, tremendous advancements in deep learning have enabled a synergy with artificial intelligence (AI), allowing for image-based diagnosis on the background of digital pathology. There are efforts for developing AI-based tools to save pathologists time and eliminate errors. Here, we describe the elements in the development of computational pathology (CPATH), its applicability to AI development, and the challenges it faces, such as algorithm validation and interpretability, computing systems, reimbursement, ethics, and regulations. Furthermore, we present an overview of novel AI-based approaches that could be integrated into pathology laboratory workflows.

Key parameters in a process-based model depicting the morphological changes during storm events should be adjusted to simulate the hydro- and morphodynamics, leading to site-, profile-, and event-specific calibration. Although area models eliminate variability in calibrated parameters along with each profile in complex bathymetry, the amount of influence datasets with different wave conditions have on model performance is still unclear in an area model in a given parameter space. This study collected hydrodynamic and bathymetric field data over four different storm conditions (two single and two cluster storms) at Maengbang Beach, South Korea. The numerical model XBeach was adopted using four storm datasets with four key parameters to examine the influence of event-specific calibration data on subaerial storm erosion. When using clustered storm data, a relatively limited number of parameter combinations showed higher model sensitivity to different parameter sets as opposed to single storm data with the same parameter sets. Model sensitivity to different storm events was correlated with cumulative storm power and resultant erosion volume in comparison with other features in the datasets. The results are expected to guide the selection of an event-specific dataset with various morphological and hydrodynamic factors in an area model under complex bathymetry.

The clustered regularly interspaced palindromic repeat (CRISPR)-Cas system has revolutionized genetic engineering due to its simplicity, stability, and precision since its discovery. This technology is utilized in a variety of fields, from basic research in medicine and biology to medical diagnosis and treatment, and its potential is unbounded as new methods are developed. The review focused on medical applications and discussed the most recent treatment trends and limitations, with an emphasis on CRISPR-based therapeutics for infectious disease, oncology, and genetic disease, as well as CRISPR-based diagnostics, screening, immunotherapy, and cell therapy. Given its promising results, the successful implementation of the CRISPR-Cas system in clinical practice will require further investigation into its therapeutic applications.

Digital pathology offers powerful tools for biomarker discovery, analysis, and translation. Despite its advantages, the clinical adoption of digital pathology has been slow. A clinical and methodological validation is required for novel digital pathological biomarkers. Four steps are required to validate a novel pathological digital biomarker for clinical use: sample collection and processing, analytical validation, clinical validation, and clinical utility. The digital biomarkers and their diagnostic, monitoring, pharmacodynamic response, predictive, prognostic, safety, and risk assessment applications are discussed. Adopting pathological digital biomarkers can be used in conjunction with other diagnostic technologies to select the most appropriate patient treatment, thereby reducing patient suffering and healthcare costs.

Abstract: This study aimed to elucidate patterns of disease transformation to secondary myelofibrosis (SMF) or secondary acute myeloid leukemia (SAML) and the development of second primary malignancies in South Korean patients with BCR-ABL1–negative myeloproliferative neoplasms (MPNs). By using nationwide public health care insurance claims data, we identified and analyzed 7454 patients with MPNs who were newly diagnosed with essential thrombocythemia (ET), polycythemia vera (PV), or primary myelofibrosis (PMF) from 2008 to 2016 and used the data to appropriately trace the disease course. Transformation to SMF or SAML was rare in patients with ET and PV, but patients with PMF had an 8-year cumulative incidence of SAML of 21.4%. Patients with PV or ET had an 8-year cumulative incidence of second primary solid tumors of ∼14%. Patients with MPNs had a 2 times higher risk of developing second primary solid tumors than that of the general South Korean population. Compared with patients with PMF, patients with SMF had a similar overall survival with a lower risk of developing SAML. The use of ruxolitinib did not increase the risk of developing B-cell lymphoma over a median follow-up period of 16.2 months. Disease transformation to SMF or SAML was rare in patients with ET or PV, but SAML was common in patients with PMF. South Korean patients with MPNs had a significantly higher risk of developing second primary solid tumors than that of the general population, particularly for kidney, prostate, brain, liver, and lung cancers.

A large portion of the Drosophila melanogaster genome is contained within heterochromatic regions of chromosomes, predominantly at centromeres and telomeres. The remaining euchromatic portions of the genome have been extensively characterized with respect to gene organization, function and regulation. However, it has been difficult to derive similar data for sequences within centromeric (centric) heterochromatin because these regions have not been as amenable to analysis by standard genetic and molecular tools. Here we present an updated genetic and molecular analysis of chromosome 3L centric heterochromatin (3L Het). We have generated and characterized a number of new, overlapping deficiencies (Dfs) which remove regions of 3L Het. These Dfs were critically important reagents in our subsequent genetic analysis for the isolation and characterization of lethal point mutations in the region. The assignment of these mutations to genetically-defined essential loci was followed by matching them to gene models derived from genome sequence data: this was done by using molecular mapping plus sequence analysis of mutant alleles, thereby aligning genetic and physical maps of the region. We also identified putative essential gene sequences in 3L Het by using RNA interference to target candidate gene sequences. We report that at least 25, or just under 2/3 of loci in 3L Het, are essential for viability and/or fertility. This work contributes to the functional annotation of centric heterochromatin in Drosophila, and the genetic and molecular tools generated should help to provide important insights into the organization and functions of gene sequences in 3L Het.

Abstract Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Abstract Background Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML). Methods Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity (Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy. Results The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1–68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety. Conclusions Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML. Trial registration Clinicaltrials.gov NCT02440178, registered May 12th 2015.

Abstract Background Silver nanoparticles (AgNP) are widely used in medical practices owing to their distinct antibacterial, antiviral and anticancer activities. However, with increasing use of AgNP, concerns over its potential toxicity are also escalating. Here, we demonstrated the potential thrombotic effect of AgNP which was mediated by the procoagulant activity of red blood cells (RBCs). Results In freshly isolated human RBCs, AgNP, but not silver microparticles (AgMP), elicited morphological changes, phosphatidylserine (PS) exposure and microvesicles (MV) generation, the key indicators of procoagulant activity in RBCs at concentration ranges (≤ 100 μg/mL) that were free of significant hemolysis. In line with this, AgNP potentiated thrombin generation and adherence of RBCs to endothelial cells, while AgMP did not. Oxidative stress, intracellular calcium increase and ATP depletion were found to underlie the procoagulant effects of AgNP, which led to altered activity of membrane aminophospholipid translocases. These in vitro findings were well reproduced in rat in vivo, where intravenously exposure to AgNP promoted venous thrombosis significantly. Of note, RBCs isolated from cancer patients, who inherently convey the risk of thrombogenesis, were more sensitive to the procoagulant effects of AgNP. In addition, AgNP significantly potentiated the procoagulant effects of a chemotherapeutic drug, paclitaxel. Conclusion Collectively, these results suggest that AgNP may have prothrombotic risks by promoting procoagulant activity of RBCs and caution shall be taken for its use in the population sensitive to thrombosis like cancer patients.

In spite of remarkable progress in machine learning techniques, the state-of-the-art machine learning algorithms often keep machines from real-time learning (online learning) due, in part, to computational complexity in parameter optimization. As an alternative, a learning algorithm to train a memory in real time is proposed, named the Markov chain Hebbian learning algorithm. The algorithm pursues efficient use in memory during training in that: 1) the weight matrix has ternary elements (-1, 0, 1) and 2) each update follows a Markov chain-the upcoming update does not need past weight values. The algorithm was verified by two proof-of-concept tasks: image (MNIST and CIFAR-10 datasets) recognition and multiplication table memorization. Particularly, the latter bases multiplication arithmetic on memory, which may be analogous to humans' mental arithmetic. The memory-based multiplication arithmetic feasibly offers the basis of factorization, supporting novel insight into memory-based arithmetic.