Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice.

Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog-/-) mice. Our findings revealed that Endog-/- mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog-/- and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog-/- and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.

Baicalein Targets MAPK9 to Induce Apoptosis of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is a significant global health concern. However, there are limited effective treatments available for it. The use of natural products in the management and treatment of HCC is gaining more attention. Baicalein is a flavonoid compound that has been reported to have antitumor activities in HCC. However, the direct binding targets of baicalein are still unknown. Therefore, we used the DNA-programmed affinity labeling method to identify the target of baicalein and validated its function in HCC cells. We set blank and competitive DNA probes as negative controls. The results showed that baicalein had 136 binding targets, of which 13 targets were differently expressed in HCC tissues. The enriched cellular process of these targets was apoptosis, which involved MAPK9. We tested the binding affinity of baicalein with MAPK9 as 89.7 nM (Kd) by surface plasmon resonance and analyzed the binding sites by virtual docking. Notably, the binding of baicalein with MAPK9 increased the protein levels of MAPK9 itself and the related downstream apoptosis signaling, triggering the apoptosis of HCC cells. However, the inhibitor of MAPK9, SP600125, blocked the baicalein-induced apoptosis, and the amounts of MAPK9 and downstream molecules were also decreased, indicating that baicalein acted through MAPK9 to induce apoptosis of HCC cells. In conclusion, we used the DNA-programmed affinity labeling method to identify the direct-binding target MAPK9 of baicalein and validated its function in baicalein-induced apoptosis of HCC cells, which would be helpful to understand and use baicalein in HCC therapy.

Artificial Intelligence Algorithm Can Predict Lymph Node Malignancy from EBUS-TBNA Images for NSCLC.

INTRODUCTION: EBUS-TBNA for lung cancer staging is operator-dependent, resulting in high rates of non-diagnostic lymph node (LN) samples. We hypothesized that an artificial intelligence (AI) algorithm can consistently and reliably predict nodal metastases from the ultrasound images of LNs, when compared to pathology. METHODS: In this analysis of prospectively-recorded B-mode images of mediastinal LNs during EBUS-TBNA, we used transfer learning to build an end-to-end ensemble of three deep neural networks (ResNet152V2, InceptionV3, and DenseNet201). Model hyperparameters were tuned, and the optimal version(s) of each model trained using 80% of the images. A learned ensemble (multi-layer perceptron) of the optimal versions were applied to the remaining 20% of the images (Test Set). All predictions were compared to final pathology from nodal biopsies and/or surgical specimen. RESULTS: A total of 2,569 LN images from 773 patients were used. The Training Set included 2,048 LNs, of which 70.02% were benign and 29.98% were malignant on pathology. The Testing Set included 521 LNs, of which 70.06% were benign and 29.94% were malignant on pathology. The final ensemble model had an overall accuracy of 80.63% [95%Confidence Interval (CI):76.93%-83.97%], 43.23% sensitivity (95%CI:35.30%-51.41%), 96.91% specificity (95%CI:94.54%-98.45%), 85.90% positive predictive value (95%CI:76.81%-91.80%), 79.68% negative predictive value (95%CI:77.34%-81.83%), and AUC of 0.701 (95%CI:0.646-0.755) for malignancy. CONCLUSION: There now exists an AI algorithm which can identify nodal metastases based only on ultrasound images with good overall accuracy, specificity, and positive predictive value. Further optimization with larger sample sizes would be beneficial prior to clinical application.

Values and preferences towards the use of prophylactic low-molecular-weight heparin during pregnancy: a convergent mixed-methods secondary analysis of data from the decision analysis in shared decision making for thromboprophylaxis during pregnancy (DASH-TOP) study.

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and mortality, and the use of preventive low-molecular-weight heparin (LMWH) can be challenging. Clinical guidelines recommend eliciting pregnant individuals' preferences towards the use of daily injections of LMWH and discussing the best option through a shared decision-making (SDM) approach. Our aim was to identify individuals' preferences concerning each of the main clinical outcomes, and categorize attributes influencing the use of LMWH during pregnancy. METHODS: Design: Convergent mixed-methods. PARTICIPANTS: Pregnant women or those planning a pregnancy with VTE recurrence risk. INTERVENTION: A SDM intervention about thromboprophylaxis with LMWH in pregnancy. ANALYSIS: Quantitatively, we report preference scores assigned to each of the health states. Qualitatively, we categorized preference attributes using Burke's pentad of motives framework: act (what needs to be done), scene (patient's context), agent (perspectives and influence of people involved in the decision), agency (aspects of the medication), and purpose (patient's goals). We use mixed-method convergent analysis to report findings using side-by-side comparison of concordance/discordance. RESULTS: We comprehensively determined preferences for using LMWH by pregnant individuals at risk of VTE: through value elicitation exercises we found that the least valued health state was to experience a pulmonary embolism (PE), followed by major obstetrical bleeding (MOB), deep vein thrombosis (DVT), and using daily injections of LMWH (valued as closest to a 'healthy pregnancy'); through interviews we found that: previous experiences, access to care (scene) and shared decision-making (agent) affected preferences. LMWH's benefits were noted, but substantial drawbacks were described (agency). For participants, the main goal of using LMWH was avoiding any risks in pregnancy (purpose). Side-by-side comparisons revealed concordance and discordance between health states and motives. CONCLUSIONS: Mixed-methods provide a nuanced understanding of LMWH preferences, by quantifying health states preferences and exploring attributes qualitatively. Incorporating both methods may improve patient-centered care around preference-sensitive decisions in thromboprophylaxis during pregnancy.

Efficient and Stable Red Perovskite Light-Emitting Diodes via Thermodynamic Crystallization Control.

Efficient and stable red perovskite light-emitting diodes (PeLEDs) demonstrate promising potential in high-definition displays and biomedical applications. Although significant progress has been made in device performance, meeting commercial demands remains a challenge in the aspects of long-term stability and high external quantum efficiency (EQE). Here, an in situ crystallization regulation strategy is developed for optimizing red perovskite films through ingenious vapor design. Mixed vapor containing dimethyl sulfoxide and carbon disulfide (CS2) is incorporated to conventional annealing, which contributes to thermodynamics dominated perovskite crystallization for well-aligned cascade phase arrangement. Additionally, the perovskite surface defect density is minimized by the CS2 molecule adsorption. Consequently, the target perovskite films exhibit smooth exciton energy transfer, reduced defect density, and blocked ion migration pathways. Leveraging these advantages, spectrally stable red PeLEDs are obtained featuring emission at 668, 656, and 648 nm, which yield record peak EQEs of 30.08%, 32.14%, and 29.04%, along with prolonged half-lifetimes of 47.7, 60.0, and 43.7 h at the initial luminances of 140, 250, and 270 cd m-2, respectively. This work provides a universal strategy for optimizing perovskite crystallization and represents a significant stride toward the commercialization of red PeLEDs.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study.

Objective: The objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. Methods: We conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. Results: After treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). Conclusion: We found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

A new toad of Oreolalax Myers & Leviton, 1962 (Anura, Megophryidae) from Sichuan Province, southwest China.

A new species of the genus Oreolalax Myers & Leviton, 1962 is described from Sichuan Province, southwest China. Molecular phylogenetic analyses based on mitochondrial gene sequences clustered the new species as an independent clade nested with O.rugosus, O.liangbeiensis, and O.major. The new species could be distinguished from its congeners by a combination of the following characters: body size moderate (39.8-52.8 mm in male); head broad; tympanum absent; interorbital region with dark triangular pattern; 1/3 toes webbed, with broad lateral fringes, belly smooth, brown yellow or medium yellow scattered variable brown spots; skin on dorsum relatively rough with fine tiny and large warts granules; middle pectoral glands are evident in males; flanks with dark-brown warts granules; upper surface of limbs with dark bars; and iris orange above and creamy-white below. The new species inhabits subtropical alpine scrub and swamp.

Validation of the Generic Version of China Health Related Outcomes Measures (CHROME-G) among individuals with type 2 diabetes in China.

OBJECTIVE: The Generic Version of China Health Related Outcomes Measures (CHROME-G) was a new preference-based health-related quality of life (HRQoL) instrument designed specifically for the Chinese population. This study aimed to validate and compare measurement properties of CHROME-G with EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), Short Form-6 Dimensions version 2 (SF-6Dv2), and Diabetes-Specific Quality of Life (DSQL) scales among the elderly Chinese population with type 2 diabetes. METHODS: A representative sample population was recruited across the country. Internal consistency was assessed using Cronbach's alpha. Hypotheses testing including convergent validity and known-groups validity were evaluated using Spearman's rank correlation and effect sizes, respectively. Sensitivity was examined using relative efficiency and receiver operating characteristic curve. RESULTS: A total of 131 individuals with type 2 diabetes (54.20% male; mean age 69.03 years) were enrolled. Cronbach's alpha was 0.94 for DSQL, 0.93 for CHROME-G, 0.87 for EQ-5D-5L, and 0.88 for SF-6Dv2. For the convergent validity of CHROME-G, 24/29 (82.76%) correlations met the predefined hypotheses, with Spearman's rank correlation coefficients ranging from 0.51 to 0.96. Among the different health subgroups, the effect sizes for CHROME-G, DSQL, EQ-5D-5L, and SF-6Dv2 were 0.19-1.26, 0.36-1.62, 0.22-1.06, and 0.49-0.87, respectively. CHROME-G, DSQL, and SF-6Dv2 had higher efficiency compared with EQ-5D-5L in detecting differences in self-reported health status, with relative efficiency of 3.18 and 1.76, 4.38 and 6.52, and 1.56 and 2.09, respectively. CONCLUSIONS: CHROME-G demonstrates relatively good measurement properties compared with EQ-5D-5L and SF-6Dv2 for measuring the HRQoL among the elderly Chinese population with type 2 diabetes. The sensitivity of DSQL appears to be better than that of the three generic instruments.

Few-Shot Learning in Wi-Fi-Based Indoor Positioning.

This paper explores the use of few-shot learning in Wi-Fi-based indoor positioning, utilizing convolutional neural networks (CNNs) combined with meta-learning techniques to enhance the accuracy and efficiency of positioning systems. The focus is on addressing the challenge of limited labeled data, a prevalent issue in extensive indoor environments. The study explores various scenarios, comparing the performance of the base CNN and meta-learning models. The meta-learning approach involves few-shot learning tasks, such as three-way N-shot, five-way N-shot, etc., to enhance the model's ability to generalize from limited data. The experiments were conducted across various scenarios, evaluating the performance of the models with different numbers of samples per class (K) after filtering by cosine similarity (FCS) during both the stages of data preprocessing and meta-learning. The scenarios included both base classes and novel classes, with and without meta-learning. The results indicated that the base CNN model achieved varying accuracy levels depending on the scenario and the number of samples per class retained after FCS. Meta-learning performed acceptably in scenarios with fewer samples, which are the distinct datasets pertaining to novel classes. With 20 samples per class, the base CNN achieved an accuracy of 0.80 during the pre-training stage, while meta-learning (three-way one-shot) achieved an accuracy of 0.78 on a new small dataset with novel classes.

Economic burden of patients with leading cancers in China: a cost-of-illness study.

BACKGROUND: China accounts for 24% of newly diagnosed cancer cases and 30% of cancer-related deaths worldwide. Comprehensive analyses of the economic burden on patients across different cancer treatment phases, based on empirical data, are lacking. This study aims to estimate the financial burden borne by patients and analyze the cost compositions of the leading cancers with the highest number of new cases in China. METHODS: This cross-sectional cost-of-illness study analyzed patients diagnosed with lung, breast, colorectal, esophageal, liver, or gastric cancer, identified through electronic health records (EHRs) from 84 hospitals across 17 provinces in China. Patients completed any one of the initial treatment phase, follow-up phase, and relapse/metastasis phase were recruited by trained attending physicians through a stratified sampling procedure to ensure enough cases for each cancer progression stage and cancer treatment phase. Direct and indirect costs by treatment phase were collected from the EHRs and self-reported surveys. We estimated per case cost for each type of cancer, and employed subgroup analyses and multiple linear regression models to explore cost drivers. RESULTS: We recruited a total of 13,745 cancer patients across three treatment phases. The relapse/metastasis phase incurred the highest per case costs, varying from $8,890 to $14,572, while the follow-up phase was the least costly, ranging from $1,840 to $4,431. Being in the relapse/metastasis phase and having an advanced clinical stage of cancer at diagnosis were associated with significantly higher cost, while patients with low socioeconomic status borne lower costs. CONCLUSIONS: There were substantial financial burden on patients with six leading cancers in China. Health policymakers should emphasize comprehensive healthcare coverage for marginalized populations such as the uninsured, less educated, and those living in underdeveloped regions.

Hypoallergenic Knee Implant Usage and Clinical Outcomes: Are They Safe and Effective?

Background: One of the most debated topics in modern total knee arthroplasty (TKA) is the impact of metal hypersensitivity (MH) as a potential cause of prosthesis failure. Implanting hypoallergenic prostheses to avoid potential problems in suspected cases of MH is one treatment option that can be used in such cases. However, their long-term clinical safety and efficacy are not well proven. Methods: All literature relevant to modern hypoallergenic implants were reviewed and summarized to provide a comprehensive synopsis. In addition, a detailed literature search was performed on PUBMED, MEDLINE, and Google Scholar to identify all the clinical studies reporting outcomes for hypoallergenic knee implants. Our search was confined to those studies published as full manuscripts in the English language from July 2018 to July 2023. Results: To minimize the risk of MH, new implant variants have been developed which are either under clinical evaluation or in routine clinical use. These include conventional metal implants with protective coatings (mono- or multilayer) and metal-free implants. However, there is insufficient clinical data to confirm the rationale and effectiveness of using these "hypoallergenic" TKA implants. Conclusions: Published studies and arthroplasty registry data analyses indicate no significant differences between hypoallergenic and standard TKAs with overall good survival rates. In the future, further high-quality studies are needed to better understand the complexity of this subject.

The profile of oral microbiome in Chinese elderly population associated with aging and systemic health status.

OBJECTIVE: The health of oral cavity is considered as an important indicator of aging. Oral microbiota is highly associated with the oral health, while the variation of oral microbiome in elderly population and characteristic microbes associated with aging remain unclear. SUBJECTS AND METHODS: In this study, 130 elderly subjects were recruited and divided into 3 groups according to their age: Stage I group (65 ≤ years < 70), Stage II group (70 ≤ years < 75), and Stage III group (75 ≤ years < 80). Their physiological indices were analyzed with using Illumina MiSeq platform and the oral microbiome was determined by high-throughput sequencing. RESULTS: Along with aging, the level of fasting blood glucose, systolic pressure and monocytes are significantly increased. No significant difference was detected on the whole structure of the oral microbiome among groups. While using Metastats and Spearman's correlation analysis, specific bacteria were identified as potential age- or health index-related bacterial genera including Fusobacterium, Parvimonas, Porphyromonas, Aminobacter, Collinsella, Clostridium and Acinetobacter. CONCLUSION: Our study revealed that the composition structure of salivary microbiota in elderly population was relatively stable while specific bacteria were correlated with age and health status, which is promising to be served as health indicators of the elderly after further exploration.

Active Heme Metabolism Suppresses Macrophage Phagocytosis via the TLR4/Type I IFN Signaling/CD36 in Uterine Endometrial Cancer.

BACKGROUND: Uterine endometrial cancer (UEC) is a common gynecological estrogen-dependent carcinoma, usually accompanied by intermenstrual bleeding. Active heme metabolism frequently plays an increasingly important role in many diseases, especially in cancers. Tumor-associated macrophages (TAMs) are the major population in the immune microenvironment of UEC. However, the roles of heme metabolisms in the crosstalk between UEC cells (UECCs) and macrophages are unclear. MATERIALS AND METHODS: In our study, by using TCGA database analysis, integration analysis of the protein-protein interaction (PPI) network and sample RNA transcriptome sequencing were done. The expression level of both heme-associated molecules and iron metabolism-related molecules were measured by quantitative real-time polymerase chain reaction. Heme level detection was done through dehydrohorseradish peroxidase assay. In addition to immunohistochemistry, phagocytosis assay of macrophages, immunofluorescence staining, intracellular ferrous iron staining, as well as enzyme-linked immune sorbent assay were performed. RESULTS: In the study, we verified that heme accumulation in UECCs is apparently higher than in endometrial epithelium cells. Low expression of succinate dehydrogenase B under the regulation of estrogen contributes to over-production of succinate and heme accumulation in UECC. More importantly, excessive heme in UECCs impaired macrophage phagocytosis by regulation of CD36. Mechanistically, this process is dependent on toll-like receptor (TLR4)/type I interferons alpha (IFN Iα) regulatory axis in macrophage. CONCLUSION: Collectively, these findings elucidate that active heme metabolism of UECCs directly decreases phagocytosis by controlling the secretion of TLR4-mediated IFN Iα and the expression of CD36, and further contributing to the immune escape of UEC.

Ultrasound enhancing agents in cardiovascular imaging: expanding horizons beyond coronary arteries.

From its inception as a two-dimensional snapshot of the beating heart, echocardiography has become an indelible part of cardiovascular diagnostics. The integration of ultrasound enhancing agents (UEAs) marks a pivotal transition, enhancing its diagnostic acumen beyond myocardial perfusion. These agents have refined echocardiography's capacity to visualize complex cardiac anatomy and pathology with unprecedented clarity, especially in non-coronary artery disease contexts. UEAs aid in detailed assessments of myocardial viability, endocardial border delineation in left ventricular opacification, and identification of intracardiac masses. Recent innovations in UEAs, accompanied by advancements in echocardiographic technology, offer clinicians a more nuanced view of cardiac function and blood flow dynamics. This review explores recent developments in these applications and future contemplated studies.

Interpreting the additive components of multi-species distributional aggregation.

Normalized Moran's I index is an indispensable component in maintaining multi-species distributional aggregation at local scales.

Serum Metabolomics and NF-κB Pathway Analysis Revealed the Antipyretic Mechanism of Ellagic Acid on LPS-Induced Fever in Rabbits.

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1ß, prostaglandin E2(PGE2), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase (p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels (p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1ß, IL-6, and TNF-α levels (p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE2 levels (p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels (p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE2, and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1ß, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1ß, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1ß, PGE2, and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism.

A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

WHAT IS THIS SUMMARY ABOUT?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2 weeks. WHAT ARE THE KEY TAKEAWAYS?: In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13 months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). WHAT ARE THE CONCLUSIONS REPORTED BY THE RESEARCHERS?: The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).

The HERIZON-BTC-01 study revealed zanidatamab as a potentially effective treatment for HER2-positive biliary tract cancer after standard chemotherapy fails. Read more in the lay summary by @hardingjjmd, @DrShubhamPant, and coauthors. #BiliaryTractCancer #HER2 #zanidatamab.

Mechanism and kinetics of ultrasound-enhanced CaCO3 precipitation for indium enrichment in zinc oxide dust leaching solution.

In this study, ultrasound-enhanced calcium carbonate precipitation was used to enrich indium in zinc oxide dust leachate, and the effects of precipitation endpoint pH and ultrasound power on the indium precipitation behaviour were investigated, and the optimal conditions of ultrasound-enhanced precipitation were obtained to be the precipitation endpoint pH of 4.0 and the ultrasound power of 200 W. The precipitation rate of indium under these conditions was 99.79 %. At the same time, the effects of ultrasonication and conventional stirring on the indium precipitation kinetics were compared, which proved that ultrasound can shorten the time for precipitation to reach equilibrium and reduce the amount of calcium carbonate used, and the theory of ultrasonication activation energy was put forward. The activation energy of ultrasonication was Eu-a = 2.63 KJ/mol, and that of conventional precipitation was 9.78KJ/mol, which proved that ultrasonication could reduce the activation energy of the precipitation reaction, and promote the rapid precipitation reaction. The kinetic model of ultrasound-enhanced indium precipitation is lnC0-lnCt = exp(0.11339-318.54/W).t + A. In addition, the mechanism of ultrasound-enhanced calcium carbonate precipitation of indium was revealed by XRD, SEM-EDS, XPS and TEM analyses of the precipitated residue, it was demonstrated that ultrasound can inhibit the precipitation of zinc, and the ZnCO3 phase was found in the ultrasonically precipitated residue. This study provides a new idea for indium enrichment, and the future focus will be on the scale-up of the ultrasound-enhanced precipitation device.

Metal-on-metal hip resurfacing arthroplasty: is it safe and reliable? A synopsis of the past, the present, and the future of HRA.

This paper discusses the existing literature in the field of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), the background (why was it developed), the past (what was the evidence leading to its rise and fall in clinical use), the present situation (why a potential resurgence), and the future directions for potential improvements. All literature relevant to MoM HRA was reviewed and summarized to provide a comprehensive summary. Furthermore, a detailed literature search was performed on PubMeD, MEDLINE, and Google Scholar to identify all clinical studies reporting a minimum 10 years of outcomes for modern MoM HRA devices from February 2018 to February 2023. In addition, joint registry data over the same time period, available in the public domain, was examined to extract related information on MoM HRA. Metal ions are present in almost all types of hip replacement; on the whole, however, the risk of revision for resurfacing due to metal-related pathologies is very low, but higher than in other types of bearings. There are studies that show that some brands of MoM resurfacing prostheses have achieved excellent clinical outcomes in long-term follow-up studies and are still in use although less commonly than in early 2000s. Use of alternative bearing surfaces has demonstrated excellent results in the short-term and a very critical long-term follow-up of these cases still will help establish their place in the hip arthroplasty world. HRA deserves a permanent place in the armamentarium of orthopedic surgeons and in the hand of experienced surgeons.

Single-cell peripheral immunoprofiling of lewy body and Parkinson's disease in a multi-site cohort.

BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.