Trust-Based Optimized Reporting for Detection and Prevention of Black Hole Attacks in Low-Power and Lossy Green IoT Networks.

The Internet of Things (IoT) is empowering various sectors and aspects of daily life. Green IoT systems typically involve Low-Power and Lossy Networks (LLNs) with resource-constrained nodes. Lightweight routing protocols, such as the Routing Protocol for Low-Power and Lossy Networks (RPL), are increasingly being applied for efficient communication in LLNs. However, RPL is susceptible to various attacks, such as the black hole attack, which compromises network security. The existing black hole attack detection methods in Green IoT rely on static thresholds and unreliable metrics to compute trust scores. This results in increasing false positive rates, especially in resource-constrained IoT environments. To overcome these limitations, we propose a delta-threshold-based trust model called the Optimized Reporting Module (ORM) to mitigate black hole attacks in Green IoT systems. The proposed scheme comprises both direct trust and indirect trust and utilizes a forgetting curve. Direct trust is derived from performance metrics, including honesty, dishonesty, energy, and unselfishness. Indirect trust requires the use of similarity. The forgetting curve provides a mechanism to consider the most significant and recent feedback from direct and indirect trust. To assess the efficacy of the proposed scheme, we compare it with the well-known trust-based attack detection scheme. Simulation results demonstrate that the proposed scheme has a higher detection rate and low false positive alarms compared to the existing scheme, confirming the applicability of the proposed scheme in green IoT systems.

Antiemetic activity of abietic acid possibly through the 5HT3 and muscarinic receptors interaction pathways.

The present study was designed to evaluate the antiemetic activity of abietic acid (AA) using in vivo and in silico studies. To assess the effect, doses of 50 mg/kg b.w. copper sulfate (CuSO4⋅5H2O) were given orally to 2-day-old chicks. The test compound (AA) was given orally at two doses of 20 and 40 mg/kg b.w. On the other hand, aprepitant (16 mg/kg), domperidone (6 mg/kg), diphenhydramine (10 mg/kg), hyoscine (21 mg/kg), and ondansetron (5 mg/kg) were administered orally as positive controls (PCs). The vehicle was used as a control group. Combination therapies with the referral drugs were also given to three separate groups of animals to see the synergistic and antagonizing activity of the test compound. Molecular docking and visualization of ligand-receptor interaction were performed using different computational tools against various emesis-inducing receptors (D2, D3, 5HT3, H1, and M1-M5). Furthermore, the pharmacokinetics and toxicity properties of the selected ligands were predicted by using the SwissADME and Protox-II online servers. Findings indicated that AA dose-dependently enhances the latency of emetic retching and reduces the number of retching compared to the vehicle group. Among the different treatments, animals treated with AA (40 mg/kg) exhibited the highest latency (98 ± 2.44 s) and reduced the number of retching (11.66 ± 2.52 times) compared to the control groups. Additionally, the molecular docking study indicated that AA exhibits the highest binding affinity (- 10.2 kcal/mol) toward the M4 receptors and an elevated binding affinity toward the receptors 5HT3 (- 8.1 kcal/mol), M1 (- 7.7 kcal/mol), M2 (- 8.7 kcal/mol), and H1 (- 8.5 kcal/mol) than the referral ligands. Taken together, our study suggests that AA has potent antiemetic effects by interacting with the 5TH3 and muscarinic receptor interaction pathways. However, additional extensive pre-clinical and clinical studies are required to evaluate the efficacy and toxicity of AA.

Investigation of Dielectric, Mechanical, and Thermal Properties of Epoxy Composites Embedded with Quartz Fibers.

Polymer matrix wave transparent composites are used in a variety of high-speed communication applications. One of the applications of these involves making protective enclosures for antennas of microwave towers, air vehicles, weather radars, and underwater communication devices. Material performance, structural, thermal, and mechanical degradation are matters of concern as advanced wireless communication needs robust materials for radomes that can withstand mechanical and thermal stresses. These polymer composite radomes are installed externally on antennas and are exposed directly to ambient as well as severe conditions. In this research, epoxy resin was reinforced with a small amount of quartz fibers to yield an improved composite radome material compared to a pure epoxy composite with better thermal and mechanical properties. FTIR spectra, SEM morphology, dielectric constant (Ɛr) and dielectric loss (δ), thermal degradation (weight loss), and mechanical properties were determined. Compared to pure epoxy, the lowest values of Ɛr and δ were 3.26 and 0.021 with 30 wt.% quartz fibers in the composite, while 40% less weight loss was observed which shows its better thermal stability. The mechanical characteristics encompassing tensile and bending strength were improved by 42.8% and 48.3%. In high-speed communication applications, compared to a pure epoxy composite, adding only a small quantity of quartz fiber can improve the composite material's dielectric performance, durability, and thermal and mechanical strength.

Respiratory Dysfunction in Epileptic Encephalopathies: Insights and Challenges.

Epileptic encephalopathies constitute a group of severe epileptic disorders characterized by intractable seizures and cognitive regression. Beyond the hallmark neurological manifestations, these disorders frequently exhibit associated respiratory dysfunction, which is increasingly recognized as a critical aspect of their pathophysiology. Respiratory abnormalities in epileptic encephalopathies encompass a spectrum of manifestations, ranging from subtle alterations in breathing patterns to life-threatening events such as apneas and hypoventilation. These respiratory disturbances often occur during seizures, the interictal period, or even persist chronically, leading to significant morbidity and mortality. We explore the varied clinical presentations and their implications on patient outcomes, emphasizing the need for heightened awareness among clinicians. This review unravels the intricate mechanisms linking epilepsy and respiratory dysfunction. GABAergic and glutamatergic imbalances, alterations in central respiratory centers, and abnormal autonomic control are among the key factors contributing to respiratory disturbances in these patients. We elucidate the neurobiological intricacies that underlie these processes and their relevance to therapeutic interventions. Accurate diagnosis of respiratory dysfunction in epileptic encephalopathies is often hindered by its diverse clinical phenotypes and the absence of routine screening protocols. We scrutinize the diagnostic hurdles, highlighting the necessity of comprehensive respiratory assessments in managing these patients. Timely recognition of respiratory issues may guide treatment decisions and mitigate complications. Management of respiratory dysfunction in epileptic encephalopathies is complex and necessitates a multidisciplinary approach. We explore various therapeutic modalities, including antiepileptic drugs (AEDs), ventilatory support, and novel interventions like neuromodulation techniques. The review emphasizes the individualized nature of treatment strategies tailored to each patient's specific needs. In conclusion, this narrative review offers a comprehensive overview of respiratory dysfunction in epileptic encephalopathies, shedding light on its clinical importance, underlying mechanisms, diagnostic challenges, and therapeutic considerations. By addressing these insights and challenges, we hope to inspire further research and innovation to enhance the care and outcomes of patients with epileptic encephalopathies.

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review.

Purpose: Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. Methods: We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Results: Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Conclusions: Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.

Recent developments and challenges in uranium extraction from seawater through amidoxime-functionalized adsorbents.

As per statistical estimations, we have only around 100 years of uranium life in terrestrial ores. In contrast, seawater has viable uranium resources that can secure the future of energy. However, to achieve this, environmental challenges need to be overcome, such as low uranium concentration (3.3 ppb), fouling of adsorbents, uranium speciation, oceanic temperature, and competition between elements for the active site of adsorbent (such as vanadium which has a significant influence on uranium adsorption). Furthermore, the deployability of adsorbent under seawater conditions is a gigantic challenge; hence, leaching-resistant stable adsorbents with good reusability and high elution rates are extremely needed. Powdered (nanostructured) adsorbents available today have limitations in fulfilling these requirements. An increase in the grafting density of functional ligands keeping in view economic sustainability is also a major obstacle but a necessity for high uranium uptake. To cope with these challenges, researchers reported hundreds of adsorbents of different kinds, but amidoxime-based polymeric adsorbents have shown some remarkable advantages and are considered the benchmark in uranium extraction history; they have a high affinity for uranium because of electron donors in their structure, and their amphoteric nature is responsible for effective uranium chelation under a wide range of pH. In this review, we have mainly focused on recent developments in uranium extraction from seawater through amidoxime-based adsorbents, their comparative analysis, and problematic factors that are needed to be considered for future research.

Early versus late endoscopic treatment of pancreatic necrotic collections: A systematic review and meta-analysis.

Background and study aims Recently studies have compared early (<4 weeks) vs. late or standard (>4 weeks) endoscopic treatment of pancreatic necrotic collections (PNC) and have reported favorable results for early treatment. In this meta-analysis, we compared the efficacy and safety of early vs. late endoscopic treatment of PNC. Patients and methods We reviewed several databases from inception to September 30, 2021 to identify studies that compared early with late endoscopic treatment of PNC. Our outcomes of interest were adverse events (AEs), resolution of PNC, performance of direct endoscopic necrosectomy, need for further interventions, and mean number of endoscopic necrosectomy sessions. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) for categorical variables and mean differences (MDs) with 95% CIs for continuous variables. Data were analyzed by random effect model. Heterogeneity was assessed by I 2 statistic. Results We included four studies with 427 patients. We found no significant difference in rates of AEs, RR (95% CI) 1.70 (range, 0.56-5.20), resolution of necrotic or fluid collections, RR (95% CI) 0.89 (range, 0.71-1.11), need for further interventions, RR (95% CI) 1.47 (range, 0.70-3.08), direct necrosectomy, RR (95% CI) 1.39 (range, 0.22-8.80), mortality, RR (95% CI) 2.37 (range, 0.26-21.72) and mean number of endoscopic necrosectomy sessions, MD (95% CI) 1.58 (range,-0.20-3.36) between groups. Conclusions Early endoscopic treatment of PNC can be considered for indications such as infected necrosis or sterile necrosis with symptoms or complications; however, future large multicenter studies are required to further evaluate its safety.

Salicylic acid-mitigates abiotic stress tolerance via altering defense mechanisms in Brassica napus (L.).

Under the changing climate due to global warming, various abiotic stresses including drought (D) and salinity (S) are expected to further trigger their devastating effects on the already vulnerable crop production systems. This experiment was designed to unravel and quantify the potential role of exogenous application of salicylic acid (SA) in mitigating both D and S stresses and their combination (D+S), with three replications using CRD (Completely Randomized Design). The obtained results of the current study demonstrated significant effects of all three types of stresses (D, S, and D+S) on various parameters in Brassica napus plants. Quantifying these parameters provides a more informative and precise understanding of the findings. Current results revealed that all three stress types (D, S, and D+S) resulted in a reduction in leaf area (13.65 to 21.87%), chlorophyll levels (30 to 50%), gaseous exchange rate (30 to 54%) and the concentration of mineral ions compared to non-stressed plants. However, application of SA helped in mitigating these stresses by ameliorating the negative effects of these stresses. Moreover, Malondialdehyde (MDA) contents, an indicator of lipid per-oxidation and oxidative stress, the levels of antioxidants, proline content, an osmolyte associated with stress tolerance, and sugar content in the leaves were elevated in response to all stress conditions. In addition, the ultra-structures within the leaves were negatively affected by the stresses, while an application of SA considerably minimized the deterioration of these structures thus providing protection to the brassica plants against the stresses. In a nutshell, the findings of this study suggest that SA application in S, D and S+ D stresses provides evasion to the plants by improving different physiological and growth indices. The application of Salicylic Acid (SA) mitigated the negative effects of the stresses on all the above parameters, reducing MDA contents (47%), antioxidants (11 to 20%), proline (28%), sugar contents (20.50%), and minimizing the deterioration of ultra-structures. The findings emphasize the potential mitigatory role of SA in mitigating D and S stresses and highlight the need for further research to understand the underlying mechanisms in detail and explore its practical application in farming practices.

Analysis of the Self-Healing Capability of Thermoplastic Elastomer Capsules in a Polymeric Beam Structure Based on Strain Energy Release Behaviour during Crack Growth.

The objective of this study was to investigate the elastic and plastic responses of 3D-printed thermoplastic elastomer (TPE) beams under various bending loads. The study also aimed to develop a self-healing mechanism using origami TPE capsules embedded within an ABS structure. These cross-shaped capsules have the ability to be either folded or elastically deformed. When a crack occurs in the ABS structure, the strain is released, causing the TPE capsule to unfold along the crack direction, thereby enhancing the crack resistance of the ABS structure. The enhanced ability to resist cracks was confirmed through a delamination test on a double cantilever specimen subjected to quasi-static load conditions. Consistent test outcomes highlighted how the self-healing process influenced the development of structural cracks. These results indicate that the suggested self-healing mechanism has the potential to be a unique addition to current methods, which mostly rely on external healing agents.

Gastrointestinal haemorrhage in extracorporeal membrane oxygenation: insights from the national inpatient sample.

Introduction: Extracorporeal membrane oxygenation (ECMO) is associated with gastrointestinal haemorrhage (GIH), which may result from coagulopathy, systemic inflammation, reduced gastric perfusion, and arteriovenous malformation from non-pulsatile blood flow. Data are limited regarding the burden of this complication in the United States. Material and methods: We analysed the National Inpatient Sample (NIS) database for the years 2007 to 2011 to identify hospitalisations in which an ECMO procedure was performed. Hospitalizations complicated by GIH in this cohort were then identified by relevant codes. Results: Between 2007 and 2011, ECMO hospitalisations increased from 1869 to 3799 (p < 0.01). The proportion of hospitalisations complicated by GIH increased from 2.12% in 2007 to 7.46% in 2011 (p < 0.01). Gastrointestinal haemorrhage was more common in men (56.7%) and in Caucasians (57.4%). Common comorbidities in this population were renal failure (71%), anaemia (55%), and hypertension (26%). All-cause inpatient mortality showed a numerical but nonsignificant increase from 56.7% to 61.9% (p = 0.49). The average cost of care per hospitalisation with GIH associated with ECMO use increased from $132,420 in 2007 to $215,673 in 2011 (p < 0.01). Conclusions: Gastrointestinal haemorrhage during ECMO hospitalisations occurred in small but significantly increasing proportions. The inpatient mortality rate and costs associated with GIH were substantial and increased significantly during the study period.

Functionalized graphene oxide-based lamellar membranes for organic solvent nanofiltration applications.

In this study, two-dimensional graphene oxide-based novel membranes were fabricated by modifying the surface of graphene oxide nanosheets with six-armed poly(ethylene glycol) (PEG) at room conditions. The as-modified PEGylated graphene oxide (PGO) membranes with unique layered structures and large interlayer spacing (∼1.12 nm) were utilized for organic solvent nanofiltration applications. The as-prepared 350 nm-thick PGO membrane offers a superior separation (>99%) against evans blue, methylene blue and rhodamine B dyes along with high methanol permeance ∼ 155 ± 10 L m-2 h-1, which is 10-100 times high compared to pristine GO membranes. Additionally, these membranes are stable for up to 20 days in organic solvent. Hence the results suggested that the as-synthesized PGO membranes with superior separation efficiency for dye molecules in organic solvent can be used in future for organic solvent nanofiltration application.

Efficacy and safety of EUS-guided gallbladder drainage for rescue treatment of malignant biliary obstruction: A systematic review and meta-analysis.

ERCP is the first line of treatment for malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. EUS-guided gallbladder drainage (EUS-GBD) has been suggested as a rescue treatment for patients who fail EUS-BD and ERCP. In this meta-analysis, we have evaluated the efficacy and safety of EUS-GBD as a rescue treatment of malignant biliary obstruction after failed ERCP and EUS-BD. We reviewed several databases from inception to August 27, 2021, to identify studies that evaluated the efficacy and/or safety of EUS-GBD as a rescue treatment in the management of malignant biliary obstruction after failed ERCP and EUS-BD. Our outcomes of interest were clinical success, adverse events, technical success, stent dysfunction requiring intervention, and difference in mean pre- and postprocedure bilirubin. We calculated pooled rates with 95% confidence intervals (CI) for categorical variables and standardized mean difference (SMD) with 95% CI for continuous variables. We analyzed data using a random-effects model. We included five studies with 104 patients. Pooled rates (95% CI) of clinical success and adverse events were 85% (76%, 91%) and 13% (7%, 21%). Pooled rate (95% CI) for stent dysfunction requiring intervention was 9% (4%, 21%). The postprocedure mean bilirubin was significantly lower compared to preprocedure bilirubin, SMD (95% CI): -1.12 (-1.62--0.61). EUS-GBD is a safe and effective option to achieve biliary drainage after unsuccessful ERCP and EUS-BD in patients with malignant biliary obstruction.

Cold snare versus cold forceps polypectomy for endoscopic resection of diminutive polyps: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The practices for resection of diminutive colon polyps vary among endoscopists, and U.S. Multi-Society Task force guidelines recommend use of cold snare polypectomy (CSP) for this purpose. In this meta-analysis, we compared CSP and cold forceps polypectomy (CFP) for resection of diminutive polyps. METHODS: Several databases were reviewed to identify randomized controlled trials that compared CSP and CFP for resection of diminutive polyps. The study outcomes of interest were complete resection of all diminutive polyps, complete resection of polyps ≤3 mm in size, failure of tissue retrieval, and polypectomy time. For categorical variables, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated; for continuous variables, mean differences (MDs) with 95% CIs were calculated. Data were analyzed by using a random-effects model, and heterogeneity was assessed by using the I2 statistic. RESULTS: We included 9 studies with 1037 patients. Rate of complete resection of all diminutive polyps was significantly higher in the CSP group (OR, 1.68; 95% CI, 1.09-2.58). Subgroup analysis, including jumbo or large-capacity forceps, found no significant difference in complete resection between groups (OR, 1.43; 95% CI, .80-2.56). We found no significant between-groups in the rates of complete resection of polyps ≤3 mm in size (OR, .83; 95% CI, .30-2.31). Rate of failure of tissue retrieval was significantly higher in the CSP group (OR, 10.13; 95% CI, 2.29-44.74). No significant between-group difference was noted in polypectomy time. CONCLUSIONS: CFP using large-capacity or jumbo biopsy forceps is noninferior to CSP for complete resection of diminutive polyps.

Over-the-Scope Clips Versus Standard Endoscopic Treatment for First Line Therapy of Non-variceal Upper Gastrointestinal Bleeding: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Over-The-Scope Clips (OTSC) use have shown promising results for first line treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). We conducted this meta-analysis to compare outcomes in patients treated with OTSC versus standard endoscopic intervention for first line endoscopic treatment of NVUGIB. METHODS: We reviewed several databases from inception to December 9, 2022 to identify studies comparing OTSC and standard treatments as the first line treatment for NVUGIB. The outcomes assessed included re-bleeding, initial hemostasis, need for vascular embolization, mortality, need for repeat endoscopy, 30 day readmission rate, and need for surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random effect model. Heterogeneity was assessed by I2 statistic. RESULTS: We included 11 studies with 1608 patients (494 patients in OTSC group and 1114 patients in control group). OTSC use was associated with significantly lower risk of re-bleeding (RR, 0.58; 95% CI 0.41-0.82). We found no significant difference in rates of initial hemostasis (RR, 1.05; 95% CI 0.99- 1.11), vascular embolization rates (RR, 0.93; 95% CI 0.40- 2.13), need for repeat endoscopy (RR, 0.78; 95% CI 0.40-1.49), 30 day readmission rate (RR, 0.59; 95% CI 0.17-2.01), need for surgery (RR, 0.81; 95% CI 0.29-2.28) and morality (RR, 0.69; 95% CI 0.38-1.23). CONCLUSIONS: OTSC are associated with significantly lower risk of re-bleeding compared to standard endoscopic treatments when used as first line endoscopic therapy for NVUGIB.

Influence of Operating and Electrochemical Parameters on PEMFC Performance: A Simulation Study.

Proton exchange membrane fuel cell, or polymer electrolyte fuel cell, (PEMFC) has received a significant amount of attention for green energy applications due to its low carbon emission and less other toxic pollution capacity. Herein, we develop a three-dimensional (3D) computational fluid dynamic model. The values of temperature, pressure, relative humidity, exchange coefficient, reference current density (RCD), and porosity values of the gas diffusion layer (GDL) were taken from the published literature. The results demonstrate that the performance of the cell is improved by modifying temperature and operating pressure. Current density is shown to degrade with the rising temperature as explored in this study. The findings show that at 353 K, the current density decreases by 28% compared to that at 323 K. In contrast, studies have shown that totally humidified gas passing through the gas channel results in a 10% higher current density yield, and that an evaluation of a 19% higher RCD value results in a similar current density yield.

Efficacy and safety of EUS-guided biliary drainage for benign biliary obstruction - A systematic review and meta-analysis.

Background and Objectives: ERCP is the first line of treatment for benign and malignant biliary obstruction and EUS-guided biliary drainage (EUS-BD) is usually used for patients who have failed ERCP. Recently, several studies have evaluated the role of EUS-BD in the management of benign biliary obstruction. This meta-analysis evaluates the efficacy and safety of EUS-BD in the management of benign biliary obstruction. Methods: We reviewed several databases from inception to July 8, 2022, to identify studies evaluating the efficacy and safety of EUS-BD in the management of benign biliary obstruction. Our outcomes of interest were technical success, clinical success, and adverse events. Pooled rates with 95% confidence intervals (CIs) for all outcomes were calculated using a random effects model. Subgroup analyses were performed including patients with normal anatomy versus surgically altered anatomy (SAA). Heterogeneity was assessed by I2 statistic. Results: We included 14 studies with 329 patients. The pooled rate (95% CI) of technical success was 88% (83%, 92%). The pooled rate (95% CI) of technical success for patients with SAA and normal anatomy was 92% (85%, 96%) and 83% (75%, 89%), respectively. The pooled rates (95% CI) of clinical success and adverse events were 89% (83%, 93%) and 19% (13%, 26%), respectively. We found low heterogeneity in most of the analyses. Conclusions: EUS-BD is an effective and safe option in patients with benign biliary obstruction and should be considered after a failed attempt at ERCP or when ERCP is not technically possible.

Diarrhea and colitis related to immune checkpoint inhibitor and BRAF/MEK inhibitor therapy.

Background: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of gastrointestinal AEs related to sequential ICI and BRAF/MEK inhibitor therapy. Methods: We identified 255 adult cancer patients who received both BRAF/MEK inhibitor therapy and ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs after receiving both therapies and were categorized based on the order of their administration. Their clinical characteristics, evaluation, treatment and outcomes were compared. Results: Of the 32 eligible patients, 18 (56.3%) received ICI therapy followed by BRAF/MEK inhibitors (early ICI group), and 14 (44.8%) received BRAF/MEK inhibitor therapy followed by ICI (early BRAF/MEK inhibitor group). Compared with the early BRAF/MEK inhibitor group, the early ICI group had higher rates of grade 3-4 diarrhea (50.0% vs. 14.3%, P=0.047) and grade 3-4 colitis (38.9% vs. 0%, P=0.010). The early ICI group had a later onset of colitis (347.5 vs. 84.5 days, P=0.011) and a higher rate of hospitalization at initial colitis presentation (100% vs. 71.4%, P=0.028). Patients in the early ICI group were more likely to have diarrhea or colitis recurrence (69.2% vs. 9.1%, P=0.019) and re-hospitalization for colitis (38.9% vs. 0%, P=0.010). Conclusion: The sequential exposure of BRAF/MEK therapy after ICI may contribute to a more aggressive clinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy.

Ultrathin Graphene Oxide-Based Nanocomposite Membranes for Water Purification.

Two-dimensional graphene oxide (GO)-based lamellar membranes have been widely developed for desalination, water purification, gas separation, and pervaporation. However, membranes with a well-organized multilayer structure and controlled pore size remain a challenge. Herein, an easy and efficient method is used to fabricate MoO2@GO and WO3@GO nanocomposite membranes with controlled structure and interlayer spacing. Such membranes show good separation for salt and heavy metal ions due to the intensive stacking interaction and electrostatic attraction. The as-prepared composite membranes showed high rejection rates (˃70%) toward small metal ions such as sodium (Na+) and magnesium (Mg2+) ions. In addition, both membranes also showed high rejection rates ˃99% for nickel (Ni2+) and lead (Pb2+) ions with good water permeability of 275 ± 10 L m-2 h-1 bar-1. We believe that our fabricated membranes will have a bright future in next generation desalination and water purification membranes.

Characteristics, treatment, and outcome of diverticulitis after immune checkpoint inhibitor treatment in patients with malignancies.

PURPOSE: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment. METHODS: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups. RESULTS: 77 eligible patients were included: 63 patients developed diverticulitis after ICI exposure (46 had initial episode after ICI exposure, 17 had a history of diverticulitis prior then recurred after ICI exposure), and 14 had diverticulitis before ICI exposure. Diverticulitis occurred after a median of 129 days after ICI initiation. Clinical characteristics overlapped with traditional diverticulitis. 93% of patients had symptom resolution after treatment, while 23.8% experienced complications. These patients exhibited higher rates of hospitalization (87% vs 48%, P = 0.015) and surgery/interventional radiology procedures (27% vs 0, P = 0.002), and worse overall survival (P = 0.022). History of diverticulitis was not associated with a more severe disease course. Immunosuppressants (e.g., corticosteroids) were rarely required unless for concurrent ICI-mediated colitis. CONCLUSION: Colonic diverticulitis can occur after ICI therapy at very low incidence (0.5%). Its clinical presentation, evaluation, and management are similar to traditional diverticulitis, but associated with higher complication rates requiring surgical intervention and has lower overall survival.