Identification of specific genes as molecular markers for rapid and accurate detection of oil-tea Camellia anthracnose pathogen Colletotrichum fructicola in China.

Introduction: Camellia anthracnose is caused by multiple Colletotrichum species, resulting in severe yield losses of oil-tea Camellia. Colletotrichum fructicola is one of the major anthracnose pathogens of oil-tea Camellia worldwide. However, developing unique molecular markers for the rapid and accurate detection of Colletotrichum fructicola from diverse Colletotrichum species, as well as early monitoring and effective control of the disease, remains largely unexplored. Methods: C. fructicola-specific genes were obtained using a BLAST search of the sequences of predicted genes in C. fructicola against the genome sequences of Colletotrichum fungal pathogens. In this study, Colletotrichum fructicola-specific molecular markers were developed for rapid and accurate detection of C. fructicola among Camellia anthracnose causing fungal pathogens. Results: Using genomic DNA-based end-point PCR and qPCR, three C. fructicola-specific genes with the ability to distinguish C. fructicola from other oil-tea Camellia anthracnose-related Colletotrichum species, including Colletotrichum camelliae, Colletotrichum gloeosporioides, and Colletotrichum siamense, and oil-tea Camellia fungal pathogens belonging to the genus Neopestalotiopsis, Pestalotiopsis, and Alternaria, were validated as molecular markers. In addition, these three molecular markers were highly sensitive to detecting C. fructicola using DNA extracted from the inoculated leaves of oil-tea Camellia. Discussion: These findings enable us to rapidly and uniquely detect the Camellia anthracnose disease caused by Colletotrichum fructicola, which will equip farmers with an effective tool for monitoring Camellia anthracnose disease in the field and taking timely control measurements in advance.

Monitoring and predicting spatio-temporal dynamics of river bankline movements: a case study for land use risk management in the lower Ganga River, India.

Changing the river course in the alluvial plain region is a common phenomenon that may have disastrous consequences. The risk of river bank erosion has increased dramatically during the last few decades. As a result, assessing the river bankline alteration is necessary. The study aims to determine the changes in the bankline in the lower Ganga River. This research presents a novel approach by using the digital shoreline analysis system (DSAS) in conjunction with geospatial data to monitor and predict long-term changes in river banks from 1965 to 2017, providing a comprehensive temporal analysis that is unprecedented in this study area. The study analyzes the bankline change along the river Ganga using DSAS using during the elapsed period. An erosion and accretion zonation was conducted based on the rate of bankline change of the river Ganga in the study area. The rate of bankline shifting was quantified using the endpoint rate (EPR) and linear regression rate (LRR) statistics computed using the DSAS model. The east bank of the Ganga in the study area experienced an average erosion of - 41.17 m/year according to the LRR model. Whereas, the west bank eroded an average of - 2.32 m/year between 1965 and 2017. 90.54% of the transect lines recorded erosion at the east bank and 53.69% of the transect lines at the west bank recorded erosion computed with LRR. For the assessment of the impact of river bankline change on the LULC of the study area, the future river banklines for 2027 and 2037 were forecasted. The result shows that by 2027 and 2037 about 133.24 and 147 km2 of agricultural land and 7.19 and 11.47 km2 of the built-up area may be affected by river bank erosion respectively. By extending the applications of DSAS and geospatial analytics to encompass predictive and impact assessment capabilities, this study significantly enriches the literature on the management of riverbank erosion and associated land use risks. This research provides important insights that improve river management and planning and enable the formulation of robust strategies to mitigate erosion risks on river banks.

Detection Limits of Insect Fragments in Spiked Whole Wheat Flour Using Multiplex Polymerase Chain Reaction (PCR).

The need for a sensitive molecular method to detect specific species of insect contaminants in food products remains a significant challenge in the food industry. This study evaluated the detection limit of a multiplex end-point PCR assay for detecting insects in food. The assay amplifies two fragments of the cytochrome oxidase subunit I gene (COI-Fa and COI-Fb) and one fragment of the protein-coding wingless (wg) gene found in insects. Five insect species, comprising three vectors of foodborne pathogens (the housefly, Musca domestica, the American cockroach, Periplaneta americana, and the pharaoh ant, Monomorium pharaonis) and two storage insect pests (the red flour beetle, Tribolium castaneum and the Indian meal moth, Plodia interpunctella), were spiked separately and in combination at levels of 1, 0.1, 0.01, and 0.001% in whole wheat flour. At spike levels greater than 0.01%, amplicon bands of expected sizes were seen in 100% of samples containing fragments from distinct insect species. At least 25% of spiked samples at the lowest spike level had amplicon bands, except for samples spiked with M. domestica. Results showed an 18.9% probability (with 11.3% and 30% lower and upper confidence limits, respectively) of detecting insect fragments at the lowest spike level (0.001%, corresponding to 3-22 fragments), which is far below the FDA's regulatory level of less than 75 fragments per 50 g of wheat flour. The intensity of amplicon bands in the gel images was higher at higher spike levels. However, this method is not quantitative enough to extrapolate the intensity of the amplicon bands to the number of insect fragments present in a sample. This multiplex assay was also evaluated in a variety of market food samples derived from plants and animals, showing its potential use in various food types. Overall, the sensitivity and specificity of this molecular approach suggest that it could be used in the future as a screening tool for detecting insect contaminants in food.

Comparing Analytical Methods for Composite End Points in Clinical Trials: Insights from the Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction Trial.

BACKGROUND: In VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), participants with heart failure (HF) and reduced ejection fraction, vericiguat decreased the primary composite outcome (time to first HF hospitalization [HFH] or cardiovascular death [CVD]) (897 events) compared with placebo (972 events) (hazard ratio, 0.90; 95% confidence interval [CI], 0.82-0.98; P = .02). In this prespecified secondary analysis, we applied the weighted composite end point (WCE) and the win ratio (WR) methods to provide complementary assessments of treatment effect. METHODS AND RESULTS: The WCE method estimated the mean HFH-adjusted survival based on prespecified weights from a Delphi panel of the VICTORIA executive committee and national leaders: mild (weight per event, 0.39), moderate (0.5), or severe (0.67) HFH, and CVD (1.0). The unmatched WR was estimated for the descending hierarchy of CVD, then recurrent HFH. The WCE used all 3412 primary clinical events: 875 severe HFH (vericiguat, 416/ placebo, 459), 1614 moderate HFH (767/847), 68 mild HFH (38/30), and 855 CVD (414/441). Improved HFH-adjusted survival occurred with vericiguat (mean 78.2% vs 75.6%, difference 2.4%, 95% CI, 1.7%-3.2%, P < .0001). Based on a comparison of 6,375,624 pairs, the WR of 1.13 (95% CI 1.03-1.24, P = .01) also indicated improved clinical outcomes with vericiguat. CONCLUSIONS: The results of the WCE and WR methods were consistent with the primary analysis of the time to first HFH or CVD. Although both WCE and WR assessed recurrent events, the WCE allowed inclusion of all recurrent events, insights on the severity of HFH events, and an absolute measure of the participant-treatment experience. This approach complements conventional assessment, better informing consumers of new therapeutics and future trial designs.

Prediction of Dynamics of Riverbank Erosion: A Tale of the Riverine Town Chandpur Sadar.

River channel migration often occurs inside the floodplain areas of the river. The structural changes occurring in rivers within floodplain zones serve as a significant ecological signal of their tremendous impact on both ecological and human survival. The aim of the research is to assess the spatial and temporal fluctuations of the Meghna River's bankline from 1990 to 2020 (for 30 years), and to predict the future bankline position. The Landsat imageries from USGS were used for this study. The bankline was extracted from satellite imageries (Landsat) using Modified Normalized Difference Water Index (MNDWI) indices. The variations in bankline dynamics were assessed through the application of Net Shoreline Movement (NSM) and End Point Rate (EPR) analyses using the Digital Shoreline Analysis System (DSAS). Predictive modeling was conducted utilizing the Modified EPR Model, with validation performed via the Root Mean Square Error (RMSE) technique. Adjustment of errors was achieved by employing error coefficients tailored to each individual transect. Over the past three decades, the cumulative river erosion in Chandpur Sadar amounted to 18.03 square kilometers, with the highest Net Shoreline Movement (NSM) recorded at -1979.62 m during the study period. The forecasted maximum Net Shoreline Movement (NSM) is anticipated to be -495.79 m, signifying that the transect is associated with erosion, resulting in landward movement. Conversely, the minimum NSM is projected to be -1.01 m. The most significant movement is expected to occur in Puran Bazar, while the least movement is foreseen in Bakharpur. On average, the NSM across all transects is predicted to be -76.25 m. This study presents a cost-effective approach for evaluating the changes in river erosion over time. This technique may be valuable for policymakers in developing effective plans to reduce the negative impacts of erosion-related risks.

End-Point RT-PCR Assays for Detection and Typing of Epizootic Hemorrhagic Disease Virus.

The emergence of EHDV in Europe during the autumn of 2022 reinforces the need for molecular tools (RT-PCR) for rapid detection of animals infected with this virus. Viral genome testing can be performed on whole blood under anticoagulant, spleen, and bloody organ homogenates from ruminants. It can also be performed on cell culture following viral isolation tests. Various so-called classical or end-point RT-PCRs will be described, which permit the amplification of a part of the viral genome (targeting segment 7) allowing the detection of EHDV whatever the serotype (pan-RT-PCR) and also to amplify a portion of the gene coding the viral protein (VP) 2 enabling serotyping. The PCR amplification products are visualized by agarose gel electrophoresis. Sequencing of the type-specific RT-PCR amplification products allows for the serotype of the virus to be determined.

Life cycle assessment of plastic waste in Suzhou, China: Management strategies toward sustainable express delivery.

The explosive growth of China's express delivery industry has greatly increased plastic waste, with low-value plastics not effectively utilized, such as PE packaging bags, which are often not recycled and end up in landfills or incinerators, causing significant resource waste and severe plastic pollution. A gate -to- grave life cycle assessment was adopted to assess the impacts of express delivery plastic waste (EDPW) management models (S1, landfill; S2, incineration; S3, mechanical pelletization), with Suzhou, China as a case. Results showed that mechanical pelletization, was the most environmentally advantageous, exhibiting a comprehensive environmental impact potential of -215.54 Pt, significantly lower than that of landfill (S1, 78.45 Pt) and incineration (S2, -121.77 Pt). The analysis identified that the end-of-life disposal and sorting stages were the principal contributors to environmental impacts in all three models, with transportation and transfer stages of residual waste having minimal effects. In terms of all environmental impact categories, human carcinogenic toxicity (HTc) emerged as the most significant contributor in all three scenarios. Specifically, S1 exhibited the most detrimental effect on human health, while S2 and S3 showed positive environmental impacts. Based on these findings, it is recommended that the application and innovation in mechanical recycling technologies be enhanced, the promotion of the eco-friendly transformation of packaging materials be pursued, and a sustainable express delivery packaging recycling management system be established. These strategies are essential for achieving more eco-friendly management of EDPW, reducing its environmental pollution, and moving towards more sustainable express delivery management practices.

Development of novel portable NIR spectroscopy process analytical technology (PAT) tool for monitoring the transition of ibuprofen to ibuprofen sodium during wet granulation process.

The aim of this research was to develop a process analytical technology (PAT) tool for monitoring the transformation of the active ingredient ibuprofen into the fast-dissolving salt ibuprofen sodium during the wet granulation process. Two near-infrared (NIR) spectrophotometers, portable and benchtop spectrophotometer, were compared. During the analysis with the built models, both demonstrated comparable accuracy and precision (R2X = 0.995, R2Y = 0.927, Q2 = 0.995, and R2X = 0.990, R2Y = 0.948, Q2 = 0.992, respectively). Considering the applicability, a model based on the portable NIR spectroscopic data was chosen for further development and application as a PAT tool for monitoring different steps during the wet granulation process. The evaluation of the model's predictive capability involved analyzing laboratory trial batches with varying amounts of sodium carbonate, resulting in different concentrations of ibuprofen sodium at the end of the wet granulation process. Subsequently, tablets were manufactured from each trial batch, followed by dissolution analysis. The dissolution rate assays were in good agreement with the NIR-predicted concentrations of ibuprofen sodium at the end of the wet granulation process. Based on the results, the proposed model provides an excellent tool to monitor the ibuprofen acid-salt transformation, to determine the end-point of the reaction, and to efficiently control the wet granulation process.

Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial.

Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger-containing (PIKfyve) inhibitor with a favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis (ALS) models. In this ALS clinical trial, the safety, tolerability, CNS penetrance and modulation of pharmacodynamic target engagement biomarkers were evaluated. This phase 2a, randomized, double-blind, placebo-controlled, biomarker-end-point clinical trial was conducted in four US centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansions were randomly assigned (2:1) to receive twice-daily oral treatment with 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent or serious adverse events attributable to the study drug and tolerability at trial completion or treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod dimesylate and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition [soluble glycoprotein nonmetastatic melanoma protein B (sGPNMB) upregulation] and disease-specific CNS target engagement [poly(GP)] were measured. Between 16 December 2021 and 7 July 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance [n = 9 (90%) apilimod dimesylate; n = 5 (100%) placebo]. At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/ml [standard deviation (SD): 0.937]. At Week 12, apilimod dimesylate increased plasma sGPNMB by >2.5-fold (P < 0.001), indicating PIKfyve inhibition, and lowered CSF poly(GP) protein levels by 73% (P < 0.001), indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker end-points in this phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to result in the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials.

Quantitative detection of cassava common mosaic virus for health certification of cassava (Manihot esculenta Crantz) germplasm using qPCR analysis.

Cassava (Manihot esculenta Crantz) is a crop of global economic and food safety importance, used for human consumption and in various industrial applications. The genebank of the Genetic Resources Program of the Alliance of Bioversity International and CIAT currently holds the world's largest cassava collection, with 5965 in vitro accessions from 28 countries. Managing this extensive collection involves indexing quarantine pathogens as a phytosanitary certification requirement for safely distributing cassava germplasm. The study therefore aimed to optimize a quantitative diagnostic protocol to detect cassava common mosaic virus (CsCMV) using quantitative PCR (qPCR) as a better alternative to other molecular techniques. This was done through designing primers and a probe in the RdRP region of CsCMV, and optimizing the qPCR conditions of the diagnostic protocol using primer concentration assays, and reaction amplification conditions such as volume and reaction time. We also evaluated the qPCR protocol by comparing the results of 140 cassava accession evaluations using three diagnostic methodologies (DAS-ELISA, end-point PCR, and qPCR) for CsCMV. Our protocol established that qPCR technique analysis is ten-times more sensitive in detecting CsCMV compared to end-point PCR, showing a maximum detection level of 77.97 copies/µL of plasmid, with 76 min of reaction time. The comparison allowed us to verify the level of CsCMV detection through the techniques evaluated, concluding that qPCR was more sensitive and allowed the quantification of viral concentration. The optimized qPCR protocol will be used to accelerate diagnostic screening of cassava germplasm for the presence or absence of CsCMV to ensure safe movement and distribution of disease-free germplasm.

Harmonization of ANA testing challenge: quantification strategy to accurately predict end-point titers avoiding serial dilution.

Despite the advantages of automated systems for antinuclear antibody (ANA) analysis, the prediction of end-point titers avoiding serial dilutions is still in progress. The aims of this study were to set a conversion table providing discriminant ranges of fluorescence signal intensity values (FI) corresponding to the end-point titers and validate this tool in a real-life laboratory setting. Eight hundred ninety-four serum samples were analyzed for ANA using Image Navigator System. In order to classify FI into non-overlapping groups corresponding to conventional end-point titers, statistical discriminant analysis was used. Validation study was performed calculating agreement and error rates between visual readings and conversion table of 1119 routine ANA positive samples. Setting of FI ranges corresponding to the end-point titers for different staining patterns was computed. For samples showing single pattern, the overall agreement between visual readings and conversion table was 98.4% for all titers ranging from 1:160 to 1:2560, of which 68.0% had the same titer and 30.4% were within ± one titer difference. Concordance rates according to ANA patterns were as follows: (1) nuclear 98.4%, of which 67.0% had the same titer and 31.4% ± one titer; (2) cytoplasmic 100%, of which 72.7% had the same titer and 27.3% than ± one titer; (3) mitotic 66.6%, of which 33.3% had more ± one titer. Our study developed a quantification method for autoantibodies titers assessment based on just one single sample dilution instead of traditional serial dilution approach, providing significant advantages in routine laboratory in terms of reduction in hand-on time and harmonization of results.

Association between Yang Deficiency Syndrome and the End-point Events of Diabetic Kidney Disease： A Retrospective Cohort Study / 中医杂志

ObjectiveTo investigate the impact of yang deficiency syndrome on the progression to end-point events of diabetic kidney disease （DKD）. MethodsA retrospective study among patients with stage Ⅳ DKD admitted to Dongzhimen Hospital of Beijing University of Chinese Medicine from September 1st， 2016 to September 30th， 2021 was conducted. Data on the patients' general information， clinical indicators including duration of diabetes， duration of proteinuria， history of smoking and drinking， hemoglobin （HGB）， fasting blood glucose （FBG）， albumin （ALB）， serum creatinine （Scr）， urea nitrogen （BUN）， uric acid （UA）， cholesterol （TC） ， triglycerides （TG）， low-density lipoprotein （LDL）， 24-hour urine protein quantification （24h-UTP） and estimated glomerular filtration rate （eGFR）， and TCM syndromes including symptoms， tongue and pulse， and syndrome scores were collected. The patients were divided into exposure group （yang-deficiency group） and non-exposure group （non-yang-deficiency group）. The general information， clinical indicators and incidence rates of end-point events were compared， and the impact of yang deficiency syndrome on the end-point events of stage Ⅳ DKD was analyzed. Survival analysis was performed using Kaplan-Meier method， and multivariate Cox proportional risk models were used to identify independent predictors of end-point events. ResultsA total of 160 patients with stage Ⅳ DKD were included in the study， including 43 cases of yang deficiency syndrome and 117 cases of non-yang deficiency syndrome. Compared to those in the non-yang deficiency group， the waist circumference， BUN and the incidence of end-point events in the yang deficiency group were significantly higher （P＜0.05 or P＜0.01）. Spearman correlation analysis showed that yang deficiency syndrome was positively correlated with incidence of end-point events of stage Ⅳ DKD （r = 0.167， P = 0.035）. Furthermore， 24h-UTP and BUN levels were also positively correlated with end-point events in stage Ⅳ DKD patients （P＜0.01）， while ALB and HGB levels were negatively correlated （P＜0.01）. Kaplan-Meier survival curves showed that yang deficiency syndrome was associated with an increased risk of end-point events （Log Rank P = 0.011）. Moreover， 24h-UTP levels ≥3500 mg， BUN level ≥8 mmol/L， ALB level ＜30 g and HGB level ＜11 g were all associated with the increase of the risk of end-point events （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that yang deficiency syndrome was an independent risk factor for patients with stage Ⅳ DKD to progress into end-point events （HR = 2.36， 1.32 to 4.21； P = 0.004）， as well as 24h-UTP ≥ 3500 mg， BUN ≥ 8 mmol/L， HGB＜11 g and ALB＜30 g （P＜0.05 or P＜0.01）. ConclusionsFor stage Ⅳ DKD， patients with yang deficiency syndrome are more likely to have end-point events， which is an independent risk factor for the progression into end-point events.

Evaluation of progression-free survival as a surrogate end point in primary CNS lymphoma: a systematic review and meta-analysis.

Purpose: To evaluate progression-free survival (PFS) as early surrogate endpoints for overall survival (OS) in primary CNS lymphoma (PCNSL). Methods: PubMed, Embase and Cochrane Central Library were searched up to 7 June 2022. Trial-level analyses were performed by weighted linear regression of logarithmic hazard ratios for PFS and OS. Treatment arm-level analyses were performed between PFS rates and 3- or 5-year OS rates. Results: 1471 PCNSL patients in nine randomized control trials were included. PFS was associated with OS (r = 0.750; 95% CI: 0.228-0.937). Strong linear correlations existed between 1-, 2- and 3-year PFS and 3-year OS (r = 0.896-0.928), moderate or weak correlations existed between 3- to 6-month PFS and 3-year OS, 3-month to 5-year PFS and 5-year OS. Conclusion: Short-term PFS can validly substitute for long-term OS in PCNSL.

Measurement of the 171Tm beta spectrum.

The beta spectrum of the main transition of the ß- decay of 171Tm was measured using a double focalizing spectrometer. The instrument was lately improved in order to reduce its low energy threshold to 34 keV. We used the spectrometer to measure the beta spectrum end-point energy of the main transition of 171Tm decay using the Kurie plot formalism. We report a new value of 97.60(38) keV, which is in agreement with previous measurements. In addition, the spectrum shape was compared with the ξ-approximation calculation where the shape factor is equal to 1 and good agreement was found between the theory and the measurement at the 1% level.

Diazotization titrations in pharmacopoeial quality control of medicines and proposals for their revision in the European Pharmacopoeia.

Based on the data in the Ph. Eur., some other newer pharmacopoeias and published experimental papers propose to revise the text of Ph. Eur. 2.5.8. First, it is necessary to specify which of the electrometric methods should be used to indicate the endpoint of diazotization titrations in Ph. Eur. (preferable potentiometry with a platinum indicating electrode). The amount of potassium bromide in the titration solution may be reduced to 1 g, the cooling of the solution before titration may be omitted from the framework procedure, and it may be specified in individual monographs if necessary to obtain accurate and correct results for some medicines. Diazotization titration can be performed in Ph. Eur. and can also be used to determine the content of some other medicines.

Treatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials?

Neoadjuvant chemotherapy is widely used in the therapy of stage II-III breast cancers and pathologic complete response (pCR; ypT0/is, ypN0) predicts excellent long-term survival. However, the correlation between improvement in pCR rate and survival is highly variable across trials. A major limitation of pCR is that it does not capture downstaging in patients with residual disease. We previously introduced the residual cancer burden score that measures pathologic response on a continuous scale. Comparison of residual cancer burden score distributions between trial arms reflects treatment efficacy more accurately than differences in pCR rate. We developed the treatment efficacy score as a new statistical metric that appears to be a better surrogate for trial arm-level survival improvement than pCR rate difference.

Role of Dermoscopy in Laser Therapy.

Lasers have revolutionized the interventional dermatology field over the last two decades. Dermatologic conditions previously untreatable are now treated with lasers and lights. A large number of laser systems with advances in technologies have expanded applications of lasers for conditions like birth marks, acne scars, wrinkles, pigmentation, etc. Newer avenues and protocols are now set to treat skin conditions with lasers. The applicability of laser for any indication is dependent on laser tissue interaction which is well documented. For a successful outcome with laser therapy, a right end point of treatment should be achieved. The laser physician often adjusts parameters for laser therapy depending on tissue response, the ultimate aim being achieving optimum outcome with minimum side effects. Gadget based skin evaluation techniques are now an integral part of dermatology and are extending to interventional dermatology too. Application of dermoscopy before, during, and after lasers in various indications has been documented and reviewed. The representative cases highlighted in article emphasize the added dimension to non-invasive diagnostic capabilities of a dermatologist by enabling subsurface microscopy and enhancing therapy outcomes, and incorporation of these into daily practice offers value addition to not only evaluation but also gauging response to therapies. Use of dermoscopy before, during, and after laser therapies is an invaluable non-invasive tool to assess the right indication, initiate appropriate priming, achieve good end point, gauge untoward side effects, achieve good results, and engage patient confidentiality. Comparison of high magnification digital images is also enabled by digital videodermoscopy. Structured studies and protocols are needed to standardize the use of dermoscopy integrated with laser procedures.

Systematic review of time to subsequent therapy as a candidate surrogate endpoint in advanced solid tumors.

Aim: Time to subsequent therapy (TST) is an end point that may complement progression-free survival (PFS) and overall survival (OS) in determining the treatment effect of anticancer drugs and may be a potential surrogate for PFS and OS. We systematically reviewed the correlation between TST and both PFS and OS in published phase 2/3 studies in advanced solid tumors. Materials & methods: Trial-level correlational analyses were performed for TST versus PFS (by investigator and/or central review) and TST versus OS. Results: Of 21 included studies, nine (43%) used 'time to first subsequent therapy or death' (TFST) as the TST end point; 11 (57%) used different definitions ('other TST end points'). There was a strong correlation between TFST and PFS by investigator (medians: R2 = 0.88; hazard ratio [HR]: R2 = 0.91) and TFST versus PFS by central review (medians: R2 = 0.86; HRs: R2 = 0.84). For TFST versus OS there was medium/poor correlation for medians (R2 = 0.64) and HRs (R2 = 0.02). Conclusion: TFST strongly correlates with PFS, but not with OS.

In a recent study, researchers investigated how we can measure the effectiveness of cancer drugs. They focused on a specific measure called 'time to next therapy', which is the duration between two treatments patients receive. By analyzing the relationship between time to next therapy and disease progression, they discovered a strong correlation. This suggests that in the future, time to next therapy could potentially help to measure how well a cancer treatment works. However, when it comes to predicting patient survival, the relationship was not as strong. This implies that time to next therapy is not a reliable indicator of patient survival. To fully understand whether time to next therapy can effectively measure the effectiveness of anticancer drugs, further research is necessary.

Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis.

BACKGROUND: In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. METHODS: The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. RESULTS: KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41-0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45-0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. CONCLUSION: KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.

ResNet14Attention network for identifying the titration end-point of potassium dichromate.

With the rapid development of industry, the increasing discharge of sewage causes the detection of water quality to be of increasing importance. Potassium dichromate titration is one of the most important testing methods in water quality detection; the ability to accurately identify the titration end-point of potassium dichromate is currently a research challenge. To identify titration end-point quickly and accurately, this study proposes a ResNet14Attention network, which utilizes residual modules that focus on original image information and an attention mechanism that focuses highly on classification targets. The proposed ResNet14Attention network is compared with 12 convolutional neural networks such as ResNet series networks, VGG, and GoogLeNet. The results of comparison experiments reveal that only the proposed ResNet14Attention network has the highest training and testing accuracy of 100% among all convolutional neural networks in the comparison experiment; the proposed ResNet14Attention network has the highest training speed compared to all the networks that over 90% accuracy.