Browse Articles
Discover research articles across all indexed journals
Characteristics and treatment patterns in patients with multiple myeloma in Japan: A retrospective cohort analysis
Background Approval of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies (mAbs), such as daratumumab, has reshaped treatment patterns in patients with multiple myeloma (MM) in Japan. This retrospective study evaluated patient characteristics, treatment patterns, and trends in MM patients using Medical Data Vision, the largest electronic health records database in Japan with anonymous inpatient and outpatient health information. Methods Patients aged ≥18 years, with ≥2 records of an MM diagnostic and disease code and ≥1 record of MM treatment between 01 April 2008 and 30 June 2023 were included. Patients starting first-line (1L) treatment on or after 01 January 2020 were categorized into the 1+L cohort; those starting second-line (2L) treatment on or after 01 January 2018 were allocated to the 2+L cohort. Results Within the study period, 21,066 patients had an MM diagnosis, including 6,337 and 5,964 patients in the 1+L and 2+L cohorts, respectively. Median age was 74 years in both cohorts and gender distribution was similar (52.4% and 51.3% males, respectively). In the 1+L cohort, most patients (5,754/6,337; 90.8%) did not receive transplant, among whom 51.0% received 1L lenalidomide-based therapy, primarily daratumumab/lenalidomide/dexamethasone (DRd; 15.0%) or lenalidomide/dexamethasone (Rd;14.0%). In non-transplant patients, 1L DRd use increased from 6.0% in January–June 2020 to 28.0% in January–June 2023. In the 2+L cohort, 2L lenalidomide-based therapy use decreased from 65.0% in January–June 2018 to 37.0% in January–June 2023; daratumumab-based therapy increased from 14.0% to 39.0%. Retreatment with lenalidomide-, daratumumab-, and isatuximab-based therapy occurred in 44.1%, 35.2%, and 5.6% of patients, respectively. Conclusion The high use of lenalidomide and DRd in 1L, and high rates of retreatment with lenalidomide and anti-CD38 mAbs in 2L+ indicate a substantial need for new treatment modalities that can be used in 2L+ patients who previously received lenalidomide with/without an anti-CD38 mAb therapy.
New obesity definition sidelines BMI to focus on health
Advanced low-power filter architecture for biomedical signals with adaptive tuning
This paper presents a low-power, second-order composite source-follower-based filter architecture optimized for biomedical signal processing, particularly ECG and EEG applications. Source-follower-based filters are recommended in the literature for high-frequency applications due to their lower power consumption when compared to filters with alternative topologies. However, they are not suitable for biomedical applications requiring low cutoff frequencies as they are designed to operate in the saturation region. The major contribution in this work are the filter is made to operate in the weak inversion zone to reduce the area needed for the capacitor and the amount of power dissipated. Process variation is one of the major issues in the weak inversion regime. To overcome this, a unique method of compensating against fluctuations in process, voltage, and temperature is put forth based on magnitude comparison is another contribution. Key findings from post-layout simulations and experimental measurements demonstrate that the filter achieves a tunable cutoff frequency range of 0.5 Hz to 150 Hz, with a total power dissipation of only 6nW at 150 Hz. The design occupies a compact silicon area of 0.065 mm2 and offers a dynamic range of 75 dB. The measured results indicate that for a 300 mVpp signal swing, the top bound on THD is -40 dB. The filter’s robustness against process, voltage, and temperature variations is validated through on-chip tuning using a current steering DAC, ensuring stable performance across different operating conditions. These results make the proposed filter a promising candidate for low-power biomedical devices. The recommended filter is developed and implemented using UMC-0.18μm CMOS technology with a 1.0V supply, and the IC is tapped out using an MPW run of Euro practice IC services.
Correction: Secure deep learning for distributed data against malicious central server
Insights into stem Batomorphii: A new holomorphic ray (Chondrichthyes, Elasmobranchii) from the upper Jurassic of Germany
The Late Jurassic fossil deposits of southern Germany, collectively known as the ’Solnhofen Archipelago’, are one of the world’s most important sources of Mesozoic vertebrates. Complete skeletons of cartilaginous fishes (Chondrichthyes), whose skeletal remains are rare in the fossil record and therefore all the more valuable, are represented, among others, by exceptionally well-preserved rays (superorder Batomorphii). Despite their potential for research in several areas, including taxonomy, morphology, ecology, and phylogeny, the number of studies on these chondrichthyans is still very limited. Here, we identify a previously unknown ray, †Apolithabatis seioma gen. et sp. nov., which represents the first record of a ray species from the upper Kimmeridgian of Painten, Germany, and thus the oldest Late Jurassic ray taxon from Germany based on skeletal remains. This new batomorph is characterised by a unique body shape and a combination of skeletal features that distinguish it readily from all other known Late Jurassic rays. Two different morphometric approaches confirm differences in body shape and proportions to all known Late Jurassic conspecifics. We thus extend the recent taxonomic revision of these rays and include all described holomorphic specimens in a phylogenetic framework using strict cladistic principles. The phylogenetic analysis reveals all Late Jurassic batomorphs to represent a monophyletic group, for which we introduce the new order Apolithabatiformes, which is sister to all other batomorphs representing a stem group. While the phylogenetic relationships within Apolithabatiformes ord. nov. remain largely unresolved, †Apolithabatis gen. nov. is placed as the sister to †Aellopobatis. This highlights that, despite considerable progress in our understanding of the diversity and phylogeny of early rays, difficulties remain in establishing robust relationships within batomorphs. We therefore emphasise the importance of comprehensive studies of completely preserved fossil cartilaginous fishes to obtain a better understanding of chondrichthyan evolution and their systematics in deep time.
Correction: Comprehensive assessment of a nationwide simulation-based course for artificial life support
Dynamics of Salmonella Dublin infection and antimicrobial resistance in a dairy herd endemic to salmonellosis
Salmonella Dublin is a serovar that causes severe infections and cattle. Despite the importance of this agent, research on achieving its elimination from dairy farms is limited, which complicates risk mitigation and control efforts. This study thus aimed to assess the prevalence of S. Dublin on a farm with a history of outbreaks, to understand the dynamics of the infection, characterize the antimicrobial resistance of the isolates, and evaluate their genetic similarity. Multiparous cows in the postpartum phase are nearly five times more likely to shed Salmonella sp. A total of 39 cases of fatal septicemic salmonellosis caused by S. Dublin were confirmed in calves aged 3–5 months. Antimicrobial susceptibility was evaluated in 45 strains of S. Dublin, with 48.9% of the isolates classified as multidrug resistant, including resistance to penicillin (48.9%), tetracyclines (42.2%), and fluoroquinolones (33.3%). Seven multidrug-resistant isolates were selected for genomic sequencing. Among the resistance determinants identified, a mutation in the gyrA gene, present in all sequenced isolates, was notable. Analyses of cgMLST and SNPs revealed that the isolates from healthy animals were closely related to those found in animals with confirmed cases of S. Dublin, confirming that the agent was circulating among healthy animals across various categories. A high similarity was also found between the isolates in this study and strains causing salmonellosis in humans in Brazil, thus reinforcing the zoonotic nature and possible epidemiological link between cattle, and the occurrence of this disease in humans.
Construction of an lncRNA-mediated ceRNA network to investigate the inflammatory regulatory mechanisms of ischemic stroke
Long non-coding RNAs (lncRNAs) are among the most abundant types of non-coding RNAs in the genome and exhibit particularly high expression levels in the brain, where they play crucial roles in various neurophysiological and neuropathological processes. Although ischemic stroke is a complex multifactorial disease, the involvement of brain-derived lncRNAs in its intricate regulatory networks remains inadequately understood. In this study, we established a cerebral ischemia-reperfusion injury model using middle cerebral artery occlusion (MCAO) in male Sprague-Dawley rats. High-throughput sequencing was performed to profile the expression of cortical lncRNAs post-stroke, with subsequent validation using RT-PCR and qRT-PCR. Among the 31,183 lncRNAs detected in the rat cerebral cortex, 551 were differentially expressed between the MCAO and sham-operated groups in the ipsilateral cortex (fold change ≥2.0, P < 0.05). An integrated analysis of the 20 most abundant and significantly differentially expressed lncRNAs (DELs) identified 25 core cytoplasmic DELs, which were used to construct an interaction network based on their targeting relationships. This led to the establishment of a comprehensive lncRNA-miRNA-mRNA regulatory network comprising 12 lncRNAs, 16 sponge miRNAs, and 191 target mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that differentially expressed mRNAs (DEmRNAs) were significantly enriched in stroke-related pathways. Our analysis predicted four key lncRNAs, four miRNAs, and eleven crucial mRNAs involved in post-transcriptional regulation through competing endogenous RNA (ceRNA) mechanisms. These molecules were shown to participate extensively in post-stroke processes, including angiogenesis, axonal regeneration, inflammatory responses, microglial activation, blood-brain barrier (BBB) disruption, apoptosis, autophagy, ferroptosis, and thrombocytopenia. These findings highlight the role of lncRNAs as multi-level regulators in the complex network of post-stroke mechanisms, providing novel insights into the pathophysiological processes of stroke.
Child diarrhea in Cambodia: A descriptive analysis of temporal and geospatial trends and logistic regression-based examination of factors associated with diarrhea in children under five years
Diarrhea is a global public health problem that is the third leading cause of death in under five years, with an estimated 1.7 billion cases in 2023 and 1.8 million deaths from diarrhea diseases every year. To better understand child diarrhea in Cambodia, we examined to describe temporal and geospatial trends of diarrhea and used multiple logistic regression to analyze its association with individual and household characteristics and diarrhea among children aged 0–59 months using combined data from the Cambodia Demographic and Health Survey for 2005 to 2022. This study included 29,742 weighted children aged 0–59 months; there were 7,220 in 2005, 7,758 in 2010, 7,010 in 2014, and 7,754 in 2022, respectively. The prevalence of diarrhea among children aged 0–59 months decreased from 19.7% in 2005 to 6.2% in 2022. The highest prevalence of childhood diarrhea was observed in Kampong Cham (30.1%), in Mondul Kiri/Ratanak Kiri (24.6%), Battambang/Pailin (20.9%), and Mondul Kiri/Ratanak Kiri (12.9%) for the years 2005, 2010, 2014 and 2022. After adjusting for other variables, factors independently associated with a protective effect against childhood diarrhea included mothers aged 25–34 years (adjusted odds ratio (AOR) = 0.68; 95% CI: 0.48–0.96), 35–49 years (AOR = 0.60; 95% CI: 0.42–0.87), completed higher education (AOR = 0.61; 95% CI: 0.41–0.91), and employed (AOR = 0.79; 95% CI: 0.72–0.96). Children were less likely to have diarrhea if they were older than 36 months, belonged to the richest households (AOR = 0.69; 95% CI: 0.55–0.86), or lived in coastal region (AOR = 0.53; 95% CI: 0.41–0.69). Conversely, children born to mothers who smoke had increased odds of diarrhea (AOR = 1.61; 95% CI: 1.25–2.08), had barrier access to healthcare services (AOR = 1.20; 95% CI: 1.07–1.35), or children aged 6–23 months. Diarrhea remains highly prevalent among children in Cambodia. Public health interventions and policies to alleviate diarrhea should be prioritized to address these factors across geographical.
A superior tool for predicting sepsis in SAH patients: The nomogram outperforms SOFA score
Objective This study aimed to develop and validate a nomogram to predict the risk of sepsis in non-traumatic subarachnoid hemorrhage (SAH) patients using data from the MIMIC-IV database. Methods A total of 803 SAH patients meeting the inclusion criteria were randomly divided into a training set (563 cases) and a validation set (240 cases). Independent prognostic factors were identified through forward stepwise logistic regression, and a nomogram was created based on these factors. The discriminative ability of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the SOFA score. The model’s consistency was evaluated using the C-index, and the improvement in performance over the SOFA score was calculated using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Results Five independent predictive factors were identified through LASSO regression analysis: mechanical ventilation, hyperlipidemia, temperature, white blood cell count, and red blood cell count. The AUC of the nomogram in the training and validation sets were 0.854 and 0.824, respectively, both higher than the SOFA score. NRI and IDI results indicated that the nomogram outperformed the SOFA score in identifying sepsis risk. Calibration curves and the Hosmer-Lemeshow test demonstrated good calibration of the nomogram. Decision curve analysis showed that the nomogram had higher net benefit in clinical application. Conclusion The nomogram developed in this study performed excellently in predicting the risk of sepsis in SAH patients, surpassing the traditional SOFA scoring system, and has significant clinical application value.
Novel euthanasia technique for zebrafish using electric shock in standard group housing aquaria
Abstract Zebrafish are widely used in research, accounting for approximately 50% of all laboratory fish across Europe. Due to their rapid reproduction and aging, effective and practical euthanasia methods are necessary for managing large stocks. This study investigated whether adult zebrafish can be euthanised by delivering an electrical current directly via the water in their housing aquaria. For this, portable plate electrodes were developed for 3.5 and 8.0 L Tecniplast™ housing aquaria. Our results show that adult zebrafish can be euthanised in groups (5 fish per litre) with electrical fields and current densities of at least 6 or 7 VRMS cm−1, and 0.7 or 0.8 ARMS dm−2 in 3.5–8 L aquaria, respectively, when delivered for 30 s in water at 28 °C with a conductivity of 800 µS cm−1 at 50 Hz. If widely implemented, this technique could improve the welfare of the vast number of zebrafish used across the world.
Urea enhances the yield and quality of bio-oil produced from corncob through pyrolysis
Lymphocyte-C-reactive protein ratio upon admission to predict disease progression and ICU admission in adult patients with diabetic ketoacidosis
Emotion dysregulation, performance concerns, and mental health among Canadian athletes
Efficient and accurate determination of the degree of substitution of cellulose acetate using ATR-FTIR spectroscopy and machine learning
Abstract Multiple linear regression models were trained to predict the degree of substitution (DS) of cellulose acetate based on raw infrared (IR) spectroscopic data. A repeated k-fold cross validation ensured unbiased assessment of model accuracy. Using the DS obtained from 1H NMR data as reference, the machine learning model achieved a mean absolute error (MAE) of 0.069 in DS on test data, demonstrating higher accuracy compared to the manual evaluation based on peak integration. Limiting the model to physically relevant areas unexpectedly showed the $${\hbox {C}{-}\hbox {H}}$$ peak to be the strongest predictor of DS. By applying a n-best feature selection algorithm based on the F-statistic of the Pearson correlation coefficient, several relevant areas were identified and the optimized model achieved an improved MAE of 0.052. Predicting the DS of other cellulose acetate data sets yielded similar accuracy, demonstrating that the developed models are robust and suitable for efficient and accurate routine evaluations. The model solely trained on cellulose acetate was further able to predict the DS of other cellulose esters with an accuracy of $$\approx 0.1-0.2$$ in DS and model architectures for a more general analysis of cellulose esters were proposed.
Prediction of ADMET profile and anti-inflammatory potential of chamuangone
Genetic analysis and heterosis breeding of seed yield and yieldattributing traits in Indian mustard (Brassica juncea (L.) Czern & Coss.)
Compact inverse designed vertical coupler with bottom reflector for sub-decibel fiber-to-chip coupling on silicon on insulator platform
Abstract Inverse design via topology optimization has led to innovations in integrated photonics and offers a promising way for designing high-efficiency on-chip couplers with a minimal footprint. In this work, we exploit topology optimization to design a compact vertical coupler incorporating a bottom reflector, which achieves sub-decibel coupling efficiency on the 220-nm silicon-on-insulator platform. The final design of the vertical coupler yields a predicted coupling efficiency of −0.35 dB at the wavelength of 1550 nm with a footprint of 14 µm $$\times$$ × 14 µm, which is considerably smaller than conventional grating couplers. Its topology-optimized geometry can be realized by applying one full-etch and one 70-nm shallow-etch process and the fabricability is also guaranteed by a minimum feature size around 150 nm. Analysis of the potential fabrication imperfections indicates that the topology-optimized coupler is more resilient to in-plane variations, as the deviation of approximately ±100 nm in the misalignment of the topology-optimized features, ±20 nm in the size of the topology-optimized features, and ±10 nm in shallow etch depth yields an additional 1-dB loss as a penalty at the wavelength of 1550 nm. The proposed vertical coupler can further miniaturize photonic integrated circuits and enable highly-efficient networks between optical fibers and other photonic devices.