Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma.

Medulloblastoma is the most common pediatric malignant brain tumor. Although current therapies improve survival, these regimens are highly toxic and are associated with significant morbidity. Here, we report that placental growth factor (PlGF) is expressed in the majority of medulloblastomas, independent of their subtype. Moreover, high expression of PlGF receptor neuropilin 1 (Nrp1) correlates with poor overall survival in patients. We demonstrate that PlGF and Nrp1 are required for the growth and spread of medulloblastoma: PlGF/Nrp1 blockade results in direct antitumor effects in vivo, resulting in medulloblastoma regression, decreased metastasis, and increased mouse survival. We reveal that PlGF is produced in the cerebellar stroma via tumor-derived Sonic hedgehog (Shh) and show that PlGF acts through Nrp1-and not vascular endothelial growth factor receptor 1-to promote tumor cell survival. This critical tumor-stroma interaction-mediated by Shh, PlGF, and Nrp1 across medulloblastoma subtypes-supports the development of therapies targeting PlGF/Nrp1 pathway.

Increased α-ketoglutarate links the C3-C4 intermediate state to C4 photosynthesis in the genus Flaveria.

As a complex trait, C4 photosynthesis has multiple independent origins in evolution. Phylogenetic evidence and theoretical analysis suggest that C2 photosynthesis, which is driven by glycine decarboxylation in the bundle sheath cell, may function as a bridge from C3 to C4 photosynthesis. However, the exact molecular mechanism underlying the transition between C2 photosynthesis to C4 photosynthesis remains elusive. Here, we provide evidence suggesting a role of higher α-ketoglutarate (AKG) concentration during this transition. Metabolomic data of 12 Flaveria species, including multiple photosynthetic types, show that AKG concentration initially increased in the C3-C4 intermediate with a further increase in C4 species. Petiole feeding of AKG increases the concentrations of C4-related metabolites in C3-C4 and C4 species but not the activity of C4-related enzymes. Sequence analysis shows that glutamate synthase (Fd-GOGAT), which catalyzes the generation of glutamate using AKG, was under strong positive selection during the evolution of C4 photosynthesis. Simulations with a constraint-based model for C3-C4 intermediate further show that decreasing the activity of Fd-GOGAT facilitated the transition from a C2-dominant to a C4-dominant CO2 concentrating mechanism. All these results provide insight into the mechanistic switch from C3-C4 intermediate to C4 photosynthesis.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

Self- and interviewer-reported cognitive problems in relation to cognitive decline and dementia: results from two prospective studies.

BACKGROUND: Little is known regarding the association of interviewer-reported cognitive problems (ICP) with age-related cognitive decline. We aimed to investigate the independent associations of ICP and the combined associations of ICP and self-reported cognitive problems (SCP) with subsequent cognitive decline and dementia in two prospective cohort studies. METHODS: We included 10,976 Chinese (age = 57.7 ± 8.7) and 40,499 European (age = 64.6 ± 9.4) adults without dementia from the China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). Self-rated memory (5-point scale) and interviewer-rated frequencies of asking for clarification (6-point scale) were used to define SCP and ICP (dichotomized). Outcomes included objective cognitive test scores (z-score transformation) and incident dementia. Generalized estimating equation models were performed to evaluate mean differences in objective cognitive decline. Logistic and Cox regression models were used to estimate the relative risk of dementia. Results from two cohorts were pooled using the random-effects models. RESULTS: ICP was associated with faster cognitive decline in CHARLS (ßCHARLS = -0.025 [-0.044, -0.006] z-score/year). ICP and SCP were also independently associated with higher risk of dementia in two cohorts (pooled relative risk for SCP = 1.73 [1.30, 2.29]; pooled relative risk for ICP = 1.40 [1.10, 1.79]). In the joint analysis, participants with coexistence of SCP and ICP had the fastest cognitive decline (ßCHARLS = -0.051 [-0.080, -0.021]; ßSHARE = -0.024 [-0.043, -0.004]; pooled ß = -0.035 [-0.061, -0.009] z-score/year) and highest risk of dementia (ORCHARLS = 1.77 [1.42, 2.20]; HRSHARE = 2.94 [2.42, 3.59]; pooled relative risk = 2.29 [1.38, 3.77]). CONCLUSIONS: The study suggested that interviewer-reported cognitive problems may be early indicators of cognitive decline and dementia in middle-aged and older adults. A combination of self- and interviewer-reported cognitive problems showed the strongest associations with cognitive decline and dementia.

Hepatocellular Carcinoma Epigenetic Patterns Correspond to Differences in Ethnoracial Status and Treatment Response in a Single-Center Retrospective Study.

PURPOSE: To correlate epigenetic patterns with ethnoracial status and locoregional therapy (LRT) response in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DNA and RNA were extracted from 47 distinct formalin-fixed paraffin-embedded tumor samples from 42 patients with HCC (n = 14 Black, n = 19 White, n = 9 Hispanic). LRT response was determined using computed tomography (CT) or magnetic resonance (MR) imaging 3 months posttreatment of 35 tumors (n = 22 complete response, n = 13 retreatment candidates). RNA expression and DNA methylation were used to stratify patients by ethnoracial status and treatment response using partial least-squares discriminant analysis (PLS-DA). Results were validated using hierarchical clustering. Ingenuity pathway analysis was performed to identify upstream regulators and pathways. RESULTS: PLS-DA identified 100 genes and 12 methylated regions that differentiated tumors from Black from White/Hispanic patients. Hierarchical clustering clustered samples with the top 16 genes or the top 5 methylation regions. Dysregulated pathways included adrenomedullin pathway (P = .030), EIF2 signaling (P = .007), and several metabolic pathways. AGTR1 (log2fold = 1.59) and GSTM3 (log2fold = 2.53) represented potential differentially expressed therapeutic targets. PLS-DA identified 100 genes and 150 methylation regions that differentiated between complete responders and retreatment candidates. Hierarchical clustering clustered samples with the top 30 genes or the top 13 methylation regions. Dysregulated pathways included metabolic and DNA repair-related pathways. ASAP2 (log2fold = 0.29) and RAD50 (log2fold = 0.22) represented potential differentially expressed therapeutic targets. CONCLUSIONS: Variation in gene expression and DNA methylation patterns in patients with HCC corresponded to ethnoracial status and LRT response. These initial results suggest tumor profiling has the potential to close ethnoracial disparities and improve treatment stratification.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

DLL1 orchestrates CD8+ T cells to induce long-term vascular normalization and tumor regression.

The immunosuppressive and hypoxic tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we showed that elevated levels of Delta-like 1 (DLL1) in the breast and lung TME induced long-term tumor vascular normalization to alleviate tumor hypoxia and promoted the accumulation of interferon γ (IFN-γ)-expressing CD8+ T cells and the polarization of M1-like macrophages. Moreover, increased DLL1 levels in the TME sensitized anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) treatment in its resistant tumors, resulting in tumor regression and prolonged survival. Mechanically, in vivo depletion of CD8+ T cells or host IFN-γ deficiency reversed tumor growth inhibition and abrogated DLL1-induced tumor vascular normalization without affecting DLL1-mediated macrophage polarization. Together, these results demonstrate that elevated DLL1 levels in the TME promote durable tumor vascular normalization in a CD8+ T cell- and IFN-γ-dependent manner and potentiate anti-CTLA4 therapy. Our findings unveil DLL1 as a potential target to persistently normalize the TME to facilitate cancer immunotherapy.

Dynamic Motion of Polar Skyrmions in Oxide Heterostructures.

Polar skyrmions have been widely investigated in oxide heterostructures due to their exotic properties and intriguing physical insights. However, the field-driven motion of polar skyrmions, akin to that of the magnetic counterpart, remains elusive. Herein, using phase-field simulations, we demonstrate the dynamic motion of polar skyrmions with integrated external thermal, electrical, and mechanical stimuli. External heating reduced the spontaneous polarization, while an applied electric field decreased the skyrmion size and weakened the interactions between the skyrmions. Together, the skyrmion motion barrier is significantly reduced from 40 to 2 eV under 9 V at 500 K. An applied mechanical force transformed the skyrmions into a c-domain region near the indenter center under the electric field, providing the space and driving force needed for the motion of the skyrmions. This study confirms that polar skyrmions can move like particles and provides concrete design principles for polar skyrmion-based electronic devices.

Ref-MEF: Reference-Guided Flexible Gated Image Reconstruction Network for Multi-Exposure Image Fusion.

Multi-exposure image fusion (MEF) is a computational approach that amalgamates multiple images, each captured at varying exposure levels, into a singular, high-quality image that faithfully encapsulates the visual information from all the contributing images. Deep learning-based MEF methodologies often confront obstacles due to the inherent inflexibilities of neural network structures, presenting difficulties in dynamically handling an unpredictable amount of exposure inputs. In response to this challenge, we introduce Ref-MEF, a method for color image multi-exposure fusion guided by a reference image designed to deal with an uncertain amount of inputs. We establish a reference-guided exposure correction (REC) module based on channel attention and spatial attention, which can correct input features and enhance pre-extraction features. The exposure-guided feature fusion (EGFF) module combines original image information and uses Gaussian filter weights for feature fusion while keeping the feature dimensions constant. The image reconstruction is completed through a gated context aggregation network (GCAN) and global residual learning GRL. Our refined loss function incorporates gradient fidelity, producing high dynamic range images that are rich in detail and demonstrate superior visual quality. In evaluation metrics focused on image features, our method exhibits significant superiority and leads in holistic assessments as well. It is worth emphasizing that as the number of input images increases, our algorithm exhibits notable computational efficiency.

Dexmedetomidine provides type-specific tumour suppression without tumour-enhancing effects in syngeneic murine models.

BACKGROUND: Dexmedetomidine is a widely used anaesthetic adjuvant for cancer resection surgeries. However, recent reports suggest that it may promote tumour growth or metastasis, so it is essential to clarify its tumour-related effects. METHODS: Seven syngeneic murine tumour models were used to assess the impact of dexmedetomidine on primary tumour growth, spontaneous tumour metastasis, and surgical resection-associated metastasis. Cancer cell proliferation and apoptosis experiments, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays, immune cell analysis, specific T-cell depletion experiments, and gene transcription analysis were conducted to identify the underlying mechanisms. RESULTS: Dexmedetomidine did not affect growth of EO771 or 4T1 breast tumours, LAP0297 or LLC lung tumours, MCA205 fibrosarcoma, or their spontaneous lung metastases. It did not promote lung metastasis after breast cancer resection. Dexmedetomidine significantly suppressed MCA38 and CT26 colorectal tumour growth (P<0.01) and promoted apoptosis in MCA38 tumour tissues (P<0.05) without affecting proliferation and apoptosis of MCA38 tumour cells in vitro, suggesting indirect anti-tumour effects. Dexmedetomidine increased the proportions of intratumour CD4+ T (P<0.01), CD8+ T (P<0.001), and natural killer cells (P<0.01), and it upregulated transcription of the cytotoxicity-related genes Infg, Tnfa, and Cxcl9 (P<0.05) in MCA38 tumours. Either CD8+ or CD4+ T-cell depletion reversed the anti-tumour effects of dexmedetomidine on MCA38 tumours (P<0.05). CONCLUSIONS: Dexmedetomidine conferred colorectal tumour-type specific suppression by modulation of tumour CD4+ and CD8+ T cells without tumour-enhancing effects.

Survival after laparoscopic radical surgery for stage IA-IIB cervical cancer: 1316 consecutive cases from a national laparoscopic training center in China.

BACKGROUND: To investigate the survival of cervical cancer patients undergoing laparoscopic radical hysterectomy (LRH) in a minimally invasive gynecology center. METHODS: A consecutive series of patients undergoing first LRH for cervical cancer from May 2008 to December 2017 at a national laparoscopic training center was retrospectively analyzed. The overall survival (OS) and progression-free survival (PFS) were compared between groups. RESULTS: In total, 1316 women with FIGO (2009) stage IA-IIB cervical cancer received LRH. Among them, 1114 (84.7%) were followed up for 3 months or longer; the median follow-up period was 48 months (range 3-144 months). In patients with stage IA, IB1 (≤ 2 cm), IB1 (> 2 cm), IB2, IIA1 and IIA2-IIB tumors, the 4-year PFS rates were 98.6, 94.5, 87.4, 65.6, 80.0 and 67.4%, respectively, and the 4-year OS rates were 98.6, 96.8, 91.1, 77.4, 85.6 and 76.2%, respectively. The 4-year PFS and OS were as high as 96.2 and 97.5%, respectively, in patients with squamous cell carcinoma of 2 cm or smaller in diameter. A stable high 4-year OS and PFS was achieved after completing 100 LRHs. In patients operated on by the same surgeon, an improvement in survival was observed after 40 LRHs. CONCLUSION: Favorable oncologic outcomes can be achieved in patients with IA-IB1 cervical cancer after LRH in a center with a high surgery volume.

Death place and palliative outcome indicators in patients under palliative home care service: an observational study.

BACKGROUND: Dying at home accompanied by loved-ones is regarded favorably and brings good luck in Taiwan. This study aimed to examine the relevant factors affecting whether an individual dies at home or not in a group of terminal patients receiving palliative home care service. METHODS: The patients who were admitted to a palliative home care service at a hospital-affiliated home health care agency were consecutively enrolled between March 1, 2021 and March 31, 2022. During the period of care, the instruments of the palliative care outcomes collaboration was used to assess patients in each home visit twice a week, including symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, resource utilization groups-activities of daily living, and palliative care phase. RESULTS: There were 56 participants (53.6% female) with a median age of 73.0 years (interquartile range (IQR) 61.3-80.3 y/o), of whom 51 (91.1%) patients were diagnosed with cancer and 49 (96.1%) had metastasis. The number of home visits was 3.5 (IQR 2.0-5.0) and the average number of days under palliative home care service was 31 (IQR 16.3-51.5) before their death. After the end of the study, there was a significant deterioration of sleeping, appetite, and breathing problems in the home-death group, and appetite problems in the non-home death patients. However, physician-reported psychological/spiritual problems improved in the home-death group, and pain improved in the non-home death patients. Physical performance deteriorated in both groups, and more resource utilization of palliative care was needed. The 44 patients who died at home had greater cancer disease severity, fewer admissions, and the proportion of families desiring a home death for the patient was higher. CONCLUSIONS: Although the differences in palliative outcome indicators were minor between patients who died at home and those who died in the hospital, understanding the determinants and change of indicators after palliative care service at different death places may be helpful for improving the quality of end-of-life care.

Evaluation of a multicomponent intervention to shorten thrombolytic door-to-needle time in stroke patients in China (MISSION): A cluster-randomized controlled trial.

BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.

Diagnosing Prostate Cancer: The Role of Intravesical Prostatic Gland Protrusion on Accuracy of Prostate Biopsies.

PURPOSE: We evaluated the association between intravesical prostate protrusion (IPP) and the detection rate of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TB). MATERIALS AND METHODS: A total of 538 consecutive men who underwent MRI-TRUS fusion TB and concomitant systematic biopsy were evaluated. IPP on MRI was independently measured by 4 blinded reviewers. The primary outcome was per-lesion detection of csPCa on TB. We assessed the association between IPP and csPCa detection on TB, controlling for age, prostate specific antigen, Prostate Imaging Reporting and Data System® (PI-RADS®) score, prostate volume, targeted cores sampled and previous biopsy experience. RESULTS: A total of 847 PI-RADS 3 or greater lesions were targeted across 570 biopsies. Intra- and interrater reliability for measuring IPP was strong. A total of 81 (14.2%), 127 (22.3%), 237 (41.6%) and 125 (21.9%) men had 0, small, medium and large IPP, respectively. A total of 230, 392 and 196 lesions were PI-RADS 3, 4 and 5, respectively. Of the lesions 198 (34.7%) had csPCa on TB. The overall relationship between IPP size and csPCa found on TB was not significant; however, large IPP is associated with a significantly lower rate of csPCa detection than 0 IPP (p=0.007). Every mm increase in IPP is associated with a 5.6% decrease in the odds of csPCa detection on TB (p=0.004) and a 66.5% decrease in odds of detection in large IPP compared to 0 IPP (p=0.003). CONCLUSIONS: As the size of the IPP and volume increase, there is a decrease in the detection rate of csPCa on MRI-guided TB. These findings may be driven by poor MRI-TRUS co-registration and prostate asymmetry.

Plasma folate levels in relation to cognitive impairment: a community-based cohort of older adults in China.

PURPOSE: Lower plasma level of folate has been associated with an increased risk of age-related cognitive impairment. However, studies that examined this relation have yielded mixed results. We aimed to examine the prospective association of plasma folate level with risk of cognitive impairment in a community-based prospective cohort of older adults in China. METHODS: This study included 615 participants (mean age: 76.3 years) without baseline cognitive impairment from the Rugao Longevity and Ageing Study (RuLAS). We used logistic regression to examine the prospective association between baseline plasma folate and risk of cognitive impairment in the next two years. Fasting blood samples were collected and assayed for plasma folate level at baseline. Cognitive impairment was defined as Hasegawa Dementia Scale (HDS) score ≤ 21.5 points. RESULTS: During two years' follow-up, 20.7% of the participants developed cognitive impairment. After controlled for age, gender, and plasma homocysteine, a higher level of plasma folate was associated with lower odds of cognitive impairment. The corresponding odds ratio (OR) with 95% confidence interval was 0.41 (0.19-0.89) comparing participants at extreme quintiles of plasma folate (median level 17.2 vs. 6.3 nmol/L). The associations were similar after further adjustment for major demographic and lifestyle factors (OR = 0.42, 0.18-0.98). Moreover, the inverse association was particularly stronger among males (OR = 0.12, 0.03-0.52) but was non-significant among females. CONCLUSION: Our findings support a potential beneficial role of higher plasma folate levels in cognitive function in older Chinese adults, particularly among males. Future studies with larger sample size and longer follow-up are warranted to confirm these findings and to identify the optimal plasma folate level for cognitive function.

Using Machine Learning to Develop a Short-Form Measure Assessing 5 Functions in Patients With Stroke.

OBJECTIVE: This study aimed to develop and validate a machine learning-based short measure to assess 5 functions (the ML-5F) (activities of daily living [ADL], balance, upper extremity [UE] and lower extremity [LE] motor function, and mobility) in patients with stroke. DESIGN: Secondary data from a previous study. A follow-up study assessed patients with stroke using the Barthel Index (BI), Postural Assessment Scale for Stroke (PASS), and Stroke Rehabilitation Assessment of Movement (STREAM) at hospital admission and discharge. SETTING: A rehabilitation unit in a medical center. PARTICIPANTS: Patients (N=307) with stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The BI, PASS, and STREAM. RESULTS: A machine learning algorithm, Extreme Gradient Boosting, was used to select 15 items from the BI, PASS, and STREAM, and transformed the raw scores of the selected items into the scores of the ML-5F. The ML-5F demonstrated good concurrent validity (Pearson's r, 0.88-0.98) and responsiveness (standardized response mean, 0.28-1.01). CONCLUSIONS: The ML-5F comprises only 15 items but demonstrates sufficient concurrent validity and responsiveness to assess ADL, balance, UE and LE functions, and mobility in patients with stroke. The ML-5F shows great potential as an efficient outcome measure in clinical settings.

Neoadjuvant chemotherapy followed by radical surgery reduces radiation therapy in patients with stage IB2 to IIA2 cervical cancer.

BACKGROUND: To investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation. METHODS: A total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2-IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group. RESULTS: The NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups. CONCLUSIONS: NACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN24104022.

A meta-analysis of survival after minimally invasive radical hysterectomy versus abdominal radical hysterectomy in cervical cancer: center-associated factors matter.

PURPOSE: To explore the possible factors that contributed to the poor performance of minimally invasive surgery (MIS) versus abdominal surgery regarding progression-free survival (PFS) and overall survival (OS) in cervical cancer. METHODS: MEDLINE, EMBASE, Cochrane Library and Web of Science were searched (January 2000 to April 2021). Study selection was performed by two researchers to include studies reported oncological safety. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were combined using random-effect model. Subgroup analyses were stratified by characteristics of disease, publication, study design and treatment center. RESULTS: Sixty-one studies with 63,369 patients (MIS 26956 and ARH 36,049) were included. The overall-analysis revealed a higher risk of recurrence (HR 1.209; 95% CI 1.102-1.327) and death (HR 1.124; 95% CI 1.013-1.248) after MIS versus ARH expect in FIGO IB1 (FIGO 2009 staging) patients with tumor size less than 2 cm. However, subgroup analyses showed comparable PFS/DFS and OS in studies published before the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in European journals, conducted in a single center, performed in centers in Europe and in centers with high sample volume or high MIS sample volume. CONCLUSION: Our findings highlight possible factors that associated with inferior survival after MIS in cervical cancer including publication characteristics, center-geography and sample volume. Center associated factors were needed to be taken into consideration when evaluating complex surgical procedures like radical hysterectomy.

Transformer-Based Model with Dynamic Attention Pyramid Head for Semantic Segmentation of VHR Remote Sensing Imagery.

Convolutional neural networks have long dominated semantic segmentation of very-high-resolution (VHR) remote sensing (RS) images. However, restricted by the fixed receptive field of convolution operation, convolution-based models cannot directly obtain contextual information. Meanwhile, Swin Transformer possesses great potential in modeling long-range dependencies. Nevertheless, Swin Transformer breaks images into patches that are single-dimension sequences without considering the position loss problem inside patches. Therefore, Inspired by Swin Transformer and Unet, we propose SUD-Net (Swin transformer-based Unet-like with Dynamic attention pyramid head Network), a new U-shaped architecture composed of Swin Transformer blocks and convolution layers simultaneously through a dual encoder and an upsampling decoder with a Dynamic Attention Pyramid Head (DAPH) attached to the backbone. First, we propose a dual encoder structure combining Swin Transformer blocks and reslayers in reverse order to complement global semantics with detailed representations. Second, aiming at the spatial loss problem inside each patch, we design a Multi-Path Fusion Model (MPFM) with specially devised Patch Attention (PA) to encode position information of patches and adaptively fuse features of different scales through attention mechanisms. Third, a Dynamic Attention Pyramid Head is constructed with deformable convolution to dynamically aggregate effective and important semantic information. SUD-Net achieves exceptional results on ISPRS Potsdam and Vaihingen datasets with 92.51%mF1, 86.4%mIoU, 92.98%OA, 89.49%mF1, 81.26%mIoU, and 90.95%OA, respectively.

Electronic Metal-Support Interactions for Electrochemiluminescence Signal Amplification.

Au nanoparticle-amplified electrochemiluminescence (ECL) signals are generally realized by nanoparticle morphology modification, functionalization, and nanoalloys formation. It remains a great challenge to utilize the intrinsic catalytic activity of spherical Au nanoparticles for ECL performance improvement. In this work, we prepared the oxygen vacancy-rich CoAl-layered double hydroxide (LDH-Ov)-supported spherical Au nanoparticles via alkali etching of LDH and electrodeposition of Au nanoparticles on the surface of LDH. It was found that the luminol ECL signals of the as-prepared system were significantly enhanced by forming the strong electronic metal-support interaction (EMSI) between Au nanoparticles and LDH-Ov. The further mechanism study demonstrated that EMSI can increase the electron density of interfacial Au atom (Auδ-) due to a redistribution of charge and promote electron transfer between Au species and LDH-Ov. This study not only introduces EMSI to the ECL field but also paves a new way to the applications of the intrinsic activity of spherical Au nanoparticles in ECL signal amplification. We anticipate that EMSI would be applied to other metal nanocatalysts for the development of highly efficient ECL systems.