Comparing multi-class classifier performance by multi-class ROC analysis: A nonparametric approach.

The area under the Receiver Operating Characteristic (ROC) curve (AUC) is a standard metric for quantifying and comparing binary classifiers. Real world applications often require classification into multiple (more than two) classes. For multi-class classifiers that produce class membership scores, a popular multi-class AUC (MAUC) variant is to average the pairwise AUC values [1]. Due to the complicated correlation patterns, the variance of MAUC is often estimated numerically using resampling techniques. This work is a generalization of DeLong's nonparameteric approach for binary AUC analysis [2] to MAUC. We first derive the closed-form expression of the covariance matrix of the pairwise AUCs within a single MAUC. Then by dropping higher order terms, we obtain an approximate covariance matrix with a compact, matrix factorization form, which then serves as the basis for variance estimation of a single MAUC. We further extend this approach to estimate the covariance of correlated MAUCs that arise from multiple competing classifiers. For the special case of binary correlated AUCs, our results coincide with that of DeLong. Our numerical studies confirm the accuracy of the variance and covariance estimates. We provide the source code of the proposed covariance estimation of correlated MAUCs on GitHub (https://tinyurl.com/euj6wvsz) for its easy adoption by machine learning and statistical analysis packages to quantify and compare multi-class classifiers.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Parahydrogen-Induced Polarization of 14N Nuclei.

Hyperpolarization techniques provide a dramatic increase in sensitivity of nuclear magnetic resonance spectroscopy and imaging. In spite of the outstanding progress in solution-state hyperpolarization of spin-1/2 nuclei, hyperpolarization of quadrupolar nuclei remains challenging. Here, hyperpolarization of quadrupolar 14N nuclei with natural isotopic abundance of >99 % is demonstrated. This is achieved via pairwise addition of parahydrogen to tetraalkylammonium salts with vinyl or allyl unsaturated moieties followed by a subsequent polarization transfer from 1H to 14N nuclei at high magnetic field using PH-INEPT or PH-INEPT+ radiofrequency pulse sequence. Catalyst screening identified water-soluble rhodium complex [Rh(P(m-C6H4SO3Na)3)3Cl] as the most efficient catalyst for hyperpolarization of the substrates under study, providing up to 1.3 % and up to 6.6 % 1H polarization in the cases of vinyl and allyl precursors, respectively. The performance of PH-INEPT and PH-INEPT+ pulse sequences was optimized with respect to interpulse delays, and the resultant experimental dependences were in good agreement with simulations. As a result, 14N NMR signal enhancement of up to 760-fold at 7.05 T (corresponding to 0.15 % 14N polarization) was obtained.

The clinical significance and prognostic value of serum beta-2 microglobulin in adult lymphoma-associated hemophagocytic lymphohistiocytosis: a multicenter analysis of 326 patients.

To investigate the prognostic impact of serum beta-2 microglobulin (B2M) in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). The clinical and laboratory characteristics of 326 adult patients in a multicenter cohort with lymphoma-associated HLH with available baseline serum B2M levels were retrospectively analyzed. A total of 326 cases were included in this study, and the median serum B2M level was 5.19 mg/L. The optimal cut-off of serum B2M was 8.73 mg/L, and the cases with serum B2M level >8.73 mg/L were older and had a more advanced stage, lower levels of platelets, albumin, and fibrinogen, and higher creatinine level. The serum B2M >8.73 mg/L, creatinine ≥133 µmol/L, fibrinogen ≤1.5 g/L, agranulocytosis (<0.5 × 109/L), severe thrombocytopenia (<50 × 109/L), and high Epstein-Barr virus DNA copy number were found to have independent prognostic values in all patients, and the serum B2M >8.73 mg/L was also an independent prognostic factor in patients with creatinine <133 µmol/L. Finally, a prognostic scoring system was established based on independent prognostic factors of all patients and categorized the patients into three groups with significant prognostic differences. This study confirmed that the serum B2M level can be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

On the bias in the AUC variance estimate.

The area under the Receiver Operating Characteristic (ROC) curve (AUC) is a standard metric for quantifying and comparing binary classifiers. A popular approach to estimating the AUCs and the associated variabilities - the variance of the AUC or the full covariance matrix of multiple correlated AUCs - is the one proposed by DeLong et al [1], which is based on the Mann Whitney two-sample U-statistics. The bias of a variance estimator is an important factor in applications such as hypothesis testing and construction of confidence intervals - a negatively biased variance estimator may lead to incorrect conclusions, and a positive bias is conservative hence preferable. In this work, we show that the (co-)variance estimate in DeLong's approach is always positively biased. More specifically, the difference matrix between the expectation of the estimated covariance and the true covariance is a positive semi-definite matrix. This bias is non-negligible when the sample size is small, and quickly diminishes as the sample size increases. Our method relies on constructing, from the AUC kernel, a random variable whose (co-)variance matrix coincides with the bias, thereby establishing the claim. We also discuss alternative approaches to AUC variance estimation that may potentially reduce the bias.

Development of a Silicone Rubber Mold with an Innovative Waterfall Cooling Channel.

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.

New prospects of cancer therapy based on pyroptosis and pyroptosis inducers.

Pyroptosis is a gasdermin-mediated programmed cell death (PCD) pathway. It differs from apoptosis because of the secretion of inflammatory molecules. Pyroptosis is closely associated with various malignant tumors. Recent studies have demonstrated that pyroptosis can either inhibit or promote the development of malignant tumors, depending on the cell type (immune or cancer cells) and duration and severity of the process. This review summarizes the molecular mechanisms of pyroptosis, its relationship with malignancies, and focuses on current pyroptosis inducers and their significance in cancer treatment. The molecules involved in the pyroptosis signaling pathway could serve as therapeutic targets for the development of novel drugs for cancer therapy. In addition, we analyzed the potential of combining pyroptosis with conventional anticancer techniques as a promising strategy for cancer treatment.

Girth-based administered activity for pediatric 99m Tc-DMSA SPECT.

BACKGROUND: Pediatric molecular imaging requires a balance between administering an activity that will yield sufficient diagnostic image quality while maintaining patient radiation exposure at acceptable levels. In current clinical practice, this balance is arrived at by the current North American Consensus Guidelines in which patient weight is used to recommend the administered activity (AA). PURPOSE: We have previously demonstrated that girth (waist circumference at the level of the kidneys) is better at equalizing image quality than patient weight for pediatric Tc-99m DMSA renal function imaging. However, the correlation between image quality (IQ), AA, and patient girth has not been rigorously and systematically developed. In this work, we generate a series of curves showing the tradeoff between AA and IQ as a function of patient girth, providing the data for standards bodies to develop the next generation of dosing guideline for pediatric DMSA SPECT. METHODS: An anthropomorphic phantom series that included variations in age (5, 10, and 15 years), gender (M, F), local body morphometry (5, 10, 50, 90, and 95th girth percentiles), and kidney size (±15% standard size), was used to generate realistic SPECT projections. A fixed and clinically challenging defect-to-organ volume percentage (0.49% of renal cortex value) was used to model a focal defect with zero uptake (i.e., full local loss of renal function). Task-based IQ assessment methods were used to rigorously measure IQ in terms of renal perfusion defect detectability. This assessment was performed at multiple count levels (corresponding to various AAs) for groups of patients that had similar girths and defect sizes. Receiver-operating characteristics (ROC) analysis was applied; the area under the ROC curve (AUC) was used as a figure-of-merit for task performance. Curves showing the tradeoff between AUC and AA were generated for these groups of phantoms. RESULTS: Overall, the girth-based dosing method suggested different amounts of AA compared to weight-based dosing for the phantoms that had a relatively large body weight but a small girth or phantoms with relatively small bodyweight but large girth. Reductions of AA to 62.9% compared to weight-based dosing guidelines can potentially be realized while maintaining a baseline (AUC = 0.80) IQ for certain 15-year-olds who have a relatively small girth and large defect size. Note that the task-based IQ results are heavily dependent on the simulated defect size for the defect detection task and the appropriate AUC value must be decided by the physicians for this diagnostic task. These results are based purely on simulation and are subject to future clinical validation. CONCLUSIONS: The study provides simulation-based IQ-AA data for a girth-based dosing method for pediatric renal SPECT, suggesting that patient waist circumference at the level of kidneys should be considered in selecting the AA needed to achieve an acceptable IQ. This data may be useful for standards bodies to develop girth-based dosing guidelines.

Synergistic co-catalytic nanozyme system for highly efficient one-pot colorimetric sensing at neutral pH: Combining molybdenum trioxide and Fe(III)-Modified covalent triazine framework.

This study investigates the co-catalytic capabilities of MoO3 nanosheets in enhancing the enzyme-like catalytic activity of a two-dimensional ultrathin Fe(III)-modified covalent triazine framework (Fe-CTF) under neutral pH conditions. The unique physicochemical surface properties and two-dimensional structures of Fe-CTF enable the direct immobilization of native enzymes (glucose oxidase (GOD) and xanthine oxidase (XOD)) through adsorption, eliminating the need for chemical processes. Efficient immobilization of the native enzymes within the Fe-CTF/GOD(XOD) hybrid is achieved through multipoint attachment involving various interactions. The Fe-CTF/MoO3 co-catalytic system exhibits enzyme-mimicking activity at neutral pH and, when combined with the high catalytic activity of the immobilized native enzymes, enables the development of a colorimetric method for glucose detection. This method demonstrates excellent facilitation, rapidity, sensitivity, and selectivity, with a linear detection range of 50-1000 µM and a limit of detection of 8.8 µM for glucose. Furthermore, a straightforward one-pot colorimetric method is established for screening XOD inhibitors. The inhibitory potential of a crude extract derived from Chinese water chestnut peel on XOD activity is evaluated using this method. The findings of this study pave the way for the utilization of nanozyme/native enzyme hybrids in pH-neutral conditions for one-pot colorimetric sensing. This work contributes to the advancement of enzyme-based sensing technologies and holds promise for various applications in biosensing and biomedical research.

In Situ Hyperpolarization Enables 15N and 13C Benchtop NMR at Natural Isotopic Abundance.

Without employing isotopic labeling, we demonstrate the generation of 15N and 13C NMR signals for molecules containing -NH2 motifs using benchtop NMR spectrometers (1-1.4 T). Specifically, high-SNR (>50) detection of ammonia, 4-aminopyridine, benzylamine, and phenethylamine dissolved in methanol or dichloromethane is demonstrated after only 10 s of parahydrogen bubbling using signal amplification by reversible exchange and applying a pulse sequence based on spin-lock-induced crossing. Optimization of the sequence parameters allows us to achieve up to 12% 15N and 0.4% 13C polarization in situ without the need for the sample transfer typically employed in other hyperpolarization methods. Moreover, hyperpolarization is generated continuously without having to stop the parahydrogen bubbling to reset magnetization, paving the way toward fast 2D spectroscopic methods and relaxometry. The provided methodology may find application for the identification of diluted chemicals relevant to industry and research with the aid of affordable benchtop NMR spectrometers.

Chidamide plus prednisone, cyclophosphamide, and thalidomide for relapsed or refractory peripheral T-cell lymphoma: A multicenter phase II trial.

BACKGROUND: Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory-particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. METHODS: We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. RESULTS: Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5 %) and 43.8% (95% CI, 28.3-59.3 %), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. CONCLUSION: The all-oral CPCT regimen was an effective and safety regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02879526.

The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.

Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Proper RPA acetylation promotes accurate DNA replication and repair.

The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair. We show that yeast RPA is acetylated on multiple conserved lysines by the acetyltransferase NuA4 upon DNA damage. Mimicking constitutive RPA acetylation or blocking its acetylation causes spontaneous mutations with the signature of micro-homology-mediated large deletions or insertions. In parallel, improper RPA acetylation/deacetylation impairs DNA double-strand break (DSB) repair by the accurate gene conversion or break-induced replication while increasing the error-prone repair by single-strand annealing or alternative end joining. Mechanistically, we show that proper acetylation and deacetylation of RPA ensure its normal nuclear localization and ssDNA binding ability. Importantly, mutation of the equivalent residues in human RPA1 also impairs RPA binding on ssDNA, leading to attenuated RAD51 loading and homologous recombination repair. Thus, timely RPA acetylation and deacetylation likely represent a conserved mechanism promoting high-fidelity replication and repair while discriminating the error-prone repair mechanisms in eukaryotes.

Etoposide, dexamethasone, and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma: A randomized phase III study.

Methotrexate, etoposide, dexamethasone, and pegaspargase (MESA) with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type (NKTCL). We explored the efficacy and safety of reduced-intensity, non-intravenous etoposide, dexamethasone, and pegaspargase (ESA) with sandwiched radiotherapy. This multicenter, randomized, phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China. Patients were randomly assigned (1:1) to receive ESA (pegaspargase 2,500 IU/m2 intramuscularly on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2-4) or MESA (methotrexate 1 g/m2 intravenously on day 1, etoposide 200 mg orally, and dexamethasone 40 mg orally on days 2-4, and pegaspargase 2,500 IU/m2 intramuscularly on day 5) regimen (four cycles), combined with sandwiched radiotherapy. The primary endpoint was overall response rate (ORR). The non-inferiority margin was -10.0%. From March 16, 2016, to July 17, 2020, 256 patients underwent randomization, and 248 (ESA [n = 125] or MESA [n = 123]) made up the modified intention-to-treat population. The ORR was 88.8% (95% confidence interval [CI], 81.9-93.7) for ESA with sandwiched radiotherapy and 86.2% (95% CI, 78.8-91.7) for MESA with sandwiched radiotherapy, with an absolute rate difference of 2.6% (95% CI, -5.6-10.9), meeting the non-inferiority criteria. Per-protocol and sensitivity analysis supported this result. Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

Targeting lysosomal HSP70 induces acid sphingomyelinase-mediated disturbance of lipid metabolism and leads to cell death in T cell malignancies.

BACKGROUND: T cell malignancies proliferate vigorously, are highly dependent on lysosomal function, with limited therapeutic options. Deregulation of lysosomal structure and function has been confirmed to be a key role in the treatment of hematologic malignant disease. METHODS: Cell counting kit 8 and Annexin V/PI staining were used to assess the cell viability and apoptosis rate. Flow cytometry, liquid chromatography mass spectrometry, immunofluorescence and western blot were performed to detect the effect on lysosomes. Drug affinity responsive target stability, molecular docking and cellular thermal shift assay were employed to confirm the target protein of V8 on lysosomes. A xenograft model was constructed in NOD/SCID mice to assess the effect and mechanism. RESULTS: V8, a new lysosomotropic compound, could be rapidly trapped by lysosomes and accumulation in lysosomes, contributing to lysosomal-dependent cell death by evoking lysosomal membrane permeabilization (LMP), accompanied with disrupted lysosome and autophagic flux. Mechanistically, heat shock protein 70 (HSP70) was identified as the binding target of V8 in lysosome. As a downstream effect of targeting HSP70, enzymatic activity of acid sphingomyelinase (ASM) was inhibited, which induced disturbance of lipid metabolism, instability of lysosomal membrane, and leakage of cathepsin B and D, leading to LMP-mediated cell death. In vivo study showed V8 well controlled the growth of the tumour and confirmed lysosomal cell death induced by V8. CONCLUSIONS: Collectively, this study suggests targeting lysosomal HSP70-ASM axis by V8 illustrates the great value of drug therapy for T cell malignancies and the unlimited potential of lysosomal targeting for cancer therapy.

Linearized Analysis of Noise and Resolution for DL-Based Image Generation.

Deep-learning (DL) based CT image generation methods are often evaluated using RMSE and SSIM. By contrast, conventional model-based image reconstruction (MBIR) methods are often evaluated using image properties such as resolution, noise, bias. Calculating such image properties requires time consuming Monte Carlo (MC) simulations. For MBIR, linearized analysis using first order Taylor expansion has been developed to characterize noise and resolution without MC simulations. This inspired us to investigate if linearization can be applied to DL networks to enable efficient characterization of resolution and noise. We used FBPConvNet as an example DL network and performed extensive numerical evaluations, including both computer simulations and real CT data. Our results showed that network linearization works well under normal exposure settings. For such applications, linearization can characterize image noise and resolutions without running MC simulations. We provide with this work the computational tools to implement network linearization. The efficiency and ease of implementation of network linearization can hopefully popularize the physics-related image quality measures for DL applications. Our methodology is general; it allows flexible compositions of DL nonlinear modules and linear operators such as filtered-backprojection (FBP). For the latter, we develop a generic method for computing the covariance images that is needed for network linearization.

Effects of Rotational Speed on Joint Characteristics of Green Joining Technique of Dissimilar Polymeric Rods Fabricated by Additive Manufacturing Technology.

Friction welding (FW) FW of dissimilar polymer rods is capable of manufacturing green products swiftly and economically. In this study, a green manufacturing technique of joining dissimilar polymer rods was proposed, and the effects of rotational speed on the joint characteristics of friction-welded dissimilar polymer rods fabricated by the fused deposition modeling process were investigated experimentally. The shore surface hardness test, impact test, three-point bending test, and differential scanning calorimetry analysis were carried out on the weld joints. The impact energy for FW of polylactic acid (PLA) and PLA, PLA and acrylonitrile butadiene styrene (ABS), PLA and PLA filled with glass fiber (GF), PLA and PLA filled with carbon fiber (CF), PLA and polycarbonate (PC), and PLA and polyamide (PA) rods can be increased by approximately 1.5, 1.5, 1.3, 1.3, 2.1, and 1.5 times by increasing the rotational speed from 330 rpm to 1350 rpm. The bending strength for FW of PLA and PLA, PLA and ABS, PLA and PLA filled with GF, PLA and PLA filled with CF, PLA and PC, and PLA and PA rods can be increased by approximately 1.3, 1.7, 1.3, 1.2, 1.2, and 1.2 times by increasing the rotational speed from 330 rpm to 1350 rpm. However, the surface hardness of the weld bead is not proportional to the rotational speed. The average surface hardness of the weld bead was increased by approximately 5% compared to the surface hardness of the welding base materials.

Second Primary Malignancy Risk in Multiple Myeloma from 1975 to 2018.

As the survival times for multiple myeloma (MM) patients continue to extend, the risk of a second primary malignancy (SPM) among MM survivors has become a topic of increasing concern within the medical community. The Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database was used to evaluate the risk and survival of SPM among MM survivors from 1975 to 2018. The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence (CMI) of SPM for MM risk were calculated. Survival and the CMI were estimated by using hazard ratios (HRs). Subgroup analyses were performed according to race, sex, age, time of myeloma diagnosis, and the SPM site. A total of 43,825 cases were recorded with the initial diagnosis of MM from 1975 to 2018. A total of 3101 (7.1%) patients developed 3407 SPMs. Solid tumors were decreased in patients with MM (SIR = 0.93; 95% CI = 0.90-0.97) compared to the general population, whereas the risk of hematological malignancy was increased (SIR = 1.90; 95% CI = 1.72-2.10). Taking death as a competing event, the CMI of SPM in the whole population was 7.38% at 10 years (6.11% solid and 1.27% hematologic). Factors associated with SPM occurrence were age, sex, race, and time of MM diagnosis. The survival of SPM patients from MM diagnosis was longer than that of patients without SPM (HR = 0.67, 95% CI = 0.58-0.63). The median survival time was 17 months from SPM diagnosis and 34 months from MM diagnosis (HR = 1.4, 95% CI = 1.35-1.46). Age, race, and sex were important factors for the risk of SPM. Site- and time-specific surveillance strategies should be recommended to monitor SPM in high-risk MM patients.

Generation of Digital Brain Phantom for Machine Learning Application of Dopamine Transporter Radionuclide Imaging.

While machine learning (ML) methods may significantly improve image quality for SPECT imaging for the diagnosis and monitoring of Parkinson's disease (PD), they require a large amount of data for training. It is often difficult to collect a large population of patient data to support the ML research, and the ground truth of lesion is also unknown. This paper leverages a generative adversarial network (GAN) to generate digital brain phantoms for training ML-based PD SPECT algorithms. A total of 594 PET 3D brain models from 155 patients (113 male and 42 female) were reviewed and 1597 2D slices containing the full or a portion of the striatum were selected. Corresponding attenuation maps were also generated based on these images. The data were then used to develop a GAN for generating 2D brain phantoms, where each phantom consisted of a radioactivity image and the corresponding attenuation map. Statistical methods including histogram, Fréchet distance, and structural similarity were used to evaluate the generator based on 10,000 generated phantoms. When the generated phantoms and training dataset were both passed to the discriminator, similar normal distributions were obtained, which indicated the discriminator was unable to distinguish the generated phantoms from the training datasets. The generated digital phantoms can be used for 2D SPECT simulation and serve as the ground truth to develop ML-based reconstruction algorithms. The cumulated experience from this work also laid the foundation for building a 3D GAN for the same application.