Two Randomized Controlled Trials to Help Teachers Develop Physical Education Students' Course-Specific Grit-Perseverance and Mental Toughness.

Adopting both a self-determination theory perspective and a proactive, asset-oriented approach to coping with stressors, we propose a hypothesized model to explain physical education students' year-long development of course-specific grit-perseverance (Study 1) and mental toughness (Study 2). In both studies, we used a randomized controlled trial research design with longitudinally assessed dependent measures (four waves) to test a hypothesized model in which teacher participation in an autonomy-supportive teaching workshop (experimental condition) would increase students' T2 perceived autonomy-supportive teaching and T2 perceived autonomy-supportive classmates, both of which would increase T3 need satisfaction, which would then explain longitudinal gains in students' T4 grit-perseverance (Study 1) and mental toughness (Study 2). In both Study 1 (57 teachers, 3,147 students) and Study 2 (38 teachers, 2,057 students), a multilevel structural equation modeling analysis showed that the hypothesized model fit the data very well. We conclude that the developmental roots of grit-perseverance and mental toughness can emerge proactively out of the asset-oriented experiences of interpersonal support and psychological need satisfaction that are central to self-determination theory.

Clinical, radiological, and pathological features of mitotically active cellular fibroma of ovary: A review of cases with literature review.

OBJECTIVE: Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, was first described in the WHO classification in 2014. However, due to its rarity, the clinicopathological characteristics of ovarian MACF have not been established. This study was performed to describe the clinical, radiological, and pathological features of MACF by analyzing 11 cases of ovarian MACF. MATERIALS AND METHODS: Between 2015 and 2022, 11 patients with ovarian MACFs underwent surgical treatment at our institution. Clinicopathologic data of the patients were retrospectively reviewed from their medical records. RESULTS: Median patient age was 53.7 years (range 21-77 years), and median tumor diameter was 7.8 cm (range 4.3-14.0 cm). Preoperative CA125 was elevated in 4 cases. Four of the eleven patients had abdominal pain, and two presented with vulvar pain or a palpable abdominal mass, respectively. Preoperative radiological impressions included fibroma, fibrothecoma, stromal tumor, and cystadenocarcinoma. A laparoscopic approach was adopted in 7 cases (64%). Intraoperative frozen section was performed in 5 patients, and all demonstrated the presence of a benign, fibromatous stromal tumor. Three patients underwent fertility-sparing surgery, including laparoscopic ovarian cystectomy and unilateral salpingo-oophorectomy. Median follow-up was 37.7 months (range 2-84 months), and no patient experienced disease relapse or died of their disease. CONCLUSION: This study shows that ovarian MACF has a benign clinical course. Fertility-sparing surgery provides a safe therapeutic option for MACF, which can be managed safely by laparoscopy. Imaging findings and final pathological diagnosis were not well matched. Intraoperative frozen section is important for determining surgical extent in mitotically active cellular fibroma of the ovary.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer.

Stratification strategies for chemotherapy plus PD-1 inhibitors in advanced non-small-cell lung cancer (NSCLC) are critically demanded. We performed high-throughput panel-based deep next-generation sequencing and low-pass whole genome sequencing on prospectively collected circulating tumor DNA (ctDNA) specimens from 460 patients in the phase 3 CHOICE-01 study at different time points. We identified predictive markers for chemotherapy plus PD-1 inhibitor, including ctDNA status and genomic features such as blood-based tumor mutational burden, intratumor heterogeneity, and chromosomal instability. Furthermore, we established an integrated ctDNA-based stratification strategy, blood-based genomic immune subtypes (bGIS) scheme, to distinguish patients who benefit from the addition of PD-1 inhibitor to first-line chemotherapy. Moreover, we demonstrated potential applications for the dynamic monitoring of ctDNA. Overall, we proposed a potential therapeutic algorithm based on the ctDNA-based stratification strategy, shedding light on the individualized management of immune-chemotherapies for patients with advanced NSCLC.

Novel cellular functions of Cys2-His2 zinc finger proteins in anthracnose development and dissemination on pepper fruits by Colletotrichum scovillei.

Colletotrichum species are notorious for causing anthracnose on many fruits, leading to significant economic losses worldwide. As a model, we functionally characterized cys2-his2 (C2H2) zinc finger proteins (CsCZFs) in Colletotrichum scovillei, a major causal agent of pepper fruit anthracnose in many countries. In all, 62 CsCZFs were identified by in silico genomic analysis. Twelve were selected based on their expression profiles to generate targeted deletion mutants for functional investigation. ΔCsczf1 markedly reduced conidiation and constitutive expression of CsCZF1 partially recovered conidiation in an asexual reproduction-defective mutant, ΔCshox2. Deletion of CsCZF12, orthologous to the calcineurin-responsive transcription factor Crz1, impaired autophagy in C. scovillei. ΔCsczf9 was defective in surface recognition, appressorium formation, and suppression of host defenses. CsCZF9 was identified as an essential and novel regulator under the control of the mitogen-activated protein kinase (CsPMK1) in an early step of appressorium development in C. scovillei. This study provides novel insights into CsCZF-mediated regulation of differentiation and pathogenicity in C. scovillei, contributing to understanding the regulatory mechanisms governing fruit anthracnose epidemics.IMPORTANCEThe phytopathogenic fungus Colletotrichum scovillei is known to cause serious anthracnose on chili pepper. However, the molecular mechanism underlying anthracnose caused by this fungus remains largely unknown. Here, we systematically analyzed the functional roles of cys2-his2 zinc finger proteins (CsCZFs) in the dissemination and pathogenic development of this fungus. Our results showed that CsCZF1 plays an important role in conidiation and constitutive expression of CsCZF1 restored conidiation in an asexual reproduction-defective mutant, ΔCshox2. The CsCZF9, a novel target of the mitogen-activated protein kinase (CsPMK1), is essential for surface recognition to allow appressorium formation and suppression of host defenses in C. scovillei. The CsCZF12, orthologous to the calcineurin-responsive transcription factor Crz1, is involved in the autophagy of C. scovillei. Our findings reveal a comprehensive mechanism underlying CsCZF-mediated regulation of differentiation and pathogenicity of C. scovillei, which contributes to the understanding of fruit anthracnose epidemics and the development of novel strategies for disease management.

Preoperative ultrasonography parathyroid gland mapping can improve identification of normal parathyroid gland during thyroidectomy: A propensity score-matched case-control study.

BACKGROUND: Accurate intraoperative identification of normal parathyroid glands (PTGs) is vital to avoid hypocalcemia post total thyroidectomy. Although ultrasonography (US) has been shown to identify normal PTGs, the significance of preoperative US PTG mapping in this context is not well studied. This study evaluated the impact of preoperative US PTG mapping on intraoperative identification of normal PTGs during total thyroidectomy. METHODS: The study involved 161 consecutive patients who underwent total thyroidectomy between January 2020 and June 2022. These included patients without preoperative US PTG mapping (group 1, n = 91) and those with the mapping (group 2, n = 70). Propensity score matching yielded 61 matched patients from each group. We developed a preoperative US PTG mapping technique combining US identification of normal PTGs with their localization on thyroid CT images. The intraoperative detectability of normal PTGs during thyroid surgery and detectability of normal PTGs by the preoperative US mapping were assessed by the number of PTGs identified per patient and by location. RESULTS: In the matched cohort, group 2 demonstrated a higher median number of identified PTGs (3 vs. 2, p = 0.011), a greater proportion of patients with three or more identified PTGs (65.5% vs. 44.3%, p = 0.018), and a higher ratio of identified to expected PTGs (70.5% vs. 60.2%, p = 0.011) than group 1. In group 2, the median number of normal PTGs identified preoperatively was 3, with at least one identified in 95.7% of patients, two or more in 84.3%, three or more in 52.9%, and four or five in 24.3%. CONCLUSIONS: Preoperative US PTG mapping identified two or more normal PTGs in the majority of adult patients undergoing total thyroidectomy. Those with preoperative mapping showed a higher number of intraoperatively identified normal PTGs, including inferior PTGs, compared to those without. This technique appears to enhance the intraoperative identification of normal PTGs, thereby potentially improving surgical outcomes in total thyroidectomy.

SiamEFT: adaptive-time feature extraction hybrid network for RGBE multi-domain object tracking.

Integrating RGB and Event (RGBE) multi-domain information obtained by high-dynamic-range and temporal-resolution event cameras has been considered an effective scheme for robust object tracking. However, existing RGBE tracking methods have overlooked the unique spatio-temporal features over different domains, leading to object tracking failure and inefficiency, especally for objects against complex backgrounds. To address this problem, we propose a novel tracker based on adaptive-time feature extraction hybrid networks, namely Siamese Event Frame Tracker (SiamEFT), which focuses on the effective representation and utilization of the diverse spatio-temporal features of RGBE. We first design an adaptive-time attention module to aggregate event data into frames based on adaptive-time weights to enhance information representation. Subsequently, the SiamEF module and cross-network fusion module combining artificial neural networks and spiking neural networks hybrid network are designed to effectively extract and fuse the spatio-temporal features of RGBE. Extensive experiments on two RGBE datasets (VisEvent and COESOT) show that the SiamEFT achieves a success rate of 0.456 and 0.574, outperforming the state-of-the-art competing methods and exhibiting a 2.3-fold enhancement in efficiency. These results validate the superior accuracy and efficiency of SiamEFT in diverse and challenging scenes.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-ß) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.

[Reasons and strategies of reoperation after oblique lateral interbody fusion].

OBJECTIVE: To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion (OLIF), and put forward preventive measures. METHODS: From October 2015 to December 2019, 23 patients who underwent reoperation after OLIF in four spine surgery centers were retrospectively analyzed. There were 9 males and 14 females with an average age of (61.89±8.80) years old ranging from 44 to 81 years old. The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases, discogenic low back pain in 1 case, degenerative lumbar spondylolisthesis in 6 cases, lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases. Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation. There were 17 cases of single fusion segment, 2 of 2 fusion segments, 4 of 3 fusion segments. All the cases underwent reoperation within 3 months after the initial surgery. The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy, cage adjustment and neurolysis in 2 cases, arthroplasty and neurolysis under endoscope in 1 case, posterior laminectomy and neurolysis in 1 case, pedicle screw adjustment in 1 case, exploration and decompression under percutaneous endoscopic in 1 case, interbody fusion cage and pedicle screw revision in 1 case. Visual analogue scale (VAS) and Oswestry disability index (ODI) index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up. During the follow-up process, the phenomenon of fusion cage settlement or re-displacement, as well as the condition of intervertebral fusion, were observed. The changes in intervertebral space height before the first operation, after the first operation, before the second operation, 3 to 5 days after the second operation, 6 months after the second operation, and at the latest follow-up were measured and compared. RESULTS: There was no skin necrosis and infection. All patients were followed up from 12 to 48 months with an average of (28.1±7.3) months. Nerve root injury symptoms were relieved within 3 to 6 months. No cage transverse shifting and no dislodgement, loosening or breakage of the instrumentation was observed in any patient during the follow-up period. Though the intervertebral disc height was obviously increased at the first postoperative, there was a rapid loss in the early stage, and still partially lost after reoperation. The VAS for back pain recovered from (6.20±1.69) points preoperatively to (1.60±0.71) points postoperatively(P<0.05). The ODI recovered from (40.60±7.01)% preoperatively to (9.14±2.66)% postoperatively(P<0.05). CONCLUSION: There is a risk of reoperation due to failure after OLIF surgery. The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone, intraoperative endplate injury, significant subsidence of the fusion cage after surgery, postoperative fusion cage displacement, nerve damage, etc. As long as it is discovered in a timely manner and handled properly, further surgery after OLIF surgery can achieve better clinical results, but prevention still needs to be strengthened.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Ultrasonographic features of normal parathyroid glands confirmed during thyroid surgery in adult patients.

PURPOSE: This study was performed to examine the ultrasonography (US) features of normal parathyroid glands (PTGs) that were identified on preoperative US and subsequently confirmed during thyroid surgery. METHODS: This retrospective study included a consecutive sample of 161 patients (mean±standard deviation age, 56±14 years; 128 women) with 294 normal PTGs identified on preoperative US PTG mapping and confirmed during thyroidectomy. A presumed normal PTG on US was defined as a small, round to oval, hyperechoic structure in the central neck. These presumed normal PTGs, as identified on preoperative US, were mapped onto thyroid computed tomography images and diagrams of the thyroid gland and neck. During the preoperative real-time US examinations, the location, size, shape, echogenicity, echotexture, and intraglandular vascular flow of the identified presumed PTGs were assessed. These characteristics were compared between superior and inferior PTGs using the generalized estimating equation method. RESULTS: The typical US features of homogeneous hyperechogenicity without intraglandular vascular flow were observed in 267 (90.8%) normal PTGs, while atypical features, including isoechogenicity (1.0%), heterogeneous echotexture with focal hypoechogenicity (5.8%), and intraglandular vascular flow (3.7%), were noted in 27 (9.2%). Inferior PTGs were more frequently identified in posterolateral (36.1% vs. 5.3%) and thyroid pole locations (29.9% vs. 5.3%), and less frequently in posteromedial locations (29.2% vs. 88.0%), compared to superior PTGs (P<0.001 for each comparison). CONCLUSION: Most normal PTGs displayed the typical US features of homogeneous hyperechogenicity without intraglandular vascular flow. However, in rare cases, normal PTGs exhibited atypical features, including isoechogenicity, heterogeneous echotexture with focal hypoechogenicity, and intraglandular vascular flow.

BioTrojans: viscoelastic microvalve-based attacks in flow-based microfluidic biochips and their countermeasures.

Flow-based microfluidic biochips (FMBs) are widely used in biomedical research and diagnostics. However, their security against potential material-level cyber-physical attacks remains inadequately explored, posing a significant future challenge. One of the main components, polydimethylsiloxane (PDMS) microvalves, is pivotal to FMBs' functionality. However, their fabrication, which involves thermal curing, makes them susceptible to chemical tampering-induced material degradation attacks. Here, we demonstrate one such material-based attack termed "BioTrojans," which are chemically tampered and optically stealthy microvalves that can be ruptured through low-frequency actuations. To chemically tamper with the microvalves, we altered the associated PDMS curing ratio. Attack demonstrations showed that BioTrojan valves with 30:1 and 50:1 curing ratios ruptured quickly under 2 Hz frequency actuations, while authentic microvalves with a 10:1 ratio remained intact even after being actuated at the same frequency for 2 days (345,600 cycles). Dynamic mechanical analyzer (DMA) results and associated finite element analysis revealed that a BioTrojan valve stores three orders of magnitude more mechanical energy than the authentic one, making it highly susceptible to low-frequency-induced ruptures. To counter BioTrojan attacks, we propose a security-by-design approach using smooth peripheral fillets to reduce stress concentration by over 50% and a spectral authentication method using fluorescent microvalves capable of effectively detecting BioTrojans.

Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy.

BACKGROUND: A minority of patients with extensive-stage small cell lung cancer (ES-SCLC) exhibit prolonged survival following first-line chemoimmunotherapy, which warrants the use of reliable biomarkers. Here, we investigated the disparities in genomics and immune cell spatial distribution between long- and short-term survival of patients with ES-SCLC. METHODS: We retrospectively recruited 11 long-term (>2 years) and 13 short-term (<9 months) ES-SCLC survivors receiving first-line chemoimmunotherapy. The samples were processed using targeted next-generation sequencing (tNGS), programmed death ligand-1 staining, multiplex immunohistochemical staining for immune cells (mIHC), tumor mutation burden (TMB), and chromosomal instability score measurements. The expression of putative genes in SCLC at the bulk and single-cell RNA-sequencing levels, as well as the role of putative genes in pan-cancer immunotherapy cohorts, were analyzed. RESULTS: At the genomic level, a greater proportion of the smoking signature and higher TMB (>3.1) were associated with favorable survival. At the single-gene and pathway levels, tNGS revealed that MCL1 and STMN1 amplification and alterations in the apoptosis pathway were more common in short-term survivors, whereas alterations in the DLL3, KMT2B, HGF, EPHA3, ADGRB3, lysine deprivation, and HGF-cMET pathways were observed more frequently in long-term survivors. mIHC analysis of immune cells with different spatial distributions revealed that long-term survivors presented increased numbers of M1-like macrophages in all locations and decreased numbers of CD8+ T cells in the tumor stroma. Bulk transcriptomic analysis demonstrated that high levels of STMN1 and DLL3 represented an immune-suppressive tumor immune microenvironment (TIME), whereas HGF indicated an immune-responsive TIME. The expression levels of our putative genes were comparative in both TP53/RB1 mutant-type and TP53/RB1 wild-type. At the single-cell level, STMN1, MCL1, and DLL3 were highly expressed among all molecular subtypes (SCLC-A, SCLC-N, and SCLC-P), with STMN1 being enriched in cell division and G2M checkpoint pathways. CONCLUSIONS: For ES-SCLC patients receiving first-line chemoimmunotherapy, alterations in DLL3, KMT2B, HGF, EPHA3, and ADGRB3 and a greater proportion of M1-like macrophages infiltration in all locations were predictors of favorable survival, while MCL1 and STMN1 amplification, as well as a greater proportion of CD8+ T cells infiltrating the tumor stroma, predicted worse survival.

Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial.

BACKGROUND: In the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. METHODS: Eligible patients received oral befotertinib of 50 mg (cohort A) or 75-100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. RESULTS: A total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1-48.3) in cohort A and 36.7 months (35.9-37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1-27.2) in cohort A and 31.5 months (26.8-35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9-26.3) and 26.4 months (95 % CI: 23.0-29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6-29.1) and 35.5 months (95 % CI: 29.3-NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. CONCLUSION: Befotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

Established the prediction model of early-stage non-small cell lung cancer spread through air spaces (STAS) by radiomics and genomics features.

BACKGROUND: This study was aimed to establish a prediction model for spread through air spaces (STAS) in early-stage non-small cell lung cancer based on imaging and genomic features. METHODS: We retrospectively collected 204 patients (47 STAS+ and 157 STAS-) with non-small cell lung cancer who underwent surgical treatment in the Jinling Hospital from January 2021 to December 2021. Their preoperative CT images, genetic testing data (including next-generation sequencing data from other hospitals), and clinical data were collected. Patients were randomly divided into training and testing cohorts (7:3). RESULTS: The study included a total of 204 eligible patients. STAS were found in 47 (23.0%) patients, and no STAS were found in 157 (77.0%) patients. The receiver operating characteristic curve showed that radiomics model, clinical genomics model, and mixed model had good predictive performance (area under the curve [AUC] = 0.85; AUC = 0.70; AUC = 0.85). CONCLUSIONS: The prediction model based on radiomics and genomics features has a good prediction performance for STAS.

SUPERFICIAL AND DEEP VASCULAR COMPLEXES DAMAGED TO DIFFERENT EXTENTS IN ADVANCED STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To identify the extent of damage to the superficial vascular complex and deep vascular complex as the stage of diabetic retinopathy (DR) increases. METHODS: Subjects were divided into four groups: patients with type 2 diabetes without DR (Group 1), those with mild-to-moderate nonproliferative DR (Group 2), those with severe-to-very severe nonproliferative DR (Group 3), and those with proliferative DR (Group 4). The vessel densities of the superficial vascular complex (superficial vessel density, SVD) and deep vascular complex (deep vessel density, DVD) and their ratios were compared. Linear regression analyses were used to identify factors associated with the SVD/DVD ratio. RESULTS: The SVDs were 25.5% ± 6.1%, 25.1% ± 7.0%, 24.5% ± 9.0%, and 21.6% ± 6.9% (P = 0.048); the DVDs 25.6% ± 5.3%, 23.0% ± 7.0%, 22.3% ± 8.8%, and 17.5% ± 5.0% (P < 0.001); and the SVD/DVD ratios 1.00 ± 0.16, 1.12 ± 0.20, 1.14 ± 0.33, and 1.24 ± 0.27 (P < 0.001) in Groups 1 to 4, respectively. In multivariate analysis, DR severity (B = 7.16, P < 0.001) and the HbA1c level (B = 1.57, P = 0.042) were significantly associated with the SVD/DVD ratio. CONCLUSION: Both the SVD and DVD tended to decrease in the advanced stages of DR, and the SVD/DVD ratio increased, indicating more severe damage to the deep vascular complex than the superficial vascular complex. The ratio was positively associated with the HbA1c level, indicating a significant relationship between that level and DVD rather than SVD damage.

The Evolution of Three Schizothoracinae Species from Two Major River Systems in Northwest China Based on Otolith Morphology and Skeletal Structure.

Schizothoracinae species are the largest group of Cypriniformes that readily adapt to the natural conditions of the Qinghai-Tibet Plateau. This group has habitat characteristics and distribution patterns centered on the Qinghai-Tibet Plateau. To study the evolution of three Schizothoracinae species in Northwest China, the evolutionary characteristics of these species were explored based on differences in otolith morphology and skeletal morphology. From 2020 to 2022, 138 samples (63 Aspiorhynchus laticeps, 35 Diptychus maculatus and 40 Schizothorax pseudaksaiensis) were collected from the Tarim River and Ili River, 6 basic morphological parameters of otoliths were measured and converted into 6 morphological factors and 7 morphological indices. A total of 77 Fourier transform coefficients of each otolith were selected The first three principal components accounted for 92.834% of the total variation in 13 otolith morphological indices of the three Schizothoracinae species, and the overall discrimination rate was 94.20%. According to the principal component analysis of 77 Fourier harmonic values of otoliths, the first 20 principal components explained 97.233% of the total variation, and the overall discrimination rate was 100%. The results of the cluster analysis directly reflected the relationships between related species. The differences in the bone morphology of the three Schizothoracinae species were particularly reflected in the number of whiskers, pharyngeal teeth and vertebrae, and there were also significant differences in the shapes of the sphenotic (SP), pterotic (PTE), preoperculum (PO), branchiostegal ray (BRA) and basibranchial (BB) bones. Their unique morphological and skeletal characteristics are closely related to geological changes and water system evolutionary trends. This study contributes to the understanding of species identification and the evolutionary status of plateau fishes, provides a reference for further evolutionary classification and for assessing the evolutionary mechanisms of plateau fishes, and provides a scientific basis for phylogeny and germplasm resource protection.

Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

PURPOSE: The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. METHODS: This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. RESULTS: As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). CONCLUSION: Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.