High-dose opioids in advanced cancer: use factors-retrospective study.

OBJECTIVES: To evaluate factors associated with high-dose opioid use in patients with advanced cancer and examine the effect of high-dose opioid use on patients' survival. METHODS: This study retrospectively searched the medical records of 416 patients with advanced cancer in a home-based hospice in central China. Age, sex, type of cancer, type of pain, the maximum oral morphine equivalent daily dose, type of opioid, preadmission oral morphine equivalent daily dose, lung cancer or not, bone metastases, opioid switch and survival time were assessed. RESULTS: There were 416 subjects included from the 455 eligible participants (91.4%). 80 patients (19.2%) received high-dose opioids at home. Male (OR 2.471; 95% CI 1.054 to 5.792; p=0.037), preadmission morphine equivalent daily dose (OR 1.022; 95% CI 1.016 to 1.028; p=0.000) and the use of morphine at maximum morphine equivalent daily dose (OR 5.123; 95% CI 1.249 to 21.014; p=0.023) were positively predicted high-dose opioid use. No difference in survival was found when comparing the high-dose and very high-dose opioid use groups. CONCLUSIONS: Male home-based patients with advanced cancer who use morphine and have greater preadmission opioid doses should be aware of the necessity for high-dose opioid use. Regulated opioid use in adequate amounts does not shorten survival.

CuI-Catalyzed Selenylation of Pyrrolo[2,1-a]isoquinolines and Other Electron-Rich Heteroarenes.

We have established a mild CuI-catalyzed selenylation of pyrrolo[2,1-a]isoquinoline derivatives in the presence of mCPBA (m-chloroperoxybenzoic acid) at ambient temperature. Corresponding organoselenides have been prepared readily in 53-92% yields. This process can also be expanded to the modification of pyrroles, azaindole, and indoles, delivering the desired heterocyclic selenides in moderate to good yields.

SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma.

The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclax and an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor and cooperates with the loss of KMT2D in lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several proapoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histone H3K4 demethylases restore BIM and BIK expression and synergize with Venetoclax in SETD1B-deficient lymphomas. These results establish SETD1B as an epigenetic regulator of cell death and reveal a pharmacological strategy to augment Venetoclax sensitivity in lymphoma.

Highly sensitive CD40L protein discrimination via label-free fiber sensing technologies.

The recombinant Cluster of Differentiation 40 Ligand (CD40L) can be expressed in various cells and is closely related to various types of cancer. This association underscores the critical need for expedited and precise measurement of CD40L levels in clinical fluid specimens. A novel optical fiber biosensor has been devised, employing single-mode fibers that are sandwiched around a coreless fiber, with the diameter refined by etching with hydrogen fluoride. This innovative configuration allows for light transmission through the evanescent field, thereby enhancing the sensor's sensitivity to changes in the surrounding refractive index. Employing chemical binding techniques, CD40 was securely immobilized onto the fiber's surface, facilitating the detection of CD40L. The sensor exhibited a sensitivity of 1.126 nm (µg mL-1)-1 and a detection limit of 0.68 nM. Furthermore, the sensor's specificity for CD40L was validated using authentic clinical serum samples spiked with artificial analytes. In addition, the specificity of CD40L of the proposed sensor was proved using natural clinical serum samples with added artificial analyte, assisted by the ELISA method, and the results ideally conformed with the detection of standard samples. With the aid of the ELISA method, the outcomes were found to be in excellent agreement with those from standard sample detection. Consequently, the findings indicate that this sensor provides a specific, label-free, and highly sensitive method for CD40L detection, showcasing its significant potential for applications in molecular biology research.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

DC-YOLOv5-based target detection algorithm for cervical vertebral maturation.

The cervical vertebral maturation (CVM) method is essential to determine the timing of orthodontic and orthopedic treatment. In this paper, a target detection model called DC-YOLOv5 is proposed to achieve fully automated detection and staging of CVM. A total of 1800 cephalometric radiographs were labeled and categorized based on the CVM stages. We introduced a model named DC-YOLOv5, optimized for the specific characteristics of CVM based on YOLOv5. This optimization includes replacing the original bounding box regression loss calculation method with Wise-IOU to address the issue of mutual interference between vertical and horizontal losses in Complete-IOU (CIOU), which made model convergence challenging. We incorporated the Res-dcn-head module structure to enhance the focus on small target features, improving the model's sensitivity to subtle sample differences. Additionally, we introduced the Convolutional Block Attention Module (CBAM) dual-channel attention mechanism to enhance focus and understanding of critical features, thereby enhancing the accuracy and efficiency of target detection. Loss functions, precision, recall, mean average precision (mAP), and F1 scores were used as the main algorithm evaluation metrics to assess the performance of these models. Furthermore, we attempted to analyze regions important for model predictions using gradient Class Activation Mapping (CAM) techniques. The final F1 scores of the DC-YOLOv5 model for CVM identification were 0.993, 0.994 for mAp0.5 and 0.943 for mAp0.5:0.95, with faster convergence, more accurate and more robust detection than the other four models. The DC-YOLOv5 algorithm shows high accuracy and robustness in CVM identification, which provides strong support for fast and accurate CVM identification and has a positive effect on the development of medical field and clinical diagnosis.

Enhanced detection of 4-nitrophenol in drinking water: ECL sensor utilizing velvet-like graphitic carbon nitride and molecular imprinting.

In this work, a molecularly imprinted electrochemiluminescence (ECL) sensor was developed for selective detection of 4-nitrophenol (4-NP) in drinking water for the first time. By synthesizing velvet-like graphitic carbon nitride (V-g-C3N4) via one-step thermal polycondensation and integrating it with a molecularly imprinted polymer (MIP), the ECL sensor was fabricated. The MIP-modified V-g-C3N4 composites (MIP/V-g-C3N4) were synthesized using a sol-gel method with 4-NP as the template molecule. Under optimal conditions, the ECL sensor exhibited a wide detection range (5 × 10-10-1 × 10-5 mol/L) and a low detection limit (1.8 × 10-10 mol/L). In testing with actual drinking water samples, it displayed high accuracy (recoveries for intraday and inter-day: 93.50-106.2% and 97.00-107.3%, separately) and precision (RSDs for intraday and inter-day: 1.54-4.59% and 1.53-4.28%, respectively). The developed MIP-based ECL sensor demonstrated excellent selectivity, stability, and reproducibility, offering a promising and reliable approach for highly sensitive and selective determination of 4-NP in drinking water.

Effects of proton pump inhibitors on inflammatory bowel disease: An updated review.

Inflammatory bowel disease (IBD) is believed to be caused by various factors, including abnormalities in disease susceptibility genes, environmental factors, immune factors, and intestinal bacteria. Proton pump inhibitors (PPIs) are the primary drugs used to treat acid-related diseases. They are also commonly prescribed to patients with IBD. Recent studies have suggested a potential association between the use of certain medications, such as PPIs, and the occurrence and progression of IBD. In this review, we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms. Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Deep learning promoted target volumes delineation of total marrow and total lymphoid irradiation for accelerated radiotherapy: A multi-institutional study.

BACKGROUND AND PURPOSE: One of the current roadblocks to the widespread use of Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) is the challenging difficulties in tumor target contouring workflow. This study aims to develop a hybrid neural network model that promotes accurate, automatic, and rapid segmentation of multi-class clinical target volumes. MATERIALS AND METHODS: Patients who underwent TMI and TMLI from January 2018 to May 2022 were included. Two independent oncologists manually contoured eight target volumes for patients on CT images. A novel Dual-Encoder Alignment Network (DEA-Net) was developed and trained using 46 patients from one internal institution and independently evaluated on a total of 39 internal and external patients. Performance was evaluated on accuracy metrics and delineation time. RESULTS: The DEA-Net achieved a mean dice similarity coefficient of 90.1 % ± 1.8 % for internal testing dataset (23 patients) and 91.1 % ± 2.5 % for external testing dataset (16 patients). The 95 % Hausdorff distance and average symmetric surface distance were 2.04 ± 0.62 mm and 0.57 ± 0.11 mm for internal testing dataset, and 2.17 ± 0.68 mm, and 0.57 ± 0.20 mm for external testing dataset, respectively, outperforming most of existing state-of-the-art methods. In addition, the automatic segmentation workflow reduced delineation time by 98 % compared to the conventional manual contouring process (mean 173 ± 29 s vs. 12168 ± 1690 s; P < 0.001). Ablation study validate the effectiveness of hybrid structures. CONCLUSION: The proposed deep learning framework achieved comparable or superior target volume delineation accuracy, significantly accelerating the radiotherapy planning process.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

Research on the evolution game of low-carbon operations in cold chain logistics considering environmental regulations and green credit.

To solve the problem of insufficient low-carbon operational motivation among cold chain logistics enterprises due to the high investment costs of low-carbon assets and considering the promotional effect of environmental regulatory policies and green credit, an evolutionary game model was constructed for the government, cold chain logistics enterprises, and financial institutions. The stability strategies of each participating entity and the stability of the system equilibrium point were analyzed, and the relevant conclusions were verified through numerical simulations. The research results indicated the following: (1) the initial willingness of the three parties to participate increased, the low-carbon operation of cold chain logistics enterprises and the speed of green credit services provided by financial institutions accelerated, and the rate of strict government regulation slowed down. (2) Moderate subsidies and taxes were conducive to the joint participation of the three parties. (3) Increasing the subsidy for green credit provided positive incentives for financial institutions to provide green credit services, while reducing credit interest rates accelerated the low-carbon operation rate of cold chain logistics enterprises.

LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Research hot spots and trends in endocrine-related adverse events caused by immune checkpoint inhibitors: a bibliometric analysis and visualization research.

Background: In recent years, with the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment, the toxicity associated with immunotherapy of ICIs has attracted more attention from scholars. Endocrine toxicity is the most likely immune-related adverse events (irAEs) and is often irreversible, posing a significant clinical treatment challenge. Methods: In this study, bibliometric methods were used to analyze relevant literature in screening endocrine-related adverse events caused by ICIs in the Web of Science core collection database (WoSCC) and to summarize the status, research hot spots, and future trends in this field. Results: 321 countries, 297 institutions, 365 authors, and 305 journals had published 671 English documents on endocrine adverse reactions of ICIs as of 1 December, 2022. The United States, Japan, and China were the top three countries with the most publications. The University of Texas MD Anderson Cancer Center, Harvard Medical School, and Memorial Sloan Kettering Cancer Center were the top three research institutions in terms of publication output. F Stephen Hodi, from the Dana-Farber Cancer Institute in the United States, contributed the largest number of publications. Frontiers in Oncology, which was the most widely distributed publication in the field. The main keywords or clusters identified that current research hotspots include the management of endocrine-related adverse events, hypophysitis, thyroid dysfunction, type I diabetes mellitus, and the impact of endocrine adverse events on survival of patients in this field. Conclusion: The basic knowledge structure of the field of endocrine-related adverse events of ICIs, including publication trends, authors, institutions, countries, keywords, journals and publications, and cited documents, was visually analyzed in this bibliometric analysis. The research results comprehensively demonstrated the hot spots and future trends in the research field, as well as its broad prospects, thus providing a reference for the researchers.

Gate Voltage- and Bias Voltage-Tunable Staggered-Gap to Broken-Gap Transition Based on WSe2/Ta2NiSe5 Heterostructure for Multimode Optoelectronic Logic Gate.

Two-dimensional (2D) materials with superior properties exhibit tremendous potential in developing next-generation electronic and optoelectronic devices. Integrating various functions into one device is highly expected as that endows 2D materials great promise for more Moore and more-than-Moore device applications. Here, we construct a WSe2/Ta2NiSe5 heterostructure by stacking the p-type WSe2 and the n-type narrow gap Ta2NiSe5 with the aim to achieve a multifunction optoelectronic device. Owing to the large interface potential barrier, the heterostructure device reveals a prominent diode feature with a large rectify ratio (7.6 × 104) and a low dark current (10-12 A). Especially, gate voltage- and bias voltage-tunable staggered-gap to broken-gap transition is achieved on the heterostructure device, which enables gate voltage-tunable forward and reverse rectifying features. As results, the heterostructure device exhibits superior self-powered photodetection properties, including a high detectivity of 1.08 × 1010 Jones and a fast response time of 91 µs. Additionally, the intrinsic structural anisotropy of Ta2NiSe5 endows the heterostructure device with strong polarization-sensitive photodetection and high-resolution polarization imaging. Based on these characteristics, a multimode optoelectronic logic gate is realized on the heterostructure via synergistically modulating the light on/off, polarization angle, gate voltage, and bias voltage. This work shed light on the future development of constructing high-performance multifunctional optoelectronic devices.

Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer's disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Recent clinical studies have yielded controversial results regarding the effect of probiotics on cognitive function in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects. To clarify the efficacy of probiotics on cognition, we conducted a meta-analysis of randomized controlled trials (RCTs). METHODS: Instructions of the PRISMA 2020 statement were followed. Literature from the PubMed, Embase and Cochrane databases were systematically searched and manually screened for relevant published RCTs. We performed statistical analysis using RevMan, and assessed the risk of bias using the R software. RESULTS: A total of 12 studies comprising 852 patients with MCI or AD were identified. The results of meta-analysis showed that probiotics improved global cognitive function (SMD=0.67; 95% CI, 0.32, 1.02), recall/delayed memory (SMD=0.67; 95% CI: 0.32, 1.02), attention (SMD=0.31; 95% CI: 0.04, 0.58) and visuospatial/constructional (SMD=0.24; 95% CI: 0.06, 0.42) cognitive domain. CONCLUSION: This meta-analysis found that probiotic supplementation is associated with an improvement in cognitive performance among patients with AD and MCI. However, current evidence is limited, and more reliable large-scale RCTs with higher methodological quality are needed.

Deficiency of Trex1 leads to spontaneous development of type 1 diabetes.

BACKGROUND: Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. METHODS: Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-ß were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. RESULTS: In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1-/- rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-ß, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic ß cells. CONCLUSIONS: Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

Preparation of Ag@lignin nanotubes for the development of antimicrobial biodegradable films from corn straw.

Current environmental and energy issues have attracted considerable attention from industries, governments, and academia. Developing alternative diverse petrochemical-based plastics with biodegradable packaging materials from renewable resources is critical for ensuring both sustainability and safety. In this study, biodegradable films are fabricated from corn straw via a facile sol-gel process. Furthermore, these films are imbued with antimicrobial properties by coupling with silver@lignin nanotube hybrid antibacterial agents, formed via the in situ reduction of silver ions into elemental silver by lignin (mild reducing agent), followed by the self-assembly of lignin molecules into nanotubes assisted by an aqueous silver nitrate electrolyte solution. The developed antibacterial corn straw film exhibits strong mechanical and antibacterial properties, with a tensile strength and elongation at break of 68.7 MPa and 11.3 %, respectively, under optimum conditions and antibacterial activity against Escherichia coli and Staphylococcus aureus of 99.9 % and 97.2 %, respectively. The as-prepared corn straw films exhibit high hydrophobicity and ultraviolet resistance. The morphology, structure, and thermal properties of the corn straw films were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, and thermogravimetric analysis. This study provides a straw-based biodegradable packaging film with antimicrobial properties.

Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals.

SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.