Flexible Printed Ultraviolet-to-Near-Infrared Broadband Optoelectronic Carbon Nanotube Synaptic Transistors for Fast and Energy-Efficient Neuromorphic Vision Systems.

To simulate biological visual systems and surpass their functions and performance, it is essential to develop high-performance optoelectronic neuromorphic electronics with broadband response, low power consumption, and fast response speed. Among these, optoelectronic synaptic transistors have emerged as promising candidates for constructing neuromorphic visual systems. In this work, flexible printed broadband (from 275 to 1050 nm) optoelectronic carbon nanotube synaptic transistors with good stability, high response speed (3.14 ms), and low-power consumption (as low as 0.1 fJ per event with the 1050 nm pulse illumination) using PbS quantum dots (QDs) modified semiconducting single-walled carbon nanotubes (sc-SWCNTs) as active layers are developed. In response to optical pulses within the ultraviolet to near-infrared wavelength range, the optoelectronic neuromorphic devices exhibit excitatory postsynaptic current, paired-pulse facilitation, and a transition from short-term plasticity to long-term plasticity, and other optical synaptic behaviors. Furthermore, a simplified neural morphology visual array is developed to simulate integrated functions such as image perception, memory, and preprocessing. More importantly, it can also emulate other complicated bionic functions, such as the infrared perception of salmon eyes and the warning behavior of reindeer in different environments. This work holds immense significance in advancing the development of artificial neural visual systems.

Preparation of Expanded Graphite-VO2 Composite Cathode Material and Performance in Aqueous Zinc-Ion Batteries.

Due to safety problems caused by the use of organic electrolytes in lithium-ion batteries and the high production cost brought by the limited lithium resources, water-based zinc-ion batteries have become a new research focus in the field of energy storage due to their low production cost, safety, efficiency, and environmental friendliness. This paper focused on vanadium dioxide and expanded graphite (EG) composite cathode materials. Given the cycling problem caused by the structural fragility of vanadium dioxide in zinc-ion batteries, the feasibility of preparing a new composite material is explored. The EG/VO2 composites were prepared by a simple hydrothermal method, and compared with the aqueous zinc-ion batteries assembled with a single type of VO2 under the same conditions, the electrode materials composited with high-purity sulfur-free expanded graphite showed more excellent capacity, cycling performance, and multiplicity performance, and the EG/VO2 composites possessed a high discharge ratio of 345 mAh g-1 at 0.1 A g-1, and the Coulombic efficiency was close to 100%. The EG/VO2 composite has a high specific discharge capacity of 345 mAh g-1 at 0.1 A g-1 with a Coulombic efficiency close to 100%, a capacity retention of 77% after 100 cycles, and 277.8 mAh g-1 with a capacity retention of 78% at a 20-fold increase in current density. The long cycle test data demonstrated that the composite with expanded graphite effectively improved the cycling performance of vanadium-based materials, and the composite maintained a stable Coulombic efficiency of 100% at a high current density of 2 A/g and still maintained a specific capacity of 108.9 mAh/g after 2000 cycles.

Spectroscopy and Kerr-lens mode-locked operation of Yb:GdScO3 crystal.

A Kerr-lens mode-locked laser based on a Yb3+-doped disordered gadolinium scandate (Yb:GdScO3) crystal is reported for the first time, to the best of our knowledge. The crystal with the perovskite structure was grown using the Czochralski method, and its room temperature (RT) and low temperature (LT) spectra were also investigated. Due to the crystal's multisite structure (Gd3+/Sc3+ site), Yb:GdScO3 offers broad and intense polarized emission spectra in the near-infrared range (975-1075 nm). The stimulated emission cross section σSE is 0.46 × 10-20 cm2 at 1000 nm with an emission band width of 75.7 nm for E // b polarization. The continuous wave (CW) laser was operated pumped by a 976 nm fiber-coupled LD laser, resulting in a maximum output power of 8.74 W with a slope efficiency of 76.1% was obtained. Additionally, a pulses as short as 74 fs are generated at ∼1061.7 nm via Kerr-lens mode-locking. The average output power amounts to 32 mW at a pulse repetition rate of 101.4 MHz. All results indicate Yb:GdScO3 a promising candidate for 1 µm ultrashort laser.

Multi-objective optimization of solar resource allocation in radial distribution systems using a refined slime mold algorithm.

The integration of distributed generation resources in power systems offers various advantages, such as peak load management and reduced transmission line congestion. However, it also introduces challenges related to voltage stability. This paper presents a novel multi-objective model for optimizing the allocation of solar resources in radial distribution systems. The model aims to achieve an optimal voltage profile, minimize losses, and maximize penetration levels. To address the conflicting nature of these objectives, a refined multi-objective slime mold algorithm (MOSMA) is proposed. This algorithm demonstrates exceptional capabilities in finding Pareto fronts, avoiding local optima, and effectively solving multi-objective problems compared to other optimization methods. Additionally, the corrected social hierarchy method is integrated to enhance performance. The proposed method is evaluated using a standard system under various operational conditions, showing superior results in terms of maintaining an acceptable voltage profile and significantly reducing losses. The study reveals that while losses decrease for penetration levels ranging from low to medium, they start to increase for levels exceeding 100 %. Notably, the proposed method achieves approximately 12 % system efficiency improvement, as measured by the voltage profile, at a penetration level of 300 %. These findings highlight the effectiveness of the proposed method, even at high penetration levels, surpassing other optimization approaches based on the inverse generation distance parameter.

Enhancement-Mode Carbon Nanotube Optoelectronic Synaptic Transistors with Large and Controllable Threshold Voltage Modulation Window for Broadband Flexible Vision Systems.

The development of large-scale integration of optoelectronic neuromorphic devices with ultralow power consumption and broadband responses is essential for high-performance bionics vision systems. In this work, we developed a strategy to construct large-scale (40 × 30) enhancement-mode carbon nanotube optoelectronic synaptic transistors with ultralow power consumption (33.9 aJ per pulse) and broadband responses (from 365 to 620 nm) using low-work function yttrium (Y)-gate electrodes and the mixture of eco-friendly photosensitive Ag2S quantum dots (QDs) and ionic liquids (ILs)-cross-linking-poly(4-vinylphenol) (PVP) (ILs-c-PVP) as the dielectric layers. Solution-processable carbon nanotube thin-film transistors (TFTs) showed enhancement-mode characteristics with the wide and controllable threshold voltage window (-1 V∼0 V) owing to use of the low-work-function Y-gate electrodes. It is noted that carbon nanotube optoelectronic synaptic transistors exhibited high on/off ratios (>106), small hysteresis and low operating voltage (≤2 V), and enhancement mode even under the illumination of ultraviolet (UV, 365 nm), blue (450 nm), and green (550 nm) to red (620 nm) pulse lights when introducing eco-friendly Ag2S QDs in dielectric layers, demonstrating that they have the strong fault-tolerant ability for the threshold voltage drifts caused by various manufacturing scenarios. Furthermore, some important bionic functions including a high paired pulse facilitation index (PPF index, up to 290%), learning and memory function with the long duration (200 s), and rapid recovery (2 s). Pavlov's dog experiment (retention time up to 20 min) and visual memory forgetting experiments (the duration of high current for 180 s) are also demonstrated. Significantly, the optoelectronic synaptic transistors can be used to simulate the adaptive process of vision in varying light conditions, and we demonstrated the dynamic transition of light adaptation to dark adaptation based on light-induced conditional behavior. This work undoubtedly provides valuable insights for the future development of artificial vision systems.

Tunable and mode-locked Tm,Ho:GdScO3 laser.

A novel, to the best of our knowledge, Tm,Ho:GdScO3 crystal grown using the Czochralski method was investigated for its polarized spectroscopic properties and laser performance in both tunable continuous-wave (CW) and mode-locked regimes. The crystal's multisite structure (Gd3+/Sc3+ site) and Tm3+/Ho3+ dopants contributed to spectral broadening, enabling a tunable laser operation from 1914 to 2125 nm (with a broad range of 215 nm). Additionally, a pulse duration of 72 fs was achieved for E || b polarization. These results demonstrate the potential of the Tm,Ho:GdScO3 perovskite crystal as a promising gain material for ultrafast lasers operating around 2 µm.

Miniaturized and Portable Laser Gas Sensor for Standoff Methane Detection With Non-Cooperative Targets.

A standoff methane (CH4) sensor with actual hard topographic targets (usually called non-cooperative targets) is essential for natural gas pipeline leakage inspection and many other practical applications. To address this requirement, a miniaturized and low-power-consumption gas sensor was developed based on tunable diode laser absorption spectroscopy for standoff CH4 detection with a non-cooperative target. Wavelength modulation spectroscopy with a 1f normalized 2f detection method was employed for calibration-free CH4 measurement. A Kalman filter algorithm was used to improve the precision of the detection. The performance of the standoff CH4 sensor was evaluated comprehensively under various conditions, including different incident angles, different hard topographic targets, and different standoff distances. The results show that the measurement precision is 0.107% and the sensitivity is 4.08 parts per million per meter (ppm·m) with a time resolution of 1 s and a standoff distance of 40 m. The detection limit can achieve 1.24 ppm·m at an optimal integration time of 70 s. This sensor can be easily integrated into mobile platforms, which lays the foundation for intelligent leak inspection.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Sarm1 Regulates Circadian Rhythm Disorder in Alzheimer's Disease in Mice.

BACKGROUND: Sarm1 (Sterile alpha and TIR motif-containing 1) is a key protein that regulates neurodegenerative pathologies. Alzheimer's disease (AD) is highly associated with neurodegenerative lesions and biorhythmic disturbances. OBJECTIVE: This study aims to decipher the role of Sarm1 in AD-induced circadian rhythm disturbances and AD progression. METHODS: Open field and water maze tests were used to assess the cognitive function of mice. Thioflavin-S staining was used to assess amyloid-ß (Aß) plaque deposition in the hippocampus and cortex. Rhythmic waveform of home cage activity and temperature was recorded to evaluate circadian rhythm. Expression of clock molecules including Bmal1 and Per2 in the hippocampus were analyzed using western blot and real-time PCR. Further, HT22 cells with Sam1 knockout were treated with Aß31-35 treatment to initiate circadian rhythm disorder in the cellular level to assess the changes in Bmal1 and Per2. RESULTS: Our data suggested that Sarm1 deficiency rescued cognitive disorder, decreased Aß plaque deposition in the hippocampus and cortex, inhibited astrocyte activation, improved circadian rhythm, altered clock molecule expression in the cortex and hippocampus in APP/PS1 mice. CONCLUSION: Sarm1 attenuates circadian rhythm disturbances and reduces AD progression. These data support the potential use of Sarm1 as a therapeutic target to improve circadian rhythm to impede AD progression.

Characterization and Modeling of a Pt-In2O3 Resistive Sensor for Hydrogen Detection at Room Temperature.

Sensitive H2 sensors at low concentrations and room temperature are desired for the early warning and control of hydrogen leakage. In this paper, a resistive sensor based on Pt-doped In2O3 nanoparticles was fabricated using inkjet printing process. The H2 sensing performance of the sensor was evaluated at low concentrations below 1% at room temperature. It exhibited a relative high response of 42.34% to 0.6% H2. As the relative humidity of 0.5% H2 decreased from 34% to 23%, the response decreased slightly from 34% to 23%. The sensing principle and the humidity effect were discussed. A dynamic current sensing model for dry H2 detection was proposed based on Wolkenstein theory and experimentally verified to be able to predict the sensing behavior of the sensor. The H2 concentration can be calculated within a short measurement time using the model without waiting for the saturation of the response, which significantly reduces the sensing and recovery time of the sensor. The sensor is expected to be a promising candidate for room-temperature H2 detection, and the proposed model could be very helpful in promoting the application of the sensor for real-time H2 leakage monitoring.

Imaging simulation of the AMCW ToF camera based on path tracking.

The time-of-flight (ToF) camera suffers from many error factors, such as multiple reflection or multipath interference and electronic and optical shot noise, making it difficult to simulate its imaging process. Aiming to test the ToF camera algorithm, it is important to obtain a depth image affected by these error factors. In order to model the light propagation behavior and the sensor effect in the imaging process of the ToF camera, an amplitude modulated continuous-wave (AMCW) ToF camera imaging simulation method based on path tracking is presented by deducing the path tracking algorithm model in the AMCW ToF camera theoretically and by realizing the physically based simulation by introducing the infrared bidirectional reflectance distribution function (BRDF) data of the actual materials. According to the constructed error evaluation indexes, the correctness of the imaging simulation method is verified based on the ground experiment. The mean absolute error (MAE) and root mean square error (RMSE) are 10.32 mm and 15.12 mm, respectively, which are less than the error results of the other two comparative simulation methods. The results show that the proposed method is reasonable and can provide reliable data support for AMCW ToF hardware development and algorithm testing.

Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients.

BACKGROUND: A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. METHODS: We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. RESULTS: Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). CONCLUSIONS: PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients.

Parthenolide alleviates peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Peritoneal fibrosis is a common complication of peritoneal dialysis (PD) with a complicated pathogenesis and limited treatments. Parthenolide (PTL), a recognized nuclear factor-κB (NF-κB) inhibitor extracted from Tanacetum balsamita, has been widely used to treat various inflammatory diseases and has been proven to improve peritoneal fibrosis in PD mice by selectively inhibiting the phosphorylation of Smad2/3. Transforming growth factor-ß1 (TGF-ß1), via Smad-dependent signaling, has a pivotal role in promoting pathogenic of fibrosis. To investigate whether PTL can inhibit peritoneal fibrosis, we affected the interaction between NF-κB and the TGF-ß/Smad2/3 pathway. Long dwell peritoneal dialysis fluid (PDF) and peritoneum tissues were collected from continuous ambulatory peritoneal dialysis (CAPD) patients. PTL was administered intragastrically into a PD mouse model by daily infusion of 4.25% dextrose-containing PDF. Treated HMrSV5 cells or rat peritoneal mesothelial cells (RPMCs) were treated with high glucose(138 mM) at the same concentration as 2.5% dextrose-containing PDF and PTL. PD-related peritoneal fibrosis samples indicated an increase in inflammation, and PTL decreased the levels of inflammatory cytokines (L-6, TNF-α, and MCP-1). PTL inhibited high glucose-induced mesothelial-to-mesenchymal transition (MMT), as indicated by a reduced expression of fibrosis markers (fibronectin, collagen I, and α-SMA) and increased expression of the epithelial marker E-cadherin. PTL also significantly decreased TGF-ß1 expression and the phosphorylation of IκBα and NF-κBp65. The changes in the levels of TGF-ß1 expression and p-p65 or p65 showed similar trends according to western blot, immunohistochemistry, and immunofluorescence assays in vitro and in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to confirm that PTL regulates the transcription of TGF-ß1 induced by high glucose through NF-κBp65. In summary, PTL induces a therapeutic effect in peritoneal fibrosis by inhibiting inflammation via the NF-κB/ TGF-ß/Smad signaling axis.

Biochemical Process and Microbial Evolution in the Conversion of Corn Straw Combined with Coal to Biogas.

The combined anaerobic fermentation of coal and straw can increase the production of biogas. To explore the mechanism of adding corn straw to increase methane production, coal with different metamorphic degrees and corn straw were collected for biogas production simulation experiments under different substrate ratios. The changes in liquid products, the structure of lignocellulose in corn straw, and microbial evolution were monitored. The results showed that the combined fermentation of bituminous coal A with corn straw and bituminous coal C with corn straw at a mass ratio of 2:1 each ((AC-2) and (CC-2)) and that of bituminous coal B and corn straw at a mass ratio of 3:1 (BC-3) had the best gas production, and methane yields reached 17.28, 12.51, and 14.88 mL/g, respectively. The fermentation liquid had organic matter with more types and higher contents during the early and peak stages of gas production, and fewer types of organic matter were detected in the terminal stage. The degradation of lignocelluloses in the corn straw of AC-2 was higher. With the increase in fermentation time, the carbohydrates in the fermentation system increased and the degradation rate of cellulose decreased gradually. The abundance of genes related to nitrate reduction gradually increased, while that of sulfate reduction was on the contrary. Bacteria in the cofermentation system mainly metabolized carbohydrates. During cofermentation with high metamorphic coal, corn straw would be preferentially degraded. The structure of the archaea community changed from Methanosarcina and Methanothrix to Methanobacterium.

Neutrophil to high-density lipoprotein ratio associates with higher all-cause mortality and new onset cardiovascular events in peritoneal dialysis patients.

BACKGROUND: Neutrophil to high-density lipoprotein ratio (NHR), a new inflammatory marker, is associated with poor clinical prognosis. However, the correlation of NHR and adverse outcomes in peritoneal dialysis (PD) patients remains unclear. METHODS: In this retrospective cohort study, a total of 1051 PD patients were recruited from three centers during Jan 1, 2009 to Dec 31, 2017. Eligible patients were distributed according to quartiles of the NHR. Kaplan-Meier cumulative incidence curves, multivariate COX regression, competitive risk analysis and restricted cubic spline (RCS) were applied to analyze the relationship between NHR and all-cause mortality as well as cardiovascular events (CVE). In addition, forest plots were used to calculate the interaction between different subgroups. RESULTS: During follow-up, a total of 240 all-cause mortality and 157 new-onset CVE were recorded. The all-cause mortality in the highest quartile of NHR (> 5.43) were higher than those in the other groups. RCS showed a non-linear relationship between NHR and adverse outcomes. Multivariate COX regression indicated elevated NHR was an independent risk factor for all-cause mortality. Compared to the highest quartile, hazard ratio (HR) of new-onset CVE equals to 0.522 (95% CI 0.321-0.849) in the secondary quartile (2.43 < NHR ≤ 3.57), and the HR of all-cause mortality analysis is 0.551 (95% CI 0.378-0.803) in the third quartile (3.57 < NHR ≤ 5.43). Kaplan-Meier analysis suggested there were significant differences in all-cause mortality and new-onset CVE among four NHR groups. CONCLUSIONS: NHR was a new independent risk factor for all-cause mortality in PD patients.

Proton pump inhibitor usage is associated with higher all-cause mortality and CV events in peritoneal dialysis patients.

OBJECTIVES: A long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients. METHODS AND DESIGN: This is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan-Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes. RESULTS: During follow-up, 162 deaths and 102 CV events were recorded. Kaplan-Meier curve demonstrated all-cause mortality (log-rank test p = .018) and CV events (log-rank test p = .024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09-1.67, p = .006) and CV events (HR = 1.78, 95%CI = 1.35-2.32, p < .001). CONCLUSIONS: PPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment.

Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects.

In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS. Significance: We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline BRCA-mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non-BRCA HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.

ACEi/ARBs associate with lower incidence of gastrointestinal bleeding in peritoneal dialysis patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is widespread in patients with impaired renal function. Whether angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) potentially take a crucial role in avoiding GIB incidence among peritoneal dialysis (PD) patients is unknown. METHODS: Overall, 734 PD patients were enrolled after using propensity score matching. Kaplan-Meier analysis and COX regression were used to explore correlation between ACEi/ARBs and GIB. Competitive risk model was aimed to identify whether other events were confounding factors. Forest plot was applied to assess the influence of ACEI/ARBs on GIB incidence in different groups. RESULTS: During 8-year follow-up, 89 (12.13%) cases of GIB were recorded. Kaplan-Meier analysis revealed that the incidence of GIB among patients taking ACEi/ARBs was lower than those subjects who had not (log rank = 6.442, P = 0.011). After adjusted different confounding factors, administration of ACEi/ARBs was associated with lowered GIB incidence (adjusted HR = 0.49, 95% CI 0.32-0.77, P = 0.002). In competitive risk model, considering of other events, the incidence of GIB in two groups was still statistically significant (P = 0.010). Subgroup analysis showed ACEi/ARBs taking impeded GIB in the ≥ 60 age group (HR = 0.52, 95% CI 0.28-0.98, P = 0.040). CONCLUSION: PD patients who were submitted to ACEi/ARBs inclined to have a lower risk for GIB. In this regard, ACEi/ARBs offered a promising choice to GIB.

Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models.

Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. The availability of multiple anti-PD-(L)1 antibodies provides treatment and dosing regimen choice for patients with cancer. Here, we describe the nonclinical characterization of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, which binds with high affinity to human PD-1 and effectively inhibits its interaction with its ligands, PD-L1 and PD-L2. Dostarlimab enhanced effector T-cell functions, including cytokine production, in vitro. Since dostarlimab does not bind mouse PD-1, its single-agent antitumor activity was evaluated using humanized mouse models. In this model system, dostarlimab demonstrated antitumor activity as assessed by tumor growth inhibition, which was associated with increased infiltration of immune cells. Single-dose and 4-week repeat-dose toxicology studies in cynomolgus monkeys indicated that dostarlimab was well tolerated. In a clinical setting, based on data from the GARNET trial, dostarlimab (Jemperli) was approved for the treatment of adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer that had progressed on or following prior treatment with a platinum-containing regimen. Taken together, these data demonstrate that dostarlimab is a potent anti-PD-1 receptor antagonist, with properties that support its continued clinical investigation in patients with cancer.