The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Enhancement of hyaline cartilage and subchondral bone regeneration in a rat osteochondral defect model through focused extracorporeal shockwave therapy.

Aims: To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-ß, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods: The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results: In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-ß, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion: ESWT promoted the effect of TGF-ß/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model.

The Feasibility and Efficacy of Remote App-Guided Home Exercises for Frozen Shoulder: A Pilot Study.

Home exercise programs are beneficial in managing frozen shoulder (FS), yet adherence remains challenging. This pilot study introduces the remote app, Defrozen, designed for home exercises and assesses its feasibility and clinical outcomes in FS patients undergoing intra-articular and sub-acromial corticosteroid treatment. Over a four-week period, patients used the Defrozen-app, engaging in guided exercises. The feasibility of the intervention was assessed through several measurement scales, including adherence, the Technology Acceptance Model 2 (TAM2), the System Usability Scale (SUS), and User Satisfaction and Engagement (USE). Clinical outcomes included pain scale, Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) Score, and passive range of motion. The TAM2 results indicated high perceived usefulness (4.5/5), ease of use (4.8/5), and intention to use (4.4/5); the SUS score was high at 81.7/100, complemented by USE scores reflecting ease of learning (4.9/5) and satisfaction (4.3/5). Clinical outcomes showed significant pain reduction, improved shoulder function, reduced shoulder-related disability, and increased shoulder range of motion. These findings suggest the Defrozen-app as a promising solution for FS, significantly improving adherence and showing potential to enhance clinical outcomes. However, these clinical outcome results are preliminary and necessitate further validation through a large-scale randomized controlled trial to definitively confirm efficacy and assess long-term benefits.

Impact of CD44 genetic variants on clinicopathological characteristics of uterine cervical cancer patients.

CD44 genetic variants have been found to be related to various cancers. However, to date, no study has demonstrated the involvement of CD44 polymorphisms in uterine cervical cancer in Taiwanese women. Therefore, we conducted a retrospective study, consecutively recruiting 113 patients with invasive cancer, 92 patients with high-grade cervical intraepithelial neoplasias, and 302 control women to assess the relationships among CD44 polymorphisms, cervical carcinogenesis, and patient survival. Real-time polymerase chain reaction was used to determine the genotypic distributions of six polymorphisms: rs1425802, rs187115, rs713330, rs11821102, rs10836347, and rs13347. The results revealed that women with the mutant homozygous genotype CC exhibited a higher risk of invasive cancer compared to those with the wild homozygous genotype TT [p=0.035; hazard ratio (HR)=10.29, 95% confidence interval (95% CI)=1.18-89.40] and TT/TC [p=0.032; HR=10.66, 95% CI=1.23-92.11] in the CD44 polymorphism rs713330. No significant association was found between CD44 genetic variants and clinicopathological parameters. Among the clinicopathological parameters, only positive pelvic lymph node metastasis (p=0.002; HR=8.57, 95% CI=2.14-34.38) and the AG/GG genotype compared to AA (p=0.014; HR=3.30, 95% CI=1.28-8.49) in CD44 polymorphism rs187115 predicted a higher risk of poor five-year survival, according to multivariate analysis. In conclusion, an important and novel finding revealed that Taiwanese women with the AG/GG genotype in CD44 polymorphism rs187115 exhibited a higher risk of poor five-year survival.

Exploration and Optimization of the Polymer-Modified NiOx Hole Transport Layer for Fabricating Inverted Perovskite Solar Cells.

The recombination of charge carriers at the interface between carrier transport layers such as nickel oxide (NiOx) and the perovskite absorber has long been a challenge in perovskite solar cells (PSCs). To address this issue, we introduced a polymer additive poly(vinyl butyral) into NiOx and subjected it to high-temperature annealing to form a void-containing structure. The formation of voids is confirmed to increase light transmittance and surface area of NiOx, which is beneficial for light absorption and carrier separation within PSCs. Experimental results demonstrate that the incorporation of the polymer additive helped to enhance the hole conductivity and carrier extraction of NiOx with a higher Ni3+/Ni2+ ratio. This also optimized the energy levels of NiOx to match with the perovskite to raise the open-circuit voltage to 1.01 V. By incorporating an additional NiOx layer beneath the polymer-modified NiOx, the device efficiency was further increased as verified from the dark current measurement of devices.

Prognostic factors of extracorporeal shockwave therapy in the treatment of nonunion in long bones: a retrospective study.

BACKGROUND: Nonunion of long bone fractures is a significant complication following surgical fixation, with an incidence ranging from 5% to 10%. Surgical intervention is the standard treatment for nonunions, but it may come with potential complications. Nonoperative approaches, such as Extracorporeal Shockwave Therapy (ESWT), have been advocated as alternatives. METHODS: The retrospective study, conducted between January 2004 and January 2018, 91 patients who underwent ESWT for tibia or femur nonunions were included. Nonunion was defined based on radiographic criteria and clinical symptoms. The nonunion morphology was categorized as hypertrophic, oligotrophic, or atrophic. ESWT was administered using the OssaTron device in a single treatment session. Bony union was defined as the presence of bridging callus over fracture site with more than three-fourths of the circumference in both planes within the 12-month postoperative period. RESULTS: The study included 91 patients, with an overall union rate of 62.6%. Higher healing rate was observed in trophic nonunion(69.9%) than atrophic nonunion(33.3%). Multivariate analysis identified the number of surgeries, maximum fracture gap, and atrophic nonunion as independent factors influencing the risk of fracture nonunion after ESWT. ROC curves were generated for these factors, providing more than one surgical interventions, and fracture gap greater than 3.94 mm as negative predictors of ESWT for long bone nonunions. CONCLUSION: The study's primary findings suggest that ESWT is effective in achieving bony union for nonunions in long bones(62.6%). Despite the overall positive results, the study highlights that atrophic nonunions, larger fracture gaps more than 3.94 mm, and multiple surgeries are associated with poorer outcomes.

Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.

Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.

Post-irradiation dysbiosis in patients with nasopharyngeal carcinoma having received radiotherapy - A pilot study.

OBJECTIVE: To compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. STUDY DESIGN: Prospective cohort study. SETTING: Unicenter, Tertiary referral hospital. METHODS: Included patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) RESULTS: Total of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). CONCLUSIONS: This is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

Glaucoma Detection through a Novel Hyperspectral Imaging Band Selection and Vision Transformer Integration.

Conventional diagnostic methods for glaucoma primarily rely on non-dynamic fundus images and often analyze features such as the optic cup-to-disc ratio and abnormalities in specific retinal locations like the macula and fovea. However, hyperspectral imaging techniques focus on detecting alterations in oxygen saturation within retinal vessels, offering a potentially more comprehensive approach to diagnosis. This study explores the diagnostic potential of hyperspectral imaging for glaucoma by introducing a novel hyperspectral imaging conversion technique. Digital fundus images are transformed into hyperspectral representations, allowing for a detailed analysis of spectral variations. Spectral regions exhibiting differences are identified through spectral analysis, and images are reconstructed from these specific regions. The Vision Transformer (ViT) algorithm is then employed for classification and comparison across selected spectral bands. Fundus images are used to identify differences in lesions, utilizing a dataset of 1291 images. This study evaluates the classification performance of models using various spectral bands, revealing that the 610-780 nm band outperforms others with an accuracy, precision, recall, F1-score, and AUC-ROC all approximately at 0.9007, indicating its superior effectiveness for the task. The RGB model also shows strong performance, while other bands exhibit lower recall and overall metrics. This research highlights the disparities between machine learning algorithms and traditional clinical approaches in fundus image analysis. The findings suggest that hyperspectral imaging, coupled with advanced computational techniques such as the ViT algorithm, could significantly enhance glaucoma diagnosis. This understanding offers insights into the potential transformation of glaucoma diagnostics through the integration of hyperspectral imaging and innovative computational methodologies.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

The applications of high-flow nasal cannulas in pediatric intensive care units in Taiwan.

BACKGROUND: /purpose: The use of high-flow nasal cannulas (HFNC) in patients admitted to the pediatric intensive care unit (PICU) has gradually increased worldwide; however, details on clinical efficacy remain limited in Taiwan. Therefore, we explored the clinical characteristics and outcomes of pediatric patients using HFNC in the PICU. METHODS: Medical records were retrospectively collected from pediatric patients (aged <18 years) who received HFNC support from December 2021 to January 2023 in the PICU of a medical center. Outcome parameters included treatment failure (defined as increased respiratory support to advanced non-invasive ventilators or intubations), duration of support from HFNC, and changes in clinical parameters after initiating HFNC. RESULTS: A total of 261 episodes of HFNC use were included, with a failure rate of 24.5% and a median support length of 4 days. Multivariable analysis showed that infant age (adjusted odds ratio [aOR]: 2.1, p = 0.02) and accompanying complex chronic disease (aOR: 4.4, p = 0.014) were risk factors for treatment failure and a diagnosis of asthma or bronchiolitis had a lower hazard of treatment failure (aOR: 0.29, p = 0.025) than other diagnoses did. Improvements in clinical parameters, including pulse rate, respiratory rate, SpO2, and CO2 levels, were observed 24 h after the initiation of HFNC. CONCLUSION: The application of HFNC in the PICU in Taiwan is effective but should be performed with care in infants with accompanying complex chronic diseases. In addition to low treatment failure, HFNC utilizations stabilized the clinical parameters of children with asthma/bronchiolitis within one day.

Evaluating the performance of an AI-powered VBAC prediction system within a decision-aid birth choice platform for shared decision-making.

Background: Vaginal birth after cesarean (VBAC) is generally regarded as a safe and viable birthing option for most women with prior cesarean delivery. Nonetheless, concerns about heightened risks of adverse maternal and perinatal outcomes have often dissuaded women from considering VBAC. This study aimed to assess the performance of an artificial intelligence (AI)-powered VBAC prediction system integrated into a decision-aid birth choice platform for shared decision-making (SDM). Materials and Methods: Employing a retrospective design, we collected medical records from a regional hospital in northern Taiwan from January 2019 to May 2023. To explore a suitable model for tabular data, we compared two prevailing modeling approaches: tree-based models and logistic regression models. We subjected the tree-based algorithm, CatBoost, to binary classification. Results: Forty pregnant women with 347 records were included. The CatBoost model demonstrated a robust performance, boasting an accuracy rate of 0.91 (95% confidence interval (CI): 0.86-0.94) and an area under the curve of 0.89 (95% CI: 0.86-0.93), surpassing both regression models and other boosting techniques. CatBoost captured the data characteristics on the significant impact of gravidity and the positive influence of previous vaginal birth, reinforcing established clinical guidelines, as substantiated by the SHapley Additive exPlanations analysis. Conclusion: Using AI techniques offers a more accurate assessment of VBAC risks, boosting women's confidence in selecting VBAC as a viable birthing option. The seamless integration of AI prediction systems with SDM platforms holds a promising potential for enhancing the effectiveness of clinical applications in the domain of women's healthcare.

Generalized Linear Models with Covariate Measurement Error and Zero-Inflated Surrogates.

Epidemiological studies often encounter a challenge due to exposure measurement error when estimating an exposure-disease association. A surrogate variable may be available for the true unobserved exposure variable. However, zero-inflated data are encountered frequently in the surrogate variables. For example, many nutrient or physical activity measures may have a zero value (or a low detectable value) among a group of individuals. In this paper, we investigate regression analysis when the observed surrogates may have zero values among some individuals of the whole study cohort. A naive regression calibration without taking into account a probability mass of the surrogate variable at 0 (or a low detectable value) will be biased. We developed a regression calibration estimator which typically can have smaller biases than the naive regression calibration estimator. We propose an expected estimating equation estimator which is consistent under the zero-inflated surrogate regression model. Extensive simulations show that the proposed estimator performs well in terms of bias correction. These methods are applied to a physical activity intervention study.

Optical, Electrical, Structural, and Thermo-Mechanical Properties of Undoped and Tungsten-Doped Vanadium Dioxide Thin Films.

The undoped and tungsten (W)-doped vanadium dioxide (VO2) thin films were prepared by electron beam evaporation associated with ion-beam-assisted deposition (IAD). The influence of different W-doped contents (3-5%) on the electrical, optical, structural, and thermo-mechanical properties of VO2 thin films was investigated experimentally. Spectral transmittance results showed that with the increase in W-doped contents, the transmittance in the visible light range (400-750 nm) decreases from 60.2% to 53.9%, and the transmittance in the infrared wavelength range (2.5 µm to 5.5 µm) drops from 55.8% to 15.4%. As the W-doped content increases, the residual stress in the VO2 thin film decreases from -0.276 GPa to -0.238 GPa, but the surface roughness increases. For temperature-dependent spectroscopic measurements, heating the VO2 thin films from 30 °C to 100 °C showed the most significant change in transmittance for the 5% W-doped VO2 thin film. When the heating temperature exceeds 55 °C, the optical transmittance drops significantly, and the visible light transmittance drops by about 11%. Finally, X-ray diffraction (XRD) and scanning electron microscope (SEM) were used to evaluate the microstructure characteristics of VO2 thin films.

New Onset and Exacerbation of Autoimmune Bullous Dermatosis Following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. OBJECTIVE: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. METHODS: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. RESULTS: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. CONCLUSIONS: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

Deep learning to assess microsatellite instability directly from histopathological whole slide images in endometrial cancer.

Molecular classification, particularly microsatellite instability-high (MSI-H), has gained attention for immunotherapy in endometrial cancer (EC). MSI-H is associated with DNA mismatch repair defects and is a crucial treatment predictor. The NCCN guidelines recommend pembrolizumab and nivolumab for advanced or recurrent MSI-H/mismatch repair deficient (dMMR) EC. However, evaluating MSI in all cases is impractical due to time and cost constraints. To overcome this challenge, we present an effective and efficient deep learning-based model designed to accurately and rapidly assess MSI status of EC using H&E-stained whole slide images. Our framework was evaluated on a comprehensive dataset of gigapixel histopathology images of 529 patients from the Cancer Genome Atlas (TCGA). The experimental results have shown that the proposed method achieved excellent performances in assessing MSI status, obtaining remarkably high results with 96%, 94%, 93% and 100% for endometrioid carcinoma G1G2, respectively, and 87%, 84%, 81% and 94% for endometrioid carcinoma G3, in terms of F-measure, accuracy, precision and sensitivity, respectively. Furthermore, the proposed deep learning framework outperforms four state-of-the-art benchmarked methods by a significant margin (p < 0.001) in terms of accuracy, precision, sensitivity and F-measure, respectively. Additionally, a run time analysis demonstrates that the proposed method achieves excellent quantitative results with high efficiency in AI inference time (1.03 seconds per slide), making the proposed framework viable for practical clinical usage. These results highlight the efficacy and efficiency of the proposed model to assess MSI status of EC directly from histopathological slides.

No Effect of High Eating Frequency Compared with Low Eating Frequency on Appetite and Inflammation Biomarkers: Results from a Randomized Crossover Clinical Trial.

BACKGROUND: Eating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health. OBJECTIVES: We sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults. METHODS: Data are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined. RESULTS: Among the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m2, and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: -0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers. CONCLUSIONS: No differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health. This trial was registered at clinicaltrials.gov as NCT02392897.

Real-world patient characteristics, treatment patterns, and treatment outcomes of patients with diffuse large B-cell lymphoma by line of therapy.

BACKGROUND: Although initial treatment of diffuse large B-cell lymphoma (DLBCL) with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be effective, up to 50% of patients will develop refractory or relapsed (R/R) disease. This study aimed to provide contemporary data on characteristics, treatment patterns, and outcomes for R/R-DLBCL. METHODS: Patients with incident (January 2016 to March 2021) DLBCL age ≥18 years who initiated first-line (1L) therapy were identified from the COTA real-world database. Baseline characteristics, treatment patterns, and real-world outcomes, including time to next treatment (rwTTNT) and overall survival (rwOS), were assessed for the study population and by line of therapy (LOT). RESULTS: A total of 1347 eligible DLBCL patients were identified. Of these, 340 (25.2%) proceeded to receive 2L, of whom 141 (41.5%) proceeded to receive 3L, of whom 51 (36.2%) proceeded to receive 4L+. Most common treatments were R-CHOP in 1L (63.6%), stem cell transplant (SCT) in 2L (17.9%), polatuzumab vedotin, bendamustine, and rituximab (Pola-BR) in 3L (9.9%), and chimeric antigen receptor T-cell therapy (CAR-T) in 4L (11.8%). Treatment patterns were more variable in later LOTs. One- and 3-year rwOS from 1L initiation were 88.5% and 78.4%, respectively. Patients who received later LOTs experienced numerically lower 1- and 3-year rwOS (from 2L initiation: 62.4% and 46.4%, respectively). CONCLUSIONS: In this real-world analysis, 25.2% of patients experienced R/R-DLBCL after 1L with poor outcomes. Given the findings of this study, there is a high unmet need for novel, safe, and effective treatment options for patients with R/R DLBCL.

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.