The potential of MXene-based materials in fluorescence-based sensing/biosensing of ionic and organic contaminants in environment and food samples: Recent advancements and challenges.

MXenes belong to one of the recently developed advanced materials with tremendous potential for diverse sensing applications. To date, various types of MXene-based materials have been developed to generate direct/indirect ultrasensitive sensing signals against various forms of analytes via fluorescence quenching or enhancement. In this work, the fluorescence sensing/biosensing capabilities of the MXene-based materials have been explored and evaluated against a list of ionic/emerging pollutants in environment and food matrices. The suitability of an MXene-based sensing approach is also validated through the assessment of the performance based on the basic quality assurance parameters, e.g., limit of detection (LOD), sensing range, and response time. Accordingly, the best performing MXene-based materials are selected and recommended for the given target(s) to help facilitate their scalable applications under real-world conditions.

The selection of a nitrogen precursor for the construction of N-doped titanium dioxide with enhanced photocatalytic activity for the removal of gaseous toluene.

The preparation of nitrogen-doped TiO2 (i.e., N-TiO2) catalysts is a highly effective option to improve the photocatalytic activity of TiO2. Nonetheless, relatively little is known about the effects of dopant precursors selected for their preparation with regard to the photocatalytic efficacy. In this study, three types of dopants are selected and used as N sources (urea (U), melamine (M), and aqueous ammonia (A)) for N-TiO2 samples with the name codes of NTU, NTM, and NTA, respectively. The photocatalytic efficacy of these N-TiO2 samples is examined against toluene in a packed bed flow reactor. Under optimal conditions (e.g., relative humidity (RH) = 20% and gas hourly space velocity (GHSV) = 1698 h-1), the superiority of NTA is evident over others with a quantum efficiency (QE) of 7.03 × 10-4 molecules photon-1, a space time yield (STY) of 1.38 × 10-4 molecules photon-1 mg-1, and a specific clean air delivery rate (SCADR) of 1148.8 L g-1 h-1. The analysis based on in-situ diffuse reflectance infrared Fourier transform spectroscopy and gas chromatography-mass spectrometry confirms the formation of several intermediates such as benzyl alcohol, benzaldehyde, benzoic acid, and alkane species through ring opening reactions. In addition, the prepared NTA photocatalyst exhibits the highest toluene photocatalytic degradation efficiency among all TiO2-based catalysts surveyed to date. Overall, this study offers as a valuable guideline for the development of advanced TiO2 catalytic systems (such as N-TiO2) for the treatment of aromatic hydrocarbons in indoor air.

Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma (IKEMA): overall survival analysis of a phase 3, randomised, controlled trial.

BACKGROUND: Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Previous analyses of the IKEMA trial showed prolonged progression-free survival in patients with this disease who received isatuximab in combination with carfilzomib-dexamethasone as compared with those who received carfilzomib-dexamethasone alone. Herein, we report the analysis of overall survival from the IKEMA trial. METHODS: This prospective, randomised, open-label, active-controlled, phase 3 study included patients with relapsed or refractory multiple myeloma aged 18 years or older, who had received one to three previous lines of treatment from 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were randomly allocated (3:2) to treatment with either isatuximab plus carfilzomib-dexamethasone (isatuximab group) or carfilzomib-dexamethasone (control group). In the isatuximab group, patients received intravenous isatuximab (10 mg/kg on days 1, 8, 15, and 22 of the first 28-day cycle, and days 1 and 15 of subsequent 28-day cycles). In both treatment groups, intravenous carfilzomib (20 mg/m2 on days 1 and 2 of the first cycle; and 56 mg/m2 on days 8, 9, 15, and 16 of the first cycle, and days 1, 2, 8, 9, 15, and 16 of subsequent cycles) and intravenous or oral dexamethasone (20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23) were administered. The primary endpoint of the trial was progression-free survival, which was reported previously. Treatment continued until progression, unacceptable toxicity, or patient request to discontine. The overall survival analysis reported here was planned to be conducted 3 years after the primary progression-free survival analysis in the intention-to-treat population. Additional analyses were conducted on the secondary endpoints of time to next treatment and second-progression-free survival. Reported p values are non-inferential due to hierarchical testing. This trial is registered with ClinicalTrials.gov (NCT03275285). FINDINGS: Between Nov 15, 2017, and March 21, 2019, 302 patients were enrolled and randomly allocated: 179 (59%) to the isatuximab group and 123 (41%) to the control group. 169 (56%) patients were male, 133 (44%) were female, 214 (71%) were White, 50 (17%) were Asian, nine (3%) were Black or African American, and three (1%) were multiracial. At data cutoff for this overall survival analysis (Feb 7, 2023), 79 (44%) overall survival events in the isatuximab group and 59 (48%) in the control group had occurred (median follow-up 56·61 months [IQR 54·90-58·02]). Median overall survival (in months) was not reached (NR; 95% CI 52·17-NR) in the isatuximab group and was 50·60 months (38·93-NR) in the control group (hazard ratio [HR] 0·855 [95% CI 0·608-1·202], nominal one-sided p=0·18). Survival probability at 48 months was 59·7% (95% CI 52·0-66·7) in the isatuximab group and 52·2% (95% CI 42·7-60·8) in the control group (based on Kaplan-Meier analysis). Improvements in time to next treatment (HR 0·583 [95% CI 0·429-0·792], nominal one-sided p=0·0002) and second-progression-free survival (0·663 [0·491-0·895], nominal one-sided p=0·0035) were observed in the isatuximab group. The most common treatment-emergent adverse events were infusion reactions (82 [46%] patients in the isatuximab group and four [3%] in the control group) and upper respiratory tract infections (71 [40%] and 34 [28%], respectively). Discontinuations due to treatment-emergent adverse events were similar between treatment groups (24 [14%] in the isatuximab group and 22 [18%] in the control group), despite an additional 30 weeks of exposure in the isatuximab group. 12 (7%) patients in the isatuximab group and six (5%) patients in the control group had a treatment-related adverse event with a fatal outcome during study treatment. INTERPRETATION: At the time of the current analysis, a difference in overall survival could not be detected between the treatment groups, and no new safety signals were observed. Collectively, the evidence suggests that isatuximab plus carfilzomib-dexamethasone is a key treatment for patients with relapsed or refractory multiple myeloma. FUNDING: Sanofi.

QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

The catalytic efficacy of modified manganese-cobalt oxides for room-temperature oxidation of formaldehyde in air.

Formaldehyde (FA) is a hazardous indoor air pollutant with carcinogenic propensity. Oxidation of FA in the dark at low temperature (DLT) is a promising strategy for its elimination from indoor air. In this light, binary manganese-cobalt oxide (0.1 to 5 mol L-1-MnCo2O4) is synthesized and modified in an alkaline medium (0.1-5 mol L-1 potassium hydroxide) for FA oxidation under room temperature (RT) conditions. Accordingly, 1-MnCo2O4 achieves 100 % FA conversion at RT (50 ppm and 7022 h-1 gas hourly space velocity (GHSV)). The catalytic activity of 1-MnCo2O4 is assessed further as a function of diverse variables (e.g., catalyst mass, relative humidity, FA concentration, molecular oxygen (O2) content, flow rate, and time on-stream). In situ diffuse reflectance infrared Fourier-transform spectroscopy confirms that FA molecules are adsorbed onto the active surface sites of 1-MnCo2O4 and oxidized into water (H2O) and carbon dioxide (CO2) through dioxymethylene (DOM) and formate (HCOO-) as the reaction intermediates. According to the density functional theory simulations, the higher catalytic activity of 1-MnCo2O4 can be attributed to the combined effects of its meritful surface properties (e.g., the firmer attachment of FA molecules, lower energy cost of FA adsorption, and lower desorption energy for CO2 and H2O). This work is the first report on the synthesis of alkali (KOH)-modified MnCo2O4 and its application toward the FA oxidative removal at RT in the dark. The results of this study are expected to provide valuable insights into the development of efficient and cost-effective non-noble metal catalysts against indoor FA at DLT.

Effect of LED Lights on Secondary Metabolites and Antioxidant Activities in Red Pakchoi Baby Leaves.

Pakchoi (Brassica rapa subsp. chinensis) is one of the most widely consumed vegetables in Asian countries, and it is high in secondary metabolites. The availability, quantity, and quality of light play a critical role in the growth and development of plants. In this study, we investigated the effect of LEDs (light-emitting diodes; white, blue, red, and red + blue) on anthocyanin, glucosinolates, and phenolic levels in red pakchoi baby leaves. On the 24th day after sowing (DAS), red baby pakchoi leaves were harvested, and shoot length, root length, and fresh weight were measured. Among the different LED treatments, there was no significant difference in shoot length, whereas the highest root length was achieved in the red + blue LED treatment (23.8 cm). The fresh weight also showed a significant difference among the different LED treatments. In total, 12 phenolic and 7 glucosinolate individual compounds were identified using high-performance liquid chromatography (HPLC) analysis. The highest total glucosinolate (2937 µg/g dry wt) and phenolic (1589 µg/g dry wt) contents were achieved in baby leaves exposed to red + blue light. Similarly, the highest contents of total anthocyanins (1726 µg/g dry wt), flavonoids (4920 µg/g dry wt), and phenolics (5900 µg/g dry wt) were achieved in the red + blue treatment. Plants exposed to red + blue LED light showed the highest accumulation of anthocyanin, glucosinolates, and phenolic compounds. For antioxidant activity, DPPH (2,2-diphenyl-1-picrylhydrazylradical) free radical scavenging, ABTS (2,2-azinobis (3-ethylbenzothiazoline)-6-sulfonic acid) radical scavenging, and reducing power assays were performed, and the antioxidant activity of red pakchoi baby leaves grown under red + blue LED light was found to be the best. The metabolic profiling of the identified metabolites revealed distinct separation based on the secondary metabolites. This research will be helpful for farmers to choose the best LED light combination to increase the secondary metabolic content in pakchoi plants.

Tumor immunogenicity regulates host immune responses, and conventional dendritic cell type 2 uptakes the majority of tumor antigens in an orthotopic lung cancer model.

Human lung cancer carries high genetic alterations, expressing high tumor-specific neoantigens. Although orthotopic murine lung cancer models recapitulate many characteristics of human lung cancers, genetically engineered mouse models have fewer somatic mutations than human lung cancer, resulting in scarce immune cell infiltration and deficient immune responses. The endogenous mouse lung cancer model driven by Kras mutation and Trp53 deletion (KP model) has minimal immune infiltration because of a scarcity of neoantigens. Fine-tuning tumor antigenicity to trigger the appropriate level of antitumor immunity would be key to investigating immune responses against human lung cancer. We engineered the KP model to express antigens of OVA peptides (minOVA) as neoantigens along with ZsGreen, a traceable fluorescent conjugate. The KP model expressing minOVA exhibited stronger immunogenicity with higher immune cell infiltration comprised of CD8+ T cells and CD11c+ dendritic cells (DCs). Consequentially, the KP model expressing minOVA exhibits suppressed tumor growth compared to its origin. We further analyzed tumor-infiltrated DCs. The majority of ZsGreen conjugated with minOVA was observed in the conventional type 2 DCs (cDC2), where cDC1 has minimal. These data indicate that tumor immunogenicity regulates host immune responses, and tumor neoantigen is mostly recognized by cDC2 cells, which may play a critical role in initiating anti-tumor immune responses in an orthotopic murine lung cancer model.

Nitrogen doped carbon dots and gold nanoparticles mediated FRET for the detection of creatinine in human urine samples.

Serum creatinine (CR) is regarded as one of the most sought out prognostic biomarkers in medical evaluation of chronic kidney disease (CKD). In light of the diagnostic significance of CR, the utility of a fluorescence biosensor for its detection in human urine specimens has been explored based on Förster resonance energy transfer (FRET) across nitrogen-doped carbon dots (N-CDs) and gold nanoparticles (GNPs). A straightforward microwave-assisted synthesis procedure has been adopted to prepare N-CDs (λexcitation = 400 nm, λemission = 540 ± 5 nm) with bright green emissions. On addition of pre-synthesized GNPs, the radiative emanation of the N-CDs is completely suppressed on account of FRET across the N-CDs and the GNPs. About 77 % of their fluorescence intensity is recovered after adding CR to GNPs@N-CDs nanocomposite. The limit of detection for CR sensing is estimated as 0.02 µg•mL-1. This biosensor is selective enough to recognize CR in the existence of potential interfering substances (e.g., ascorbic acid, glucose, glutathione, urea, and electrolytes). Its practical utility for CR detection has been validated further on the basis of satisfactory correlation with the benchmark Jaffe method, as observed in artificial/human urine specimens. Consequently, this manuscript marks a pioneering report on employing CDs and GNPs-based FRET for identifying CR in urine specimens of CKD patients.

Benzene Oxidation in Air by an Amine-Functionalized Metal-Organic Framework-Derived Carbon- and Nitrogen-Loaded Zirconium Dioxide-Supported Platinum Catalyst.

To learn more about the behavior of amine (NH2)-functionalized metal-organic framework (MOF)-derived noble metal catalysts in the removal of aromatic volatile organic compounds in air, benzene oxidation at low temperatures has been investigated using 0.2-, 0.8-, and 1.5%-platinum (Pt)/Universitetet i Oslo (UiO)-66-NH2. The benzene conversion (XB) of x%-Pt/UiO-66-NH2-R under dry conditions (175 °C) was 23% (x = 0.2%) < 52% (x = 0.8%) < 100% (x = 1.5%): 'R' suffix denotes reduction pretreatment using a hydrogen (10 vol %) and nitrogen mixture at 300 °C for the generation of metallic Pt (Pt0) sites and simultaneous partial MOF decomposition into carbon- and nitrogen-loaded zirconium dioxide. The prominent role of reduction pretreatment was apparent in benzene oxidation as 1.5%-Pt/UiO-66-NH2 did not exhibit catalytic activity below 175 °C (dry condition). The promotional role of moisture in benzene oxidation by 1.5%-Pt/UiO-66-NH2-R was evident with a rise in the steady-state reaction rate (r) at 110 °C (21 kPa molecular oxygen (O2)) from 1.3 × 10-3 to 5.0 × 10-3 µmol g-1 s-1 as the water (H2O) partial pressure increased from 0 to 1.88 kPa. In contrast, the activity was lowered with increasing RH due to catalyst poisoning by excess moisture (r (110 °C) of 6.6 × 10-04 µmol g-1 s-1 at 2.83 kPa H2O (21 kPa O2)). Kinetic modeling suggests that XB proceeds through the Langmuir-Hinshelwood mechanism on the Pt/UiO-66-NH2-R surface (dissociative O2 chemisorption and the involvement of two oxygen species in benzene oxidation). According to the density functional theory simulation, the carbon and nitrogen impurities are to make the first XB step (i.e., hydrogen migration from the benzene molecule to the substrate) energetically favorable. The second hydrogen atom from the benzene molecule is also extracted effectively, while the oxygen derived from O2 facilitates further XB. The Pt0 sites dissociate the O2 and H2O molecules, while the product of the latter, i.e., free hydrogen and hydroxyl, makes the subsequent XB steps energetically favorable.

The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors.

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Tuning strategies of MIL metal organic frameworks for adsorptive removal of formaldehyde in air.

Materials Institute Lavoisier (MIL) metal organic frameworks (MOFs) are known for their potential to adsorb gaseous organic pollutants. This study explores the synergistic effects between the selection of central metals (e.g., titanium, iron, and aluminum) and the incorporation of -NH2 groups in terms of adsorption efficiency against gaseous formaldehyde (FA). A group of the pristine MIL MOFs is synthesized using three different metals (i.e., titanium, iron, and aluminum) and terephthalic acid along with their NH2 derivatives using 2-aminoterephthalic acid. Among the pristine forms, MIL-125(Ti) achieves the highest FA adsorption capacity (Q) of 26.96 mg g-1 and a partition coefficient (PC) of 0.0898 mol kg-1 Pa-1. Further, amination significantly improves the FA adsorption potential of NH2-MIL-125(Ti) with a Q value of 91.22 mg g-1 (PC = 0.3038 mol kg-1 Pa-1). In situ diffuse reflectance infrared Fourier-transform spectroscopy reveals that the FA adsorption of plain MILs should be governed primarily by physisorption. In contrast, FA adsorption of NH2-MILs appears to be regulated by both physisorption and chemisorption, while the latter being affected mainly through FA-NH2 interactions (Schiff base reactions). These findings provide valuable insights into the utility of aminated MIL sorbents, possibly toward the efficient management of indoor air quality.

Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

BACKGROUND: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse. METHODS: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed. RESULTS: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group. CONCLUSIONS: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.).

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Short-term storability of volatile organic compounds in bag sampling systems under ambient conditions.

Although bag sampling is a common quantification tool for volatile organic compounds (VOCs), it can serve as a major source of experimental bias, when storing even over a short duration (<24 h). To learn more about the reliability of the bag sampling method, the temporal stability of 27 VOCs (classified into five groups (i.e., aldehydes, nonpolar aromatic hydrocarbons, aliphatic carboxylic acids, phenol and methylphenols, and miscellaneous odorants) is assessed using poly-ester aluminum (PEA) bags at five intervals over a day (0.17, 1, 2, 6, and 24 h). In terms of reproducibility (e.g., relative standard error [RSEt, %]), nonpolar aromatic hydrocarbons (BTXS) exhibit the highest consistency (e.g., average RSE <1.55%). Considerable loss of VOCs is observed in the preparation of gaseous standards from a liquid phase standard when assessed by gas/liquid (G/L) ratio. Further, VOCs with lower molecular weights (e.g., propionaldehyde: 77%-94.4%) and branched molecular structures (e.g., isovaleraldehyde: 67.2%-78.9%) tend to have high G/L ratio (e.g., relative to valeraldehyde: 55.1%-66%). The overall relative recovery (RR; %) values of VOCs indicate an exponential decrease over 24 h. BTXS maintain fairly good RR values (above 94.3% at all intervals), possibly due to the nonpolar structure with uniform distribution of π electrons. In contrast, indole and skatole show the least preservation after 24 h (e.g., RR4 values of 10.9% and 24.6%, respectively) due to their highly reactive characteristics. The storability of VOCs appears to be affected by a number of variables (e.g., molecular weight, presence of ethyl branch, and time: e.g., R2 > 0.9). The results of this study offer valuable guidelines for the accurate quantification of VOC levels in air.

Constructed wetlands for the removal of organic micropollutants from wastewater: Current status, progress, and challenges.

In this work, the practical utility of constructed wetlands (CWs) is described as a promising treatment option for micropollutants (MPs) in wastewater with the aid of their eco-friendly, low-energy, economically feasible, and ecologically sustainable nature. This paper offers a comprehensive review on CW technology with respect to the key strategies for MP removal such as phytoremediation, substrate adsorption, and microbial degradation. It explores the important factors controlling the performance of CWs (e.g., in terms of configurations, substrates, plant-microbe interactions, temperature, pH, oxygen levels, hydraulic loading rate, and retention time) along with the discussions on the pivotal role of microbial populations in CWs and plant-microbe cooperative remediation dynamics, particularly in relation to diverse organic MP patterns in CWs. As such, this review aims to provide valuable insights into the key strategies for optimizing MP treatment and for enhancing the efficacy of CW systems. In addition, the process-based models of constructed wetlands along with the numerical simulations based on the artificial neural network (ANN) method are also described in association with the data exploratory techniques. This work is thus expected to help open up new possibilities for the application of plant-microbe cooperative remediation approaches against diverse patterns of organic MPs present in CWs.

Development of a FRET aptasensor based on MoS2-doped Zn-MOF as luminophore for selective detection of cadmium in aqueous solutions.

A robust "on-off" fluorescent aptasensor was developed using nanohybrids of molybdenum sulfide (MoS2) quantum dot (QD)-doped zinc metal-organic frameworks (Zn-MOF) for selective and sensitive detection of cadmium ions (Cd2+) in water. This nanohybrid (MoS2@Zn-MOF), synthesized via "bottle around the ship" methodology, exhibited a high-intensity fluorescence emission centered at 430 nm (λEm) (blue) on excitation at 320 nm (λEx). Further, the conjugation of this fluorophore to phosphate-modified cadmium aptamer (Cd-2-2) was achieved through carbodiimide reaction. The hybridization of prepared sensing probe (MoS2@Zn-MOF/Cd-2-2 aptamer) was done with dabcyl-conjugated complementary DNA (cDNA), acting as energy donor-acceptor pair in the fluorescence resonance energy transfer (FRET) system. This hybridization causes the fluorescence quenching of the nanohybrid. In the presence of Cd2+, the aptamer from the fabricated nano-biosensing probe binds to these ions, resulting in release of dabcyl-cDNA oligomer. This release of dabcyl-cDNA oligomer from the sensing probes restores the fluorescence of the nanohybrid. Under optimized conditions (sensing probe/dabcyl-cDNA ratio 1/7, pH 7.4, and temp 28 °C), the sensing probe showed a fast response time of 1 min. The fluorescence intensity of the nanohybrid can be utilized to determine the concentration of Cd2+. The proposed aptasensor achieved highly sensitive detection of Cd2+ with a limit of detection (LOD) of 0.24 ppb over the range of 1 × 10-9 to 1 × 10-4 M along with minimal effects of interferences (e.g., Hg2+, Pb2+, and Zn2+) and good reproducibility. The designed aptasensor based on MoS2@Zn-MOF nanofluorophore offers a highly sensitive and selective approach for rapid screening of metal ions in aqueous environments.

Low-temperature thermocatalytic removal of formaldehyde in air using copper manganite spinels.

The removal of formaldehyde (FA) is vital for indoor air quality management in light of its carcinogenic propensity and adverse environmental impact. A series of copper manganite spinel structures (e.g., CuMn2O4) are prepared using the sol-gel combustion method and treated with reduction or oxidation pretreatment at 300 °C condition. Accordingly, CuMn2O4-O ("O" suffix for oxidation pre-treatment in air) is identified as the best performer to achieve 100% conversion (XFA) of FA (50 ppm) at 90 °C; its performance, if assessed in terms of reaction kinetic rate (r) at XFA = 10%, is 5.02E-03 mmol g-1 h-1. The FA removal performance increases systematically with decreases in flow rate, FA concentration, and relative humidity (RH) or with increases in bed mass. The reaction pathways and intermediates of FA catalytic oxidation on CuMn2O4-A are studied with density functional theory simulations, temperature-programmed characterization experiments, and in-situ diffuse reflectance infrared Fourier transform spectroscopy. The synergistic combination of large quantities of adsorbed oxygen (OA) species and oxidized metal species (e.g., Cu2+) contribute to the enhanced catalytic performance of CuMn2O4-O to oxidize FA into CO2 with the reaction intermediates of H2CO2 (DOM), HCOO-, and CO. The present study is expected to provide valuable insights into the thermocatalytic oxidation of FA over spinel CuMn2O4 materials and their catalytic performances in relation to the key process variables.

The establishment of a multiple myeloma clinical registry in the Asia-Pacific region: The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR).

BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry's design and development, initial data, progress and future plans. METHODS: The APAC MRDR was established in 2018 as a multicentre collaboration across the Asia-Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024. RESULTS: Over 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues. CONCLUSION: The APAC MRDR is providing 'real-world' data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.