Single-shot inline holography using a physics-aware diffusion model: errata.

We present an erratum to our paper [Opt. Express32, 10444 (2024)10.1364/OE.517233]. This erratum aims to address an unintentional error in the methodology presented in Part 3.1. The error may lead to confusion among readers, and we provide additional clarification to ensure a comprehensive understanding of the technique. It is important to note that these corrections do not affect the results or conclusions of the original work.

Single-shot inline holography using a physics-aware diffusion model.

Among holographic imaging configurations, inline holography excels in its compact design and portability, making it the preferred choice for on-site or field applications with unique imaging requirements. However, effectively holographic reconstruction from a single-shot measurement remains a challenge. While several approaches have been proposed, our novel unsupervised algorithm, the physics-aware diffusion model for digital holographic reconstruction (PadDH), offers distinct advantages. By seamlessly integrating physical information with a pre-trained diffusion model, PadDH overcomes the need for a holographic training dataset and significantly reduces the number of parameters involved. Through comprehensive experiments using both synthetic and experimental data, we validate the capabilities of PadDH in reducing twin-image contamination and generating high-quality reconstructions. Our work represents significant advancements in unsupervised holographic imaging by harnessing the full potential of the pre-trained diffusion prior.

Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial.

BACKGROUND: Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP. METHODS: Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure "worst pain" and "pain with daily activity". Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system. RESULTS: Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported. CONCLUSION: Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056224 ( https://www.chictr.org.cn/showproj.aspx?proj=135506 ). Registered on February 1, 2022.

Enhancer RNA facilitates NELF release from immediate early genes.

Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons. eRNAs are synthesized prior to the culmination of target gene transcription and interact with the NELF complex. Knockdown of eRNAs expressed at neuronal enhancers impairs transient release of NELF from the specific target promoters during transcriptional activation, coinciding with a decrease in target mRNA induction. The enhancer-promoter interaction was unaffected by eRNA knockdown. Instead, chromatin looping might enable eRNAs to act locally at a specific promoter. Our findings highlight the spatiotemporally regulated action mechanism of eRNAs during early transcriptional elongation.

Loss of NSE-4 Perturbs Genome Stability and DNA Repair in Caenorhabditis elegans.

The Structural Maintenance of Chromosomes (SMC) complex plays an important role in maintaining chromosome integrity, in which the SMC5/6 complex occupies a central position by facilitating mitotic and meiotic processes as well as DNA repair. NSE-4 Kleisin is critical for both the organization and function of the SMC5/6 complex, bridging NSE1 and NSE3 (MAGE related) with the head domains of the SMC5 and SMC6 proteins. Despite the conservation in protein sequence, no functional relevance of the NSE-4 homologous protein (NSE-4) in Caenorhabditis elegans has been reported. Here, we demonstrated the essential role of C. elegans NSE-4 in genome maintenance and DNA repair. Our results showed that NSE-4 is essential for the maintenance of chromosomal structure and repair of a range of chemically induced DNA damage. Furthermore, NSE-4 is involved in inter-sister repair during meiosis. NSE-4 localizes on the chromosome and is indispensable for the localization of NSE-1. Collectively, our data from this study provide further insight into the evolutionary conservation and diversification of NSE-4 function in the SMC-5/6 complex.

Genome-wide identification and expression profiling of DREB genes in Saccharum spontaneum.

BACKGROUND: The dehydration-responsive element-binding proteins (DREBs) are important transcription factors that interact with a DRE/CRT (C-repeat) sequence and involve in response to multiple abiotic stresses in plants. Modern sugarcane are hybrids from the cross between Saccharum spontaneum and Saccharum officinarum, and the high sugar content is considered to the attribution of S. officinaurm, while the stress tolerance is attributed to S. spontaneum. To understand the molecular and evolutionary characterization and gene functions of the DREBs in sugarcane, based on the recent availability of the whole genome information, the present study performed a genome-wide in silico analysis of DREB genes and transcriptome analysis in the polyploidy S. spontaneum. RESULTS: Twelve DREB1 genes and six DREB2 genes were identified in S. spontaneum genome and all proteins contained a conserved AP2/ERF domain. Eleven SsDREB1 allele genes were assumed to be originated from tandem duplications, and two of them may be derived after the split of S. spontaneum and the proximal diploid species sorghum, suggesting tandem duplication contributed to the expansion of DREB1-type genes in sugarcane. Phylogenetic analysis revealed that one DREB2 gene was lost during the evolution of sugarcane. Expression profiling showed different SsDREB genes with variable expression levels in the different tissues, indicating seven SsDREB genes were likely involved in the development and photosynthesis of S. spontaneum. Furthermore, SsDREB1F, SsDREB1L, SsDREB2D, and SsDREB2F were up-regulated under drought and cold condition, suggesting that these four genes may be involved in both dehydration and cold response in sugarcane. CONCLUSIONS: These findings demonstrated the important role of DREBs not only in the stress response, but also in the development and photosynthesis of S. spontaneum.

The associations of plant-based protein intake with all-cause and cardiovascular mortality in patients on peritoneal dialysis.

BACKGROUND AND AIMS: Plant-based protein intake is associated with all-cause and/or cardiovascular disease (CVD) mortality in general population, but such data are scarce in dialysis patients. Thus, we examined the associations of plant-based protein-total protein ratio with all-cause and CVD mortality in patients on peritoneal dialysis (PD). METHODS AND RESULTS: The study enrolled 884 incident patients who started PD between October 2002 and August 2014. All demographic and laboratory data were recorded at baseline. Repeated measurements for laboratory and nutrition parameters were recorded at regular intervals and thus calculated as time-averaged values. Multivariable Cox regression models were used to estimate the hazard ratio (HR) of plant-based protein-total protein ratio and mortality based on baseline and time-averaged covariates, respectively. There were 437 (49%) patients died during a mean follow-up period of 45 months, of which 178 (40.8%) were due to CVD. Each 10% in increase in time-averaged plant-based protein-total protein ratio was associated with a reduction of 71% (95% CI, 90%-14%) and 89% (95% CI, 98%-29%) for all-cause and CVD mortality, respectively. Based on examination on interactive effects, we further found both baseline and time-averaged plant-based protein-total protein ratio were inversely associated with all-cause and CVD mortality in the subgroups of female, age ≥60 years, and albumin >35 g/L. CONCLUSIONS: The present study suggested that a diet with a higher plant-based protein-total protein ratio is associated with lower all-cause and CVD mortality in PD patients, and is more significant in female and elderly patients, and those without hypoalbuminemia.

[Current quality standards of Andrographis Herba of different countries and regions].

Andrographis Herba is a commonly used plant medicine, and has been recorded in pharmacopeias of different countries. However, there are some differences in the quality standards. Based on this, this paper compare the quality standards of Andrographis Herba between Chinese Pharmacopoeia, Hong Kong Chinese Materia Medica Standards, United States Pharmacopoeia, European Pharmacopoeia and Indian Pharmacopoeia, including origin, botanical characteristics, identification(microscopic identification and chromatographic identification), content determination, specific test(such as impurities, loss on drying, extractives, pesticides, heavy metals, mycotoxins, and other items) and storage requirements, so as to provide a reference for studying international quality standards of Andrographis.

Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.

BACKGROUND: CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) are approved for the treatment of ER+ advanced breast cancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. We previously reported a novel therapeutic agent, ERX-11, that binds to the estrogen receptor (ER) and modulates ER-coregulator interactions. Here, we tested if the combination of ERX-11 with agents approved for ER+ BCa would be more potent. METHODS: We tested the effect of combination therapy using BCa cell line models, including those that have acquired resistance to tamoxifen, letrozole, or CDK4/6 inhibitors or have been engineered to express mutant forms of the ER. In vitro activity was tested using Cell Titer-Glo, MTT, and apoptosis assays. Mechanistic studies were conducted using western blot, reporter gene assays, RT-qPCR, and mass spectrometry approaches. Xenograft, patient-derived explants (PDEs), and xenograft-derived explants (XDE) were used for preclinical evaluation and toxicity. RESULTS: ERX-11 inhibited the proliferation of therapy-resistant BCa cells in a dose-dependent manner, including ribociclib resistance. The combination of ERX-11 and CDK4/6 inhibitor was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BCa cells, in vitro, in xenograft models in vivo, xenograft-derived explants ex vivo, and in primary patient-derived explants ex vivo. Importantly, the combination caused xenograft tumor regression in vivo. Unbiased global mass spectrometry studies demonstrated profound decreases in proliferation markers with combination therapy and indicated global proteomic changes in E2F1, ER, and ER coregulators. Mechanistically, the combination of ERX-11 and CDK4/6 inhibitor decreased the interaction between ER and its coregulators, as evidenced by immunoprecipitation followed by mass spectrometry studies. Biochemical studies confirmed that the combination therapy significantly altered the expression of proteins involved in E2F1 and ER signaling, and this is primarily driven by a transcriptional shift, as noted in gene expression studies. CONCLUSIONS: Our results suggest that ERX-11 inhibited the proliferation of BCa cells resistant to both endocrine therapy and CDK4/6 inhibitors in a dose-dependent manner and that the combination of ERX-11 with a CDK4/6 inhibitor may represent a viable therapeutic approach.

Ethylene-mediated improvement in sucrose accumulation in ripening sugarcane involves increased sink strength.

BACKGROUND: Sugarcane is a major crop producing about 80% of sugar globally. Increasing sugar content is a top priority for sugarcane breeding programs worldwide, however, the progress is extremely slow. Owing to its commercial significance, the physiology of sucrose accumulation has been studied extensively but it did not lead to any significant practical outcomes. Recent molecular studies are beginning to recognize genes and gene networks associated with this phenomenon. To further advance our molecular understanding of sucrose accumulation, we altered sucrose content of sugarcane genotypes with inherently large variation for sucrose accumulation using a sugarcane ripener, ethylene, and studied their transcriptomes to identify genes associated with the phenomenon. RESULTS: Sucrose content variation in the experimental genotypes was substantial, with the top-performing clone producing almost 60% more sucrose than the poorest performer. Ethylene treatment increased stem sucrose content but that occurred only in low-sugar genotype. Transcriptomic analyses have identified about 160,000 unigenes of which 86,000 annotated genes were classified into functional groups associated with carbohydrate metabolism, signaling, localization, transport, hydrolysis, growth, catalytic activity, membrane and storage, suggesting the structural and functional specification, including sucrose accumulation, occurring in maturing internodes. About 25,000 genes were differentially expressed between all genotypes and treatments combined. Genotype had a dominant effect on differential gene expression than ethylene treatment. Sucrose and starch metabolism genes were more responsive to ethylene treatment in low-sugar genotype. Ethylene caused differential gene expression of many stress-related transcription factors, carbohydrate metabolism, hormone metabolism and epigenetic modification. Ethylene-induced expression of ethylene-responsive transcription factors, cytosolic acid- and cell wall-bound invertases, and ATPase was more pronounced in low- than in high-sugar genotype, suggesting an ethylene-stimulated sink activity and consequent increased sucrose accumulation in low-sugar genotype. CONCLUSION: Ethylene-induced sucrose accumulation is more pronounced in low-sugar sugarcane genotype, and this is possibly achieved by the preferential activation of genes such as invertases that increase sink strength in the stem. The relatively high enrichment of differentially expressed genes associated with hormone metabolism and signaling and stress suggests a strong hormonal regulation of source-sink activity, growth and sucrose accumulation in sugarcane.

Dietary fibre and mortality risk in patients on peritoneal dialysis.

Higher fibre intake reduced all-cause and cardiovascular mortality among healthy population, but such data in dialysis patients are limited. We aimed to examine these associations in patients on peritoneal dialysis (PD). This single-centre prospective cohort study enrolled 881 incident PD patients between October 2002 and August 2014. All patients were followed until death, transfer to haemodialysis, renal transplantation or until being censored in June 2018. Demographic data were collected at baseline. Biochemical, dietary and nutrition data were examined at baseline and thereafter at regular intervals to calculate the average values throughout the study. The outcomes were defined as all-cause and cardiovascular death. Cox proportional regression models were applied to explore the relationship between fibre intake and outcomes. Participants with higher fibre intake were more likely to be younger, male and have better residual renal function and serum lipids at baseline. They were prone to maintain better nutrient status, higher blood pressure and lower inflammatory status at baseline and afterwards. Neither baseline nor time-averaged fibre intake did show protective effects on all-cause mortality after multivariate adjustment in the whole cohort. Among non-diabetic PD patients, an independent association between fibre intake and all-cause mortality was found, in which each 1 g/d increase in time-averaged fibre intake correlated to 13 % of reduction in all-cause mortality. We did not observe any benefits of fibre intake in the CVD mortality for both whole cohort and subgroups. The present study revealed that higher dietary fibre intake appeared to have a protective effect on all-cause mortality in non-diabetic PD patients, which suggest that PD patients should be encouraged to eat a diet rich in fibres.

Effects of prophylactic antibiotics before peritoneal dialysis catheter implantation on the clinical outcomes of peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) related infections, such as peritonitis, are still the main obstacle for the development of PD. Prophylactic antibiotic as one of the interventions to prevent early peritonitis was recommended to use before PD catheter insertion by International Society for Peritoneal Dialysis (ISPD) guidelines, In our hospital, however, since 2012, the prophylactic antibiotics for insertion of PD catheters were not allowed to use because of our hospital's regulation. In order to analyze the outcomes of PD patients without using prophylactic antibiotics before the PD catheter insertion, we compared the PD patients with or without prophylactic antibiotics before PD catheter insertion. METHODS: This retrospective study included 247 patients undergoing permanent PD catheter placement with conventional open surgical method consecutively between February 2008 and June 2013. Of these, 154 patients were given intravenous cefazolin, 1.0 g, 0.5-2 h before the procedure (antibiotic group) and 93 patients were not given prophylactic antibiotics (nonantibiotic group). All the patients were administered intermittent PD within 24 h after PD catheter insertion. The early complications and long-term outcomes were recorded respectively. RESULTS: There was no significant difference in the incidence of peritonitis and exit-site/tunnel infection and mechanical complications between the two groups in the first 30 days after the PD catheter implantation. In addition, after 6 years of follow-up, no difference was seen between the two groups in patient survival, technique survival, and peritonitis-free survival. CONCLUSIONS: Our study does not show any beneficial effect of antibiotic prophylaxis in reducing the postoperative peritonitis.

Comprehensive transcriptome analysis reveals genes in response to water deficit in the leaves of Saccharum narenga (Nees ex Steud.) hack.

BACKGROUND: Sugarcane is an important sugar and energy crop that is widely planted in the world. Among the environmental stresses, the water-deficit stress is the most limiting to plant productivity. Some groups have used PCR-based and microarray technologies to investigate the gene expression changes of multiple sugarcane cultivars under water stress. Our knowledge about sugarcane genes in response to water deficit is still poor. RESULTS: A wild sugarcane type, Saccharum narenga, was selected and treated with drought stress for 22 days. Leaves from drought treated (DTS) and control (CK) plants were obtained for deep sequencing. Paired-end sequencing enabled us to assemble 104,644 genes (N50 = 1605 bp), of which 38,721 were aligned to other databases, such as UniProt, NR, GO, KEGG and Pfam. Single-end and paired-end sequencing identified 30,297 genes (> 5 TPM) in all samples. Compared to CK, 3389 differentially expressed genes (DEGs) were identified in DTS samples, comprising 1772 up-regulated and 1617 down-regulated genes. Functional analysis showed that the DEGs were involved in biological pathways like response to blue light, metabolic pathways and plant hormone signal transduction. We further observed the expression patterns of several important gene families, including aquaporins, late embryogenesis abundant proteins, auxin related proteins, transcription factors (TFs), heat shock proteins, light harvesting chlorophyll a-b binding proteins, disease resistance proteins, and ribosomal proteins. Interestingly, the regulation of genes varied among different subfamilies of aquaporin and ribosomal proteins. In addition, DIVARICATA and heat stress TFs were first reported in sugarcane leaves in response to water deficit. Further, we showed potential miRNAs that might be involved in the regulation of gene changes in sugarcane leaves under the water-deficit stress. CONCLUSIONS: This is the first transcriptome study of Saccharum narenga and the assembled genes are a valuable resource for future research. Our findings will improve the understanding of the mechanism of gene regulation in sugarcane leaves under the water-deficit stress. The output of this study will also contribute to the sugarcane breeding program.

Role of Erbin in ErbB2-dependent breast tumor growth.

ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.

Association between passing return-to-sport testing and re-injury risk in patients after anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis.

Background: Inconsistent results have been obtained regarding the association between return-to-sport (RTS) testing and the risk of subsequent re-injury following anterior cruciate ligament reconstruction (ACLR). We therefore conducted a systematic review and meta-analysis to assess the potential association between passing of RTS and the risk of re-injury for patients after ACLR. Methods: This meta-analysis was registered in INPLASY with the registration number INPLASY202360027. The electronic databases MedLine, EmBase, and the Cochrane library were systematically searched to identify eligible studies from their inception up to September 2023. The investigated outcomes included knee injury, secondary ACL, contralateral ACL injury, and graft rupture. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Results: A total number of nine studies involving 1410 individuals were selected for the final quantitative analysis. We noted that passing RTS test was not associated with the risk of subsequent knee injury (OR: 0.95; 95% CI: 0.28-3.21; P = 0.929), secondary ACL injury (OR: 0.98; 95% CI: 0.55-1.75; P = 0.945), and contralateral ACL injury (OR: 1.53; 95% CI: 0.63-3.71; P = 0.347). However, the risk of graft rupture was significantly reduced (OR: 0.49; 95% CI: 0.33-0.75; P = 0.001). Conclusions: This study found that passing RTS test was not associated with the risk of subsequent knee injury, secondary ACL injury, and contralateral ACL injury, while it was associated with a lower risk of graft rupture. Thus, it is recommended that patients after ACLR pass an RTS test in clinical settings.

Intermittent blood flow restriction with low-load resistance training for older adults with knee osteoarthritis: a randomized, controlled, non-inferiority trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.

A cutting-edge deep learning-and-radiomics-based ultrasound nomogram for precise prediction of axillary lymph node metastasis in breast cancer patients ≥ 75 years.

Objective: The objective of this study was to develop a deep learning-and-radiomics-based ultrasound nomogram for the evaluation of axillary lymph node (ALN) metastasis risk in breast cancer patients ≥ 75 years. Methods: The study enrolled breast cancer patients ≥ 75 years who underwent either sentinel lymph node biopsy or ALN dissection at Fudan University Shanghai Cancer Center. DenseNet-201 was employed as the base model, and it was trained using the Adam optimizer and cross-entropy loss function to extract deep learning (DL) features from ultrasound images. Additionally, radiomics features were extracted from ultrasound images utilizing the Pyradiomics tool, and a Rad-Score (RS) was calculated employing the Lasso regression algorithm. A stepwise multivariable logistic regression analysis was conducted in the training set to establish a prediction model for lymph node metastasis, which was subsequently validated in the validation set. Evaluation metrics included area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1-score. The calibration of the model's performance and its clinical prediction accuracy were assessed using calibration curves and decision curves respectively. Furthermore, integrated discrimination improvement and net reclassification improvement were utilized to quantify enhancements in RS. Results: Histological grade, axillary ultrasound, and RS were identified as independent risk factors for predicting lymph node metastasis. The integration of the RS into the clinical prediction model significantly improved its predictive performance, with an AUC of 0.937 in the training set, surpassing both the clinical model and the RS model alone. In the validation set, the integrated model also outperformed other models with AUCs of 0.906, 0.744, and 0.890 for the integrated model, clinical model, and RS model respectively. Experimental results demonstrated that this study's integrated prediction model could enhance both accuracy and generalizability. Conclusion: The DL and radiomics-based model exhibited remarkable accuracy and reliability in predicting ALN status among breast cancer patients ≥ 75 years, thereby contributing to the enhancement of personalized treatment strategies' efficacy and improvement of patients' quality of life.

Deep learning based ultrasound analysis facilitates precise distinction between parotid pleomorphic adenoma and Warthin tumor.

Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.

Harmonizing international quality standards for Andrographis paniculata: A comparative analysis of content determination methods across pharmacopeias.

The quality standards for Andrographis paniculata, a widely used medicinal herb, exhibited significant variations across different pharmacopeias. In this study, we compared the HPLC content determination methods and total lactone content of A. paniculata samples from different regions, as specified in the Chinese (CP), United States (USP), European (EP), Thai (TP), and Indian pharmacopeias (IP), as well as the Hong Kong Chinese Materia Medica Standards (HK). We aimed to assess the differences and similarities among these pharmacopeias and harmonized international quality standards for A. paniculata. The analysis revealed variations in sample preparation, liquid chromatographic conditions, fingerprint profiles, and total lactone content among the different pharmacopeias. Specifically, the CP and HK methods exhibited superior sample preparation and chromatographic separation. Further comparing the content of 20 A. paniculata samples with the CP, USP, EP and HK methods showed consistent determinations for the same components, indicating similar detection capabilities. The discrepancies in total lactone content primarily stemmed from differences in the number and types of detected compounds. Moreover, the acceptance criteria exhibited a stringency in the order CP > HK > EP > USP. In conclusion, this comparison analysis of content determination in CP, USP, HK, EP, TP and IP provided a scientific foundation for the international standardization and trade regulations of A. paniculata. It also served as a valuable reference for the development of international quality standards for other medicinal herbs, facilitating the harmonization of global pharmaceutical standards.

Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.