Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.

BACKGROUND: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC. METHODS: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023. Outcomes included the objective response rate (ORR) for ADC1 and ADC2, progression free survival 2 (PFS2), defined as the time from initiation of ADC2 to progression, and overall survival (OS). RESULTS: Seventy-nine female patients were included, 64 of whom had HER2-positive disease. The ORR for ADC2 with similar payload of ADC1 was found to be 5.3%. When switching to a different payload, the ORR of ADC2 increased to 22.6%. The PFS2 for ADC2 remained similar regardless of whether the payload was similar or different. Switching to different payload showed a higher ORR in patients with rapid progression and a durable response longer than 6 months (41.2% vs 15.0%). Specifically, significantly longer PFS2 and OS were seen in patients treated with trastuzumab deruxtecan (T-Dxd) compared to those treated with disitamab vedotin (RC48) after progression from trastuzumab emtansine (T-DM1; median PFS2 5.37 months vs 3.30 months, HR = 0.40, 95% CI 0.17-0.93, P = .034; median OS 50.6 months vs 20.2 months, HR = 0.27, 95% CI 0.08-0.91, P = .034). For patients who progressed after T-Dxd, the median PFS2 was 6.05 months for those treated with RC48 versus 0.93 months for those treated with T-DM1 (HR = 0.03, 95% CI 0.002-0.353, P = .0093). Genomic analysis revealed that alternation of retinoblastoma1 was significantly associated with superior PFS. CONCLUSION: The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

Transcriptome data-based status of PI3K/AKT/mTOR pathway indicates heterogeneity and immune modulation in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options. The PI3K/AKT/mTOR pathway is commonly activated in PDAC and plays a critical role in its progression. METHODS AND RESULTS: In this study, the effect of taselisib (a selective PI3K inhibitor) on PDAC cell proliferation was investigated, and a significant decrease in viability was observed with increasing concentrations of taselisib. Differential analysis on samples from the Genotype-Tissue Expression and The Cancer Genome Atlas databases revealed 24 dysregulated PI3K/AKT/mTOR pathway-related genes (PRGs). Unsupervised clustering-based analysis of transcriptome cohorts revealed two clusters with high consistency between RNA-seq and microarray cohorts. Cluster B had higher enrichment of immune cells, particularly CD8+ T cells, and lower levels of immunosuppressive Treg cells. Moreover, we investigated the relationship between drug sensitivity and different clusters and found that cluster A had a better response to PI3K/AKT/mTOR pathway-related inhibitors and chemotherapy. Finally, cluster A exhibited significant activation of PI3K/AKT/mTOR and related oncogenic pathways, contributing to poor prognosis. The study also developed a risk score based on the expression profiles of PRGs and machine learning, which showed a significant increase in overall survival time among patients in the low-risk group. Importantly, the PI3K/AKT/mTOR pathway could be used to better predict individual risk scores, as evidenced by stratified survival analysis. CONCLUSIONS: These findings suggest that targeting the PI3K/AKT/mTOR pathway may have therapeutic potential in PDAC, and distinct pathway states, immune modulation and tumor microenvironments have prognostic value.

Opportunistic use of lumbar computed tomography and magnetic resonance imaging for osteoporosis screening.

Compared with the healthy patients, patients with osteoporosis had a lower Hounsfield unit (HU) value and a higher vertebral bone quality (VBQ) score. Both the HU value and VBQ score can simply distinguish patients with osteoporosis (OP), with a cutoff value of HU value < 97.06 and VBQ score > 3.08. INTRODUCTION: The purpose of this study is to determine whether the opportunistic use of computed tomography (CT) or magnetic resonance imaging (MRI) is effective for identifying spine surgical patients with OP. METHODS: We retrospectively evaluated 109 lumbar spine surgery patients who received lumbar quantitative CT (QCT) and MRI. Using the area under the curve, the CT-based HU value and MRI-based VBQ score were calculated. Then, based on the QCT results, receiver operating characteristic (ROC) curves were constructed to determine the diagnostic performance of the HU value and VBQ score. RESULTS: The HU value was significantly lower in the OP group, and the VBQ score was significantly higher in the OP group. Using the area under the curve, the diagnostic performance of the HU value and VBQ score for OP were 0.959 and 0.880, respectively. The diagnostic threshold values determined with optimal sensitivity and specificity were an HU value of 97.06 and a VBQ score of 3.08. CONCLUSION: Opportunistic use of CT and MRI can simply distinguish patients with OP, which are expected to be potential alternatives to T-score for the osteoporosis screening.

Phosphate solubilization and plant growth properties are promoted by a lactic acid bacterium in calcareous soil.

On the basis of good phosphate solubilization ability of a lactic acid bacteria (LAB) strain Limosilactobacillus sp. LF-17, bacterial agent was prepared and applied to calcareous soil to solubilize phosphate and promote the growth of maize seedlings in this study. A pot experiment showed that the plant growth indicators, phosphorus content, and related enzyme activity of the maize rhizospheric soils in the LF treatment (treated with LAB) were the highest compared with those of the JP treatment (treated with phosphate solubilizing bacteria, PSB) and the blank control (CK). The types of organic acids in maize rhizospheric soil were determined through LC-MS, and 12 acids were detected in all the treatments. The abundant microbes belonged to the genera of Lysobacter, Massilia, Methylbacillus, Brevundimonas, and Limosilactobacillus, and they were beneficial to dissolving phosphate or secreting growth-promoting phytohormones, which were obviously higher in the LF and JP treatments than in CK as analyzed by high-throughput metagenomic sequencing methods. In addition, the abundance values of several enzymes, Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology, and Carbohydrate-Active Enzymes (CAZys), which were related to substrate assimilation and metabolism, were the highest in the LF treatment. Therefore, aside from phosphate-solubilizing microorganisms, LAB can be used as environmentally friendly crop growth promoters in agriculture and provide another viable option for microbial fertilizers. KEY POINTS: • The inoculation of LAB strain effectively promoted the growth and chlorophyll synthesis of maize seedlings. • The inoculation of LAB strain significantly increased the TP content of maize seedlings and the AP concentration of the rhizosphere soil. • The inoculation of LAB strain increased the abundances of the dominant beneficial functional microbes in the rhizosphere soil.

Angular uniformity improvement of diffractive waveguide display based on region geometry optimization.

Augmented reality (AR) near-eye displays have significantly progressed due to advances in nanostructure fabrication. However, for diffractive waveguide AR displays requiring exit pupil expansion, the angular uniformity of each exit pupil position still needs to improve. In this paper, an angular uniformity improvement method based on region geometry optimization is proposed. This optimization method essentially introduces the interaction number of the light with the grating as one of the variables to manipulate the energy distribution. This distribution is obtained by the rigorous coupled wave analysis (RCWA) method and ray tracing process and is further optimized by a multi-objective genetic algorithm. A model is built, and the feasibility of the proposed method is verified. The diffractive waveguide system has a 10m m×10m m exit pupil size at the eye relief of 25 mm and a field of view (FOV) of 21∘×12∘. After the optimization, the overall optical efficiency of the central field and the angular uniformity at the center exit pupil position increased from 0.9% and 66% to 3.1% and 80%, respectively.

Simultaneous comparison of three methods for bone quality assessment.

PURPOSE: The study aims to investigate the correlations between the T score, Hounsfield units (HU) value, and vertebral bone quality (VBQ) score, and to compare their discrimination capability for patients with osteoporotic vertebral compression fracture (OVCF). METHODS: One hundred and sixty-three eligible participants were enrolled (49 OVCF group,114 non-OVCF group). The T score, HU value, and VBQ score were collected retrospectively. Then, those three parameters were compared between the OVCF and non-OVCF groups and the correlations among the three were assessed. Finally, the discrimination capability of those parameters was compared by the receiver operating characteristic (ROC) curves. RESULTS: The OVCF group showed a lower T score, lower HU value, and higher VBQ score (all P < 0.001) than the non-OVCF group. Correlations were observed among the T score, HU value, and VBQ score (all P < 0.001, HU VS. mean T score, r = 0.66; HU VS. minimum T score, r = 0.67; VBQ VS. mean/ minimum T score, r=-0.33; VBQ VS. HU, r=-0.45). The HU value indicated the maximum area under curve (AUC), followed by the VBQ score and then the T score. Moreover, the AUC of combining the VBQ score and the HU value was similar to that of the HU value. CONCLUSIONS: Both the HU value and the VBQ score had superior discrimination capability for patients with OVCF compared to the T score, especially for the HU value. For patients with routinely performed lumbar MRI or CT scans, the HU value or the VBQ score may provide alternative options for assessing the bone condition.

Comprehensive classification and its value of capitellar cartilage injury concomitant with radial head fracture.

BACKGROUND: There are defects in the existing classification of capitellar cartilage injury (CCI) concomitant with radial head fracture (RHF). This study aimed to introduce a comprehensive classification of CCI and to analyze its surgical guidance value. METHODS: According to the affected site and severity, CCI was classified into four types: Type I - partial-thickness loss of articular cartilage, Type II - full-thickness loss of articular cartilage, Type III - full-thickness loss of articular cartilage with subchondral bone loss, Type IV - full-thickness loss of articular cartilage with thin cortex loss on the border of the capitellum; Different types suggest different surgical methods. Between January 2017 and January 2023, this comprehensive CCI classification was applied in 31 operated patients with CCI concomitant with RHF. The ranges of motion (ROM), Mayo Elbow Performance Index (MEPI) score, Hospital for Special Surgery (HSS) score and visual analog scale (VAS) for pain, were used to evaluate the functional recovery of the affected limb. RESULTS: Mason Type I-IV RHF accounted for 6.45%, 38.71%, 48.39%, and 6.45%, respectively. Type I-IV CCI accounted for 12.90%, 35.48%, 45.16% and 6.45%, respectively. There was no relationship between the CCI and RHF types (p > 0.05). At the end of the follow-up period of 11-26 months with an average of 16 months, the elbow flexion and extension ROM recovered to (147.39 ± 9.84)°, forearm rotation ROM recovered to (168.74 ± 11.70)°, MEPI score recovered to (89.19 ± 4.17), HSS score recovered to (88.74 ± 4.62), VAS score recovered to (0.50 ± 0.57), indicating significant differences compared to preoperative measurements (p < 0.05). According to the MEPI and HSS scores, the excellent and good rate of functional recovery was 100%. CONCLUSION: Different types of CCI differ not only in pathology but also in treatment methods. Surgical strategy according to the comprehensive CCI classification introduced in this paper may lead to a satisfactory outcome.

Transcriptomic landscape of endothelial cells: Key tumor microenvironment components indicating variable clinical outcomes in pancreatic ductal adenocarcinoma.

Endothelial cells (ECs) present in the tumor microenvironment (TME) exhibit significant diversity that may impact the efficacy of anti-tumor treatments. Thus, our study sought to elucidate the various clusters of ECs present in pancreatic ductal adenocarcinoma (PDAC) and explore their possible interactions and influence on clinical outcomes. We obtained single-cell transcriptome data from 24 PDAC tumors and 11 normal pancreases, minimizing any batch effects between samples. Next, we compared the relative abundance of various ECs clusters across distinct sample types. Pseudo-time analysis was employed to investigate the differentiation origin of ECs. A variety of bioinformatics methods were used to investigate potential communication between ECs and malignant cells, as well as assess metabolic changes, pathway alterations, and immune-related markers expression within distinct EC clusters. Lastly, we investigated the impact of particular ECs clusters on patient prognosis in bulk transcriptome data. Our study identified seven distinct clusters of ECs, denoted as CA4+ ECs, MMP2+ ECs, SPP1+ ECs, MT1F+ ECs, CCL5+ ECs, RGS5+ ECs, and TYROBP+ ECs. Pseudo-time analysis suggested that the loss of CA4+ ECs and MT1F+ ECs may promote malignant progression. Cell communication elucidated that MT1F+ ECs exhibited the strongest outgoing interaction strength, whereas RGS5+ ECs displayed the strongest incoming interaction strength. Furthermore, TYROBP+ ECs exhibited greater metabolic activity, and notably, CCL5+ ECs displayed increased expression of immune-related molecules. Lastly, across cohorts of bulk transcriptome levels, CA4+ ECs, MT1F+ ECs, and RGS5+ ECs consistently demonstrated prognostic indicative effects. PDAC patients exhibit the presence of seven distinct EC clusters, each demonstrating significant metabolic and immunological heterogeneity. Targeted therapeutic approaches directed toward CA4+ ECs and MT1F+ ECs may prove advantageous in addressing challenges associated with PDAC treatment. Additionally, variations in the relative abundance of CA4+ ECs, MT1F+ ECs, and RGS5+ ECs were indicated as predictive of patient prognosis.

Histone Methyltransferase SUV39H2 Supports Nasopharyngeal Carcinoma Cell Metastasis by Regulation of SIRT1.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. However, the underlying mechanism of Suppressor of variegation 3-9 homolog 2 (SUV39H2) in NPC remains poorly understood. RT-qPCR was carried out to examine SUV39H2 and SIRT1 expression in NPC tissues and cells. Kaplan-Meier method was utilized to evaluate the association between SUV39H2 level and overall survival. The function of SUV39H2 and SIRT1 in NPC cell viability, metastasis, and apoptosis was tested through CCK-8, transwell, and flow cytometry experiments. Here, it was uncovered that SUV39H2 level was augmented in NPC tissues and cells. Moreover, SUV39H2 expedited NPC cell viability, metastasis, and inhibited apoptosis, while SIRT1 addition reversed these impacts. Besides, SUV39H2 induced H3K9me3 enhancement to repress SIRT1 transcription via binding to SIRT1 promoter. Collectively, our results demonstrated upregulated SUV39H2 aggravated NPC tumorigenesis through SIRT1, which may offer a potential therapeutic target for NPC.

Association between body composition and incisional surgical site infection after laparoscopic appendectomy for complicated appendicitis.

PURPOSE: Surgical site infection (SSI) is common after laparoscopic appendectomy, resulting in prolonged hospital stay and increased costs. This study examined the relationship between body composition parameters and risk of incisional SSI in patients with complicated appendicitis. METHODS: We included 411 patients who underwent laparoscopic surgery for complicated appendicitis at a single institution between March 2015 and October 2023. Body composition parameters were derived from preoperative computed tomography (CT). A nomogram was constructed based on the independent predictors of incisional SSI. RESULTS: Overall, 45 (10.9%) patients developed incisional SSI. Visceral fat area (VFA) was independently associated with risk of incisional SSI (hazard ratio 1.015, 95% confidence interval 1.010-1.020, P < 0.001). A nomogram integrating VFA and two other independent predictors (diabetes and conversion) demonstrated high discriminative (area under the curve = 0.793) and calibration abilities. CONCLUSIONS: CT-derived VFA could be a valuable predictor of incisional SSI in patients with complicated appendicitis undergoing laparoscopic surgery. A VFA-based nomogram may help in identifying patients at high risk of SSI.

Efficacy of the newly designed "SkyWalker" robot compared to the MAKO robotic system in primary total knee arthroplasty: a one-year follow-up study.

PURPOSE: Robot-assisted surgical systems for performing total knee arthroplasty (TKA) have gained significant attention. This study was designed to compare the surgical outcomes in primary TKA surgery between the recently developed "SkyWalker" robot system and the more commonly used MAKO robot. METHODS: A total of 75 patients undergoing primary TKA surgery by the same surgical team were included in this study, with 30 patients in the "SkyWalker" group and 45 patients in the "MAKO" group. We documented the osteotomy plan for both robotic systems. The lower limb alignment angles were evaluated by postoperative radiographic assessment. The operation time, estimated blood loss, postoperative hospital stays, and changes in laboratory indexes were collected during hospitalization. In addition, a comparative evaluation of knee functional assessments and complications was conducted during six month and one year follow-ups. RESULTS: There were no significant differences between the two groups in terms of the accuracy of restoring lower limb alignment, estimated blood loss, or operation time. The knee function assessments at six months and one year postoperatively were similar in both groups. Except for day three after surgery, the level of interleukin-6 (IL-6) and the change in IL-6 (∆IL-6) from preoperative baseline were higher in the "SkyWalker" group than in the MAKO group (median: 20.53 vs. 14.17, P=0.050 and median: 17.30 vs. 10.09, P=0.042, respectively). Additionally, one patient from the MAKO group underwent revision surgery at nine months postoperatively due to ongoing periprosthetic discomfort. CONCLUSIONS: The newly developed "SkyWalker" robot showed comparable efficacy to the MAKO robot in terms of lower limb alignment accuracy and postoperative six month and one year follow-up of clinically assessed resumption of knee function.

Prevalence and risk factors of osteoporotic fracture among the elderly population in China: a multicenter cross-sectional study.

PURPOSE: Prevalence of osteoporotic fracture (OPF) is increasing with ageing, resulting in a significant financial burden for healthcare. However, research on the nationwide epidemiological data of OPF in Chinese elderly is still scarce. The aim of this study was to investigate the prevalence and risk factors of OPF in Chinese population aged 60 years or order. METHODS: A cross-sectional survey was conducted in an elderly Chinese population in five centres. Questionnaire investigation and imaging examination were taken in all participants to identify OPF prevalence and risk factors. Diagnosis of OPF was determined based on imaging of vertebral fractures or history of fall-related fractures. We then used multivariate logistic regression model to analyze the associations between the potential risk factors and OPF. RESULTS: The overall prevalence of OPF in population aged 60 years or older was 24.7% (1,071/4,331), showing an increasing trend with age (P < 0.001). The prevalence of OPF was geographically distinct (P < 0.001), but similar between men and women (P > 0.05). Up to 96.8% of OPFs consisted of vertebral fractures, especially involving T11, T12, and L1 segments. Advanced age (≥ 80), vision loss, severe hearing loss, multiple exercise forms, chronic kidney disease, osteoarthritis, and trauma-related vertebral fractures were significantly associated with risk factors, while education level and vitamin D supplementation were associated with protective factors of OPF. CONCLUSION: High prevalence of OPF is a serious threat to bone health among elderly people in China. There is an urgent need for effective strategies to diagnose, prevent, and treat OPF in elderly adults.

Using Transcriptomics to Determine the Mechanism for the Resistance to Fusarium Head Blight of a Wheat-Th. elongatum Translocation Line.

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, is a destructive disease in wheat worldwide. The lack of FHB-resistant germplasm is a barrier in wheat breeding for resistance to FHB. Thinopyrum elongatum is an important relative that has been successfully used for the genetic improvement of wheat. In this study, a translocation line, YNM158, with the YM158 genetic background carrying a fragment of diploid Th. elongatum 7EL chromosome created using 60Co-γ radiation, showed high resistance to FHB under both field and greenhouse conditions. Transcriptome analysis confirmed that the horizontal transfer gene, encoding glutathione S-transferase (GST), is an important contributor to FHB resistance in the pathogen infection stage, whereas the 7EL chromosome fragment carries other genes regulated by F. graminearum during the colonization stage. Introgression of the 7EL fragment affected the expression of wheat genes that were enriched in resistance pathways, including the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, plant-pathogen interaction, and the mitogen-activated protein kinase (MAPK) signaling pathway at different stages after F. graminearium infection. This study provides a novel germplasm for wheat resistance to FHB and new insights into the molecular mechanisms of wheat resistance to FHB.

Chaos with Gaussian invariant distribution by quantum-noise random phase feedback.

We experimentally present a random phase feedback based on quantum noise to generate a chaotic laser with Gaussian invariant distribution. The quantum noise from vacuum fluctuations is acquired by balanced homodyne detection and injected into a phase modulator to form a random phase feedback. An optical switch using high-speed intensity modulator is employed to reset the chaotic states repeatedly and the time evolutions of intensity statistical distributions of the chaotic states stemming from the initial noise are measured. By the quantum-noise random phase feedback, the transient intensity distributions of the chaotic outputs are improved from asymmetric invariant distributions to Gaussian invariant distributions, and the Gaussian invariant distribution indicates a randomly perturbed dynamical transition from microscopic initial noise to macroscopic stochastic fluctuation. The effects of phase feedback bandwidth and modulation depth on the invariant distributions are investigated experimentally. The chaotic time-delay signature and mean permutation entropy are suppressed to 0.036 and enhanced to 0.999 using the random phase feedback, respectively. The high-quality chaotic laser with Gaussian invariant distribution can be a desired random source for ultrafast random number generation and secure communication.

Convolutional symmetric compressed look-up-table method for 360° dynamic color 3D holographic display.

In this paper, we propose a convolutional symmetric compressed look-up-table (CSC-LUT) method to accelerate computer-generated hologram (CGH) computation based on the Fresnel diffraction theory and LUT. The proposed method can achieve one-time high-quality fast generation of color holograms by utilizing dynamic convolution operation, which is divided three processes. Firstly, the pre-calculated data of maximum horizontal modulation factor is compressed in 1D array by coordinate symmetry. Then, the test object is resampled to satisfy convolutional translation invariance. Finally, the dynamic convolution operation is used to simplify CGH computation process rather than the point-by-point computation. Numerical simulation and optical experimental results show that our proposed method can achieve faster computation speed, higher reconstruction quality and wider application compared to conventional SC-LUT method. The further optimization method for parallel acceleration on the GPU framework can achieve real-time (>24fps) color holographic display corresponding to three perspectives of a 3D scene.

Single-image-source binocular waveguide display based on polarization volume gratings and lenses.

Waveguide displays, a highly competitive solution for augmented reality (AR), have attracted a lot of interest. A polarization-dependent binocular waveguide display using polarization volume lenses (PVLs) and polarization volume gratings (PVGs) as input and output couplers, respectively, is proposed. Light from a single image source is delivered to the left and right eyes independently according to its polarization state. Compared with traditional waveguide display systems, no additional collimation system is needed due to the deflection and collimation capabilities of PVLs. Leveraging the high efficiency, wide angular bandwidth, and polarization selectivity of liquid crystal elements, different images can be independently and accurately produced in the two eyes when the polarization of the image source is modulated. The proposed design paves the way for a compact and lightweight binocular AR near-eye display.

Design and fabricate freeform holographic optical elements on curved optical surfaces using holographic printing.

Freeform holographic optical elements (HOEs), due to the high degrees of design freedom, can be used to enhance performance of display systems. In this Letter, we propose a method for designing and fabricating freeform HOEs on curved optical surfaces that can be utilized to implement curved augmented reality (AR) displays. In our method, the phase profile of the freeform HOE laminated on a curved surface is first optimized to achieve a good image performance. Then, two recording wavefronts are optimized to produce the phase profile of the freeform HOE on the curved surface with a high uniformity of diffraction efficiency. The two recording wavefronts used for a curved substrate are converted into two wavefronts for a planar substrate based on a conversion relationship between the curved HOE and the planar HOE. A home-built holographic printer is used to fabricate freeform HOEs on a flat substrate, and then the freeform HOEs are laminated onto a curved optical surface. Two interesting AR display systems are presented to demonstrate the effectiveness of the proposed design and fabrication method.

Nonlinear optical switch based on coherent perfect absorption.

Coherent perfect absorption (CPA) or reflection (CPR) are methods to realize the extreme manipulation on an optical field. We propose a scheme to operate a bistable switch with convertible CPA and/or CPR. Generally, CPA and CPR occur with different input-field phases. For example, CPA is realized when two input probe beams are in phase; instead, CPR is achieved when they are out of phase. In this scheme, a CPA state can be converted to a CPR state by an incoherent field although two input fields are in phase. When we use the incoherent field as a switching field, the CPA (CPR) state is treated as the closed (open) state. As a result, the switching efficiency can theoretically reach a maximum value, i.e., η = 1. In addition, the switch can be operated in the linear regime with a weak input field, and in the nonlinear or bistable regime with a strong input field. Moreover, the efficiency of the bistable switch is sensitively dependent on the input-field intensity. It provides a potential application of this work on sensitive optical detecting.

Effect of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma: a real-world retrospective study.

BACKGROUND: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). METHODS: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. RESULTS: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84-21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08-0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. CONCLUSIONS: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Rapid development of wheat-Dasypyrum villosum compensating translocations resistant to powdery mildew using a triple marker strategy conducted on a large ph1b-induced population.

KEY MESSAGE: Twenty-two compensating wheat-Dasypyrum villosum translocations carrying the powdery mildew resistance gene PmV were developed using a triple marker selection strategy in a large homozygous ph1bph1b population. Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a destructive wheat disease in China. Currently, nearly all resistant varieties grown in the middle and lower reaches of the Yangtze River carry Pm21 which is present in a wheat-Dasypyrum villosum T6V#2S·6AL translocation. Its widespread use poses a strong risk of loss of effectiveness if the pathogen were to change. PmV, a Pm21 homolog carried by a wheat-D. villosum T6V#4S·6DL translocation, is also resistant to powdery mildew but is less transmittable and exploited in cultivars. To utilize PmV more effectively, a new recombinant translocation T6V#4S-6V#2S·6AL carrying PmV with a higher transmission rate was used as a basic material for inducing smaller alien translocations. A locally adapted ph1b-carrying line, Yangmai 23-ph1b, was crossed with T6V#4S-6V#2S·6AL to generate a homozygous ph1bph1b population of 6300 F3 individuals. A modified triple marker strategy based on three co-dominant markers including the functional marker MBH1 for PmV in combination with distal and proximal markers 6VS-GX4 and 6VS-GX17, respectively, was used to screen for new recombinants efficiently. Forty-eight compensating translocations were identified, 22 of which carried PmV. Two translocation lines, Dv6T25 with the shortest distal segment carrying PmV and Dv6T31 with the shortest proximal segment carrying PmV were identified, both expressed normal transmission and therefore could promote PmV in wheat breeding. This work exemplifies a model for rapid development of wheat-alien compensating translocations.