Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

Retinal Adaptation in Response to Light and Dark Regimes in the Oriental Armyworm Mythimna separata (Lepidoptera: Noctuidae).

The oriental armyworm, Mythimna separata (Walker), is a well-known nocturnal migratory pest that relies on its exceptional nocturnal vision for navigation during long-distance flights. In this study, we investigated the ultrastructure of the compound eyes of adult M. separata using transmission electron microscopy and quantitatively evaluated adaptational changes in the retina under light and dark conditions. The compound eyes of M. separata are superposition eyes with a clear zone. The retina shows remarkable anatomical differences under light and dark adaptation, primarily characterized by distinct patterns of rhabdoms within the clear zone: the rhabdoms are nearly absent under light adaptation, but become more voluminous under dark adaptation. In the distal, middle, and proximal sections of the clear zone, the cross-sectional areas of retinulae and rhabdoms, as well as the rhabdom occupation ratio, are significantly larger under dark adaptation than under light adaptation. Conversely, the opposite trend is observed beneath the clear zone. These results indicate remarkable plasticity in the M. separata retina throughout a normal daily cycle, providing a theoretical basis for improving searchlight and ground light trap techniques for the management of this migratory species.

Predicting sequenced dental treatment plans from electronic dental records using deep learning.

BACKGROUND: Designing appropriate clinical dental treatment plans is an urgent need because a growing number of dental patients are suffering from partial edentulism with the population getting older. OBJECTIVES: The aim of this study is to predict sequential treatment plans from electronic dental records. METHODS: We construct a clinical decision support model, MultiTP, explores the unique topology of teeth information and the variation of complicated treatments, integrates deep learning models (convolutional neural network and recurrent neural network) adaptively, and embeds the attention mechanism to produce optimal treatment plans. RESULTS: MultiTP shows its promising performance with an AUC of 0.9079 and an F score of 0.8472 over five treatment plans. The interpretability analysis also indicates its capability in mining clinical knowledge from the textual data. CONCLUSIONS: MultiTP's novel problem formulation, neural network framework, and interpretability analysis techniques allow for broad applications of deep learning in dental healthcare, providing valuable support for predicting dental treatment plans in the clinic and benefiting dental patients. CLINICAL IMPLICATIONS: The MultiTP is an efficient tool that can be implemented in clinical practice and integrated into the existing EDR system. By predicting treatment plans for partial edentulism, the model will help dentists improve their clinical decisions.

Ultramorphology of the proboscis and sensilla of the Asian corn borer Ostrinia furnacalis (Lepidoptera: Crambidae).

The Asian corn borer, Ostrinia furnacalis (Guenée), is one of the most destructive lepidopteran pests affecting maize in Asia. Previous research on the feeding behavior of O. furnacalis has mostly focused on larvae, but the adult feeding preference has been unclear hitherto. In this study, we investigated the ultramorphology of the proboscis and sensilla of O. furnacalis using scanning electron microscopy and made morphological comparisons between the sexes, attempting to make predictions on the food preference and feeding behavior of the adults. The proboscis of O. furnacalis is divided into zones 1 and 2 with three types of sensilla, namely chaetica, basiconica, and styloconica. The entire proboscis and zone 2 of the females are significantly longer than those of the males. The main sexual difference in the sensilla is shown in the number of sensilla styloconica, which are eight in females but nine in males. The feeding preference of adult O. furnacalis is discussed based on the morphology of the proboscis and sensilla.

TRIM21 enhances bortezomib sensitivity in multiple myeloma by halting prosurvival autophagy.

Bortezomib (bort) is an effective therapeutic agent for patients with multiple myeloma (MM); however, most patients develop drug resistance. Autophagy, a highly conserved process that recycles cytosol or entire organelles via lysosomal activity, is essential for the survival, homeostasis, and drug resistance in MM. Growing evidence has highlighted that E3 ligase tripartite motif-containing protein 21 (TRIM21) not only interacts with multiple autophagy regulators but also participates in drug resistance in various cancers. However, to date, the direct substrates and additional roles of TRIM21 in MM remain unexplored. In this study, we demonstrated that low TRIM21 expression is a factor for relapse in MM. TRIM21 knockdown (KD) made MM cells more resistant to bort, whereas TRIM21 overexpression (OE) resulted in increased MM sensitivity to bort. Proteomic and phosphoproteomic studies of TRIM21 KD MM cells showed that bort resistance was associated with increased oxidative stress and elevated prosurvival autophagy. Our results showed that TRIM21 KD MM cell lines induced prosurvival autophagy after bort treatment, suppressing autophagy by 3-methyladenine treatment or by the short hairpin RNA of autophagy-related gene 5 (ATG5)-restored-bort sensitivity. Indeed, ATG5 expression was increased and decreased by TRIM21 KD and OE, respectively. TRIM21 affected autophagy by ubiquitinating ATG5 through K48 for proteasomal degradation. Importantly, we confirmed that TRIM21 could potentiate the antimyeloma effect of bort through in vitro and in vivo experiments. Overall, our findings define the key role of TRIM21 in MM bort resistance and provide a foundation for a novel targeted therapeutic approach.

Cytomegalovirus and Epstein-Barr virus infection during daratumumab treatment in patients with multiple myeloma.

ABSTRACTSWe explored the incidence of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections in 131 patients with multiple myeloma (MM), 53 of whom received daratumumab (Dara) treatments. The Dara group had more RRMM patients than the group without Dara. CMV infection was significantly more common in patients treated with Dara (16.98%) than in patients treated with regimens without Dara (2.56%). During Dara treatments, 24.53% of patients developed CMV and/or EBV infections. Patients who developed infections had significantly lower levels of albumin and lymphocytes in their peripheral blood. The median time from the first Dara infusion to infection was 27 days. We observed NK cell depletion and T cell expansion during Dara-treatment. Patients with CMV and/or EBV infections had significantly lower numbers of NK cells, total T cells, and CD8 + T cells at 1 month, and lower numbers of CD8 + T cells at 2 months after the first Dara infusion than those without infections.

Ultrastructure of the dorsal ocellus of Bittacus planus larvae (Mecoptera: Bittacidae) with evolutionary significance.

The Bittacidae are unique in holometabolous insects in that their larvae bear a dorsal ocellus on the frons. The fine structure of the dorsal ocellus, however, has not been investigated to date. Here, the ultrastructure of the larval dorsal ocellus was studied in the hangingfly Bittacus planus Cheng, 1949 using light, scanning, and transmission electron microscopy. The dorsal ocellus of the larvae comprises a cornea, corneagenous cells, and retinula cells. The cornea is a laminated structure. A layer of corneagenous cells is located below the cornea. Numerous retinula cells are arranged tightly beneath the corneagenous cells. The retinula cells modify their adjacent membranes into numerous linear microvilli, which form an analogue of the rhabdom among adjacent retinula cells. The results show that the dorsal ocellus of larval Bittacidae is a highly vestigial organ and appears to be degenerating during the postembryonic development. The presence of the vestigial dorsal ocellus is likely to represent an ancestral plesiomorphy of holometabolous insects, providing new evidence for exploring the evolutionary origin of holometabolous larvae.

Phylogenetic implications based on an ultrastructural study with emphasis on the tracheal system of the compound eyes of three species of nymphalid butterflies.

Compound eyes are the prominent visual organs of insects and can provide valuable information for the reconstruction of insect phylogeny. Although the largest butterfly family (Nymphalidae) has been well defined, the infrafamilial phylogenetic relationships remain controversial hitherto. In the present study the ultrastructure of the compound eyes of three nymphalids Neptis beroe, Childrena zenobia, and Palaeonympha opalina was investigated using light and transmission electron microscopy in an attempt to seek potentially important phylogenetic characters. The compound eyes of the nymphalids share a tracheal system in a "1-4-8" branching pattern. The eight tracheal subbranches exhibit distinct distribution patterns along the basal retinula cell as follows: the tracheal subbranches of Palaeonympha opaline are close to the rhabdom in the distance from the distalmost part of the basal retinula cell to the rhabdom end, while those of N. beroe and C. zenobia are on the periphery of the retinula along almost the whole basal retinula cell and become close to the rhabdom just at the proximal end of the basal retinula cell. The tracheal structure of the three nymphalids is discussed for their potential phylogenetic implications.

Analysis of High-Risk Extramedullary Relapse Factors in Newly Diagnosed MM Patients.

Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis, but our understanding of extramedullary relapse is still limited. The incidence, clinical characteristics, impact on the prognosis of extramedullary relapse, and the risk factors for extramedullary relapse in NDMM patients were analyzed. Among the 471 NDMM patients, a total of 267 patients had disease relapse during follow-up, including 64 (24.0%) patients with extramedullary relapse. Extramedullary relapse was more common in patients with younger age, IgD subtype, elevated LDH, extensive osteolytic lesions, extramedullary involvement, and spleen enlargement at the time of MM diagnosis. Survival analysis showed that extramedullary relapse patients had significantly worse median OS than patients with relapse but without extramedullary involvement (30.8 months vs. 53.6 months, p = 0.012). Multivariate analysis confirmed that elevated LDH (OR = 2.09, p = 0.023), >2 osteolytic lesions (OR = 3.70, p < 0.001), extramedullary involvement (OR = 3.48, p < 0.001) and spleen enlargement (OR = 2.27, p = 0.011) at the time of MM diagnosis were independent risk factors for extramedullary relapse in NDMM patients. Each of the above four factors was assigned a value of 1 to form the extramedullary relapse prediction score, and the 3-year extramedullary relapse rates of patients in the 0−2 and 3−4 score groups were 9.0 % and 76.7 %, respectively. This study suggested that extramedullary relapse was associated with poor clinical characteristics and poor prognosis in NDMM patients. The extramedullary relapse prediction score model composed of LDH, osteolytic lesions, extramedullary involvement and spleen enlargement has a better ability to predict extramedullary relapse than the existing ISS and R-ISS stages.

Ultrastructure of Ejaculatory Ducts of Cerapanorpa nanwutaina and Furcatopanorpa longihypovalva (Mecoptera: Panorpidae).

The ultrastructure of the ejaculatory duct was investigated in the scorpionflies Cerapanorpa nanwutaina (Chou 1981) and Furcatopanorpa longihypovalva (Hua & Cai, 2009) (Mecoptera: Panorpidae) using light and transmission electron microscopy. The ejaculatory ducts of both species comprise a median duct and an accessory sac. The median duct consists of a basal lamina, a mono-layered epithelium, a subcuticular cavity, and an inner cuticle. The accessory sac contains a single layer of epithelium and a basal lamina. A muscular layer is present in the accessory sac of C. nanwutaina and in the median duct of F. longihypovalva. The epithelia in the median duct and the accessory sac are well developed, their cells containing numerous cisterns of rough endoplasmic reticulum, mitochondria, and microvilli. The secretions of the median duct are first extruded into the subcuticular cavity and then into the lumen through an inner cuticle, while the secretions of the accessory sac are discharged directly into the lumen. The ejaculatory duct of F. longihypovalva is longer and has thicker epithelium with more cell organelles and secretions than that of C. nanwutaina.

High serum IL-17A is associated with bone destruction in newly diagnosed multiple myeloma patients.

Background: Multiple myeloma (MM) is a malignant proliferative disease of the blood system, characterized by the abnormal growth of clonal plasma cells in the bone marrow. The bone marrow microenvironment (BMM) is highly critical in the pathological process of MM. Many studies have shown that serum interleukin-17A (IL-17A) plays a key role in various infectious diseases, autoimmune diseases, and cancers. However, more clinical studies need to be performed to further prove the influence of serum IL-17A levels on multiple myeloma patients. Methods: Among a total of 357 participants in our institution's MM cohort, 175 were eligible for the retrospective study. Multivariate regression models adjusted by potential confounding factors, the violin plots, the generalized additive model and smooth curve fittings, receiver operating characteristic (ROC) curve, and Kaplan-Meier (K-M) curve analysis were applied to the research. Results: A total of 175 patients with newly diagnosed MM were enrolled in this study. The multivariate linear regression analysis showed that serum IL-17A level in MM patients correlated with the degree of bone lesions and fracture incidence (fully adjusted model, pbone lesion < 0.0001, pfracture < 0.0001). The violin plot showed that MM patients with higher serum IL-17A levels had more severe bone lesions and higher fracture incidence than those with lower serum IL-17A levels. A total of 171 patients were included in the study of the relationship between serum IL-17A and best overall effect (BOE). We found that serum IL-17A levels were independently related to the best inductive therapeutic efficacy (fully adjusted model, p = 0.037), and the relationship was especially obvious in the light chain group (fully adjusted model, p = 0.009) and IgA group (fully adjusted model, p = 0.0456). It could be deduced from the smooth curve that the higher the serum IL-17A level, the worse the BOE (p = 0.0163). The ROC prediction curve suggested that serum IL-17A could predict the BOE to a certain extent (area under the curve (AUC) = 0.717, p = 0.0327). A total of 148 MM patients were observed in the longitudinal study of the relationship between serum IL-17A and progression-free survival/overall survival (PFS/OS). The K-M curve analysis indicated that serum IL-17A levels in MM patients were not significantly correlated with PFS and OS. However, in the light chain subgroup, MM patients with high serum IL-17A had worse PFS (p = 0.015) and OS (p = 0.0076) compared to those with low serum IL-17A. In the IgA type subgroup, the higher IL-17A level was related to worse OS (p = 0.0061). Conclusion: This retrospective study found that higher levels of serum IL-17A were independently correlated with higher severity of bone disease and fracture incidence in newly diagnosed MM patients. High serum IL-17A level was related to poor best overall efficacy in the light chain type. High serum IL-17A was also associated with poor PFS and OS in the light chain type and OS in the IgA type subgroup.

Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression.

BACKGROUND: Multiple myeloma (MM) is the second most common hematologic malignancy with almost all patients eventually having relapse or refractory MM (RRMM), thus novel drugs or combination therapies are needed for improved prognosis. Chidamide and venetoclax, which target histone deacetylase and BCL2, respectively, are two promising agents for the treatment of RRMM. RESULTS: Herein, we found that chidamide and venetoclax synergistically exert an anti-myeloma effect in vitro in human myeloma cell lines (HMCLs) with a combination index (CI) < 1. Moreover, the synergistic anti-myeloma effect of these two drugs was demonstrated in primary MM cells and MM xenograft mice. Mechanistically, co-exposure to chidamide and venetoclax led to cell cycle arrest at G0/G1 and a sharp increase in DNA double-strand breaks. In addition, the combination of chidamide and venetoclax resulted in BCL-XL downregulation and BIM upregulation, and the latter protein was proved to play a critical role in sensitizing HMCLs to co-treatment. CONCLUSION: In conclusion, these results proved the high therapeutic potential of venetoclax and chidamide combination in curing MM, representing a potent and alternative salvage therapy for the treatment of RRMM.

The adverse impact of a gain in chromosome 1q on the prognosis of multiple myeloma treated with bortezomib-based regimens: A retrospective single-center study in China.

Background: Multiple myeloma is genetically heterogeneous, and chromosome abnormalities play a pivotal role in prognosis. A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities; however, its relationship with overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma is still unclear. We aim to clarify the impact of +1q on the clinical characteristics and survival outcomes of patients treated with bortezomib-based combination regimes. Materials and methods: We retrospectively analyzed 258 patients first diagnosed with myeloma who underwent bortezomib-based therapy at the bone marrow transplantation department of a multiple myeloma treatment center in the first affiliated hospital of Zhejiang University, China. Results: We identified 258 newly diagnosed patients with multiple myeloma in our department from July 2013 to September 2018. We observed that 127 (49.2%) of the patients acquired +1q at diagnosis, and +1q strongly correlated with the occurrence of del(13q) and IgH rearrangement (P < 0.001). In the patients with +1q, the PFS was 22.2 months (95% CI 15.8-28.5 months), and the three-year and five-year PFS was 35.1% and 15.3%, respectively. Univariate analysis revealed that albumin, lactate dehydrogenase (LDH), and the percentage of plasma cells significantly affected PFS. Multivariate analysis showed that LDH and the percentage of plasma cells significantly affected PFS in the +1q patients. In terms of OS, the median OS for the +1q patients was 47.4 months (95% CI 34.7-59.5), while the OS of the non-+1q patients was not reached (P = 0.048). The univariate and multivariate analyses revealed that age, platelet count, and extramedullary lesions were significant adverse factors for OS in the +1q patients. There were no statistical differences between PFS and OS when there were other chromosomal abnormalities, but there was a decreased tendency in PFS. LDH and +1q also had a synergistic adverse effect on survival. Conclusion: +1q is associated with a higher tumor burden and correlated with the occurrence of del(13q) and IgH rearrangement at diagnosis. In the era of novel agents, +1q still significantly affects PFS and OS.

RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways.

N6-methyladenosine (m6A), an internal modification in mRNA, plays a critical role in regulating gene expression. Dysregulation of m6A modifiers promotes oncogenesis through enzymatic functions that disrupt the balance between the deposition and removal of m6A modification on critical transcripts. However, the roles of mRNA m6A in multiple myeloma (MM) are poorly understood. The present study showed that RNA demethylase ALKBH5 was overexpressed in MM and associated with a poor prognosis in MM patients. Knocking down ALKBH5 induced apoptosis and inhibited the growth of MM cells in vitro. Xenograft models and gene set enrichment analysis with patient transcriptome datasets also supported the oncogenic role of ALKBH5 in MM. Mechanistic studies showed that ALKBH5 exerted tumorigenic effects in myeloma in an m6A-dependent manner, and TNF receptor-associated factor 1 (TRAF1) was a critical target of ALKBH5. Specifically, ALKBH5 regulated TRAF1 expression via decreasing m6A abundance in the 3'-untranslated region (3'-UTR) of TRAF1 transcripts and enhancing TRAF1 mRNA stability. As a result, ALKBH5 promoted MM cell growth and survival through TRAF1-mediated activation of NF-κB and MAPK signaling pathways. Collectively, our data demonstrated that ALKBH5 played a critical role in MM tumorigenesis and suggested that ALKBH5 could be a novel therapeutic target in MM.

Ultrastructure of the larval eyes of the hangingfly Terrobittacus implicatus (Mecoptera: Bittacidae).

The fine structure of the larval eyes of the hangingfly Terrobittacus implicatus (Huang & Hua) was investigated using scanning and transmission electron microscopy. The results show that the larval eyes of T. implicatus each consist of seven spaced ommatidia. Each ommatidium is composed of a corneal lens with about 45 lamellae, a tetrapartite eucone type of crystalline cone, eight retinula cells, two primary pigment cells, and an undetermined number of secondary pigment cells. The rhabdomeres of eight retinula cells effectively fuse into a centrally-fused, tiered funnel-shaped rhabdom extending from the base of the crystalline cone deeply into the ommatidium. In light of different positions in the ommatidium, the retinula cells can be divided into four distal and four proximal retinula cells. Pigment cells envelop the entire ommatidium. Electron-lucent vesicles are abundant throughout the cytoplasm of the eight retinula cells. The larval ommatidia of T. implicatus are similar to those of the Panorpidae, except for the distal retinula cells that also participate in the formation of the proximal rhabdom. In this case, the larval eyes of T. implicatus may lie in the transitional stage during the larval eye evolution of insects from ommatidia to stemmata.

Identification and comparative expression analysis of odorant-binding proteins in the reproductive system and antennae of Athetis dissimilis.

Odorant-binding proteins (OBPs) are prevalent in the antennal transcriptomes of different orders of insects. Studies on OBPs have focused on their role in the insect chemosensory system, but knowledge of their functions in the insect testis is limited. We sequenced the transcriptomes of the Athetis dissimilis reproductive organs and analyzed the expression of AdisOBP genes in different tissues. We identified 23 OBPs in the testis and ovaries and 31 OBPs in antennal transcriptomes. The results of real-time quantitative PCR revealed that 23 of the 54 OBP genes were highly expressed in both female and male antennae, including three that exhibited male-biased expression and 15 that exhibited female-biased expression. A total of 24 OBPs were highly expressed in the testis of A. dissimilis, while expression of OBPs in the ovaries was very low. These findings highlight the functional diversity of OBPs in insects and can facilitate further studies on the OBPs in A. dissimilis and lepidopteran species.

Sensilla of the antenna and proboscis of Athetis lepigone (Möschler) (Lepidoptera: Noctuidae).

Sensory structures on the antennae and mouthparts of insects are associated with various activities, such as host location, feeding, attracting a mate, and identifying a suitable oviposition site. Athetis lepigone (Möschler) is an important polyphagous Eurasian pest with more than 30 species of host plants. The larvae target bud leaves, prop roots, and tender stems of many agricultural crops, but the feeding habits of the adults remain poorly known. Aiming to understand the feeding behavior of the species, we investigated the fine morphology of its antennae and proboscis using scanning electron microscopy. The antennae of both sexes are filiform, and bear eight types of sensilla: Böhm's bristles, sensilla squamiformia, trichodea, chaetica, basiconica, coeloconica, styloconica, and auricillica. Sensilla trichodea are the most abundant among these sensillum types. The proboscis consists of two elongated, interlocked maxillary galeae that enclose the food canal by dorsal and ventral legulae. The external galeal surface is covered with numerous triangular microtrichia on Zone 1 and abundant blunt microbumps on Zone 2. The surface of the food canal bears closely connected and smooth semicircular ridges, gradually tapering toward the proboscis tip. Three types of sensilla are noticeable on the proboscis: sensilla trichodea, basiconica, and styloconica. We briefly discuss the putative functional significance of the antennal and proboscis sensilla and, based on the specific structural modifications of the proboscis, predict a flower-visiting habit for A. lepigone.

Structuring electronic dental records through deep learning for a clinical decision support system.

Extracting information from unstructured clinical text is a fundamental and challenging task in medical informatics. Our study aims to construct a natural language processing (NLP) workflow to extract information from Chinese electronic dental records (EDRs) for clinical decision support systems (CDSSs). We extracted attributes, attribute values, and tooth positions based on an existing ontology from EDRs. A workflow integrating deep learning with keywords was constructed, in which vectors representing texts were unsupervised learned. Specifically, we implemented Sentence2vec to learn sentence vectors and Word2vec to learn word vectors. For attribute recognition, we calculated similarity values among sentence vectors and extracted attributes based on our selection strategy. For attribute value recognition, we expanded the keyword database by calculating similarity values among word vectors to select keywords. Performance of our workflow with the hybrid method was evaluated and compared with keyword-based method and deep learning method. In both attribute and value recognition, the hybrid method outperforms the other two methods in achieving high precision (0.94, 0.94), recall (0.74, 0.82), and F score (0.83, 0.88). Our NLP workflow can efficiently structure narrative text from EDRs, providing accurate input information and a solid foundation for further data-based CDSSs.

Clinical decision support model for tooth extraction therapy derived from electronic dental records.

STATEMENT OF PROBLEM: Tooth extraction therapy serves as a key initial step in many prosthodontic treatment plans. Dentists must make an appropriate decision on the tooth extraction therapy considering multiple determinants and whether a clinical decision support (CDS) model might help. PURPOSE: The purpose of this retrospective records study was to construct a CDS model to predict tooth extraction therapy in clinical situations by using electronic dental records (EDRs). MATERIAL AND METHODS: The cohort involved 4135 deidentified EDRs of 3559 patients from the database of a prosthodontics department. Knowledge-based algorithms were first proposed to convert raw data from EDRs into structured data for feature extraction. Redundant features were filtered by a recursive feature-elimination method. The tooth extraction problem was then modeled alternatively as a binary or triple classification problem to be solved by 5 machine learning algorithms. Five machine learning algorithms within each model were compared, as well as the efficiency between 2 models. In addition, the proposed CDS was verified by 2 prosthodontists. RESULTS: The triple classification model outperformed the binary model with the F1 score of the Extreme Gradient Boost (XGBoost) algorithm as 0.856 and 0.847, respectively. The XGBoost outperformed the other 4 algorithms. The accuracy, precision, and recall of the XGBoost algorithm were 0.962, 0.865, and 0.830 in the binary classification and 0.924, 0.879, and 0.836 in the triple classification, respectively. The performance of the 2 prosthodontists was inferior to the models. CONCLUSIONS: The CDS model for tooth extraction therapy achieved high performance in terms of decision-making derived from EDRs.

Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies.

Venetoclax has been approved by the United States Food and Drug Administration since 2016 as a monotherapy for treating patients with relapsed/refractory chronic lymphocytic leukemia having 17p deletion. It has led to a breakthrough in the treatment of hematologic malignancies in recent years. However, unfortunately, resistance to venetoclax is inevitable. Multiple studies confirmed that the upregulation of the anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family mediated by various mechanisms, such as tumor microenvironment, and the activation of intracellular signaling pathways were the major factors leading to resistance to venetoclax. Therefore, only targeting BCL2 often fails to achieve the expected therapeutic effect. Based on the mechanism of resistance in specific hematologic malignancies, the combination of specific drugs with venetoclax was a clinically optional treatment strategy for overcoming resistance to venetoclax. This study aimed to summarize the possible resistance mechanisms of various hematologic tumors to venetoclax and the corresponding clinical strategies to overcome resistance to venetoclax in hematologic malignancies.