Morphology and Performance Enhancement through the Strong Passivation Effect of Amphoteric Ions in Tin-based Perovskite Solar Cells.

Despite the optoelectronic similarities between tin and lead halide perovskites, the performance of tin-based perovskite solar cells remains far behind, with the highest reported efficiency to date being ≈14%. This is highly correlated to the instability of tin halide perovskite, as well as the rapid crystallization behavior in perovskite film formation. In this work, l-Asparagine as a zwitterion plays a dual role in controlling the nucleation/crystallization process and improving the morphology of perovskite film. Furthermore, tin perovskites with l-Asparagine show more favorable energy-level matching, enhancing the charge extraction and minimizing the charge recombination, leading to an enhanced power conversion efficiency of 13.31% (from 10.54% without l-Asparagine) with remarkable stability. These results are also in good agreement with the density functional theory calculations. This work not only provides a facile and efficient approach to controlling the crystallization and morphology of perovskite film but also offers guidelines for further improved performance of tin-based perovskite electronic devices.

Analyzing the contribution of gully erosion to land degradation in the upper Blue Nile basin, Ethiopia.

Soil erosion has become a worldwide problem that threatens the environment and the future of economic and social development. The purpose of this study is to investigate the contribution of steep slopes and gullies to erosion in high precipitation tropical areas of the Ethiopian highlands. A trapezoidal weir was installed at the head and tail of the gully to monitor the discharge and sediment concentration from 2017 to 2020. Sediment yield and runoff are heavily influenced by the amount and timing of precipitation. The coefficients of variation for total sediment loads ranged from 65.1 to 96.1% at the head and 17.1-78.1% at the tail; the lowest coefficients were found in 2018 and the highest in 2020. Furthermore, 85% of the sediment at the tail comes from the gully, according to the four-year sediment budget. Further, a hysteretic analysis of suspended sediment concentration and runoff revealed that hilly sediment sources are limited (clockwise), then sediment can be transported through the gully via bank failures (counterclockwise). Study findings contributed to a classification of runoff patterns and an investigation of suspended sediment dynamics. In the gully tail, sediment yield was higher than in the head, suggesting gully sediment contributed more to sediment yield than large upland catchments. As a result of the study, we have been able to develop practical recommendations for managing gully erosion in the future.

High-Speed Screening of Lipoprotein Components Using Online Miniaturized Asymmetrical Flow Field-Flow Fractionation and Electrospray Ionization Tandem Mass Spectrometry: Application to Hepatocellular Carcinoma Plasma Samples.

This study introduces a high-speed screening method for the quantitative analysis of lipoprotein components in human plasma samples using online miniaturized asymmetrical flow field-flow fractionation and electrospray ionization-tandem mass spectrometry (mAF4-ESI-MS/MS). Using an mAF4 channel, high-density lipoproteins and low-density lipoproteins can be fractionated by size at a high speed (<10 min) and directly fed to ESI-MS/MS for the simultaneous screening of targeted lipid species and apolipoprotein A1 (ApoA1). By employing the heated electrospray ionization probe as an ionization source, an mAF4 effluent flow rate of up to a few tens of microliters per minute can be used, which is adequate for direct feeding to MS without splitting the outflow, resulting in a consistent feed rate to MS for stable MS detection. mAF4-ESI-MS/MS was applied to hepatocellular carcinoma (HCC) plasma samples for targeted quantification of 25 lipid biomarker candidates and ApoA1 compared with healthy controls, the results of which were in statistical agreement with the quantified results obtained by nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry. Moreover, the present method provided the simultaneous detection of changes in lipoprotein size and the relative amount. This study demonstrated the potential of mAF4-ESI-MS/MS as an alternative high-speed screening platform for the top-down analysis of targeted lipoprotein components in patients with HCC, which is applicable to other diseases that involve the perturbation of lipoproteins.

Exercise-induced recovery of plasma lipids perturbed by ageing with nanoflow UHPLC-ESI-MS/MS.

Daily physical exercise is an essential part of life and is required for remaining healthy; it enhances therapeutic efficacy in the elderly and prevents age-related diseases associated with lipid profile alterations, such as cardiovascular disease, diabetes mellitus, and dementia. To more efficiently analyse the lipid profiles and unveil the effect of exercise in aged mice, we optimized our study by examining the effects of using ionization modifiers in the mobile phase and in-source fragmentation of lysophospholipids on the simultaneous analysis of fatty acids (FAs) including hydroxyl fatty acids, glycerophospholipids, sphingolipids, and glycerolipids using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. We applied the optimization to investigate the lipidomic plasma alterations in young (7 weeks old) and aged (84 weeks old) mice (C57BL/6) subjected to treadmill exercise. Of the 390 identified lipid species, 159 were quantified to investigate ageing-related lipid species responsive to physical exercise. In particular, circulating lysophosphatidylcholine and lysophosphatidylethanolamine levels showed a significant decrease, and lysophosphatidic acid showed a simultaneous increase with ageing. The saturated FA (16:0 and 18:0) increased with ageing while the unsaturated FA 22:6 decreased. Dihydroxy fatty acid (18:1_2OH) showed an exercise-induced recovery against ageing. It is notable that the levels of five triacylglycerol species significantly increased by as much as threefold with ageing, but their levels largely recovered to those observed in the young mice after exercise. These findings can help understand the influence of ageing on lipid perturbation and the role of physical exercise on lipidomic recovery in response to ageing-associated loss of physical status. Graphical abstract.

Simultaneous Relative Quantification of Various Polyglycerophospholipids with Isotope-Labeled Methylation by Nanoflow Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry.

Herein, we introduce a comprehensive analytical method for the separation and relative quantification of polyglycerophospholipids (PGPLs), including phosphatidylglycerol (PG), bis(monoacylglycero)phosphate (BMP), bis(diacylglycero)phosphate (BDP), Hemi BDP, cardiolipin (CL), monolysocardiolipin (MLCL), and dilysocardiolipin (DLCL), using isotope-labeled methylation (ILM) with nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUHPLC-ESI-MS/MS). Abnormal levels of BMP and CL have been associated with the pathology of lysosomal storage and neurodegenerative diseases. Thus, simultaneous analysis of all PGPLs is important to understand the mechanisms and pathologies of such diseases. In this study, improved separation and MS detection of PGPLs, including their regioisomers, was achieved by the methylation of PGPL. ILM-based relative quantification was applied to lipid extracts from a dopaminergic cell line (SH-SY5Y) treated with drugs commonly used for Parkinson's disease (PD), resulting in the identification of 229 unique PGPLs, including 121 CLs, 71 MLCLs, and 16 Hemi BDP species. The drug treatment induced significant increases in the amount of CLs containing polyunsaturated fatty acyl chains, including 20:4 and 22:6, as well as decreased levels of BMP, Hemi BDP, and BDP species, demonstrating the feasibility of using ILM for the comprehensive and high-speed relative quantification of PGPLs.

High-fat diet-induced lipidome perturbations in the cortex, hippocampus, hypothalamus, and olfactory bulb of mice.

Given their important role in neuronal function, there has been an increasing focus on altered lipid levels in brain disorders. The effect of a high-fat (HF) diet on the lipid profiles of the cortex, hippocampus, hypothalamus, and olfactory bulb of the mouse brain was investigated using nanoflow ultrahigh pressure liquid chromatography-electrospray ionization-tandem mass spectrometry in the current study. For 8 weeks, two groups of 5-week-old mice were fed either an HF or normal diet (6 mice from each group analyzed as the F and N groups, respectively). The remaining mice in both groups then received a 4-week normal diet. Each group was then subdivided into two groups for another 4-week HF or normal diet. Quantitative analysis of 270 of the 359 lipids identified from brain tissue revealed that an HF diet significantly affected the brain lipidome in all brain regions that were analyzed. The HF diet significantly increased diacylglycerols, which play a role in insulin resistance in all regions that were analyzed. Although the HF diet increased most lipid species, the majority of phosphatidylserine species were decreased, while lysophosphatidylserine species, with the same acyl chain, were substantially increased. This result can be attributed to increased oxidative stress due to the HF diet. Further, weight-cycling (yo-yo effect) was found more critical for the perturbation of brain lipid profiles than weight gain without a preliminary experience of an HF diet. The present study reveals systematic alterations in brain lipid levels upon HF diet analyzed either by lipid class and molecular levels.

Lipidomic differentiation of Graves' ophthalmopathy in plasma and urine from Graves' disease patients.

Approximately 50% of patients with Graves' disease (GD) develop retracted eyelids with bulging eyes, known as Graves' ophthalmopathy (GO). However, no simple diagnostic blood marker for distinguishing GO from GD has been developed yet. The objective of this study was to conduct comprehensive profiling of lipids using plasma and urine samples from patients with GD and GO undergoing antithyroid therapy using nanoflow ultrahigh performance liquid chromatography electrospray ionization tandem mass spectrometry. Plasma (n = 86) and urine (n = 75) samples were collected from 23 patients with GD without GO, 31 patients with GO, and 32 healthy controls. Among 389 plasma and 273 urinary lipids that were structurally identified, 281 plasma and 191 urinary lipids were quantified in selected reaction monitoring mode. High-abundance lipids were significantly altered, indicating that the development of GD is evidently related to altered lipid metabolism in both plasma and urine. Several urinary lysophosphatidylcholine species were found to be increased (3- to 10-fold) in both GD and GO. While the overall lipid profiles between GD and GO were similar, significant changes (area under receiver operating curve > 0.8) in GO vs. GD were observed in a few lipid profiles: 58:7-TG and (16:1,18:0)-DG from plasma, 16:1-PC and 50:1-TG from urine, and d18:1-S1P from both plasma and urine samples. An altered metabolism of lipids associated with the additional development of ophthalmopathy was confirmed with the discovery of several candidate markers. These can be suggested as candidate markers for differentiating the state of GO and GD patients based on plasma or urinary lipidomic analysis. Graphical abstract.

Relative Quantification of Phospholipids Based on Isotope-Labeled Methylation by Nanoflow Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry: Enhancement in Cardiolipin Profiling.

In this study, lipid analysis based on isotope-labeled methlylation (ILM) was performed by nanoflow ultrahigh performance liquid chromatography-eletrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS) for enhanced detection and quantification of targeted phospholipids. ILM depends on methylation of phosphate groups by (trimethylsilyl)diazomethane, and the ILM based quantitation with reversed phase nUPLC-ESI-MS/MS provides advantages in PL profiling such as enhanced detectability of methylated PLs owing to increased hydrophobicity and substantial increase in resolution due to the increase of retention. Efficacy of ILM in nUPLC-ESI-MS/MS analysis was evaluated in the selected reaction monitoring (SRM) method by varying the mixing ratio of H-/D-methylated PL standards, which resulted in the successful quantification of 24 species, including phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylglycerol (PG), ceramide-1-phosphate (Cer1P), phosphoinositides, and cardiolipin (CL), with ∼6.6% variation in the calculated ratio of H-/D-methylated PLs. The method was applied to the lipid extracts from a DU145 cell line after D-allose treatment, resulting in the quantification of 83 PLs of which results were not statistically different from those obtained by conventional quantification methods. Morever, detection and quantification of CLs and PAs were evidenced to be highly effective when used with the ILM method as 43 CLs and 20 PAs from cellular lipid extracts were analyzed while only 18 CLs and 12 PAs were identified when conventional methods were carried out. This proves the ILM combined with LC-MS to be a promising method for analysis of the aforementioned classes of lipids. Overall, the study highlighted the applicability of targeted quantification by the ILM method in lipidomic analysis and demonstrated an improvement in the detection of less abundant anionic PLs.

Size Dependent Lipidomic Analysis of Urinary Exosomes from Patients with Prostate Cancer by Flow Field-Flow Fractionation and Nanoflow Liquid Chromatography-Tandem Mass Spectrometry.

Exosomes are membrane-bound extracellular vesicles involved in intercellular communication and tumor cell metastasis. In this study, flow field-flow fractionation (FlFFF) was utilized to separate urinary exosomes by size, demonstrating a significant difference in exosome sizes between healthy controls and patients with prostate cancer (PCa). Exosome fractions of different sizes were collected for microscopic analysis during an FlFFF run and evaluated with exosome marker proteins using Western blot analysis. The results indicated that exosomes of different sizes originated from different types of cells. Collected exosome fractions were further examined using nanoflow ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUPLC-ESI-MS/MS) for lipidomic analysis. A total of 162 lipids (from 286 identified) were quantified using a selected reaction monitoring (SRM) method. The overall amount of lipids increased by 1.5- to 2-fold in patients with PCa and degree of increase was more significant in the smaller fractions (diameter <150 nm) than in the larger ones (diameter >150 nm) some classes of lipids. In addition, neutral lipids like diacylglycerol (DAG) and triacylglycerol (TAG) decreased in all exosomes without size dependency. Moreover, a dramatic increase in 22:6/22:6-phosphatidylglycerol (PG) was observed and significant decrease in (16:0,16:0)- and (16:1, 18:1)-DAG species (nearly 5-fold) and high abundant TAG species (>2.5-fold) was observed in patients with PCa. The results of this study indicate that FlFFF can be employed for the high-speed screening of urinary exosome sizes in patients with PCa and lipidomic analysis of the fractionated exosomes has potential for developing and distinguishing biomarkers of PCa.

High-throughput and rapid quantification of lipids by nanoflow UPLC-ESI-MS/MS: application to the hepatic lipids of rabbits with nonalcoholic fatty liver disease.

A rapid and high-throughput quantification method (approximately 300 lipids within 20 min) was established using nanoflow ultrahigh-pressure liquid chromatography-tandem mass spectrometry (nUPLC-ESI-MS/MS) with selective reaction monitoring (SRM) and applied to the quantitative profiling of the hepatic lipids of rabbits with different metabolic conditions that stimulate the development of nonalcoholic fatty liver disease (NAFLD). Among the metabolic conditions of rabbits in this study [inflammation (I), high-cholesterol diet (HC), and high-cholesterol diet combined with inflammation (HCI)], significant perturbation in hepatic lipidome (>3-fold and p < 0.01) was observed in the HC and HCI groups, while no single lipid showed a significant change in group I. In addition, this study revealed a dramatic increase (>2-fold) in relatively high-abundant monohexosylceramides (MHCs), sphingomyelins (SMs), and triacylglycerols (TGs) in both the HC and HCI groups, especially in MHCs as all 11 MHCs increased by larger than 3- to 12-fold. As the levels of the relatively high-abundant lipids in the above classes increased, the total lipidome level of each class increased significantly by approximately 2-fold to 5-fold. Other classes of lipids also generally increased, which was likely induced by the increase in mitogenic and nonapoptotic MHCs and SMs, as they promote cell proliferation. On the other hand, a slight decrease in the level of apoptotic ceramides (Cers) was observed, which agreed with the general increase in total lipid level. As distinct changes in hepatic lipidome were observed from HC groups, this suggests that HC or HCI is highly associated with NAFLD but not inflammation alone itself. Graphical Abstract Schematic of lipidomic analysis from hepatic tissue using nanoflow LC-ESI-MS/MS and nUPLC-ESI-MS/MS.

Oxidative stress in schoolchildren with allergic rhinitis: propensity score matching case-control study.

BACKGROUND: Oxidative stress is defined as an imbalance between the level of reactive oxygen species and antioxidant mechanisms. Compared with asthma, the role of oxidative stress in allergic rhinitis (AR) has received little attention. OBJECTIVE: To investigate the association between overall systemic oxidative stress and AR. METHODS: We used a propensity score matching case-control study and selected 90 children who had experienced AR in the previous year. This AR group was then matched with 90 healthy children who comprised the control group. Propensity score matching, a statistical matching technique that accounts for the conditional probability of receiving an exposure given a vector of measured covariates, is used to reduce selection bias and potential confounders in observational study. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels were determined using a commercially available assay kit. Medical records and personal information were also reviewed. RESULTS: No statistically significant differences were found between patients with regard to age, sex, height, weight, educational level of parent, monthly household income, or distance of home from a main road. The mean TAS and TOS levels in the patient group were significantly higher than those of the control group (P = .03 and .048, respectively). The oxidative stress index, which is defined as the ratio of TOS to TAS, also increased in the AR group with statistical propensity (P = .08). In a multivariate logistic analysis, only TAS and TOS levels were significantly associated with increased risk of allergic rhinitis. CONCLUSION: Patients with AR have systemically elevated oxidative stress and systemically elevated TAS levels.

Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells.

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells.

Mounting evidence suggests that metformin (N,N-dimethylbiguanide), a widely prescribed drug for the treatment of type II diabetes, exerts an anti-tumor effect on several cancers including breast cancer. Breast cancer has been estimated as one of the most commonly diagnosed types of cancer among women. In particular, triple-negative breast cancers are associated with poor prognosis and metastatic growth. In the present study, we synthesized a novel metformin derivative 5 (HL010183) and metformin salts, 9a, 9b, and 9c (metformin gamma-aminobutyric acid (GABA) salt, metformin pregabalin salt and metformin gabapentin salt), which exerted more potent inhibitory effects on the proliferation and invasiveness of Hs578T triple-negative breast carcinoma cells than metformin. Importantly, 5 showed approximately 100-fold more potent effects compared to metformin. In a triple-negative breast cancer xenograft model, 5 showed a comparable degree of inhibitory effect on in vivo tumor growth at the 100mg/kg dose to that of metformin at 500 mg/kg. Our results clearly demonstrate that 5 exerts a potent anti-tumor effect both in vitro and in vivo, paving the way for a strategy for treatment of triple-negative breast cancer.

Vallecular rupture with cervical spine fracture after a failed hanging suicide attempt.

Hanging is a common method of suicide. We present a case of vallecular rupture and cervical spine fracture without an external wound after a failed hanging suicide attempt. Surgical treatment involved posterior fusion of C2 to 3, followed by repair of the vallecular rupture via an external approach. The patient recovered with no residual physical or mental sequelae.

Control of lateral dimension in metal-catalyzed germanium nanowire growth: usage of carbon sheath.

We report on the catalytic growth of thin carbon sheathed single crystal germanium nanowires (GeNWs), which can solve the obstacles that have disturbed a wide range of applications of GeNWs. Single crystal Ge NW core and amorphous carbon sheath are simultaneously grown via vapor-liquid-solid (VLS) process. The carbon sheath completely blocks unintentional vapor deposition on NW surface, thus ensuring highly uniform diameter, dopant distribution, and electrical conductivity along the entire NW length. Furthermore, the sheath not only inhibits metal diffusion but also improves the chemical stability of GeNWs at even high temperatures.

US Features of the Parathyroid Glands: An Intraoperative Surgical Specimen Study.

Purpose: This study aimed to evaluate the US features of the parathyroid glands (PTGs) using surgical specimens of normal PTGs obtained during thyroid surgery. Materials and Methods: This study included 34 normal PTGs from 17 consecutive patients who underwent thyroid surgery between December 2020 and March 2021. All normal PTGs were histologically confirmed by intraoperative frozen-section biopsy for autotransplantation. Surgically resected parathyroid specimens were scanned in sterile normal saline using high-resolution US prior to autotransplantation. The US features of echogenicity (hyperechogenicity or hypoechogenicity), echotexture (homogeneous or heterogeneous), size, and shape (ovoid or round) were retrospectively evaluated. The echogenicity of the three PTGs was compared with that of the thyroid parenchyma of the resected thyroid specimens in two patients. Results: All PTGs showed hyperechogenicity similar to that of gauze soaked in normal saline. Homogeneous hyperechogenicity was observed in 32/34 (94.1%) patients, and the echogenicity of the three PTGs was hyperechoic compared with that of the thyroid parenchyma. The long diameter of the PTGs ranged from 5.1 mm to 9.8 mm (mean, 7.1 mm) and the shape of the PTGs was ovoid in 33/34 (97.1%) patients. Conclusion: The echogenicity of normal PTG specimens was consistently hyperechoic, and the small ovoid homogeneously hyperechoic structure was a characteristic US feature of the PTGs.

Risk assessment of toxic and hazardous metals in paddy agroecosystem by biochar-for bio-membrane applications.

Toxic and carcinogenic metal (loid)s, such arsenic (As) and cadmium (Cd), found in contaminated paddy soils pose a serious danger to environmental sustainability. Their geochemical activities are complex, making it difficult to manage their contamination. Rice grown in Cd and As-polluted soils ends up in people's bellies, where it can cause cancer, anemia, and the deadly itai sickness. Solving this issue calls for research into eco-friendly and cost-effective remediation technology to lower rice's As and Cd levels. This research delves deeply into the origins of As and Cd in paddy soils, as well as their mobility, bioavailability, and uptake mechanisms by rice plants. It also examines the current methods and reactors used to lower As and Cd contamination in rice. Iron-modified biochar (Fe-BC) is a promising technology for reducing As and Cd toxicity in rice, improving soil health, and boosting rice's nutritional value. Biochar's physiochemical characteristics are enhanced by the addition of iron, making it a potent adsorbent for As and Cd ions. In conclusion, Fe-BC's biomembrane properties make them an attractive option for remediating As- and Cd-contaminated paddy soils. More efficient mitigation measures, including the use of biomembrane technology, can be developed when sustainable agriculture practices are combined with these technologies.

Clinical effectiveness of decoction form of herbal medicine in primary care treatment of allergic rhinitis: A retrospective cohort study.

Background: The decoction form of herbal medicine (D-HM) is mainly prescribed to patients with allergic rhinitis (AR) in Korean Medicine (KM) clinics in the Republic of Korea; however, it is difficult to conduct clinical trials of D-HM due to regulatory issues. This study investigated the clinical safety and effectiveness of D-HM combination therapy for the treatment of AR by analyzing the AR outpatient data from 17 KM clinics. Methods: This retrospective cohort study included patients who visited KM clinics for AR treatment from January 1, 2021, to March 31, 2022. Cases were collated using structured case report forms and divided into the D-HM with KM usual care group (D-HM group) and the KM usual care group (UC group). Since D-HM therapy could not be randomly assigned to the study population, we used optimal propensity score (PS) matching to investigate the effectiveness and safety of D-HM combination therapy in the treatment of AR. Results: Data from 228 patients were collected. After PS matching, 144 patients were finally analyzed. The total nasal symptom score (TNSS) and mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) were significantly improved in the D-HM group compared with those in the UC group (TNSS: p=0.02; mini-RQLQ: p=0.04). Four patients in the D-HM group experienced minor adverse events that were mild and resolved within 15 days. Conclusions: D-HM combination therapy may be beneficial in the management of symptoms and rhinitis-associated quality of life and potentially useful in clinical practice. However, randomized placebo-controlled clinical trials are required to confirm their effectiveness. Study registration: This study has been registered at Clinical Research Information Service (KCT0007242).

ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma.

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens-bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04-0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.