Diffusion and structural MRI as potential biomarkers in people with Parkinson's disease and cognitive impairment.

OBJECTIVE: To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. METHODS: Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5 years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. RESULTS: Significant correlation was found between plasma Aß-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. CONCLUSION: In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. CLINICAL RELEVANCE STATEMENT: Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. KEY POINTS: • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aß-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

Percutaneous transluminal angioplasty and stenting of post-irradiated stenosis of subclavian artery: A matched case-control study.

BACKGROUND: Although radiotherapy is common for head/neck and chest cancers (HNCC), it can result in post-irradiation stenosis of the subclavian artery (PISSA). The efficacy of percutaneous transluminal angioplasty and stenting (PTAS) to treat severe PISSA is not well-clarified. AIMS: To compare the technical safety and outcomes of PTAS between patients with severe PISSA (RT group) and radiation-naïve counterparts (non-RT group). METHODS: During 2000 and 2021, we retrospectively enrolled patients with severe symptomatic stenosis (>60%) of the subclavian artery who underwent PTAS. The rate of new recent vertebrobasilar ischaemic lesions (NRVBIL), diagnosed on diffusion-weight imaging (DWI) within 24 h of postprocedural brain MRI; symptom relief; and long-term stent patency were compared between the two groups. RESULTS: Technical success was achieved in all 61 patients in the two groups. Compared with the non-RT group (44 cases, 44 lesions), the RT group (17 cases, 18 lesions) had longer stenoses (22.1 vs 11.1 mm, P = 0.003), more ulcerative plaques (38.9% vs 9.1%, P = 0.010), and more medial- or distal-segment stenoses (44.4% vs 9.1%, P<0.001). The technical safety and outcome between the non-RT group and the RT group were NRVBIL on DWI of periprocedural brain MRI 30.0% vs 23.1%, P = 0.727; symptom recurrence rate (mean follow-up 67.1 ± 50.0 months) 2.3% vs 11.8%, P = 0.185; and significant in-stent restenosis rate (>50%) 2.3% vs 11.1%, P = 0.200. CONCLUSION: The technical safety and outcome of PTAS for PISSA were not inferior to those of radiation-naïve counterparts. PTAS for PISSA is an effective treatment for medically refractory ischaemic symptoms of HNCC patients with PISSA.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Test of Social Functioning in Persons With Stroke.

OBJECTIVE: To examine the test-retest reliability, minimal detectable change (MDC), responsiveness, and efficiency of the Computerized Adaptive Test of Social Functioning (Social-CAT) in patients with stroke. DESIGN: Repeated-assessments design. SETTING: A department of rehabilitation of a medical center. PARTICIPANTS: In total, 31 patients with chronic stroke and 65 patients with subacute stroke were recruited. INTERVENTION: Not available. MAIN OUTCOME MEASURE: Social-CAT. RESULTS: The Social-CAT showed acceptable test-retest reliability (intraclass correlation coefficient, 0.80) and small random measurement error (MDC%: 18.0%). However, heteroscedasticity was found (r between the means and the absolute change scores: 0.32), so the MDC% adjusted cut-off score is recommended for determining real improvement. Regarding responsiveness, the Social-CAT showed large differences (Kazis' effect size and standardized mean response: 1.15 and 1.09, respectively) in subacute patients. Regarding efficiency, the Social-CAT required an average of 5 items and less than 2 minutes for completion. CONCLUSIONS: Our findings indicate that the Social-CAT is a reliable and efficient measure with good test-retest reliability, small random measurement error, and good responsiveness. Thus, the Social-CAT is a useful outcome measure for routine monitoring of the changes in social function of patients with stroke.

Percutaneous transluminal angioplasty and stenting of post-irradiation stenosis of the vertebral artery.

BACKGROUND: The outcomes of percutaneous transluminal angioplasty and stenting (PTAS) in patients with medically refractory post-irradiation stenosis of the vertebral artery (PISVA) have not been clarified. AIM: This retrospective study evaluated the safety and outcomes of PTAS in patients with severe PISVA compared with their radiation-naïve counterparts (non-RT group). METHODS: Patients with medically refractory severe symptomatic vertebral artery stenosis and undergoing PTAS between 2000 and 2021 were classified as the PISVA group or the non-RT group. The periprocedural neurological complications, periprocedural brain magnetic resonance imaging, the extent of symptom relief, and long-term stent patency were compared. RESULTS: As compared with the non-RT group (22 cases, 24 lesions), the PISVA group (10 cases, 10 lesions) was younger (62.0 ± 8.6 vs 72.4 ± 9.7 years, P = 0.006) and less frequently had hypertension (40.0% vs 86.4%, P = 0.013) and diabetes mellitus (10.0% vs 54.6%, P = 0.024). Periprocedural embolic infarction was not significantly different between the non-RT group and the PISVA group (37.5% vs 35.7%, P = 1.000). At a mean follow-up of 72.1 ± 58.7 (3-244) months, there was no significant between-group differences in the symptom recurrence rate (0.00% vs 4.55%, P = 1.000) and in-stent restenosis rate (10.0% vs 12.5%, P = 1.000). CONCLUSION: PTAS of severe medically refractory PISVA is effective in the management of vertebrobasilar ischemic symptoms in head and neck cancer patients. Technical safety and outcome of the procedure were like those features in radiation-naïve patients.

Increase in the efficiency of III-nitride micro LEDs by atomic layer deposition.

The effect of atomic-layer deposition (ALD) sidewall passivation on the enhancement of the electrical and optical efficiency of micro-light-emitting diode (µ-LED) is investigated. Various blue light µ-LED devices (from 5 × 5 µm2 to 100 × 100 µm2) with ALD-Al2O3 sidewall passivation were fabricated and exhibited lower leakage and better external quantum efficiency (EQE) comparing to samples without ALD-Al2O3 sidewall treatment. Furthermore, the EQE values of 5 × 5 and 10 × 10 µm2 devices yielded an enhancement of 73.47% and 66.72% after ALD-Al2O3 sidewall treatments process, and the output power also boosted up 69.3% and 69.9%. The Shockley-Read-Hall recombination coefficient can be extracted by EQE data fitting, and the recombination reduction in the ALD samples can be observed. The extracted surface recombination velocities are 551.3 and 1026 cm/s for ALD and no-ALD samples, respectively.

Efficacy and safety of belimumab therapy in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Belimumab is the first biological agent approved for the treatment of systemic lupus erythematosus (SLE). The efficacy and safety of belimumab for SLE patients are not clear. Therefore, this meta-analysis is integrating the efficacy and safety of belimumab for patients with SLE. METHODS: PubMed, EMBASE, and Cochrane Library were searched for randomized clinical trials (RCTs) that studied the efficacy and safety of belimumab plus standard therapy before November 1, 2021. Data were pooled using the random-effects model and are expressed as risk ratios (RRs) or mean difference (MD) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified using I2. RESULTS: Seven RCTs with 3,009 participants were included in this meta-analysis. Belimumab showed significantly decreased at least a 4-point improvement in Safety of Estrogen in Lupus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score than placebo (RR, 1.32; 95% CI, 1.21-1.44; p < 0.001). However, belimumab significantly reduced the prednisone dose by 50% or more than placebo (RR, 1.59; 95% CI, 1.17-2.15; p = 0.003) and belimumab significantly increased the 36 Physical Component Summary (PCS) score (MD, 1.60; 95% CI, 0.30-2.90; p = 0.02). Regarding adverse events, there was no significant difference between the belimumab group and the control group. CONCLUSION: The results suggest that belimumab plus standard therapy is more effective than placebo plus standard therapy in SLE patients.

Canine transmissible venereal tumour established in immunodeficient mice reprograms the gene expression profiles associated with a favourable tumour microenvironment to enable cancer malignancy.

BACKGROUND: Canine transmissible venereal tumours (CTVTs) can cross the major histocompatibility complex barrier to spread among dogs. In addition to the transmissibility within canids, CTVTs are also known as a suitable model for investigating the tumour-host immunity interaction because dogs live with humans and experience the same environmental risk factors for tumourigenesis. Moreover, outbred dogs are more appropriate than inbred mice models for simulating the diversity of human cancer development. This study built a new model of CTVTs, known as MCTVTs, to further probe the shaping effects of immune stress on tumour development. For xenotransplantation, CTVTs were first injected and developed in immunodeficient mice (NOD.CB17-Prkdcscid/NcrCrl), defined as XCTVTs. The XCTVTs harvested from NOD/SCID mice were then inoculated and grown in beagles and named mouse xenotransplantation of CTVTs (MCTVTs). RESULTS: After the inoculation of CTVTs and MCTVTs into immune-competent beagle dogs separately, MCTVTs grew faster and metastasized more frequently than CTVTs did. Gene expression profiles in CTVTs and MCTVTs were analysed by cDNA microarray to reveal that MCTVTs expressed many tumour-promoting genes involved in chronic inflammation, chemotaxis, extracellular space modification, NF-kappa B pathways, and focal adhesion. Furthermore, several well-known tumour-associated biomarkers which could predict tumour progression were overexpressed in MCTVTs. CONCLUSIONS: This study demonstrated that defective host immunity can result in gene instability and enable transcriptome reprogramming within tumour cells. Fast tumour growth in beagle dogs and overexpression of tumour-associated biomarkers were found in a CTVT strain previously established in immunodeficient mice. In addition, dysregulated interaction of chronic inflammation, chemotaxis, and extracellular space modification were revealed to imply the possibly exacerbating mechanisms in the microenvironments of these tumours. In summary, this study offers a potential method to facilitate tumour progression and provide a niche for discovering tumour-associated biomarkers in cancer research.

Fumigant Activity of Bacterial Volatile Organic Compounds against the Nematodes Caenorhabditis elegans and Meloidogyne incognita.

Plant-parasitic nematodes infect a diversity of crops, resulting in severe economic losses in agriculture. Microbial volatile organic compounds (VOCs) are potential agents to control plant-parasitic nematodes and other pests. In this study, VOCs emitted by a dozen bacterial strains were analyzed using solid-phase microextraction followed by gas chromatography-mass spectrometry. Fumigant toxicity of selected VOCs, including dimethyl disulfide (DMDS), 2-butanone, 2-pentanone, 2-nonanone, 2-undecanone, anisole, 2,5-dimethylfuran, glyoxylic acid, and S-methyl thioacetate (MTA) was then tested against Caenorhabditis elegans. DMDS and MTA exhibited much stronger fumigant toxicity than the others. Probit analysis suggested that the values of LC50 were 8.57 and 1.43 µg/cm3 air for DMDS and MTA, respectively. MTA also showed stronger fumigant toxicity than DMDS against the root-knot nematode Meloidogyne incognita, suggesting the application potential of MTA.

Assessment of Low Back Pain: Reliability and Minimal Detectable Change of the Brief Pain Inventory.

IMPORTANCE: The Brief Pain Inventory (BPI) is one of the most widely used measures to assess pain and related impacts among patients with low back pain (LBP). However, its test-retest reliability and minimal detectable change (MDC) have rarely been examined in patients with LBP, interfering with its utility. OBJECTIVE: To investigate the test-retest reliability and MDC of the BPI among patients with LBP. DESIGN: Repeated assessments design with a 1-wk interval. SETTING: Department of Physical Medicine and Rehabilitation in a hospital in Taiwan. PARTICIPANTS: Fifty-four patients with stable LBP conditions. OUTCOMES AND MEASURES: The BPI has two subscales-Intensity and Interference-that assess pain intensity and pain interference, respectively. Their test-retest reliability was examined using the intraclass correlation coefficient (ICC), and MDCs were calculated. RESULTS: The ICCs of the Intensity and Interference subscales were .62 and .76, respectively. The MDC values for the two subscales were 2.57 and 2.34, respectively. For the four Intensity items, the average-pain score had a higher ICC (.60) than scores on the other items (worst, least, and current pain, which had ICCs of about .40). CONCLUSIONS AND RELEVANCE: The results suggest that although the BPI is a commonly used measure of pain intensity and pain interference among patients with LBP, caution should be exercised in interpreting the Intensity subscale score and its item scores. What This Article Adds: The BPI is widely used to assess pain and related impacts on daily occupation and functioning among patients with LBP. This study provides information regarding its test-retest reliability. Moreover, the MDC values provide clinicians and researchers with the thresholds for determining real improvement (beyond random measurement error).

Monopronucleated (1PN) and tripronuclear (3PN) zygotes formation during assisted reproduction in POSEIDON group 4 patients: Emphasizing on polar bodies.

AIM: Abnormal fertilization (1PN/3PN) and its accompanying polar body (PB) conditions have been less discussed in poor ovarian responders. By observing the PBs, we analyzed the mechanisms of abnormal fertilization and aimed to explore the role of intracytoplasmic sperm injection/in vitro fertilization (ICSI/IVF) in POSEIDON group 4 patients. METHODS: An observational study. All fresh IVF/ICSI cycles from January 2018 to December 2019 were evaluated. The inclusion criteria were POSEIDON group 4. Fertilization and PB conditions were assessed 16-18 h post-insemination. Primary observation endpoints including normal fertilization, abnormal fertilization, and total fertilization failure rate. RESULTS: A total of 351 cycles involving 180 patients met the inclusion criteria. Of these, 15 cycles reported no retrieved oocytes. Finally, 336 cycles (IVF, n = 267; ICSI, n = 69) were included. A total of 1005 oocytes and 939 embryos were assessed. The mean female age was 40.8 years, and the mean AMH level was 0.6 ng/mL. The normal fertilization rate was 69.7%. The zygote distribution was 18.7% 0PN, 3.9% 1PN, 66.9% 2PN, 9.5% 3PN, and 1.0% ≥4PN. For 1PN zygotes, 59% were denoted as 1PN2PB. The mean 3PN rate was 8.9%. CONCLUSIONS: In POSEIDON group 4, most of the monopronucleated zygotes were 1PN2PB. Digyny (3PN1PB), due to failure to extrude the second PB, was the major cause of triploidy in which ICSI could not circumvent. The distribution of abnormally fertilized zygotes was similar in IVF and ICSI. To investigate the mechanisms of abnormal fertilization and assess whether ICSI is necessary, analysis of PB will provide important clues.

Association between paternal age and risk of schizophrenia: a nationwide population-based study.

PURPOSE: To study the association between paternal age and schizophrenia in offspring. METHODS: This report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan's National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596). RESULTS: The median age at first presentation with schizophrenia was 20 years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father's age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32 years), mother's age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29 years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01). CONCLUSION: This study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.

Risk of major adverse cardiovascular and cerebrovascular events in Taiwanese women with endometriosis.

BACKGROUND/PURPOSE: Endometriosis (EM) is linked to cardiovascular disease (CVD). However, whether this finding can be applied to the Taiwanese population remained unanswered. To investigate the association between EM and major adverse cardiovascular and cerebrovascular events (MACCE) and the therapeutic effect on the risk of MACCE in Asian women with EM. A retrospective population-based cohort study was performed. METHODS: A total of 17 543 patients with EM aged between 18 and 50 years were identified from a general population of 1 million Taiwanese after excluding diagnoses of major CVD and cerebrovascular accident (CVA) prior to EM. The comparison group (n = 70 172) without EM was selected by matching the study cohort with age, sex, and income and urbanization levels in a 4:1 ratio. RESULTS: During a median follow-up period of 9.2 years, Taiwanese women with EM had a significantly higher frequency of comorbidities, medical and surgical treatment, and MACCE than did their non-EM counterparts (2.76% vs 2.18%, P < .0001). After adjustment for comorbidities, patients with EM had an approximately 1.2-fold increased risk of MACCE (95% CI 1.05-1.29; P = .0053) and a higher cumulative incidence of MACCE compared with the normal population. Neither medical nor surgical treatment increased the risk of MACCE. Furthermore, medical treatment for EM appeared to be protective against MACCE. CONCLUSION: Taiwanese women with EM not only had a substantially higher frequency of comorbidities but also an increased risk of MACCE compared with the general population.

Increase in Akkermansiaceae in Gut Microbiota of Prostate Cancer-Bearing Mice.

Gut microbiota are reported to be associated with many diseases, including cancers. Several bacterial taxa have been shown to be associated with cancer development or response to treatment. However, longitudinal microbiota alterations during the development of cancers are relatively unexplored. To better understand how microbiota changes, we profiled the gut microbiota composition from prostate cancer-bearing mice and control mice at five different time points. Distinct gut microbiota differences were found between cancer-bearing mice and control mice. Akkermansiaceae was found to be significantly higher in the first three weeks in cancer-bearing mice, which implies its role in the early stage of cancer colonization. We also found that Bifidobacteriaceae and Enterococcaceae were more abundant in the second and last sampling week, respectively. The increments of Akkermansiaceae, Bifidobacteriaceae and Enterococcaceae were previously found to be associated with responses to immunotherapy, which suggests links between these bacteria families and cancers. Additionally, our function analysis showed that the bacterial taxa carrying steroid biosynthesis and butirosin and neomycin biosynthesis were increased, whereas those carrying naphthalene degradation decreased in cancer-bearing mice. Our work identified the bacteria taxa altered during prostate cancer progression and provided a resource of longitudinal microbiota profiles during cancer development in a mouse model.

Capital and symbolic power in water quality governance: stakeholder dynamics in managing nonpoint sources pollution.

Maintaining quantity and quality is a primary concern in the supply of drinking water. One critical indicator of water quality is nonpoint sources (NPS) pollution. However, persistent risks regarding water quality maintenance have often resulted from compounded social dynamics occurring within and between institutions, while solutions tend to concentrate on scientific/technological treatments. The present study aims to analyse the social dynamics operating within and between such institutions, with a particular focus on the management of NPS pollution that involves the participation of headwater residents. A qualitative case study was conducted on the management of the headwater in Taipei metropolis. The study applied Bourdieu's field theory to understand the mechanism of social interaction and diverse interests among stakeholders. Through in-depth interviews with stakeholders, this research investigated their perceptions regarding various water quality threats and treatments, also mechanisms and gaps in the implementation of NPS pollution-related policies. The study then interpreted emerging issues by considering the stakeholders' various forms of capital input, their strategies in capital exchange and accumulation, as well as the diverse symbolic powers in water quality governance. The research indicates that the ambiguous character of NPS pollution leads to diverse perceptions towards water quality risk, and the ambivalent strategies in negotiation also create barriers to stable stakeholder relationships. Consequently, the research suggests that technocratic-centred governance should also contain sociological perspectives on personal mentality and power dynamic in the society.

Cross-Validation of the Factorial Validity of the Stroke Impact Scale 3.0 in Patients With Stroke.

IMPORTANCE: The Stroke Impact Scale 3.0 appears to be a promising outcome measure of health-related quality of life (HRQOL) for clients with stroke. However, because the factorial validity of the Stroke Impact Scale 3.0 remains unclear, its validity is limited. OBJECTIVE: To examine the underlying structure of the Stroke Impact Scale 3.0 by comparing the currently available eight- and four-domain structures simultaneously. DESIGN: Secondary data analysis of responses to the Stroke Impact Scale 3.0 from a previous psychometric validation study. SETTING: Five general hospitals in northern and southern Taiwan. PARTICIPANTS: Two hundred sixty-three patients with stroke from rehabilitation wards (inpatients) and neurology and rehabilitation clinics (outpatients). OUTCOMES AND MEASURES: Confirmatory factor analysis was used to examine the eight- and four-domain structures of the Stroke Impact Scale 3.0. Four fit indices were considered simultaneously to examine the model fits of both structures. RESULTS: The eight- and four-domain structures of the Stroke Impact Scale 3.0 were not supported by all four indices (χ²/df = 2.7 and 5.0, comparative fit index = .79 and .86, root mean square error of approximation = .08 and .12, standardized root mean square residual = .08 and .08, respectively). The unidimensionality of each domain in the two structures was not supported. CONCLUSIONS AND RELEVANCE: Neither the eight- nor the four-domain structure of the Stroke Impact Scale 3.0 was supported, suggesting that scores may not provide valid assessments of HRQOL in clients with stroke. Further modification and validation of the Stroke Impact Scale 3.0 are warranted. WHAT THIS ARTICLE ADDS: Our findings suggest that the eight- and four-domain scores of the Stroke Impact Scale 3.0 may not be valid. Therefore, until more supporting evidence is developed, these scores should be interpreted cautiously in regard to clients' HRQOL; alternatively, other measures could be used.

Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.

BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

Rapamycin and hydroxychloroquine combination alters macrophage polarization and sensitizes glioblastoma to immune checkpoint inhibitors.

INTRODUCTION: The failure of immune checkpoint inhibitor (ICPi) on glioblastoma (GBM) treatment underscores the need for improving therapeutic strategy. We aimed to change tumor associated macrophage (TAM) from M2 type (anti-inflammatory) to M1 (pro-inflammatory) type to increase the therapeutic response of ICPi. We proposed that combined rapamycin (R) and hydroxychloroquine (Q) preferentially induce M2 cells death, as fatty acid oxidation was their major source of energy. METHODS: Macrophage polarization was characterized on mice and human macrophage cell lines by specific cytokines stimulation with or without RQ treatment under single culture or co-culture with GBM cell lines. Tumor sizes were evaluated on subcutaneous and intracranial GL261 mice models with or without RQ, anti-PD1 mAb treatment. Tumor volumes assessed by MRI scan and proportions of tumor infiltrating immune cells analyzed by flow cytometry were compared. RESULTS: In vitro RQ treatment decreased the macrophages polarization of M2, increased the phagocytic ability, and increased the lipid droplets accumulation. RQ treatment decreased the expression levels of CD47 and SIRPα on tumor cells and macrophage cells in co-culture experiments. The combination of RQ and anti-PD1 treatment was synergistic in action. Enhanced the intra-tumoral M1/M2 ratio, the CD8/CD4 ratio in the intracranial GL261 tumor model after RQ treatment were evident. CONCLUSION: We provide a rationale for manipulating the macrophage phenotype and increased the therapeutic effect of ICPi. To re-educate and re-empower the TAM/microglia opens an interesting avenue for GBM treatment.

Deep learning for fully automated tumor segmentation and extraction of magnetic resonance radiomics features in cervical cancer.

OBJECTIVE: To develop and evaluate the performance of U-Net for fully automated localization and segmentation of cervical tumors in magnetic resonance (MR) images and the robustness of extracting apparent diffusion coefficient (ADC) radiomics features. METHODS: This retrospective study involved analysis of MR images from 169 patients with cervical cancer stage IB-IVA captured; among them, diffusion-weighted (DW) images from 144 patients were used for training, and another 25 patients were recruited for testing. A U-Net convolutional network was developed to perform automated tumor segmentation. The manually delineated tumor region was used as the ground truth for comparison. Segmentation performance was assessed for various combinations of input sources for training. ADC radiomics were extracted and assessed using Pearson correlation. The reproducibility of the training was also assessed. RESULTS: Combining b0, b1000, and ADC images as a triple-channel input exhibited the highest learning efficacy in the training phase and had the highest accuracy in the testing dataset, with a dice coefficient of 0.82, sensitivity 0.89, and a positive predicted value 0.92. The first-order ADC radiomics parameters were significantly correlated between the manually contoured and fully automated segmentation methods (p < 0.05). Reproducibility between the first and second training iterations was high for the first-order radiomics parameters (intraclass correlation coefficient = 0.70-0.99). CONCLUSION: U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. First-order radiomics features extracted from whole tumor volume demonstrate the potential robustness for longitudinal monitoring of tumor responses in broad clinical settings. U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. KEY POINTS: • U-Net-based deep learning can perform accurate fully automated localization and segmentation of cervical cancer in diffusion-weighted MR images. • Combining b0, b1000, and apparent diffusion coefficient (ADC) images exhibited the highest accuracy in fully automated localization. • First-order radiomics feature extraction from whole tumor volume was robust and could thus potentially be used for longitudinal monitoring of treatment responses.

Attitudes towards Interprofessional education in the medical curriculum: a systematic review of the literature.

BACKGROUND: There is agreement among educators and professional bodies that interprofessional education needs to be implemented at the pre-registration level. We performed a systematic review assessing interprofessional learning interventions, measuring attitudes towards interprofessional education and involving pre-registration medical students across all years of medical education. METHODS: A systematic literature review was performed using PubMed, PsycINFO, EThOS, EMBASE, PEDro and SCOPUS. Search terms were composed of interprofession*, interprofessional education, inter professional, inter professionally, IPE, and medical student. Inclusion criteria were 1) the use of a validated scale for assessment of attitudes towards IPE, and results for more than 35 medical students; 2) peer-reviewed articles in English and German, including medical students; and 3) results for IPE interventions published after the 2011 Interprofessional Education Collaborative (IPEC) report. We identified and screened 3995 articles. After elimination of duplicates or non-relevant topics, 278 articles remained as potentially relevant for full text assessment. We used a data extraction form including study designs, training methods, participant data, assessment measures, results, and medical year of participants for each study. A planned comprehensive meta-analysis was not possible. RESULTS: This systematic review included 23 articles with a pre-test-post-test design. Interventions varied in their type and topic. Duration of interventions varied from 25 min to 6 months, and interprofessional groups ranged from 2 to 25 students. Nine studies (39%) reported data from first-year medical students, five (22%) from second-year students, six (26%) from third-year students, two (9%) from fourth-year students and one (4%) from sixth-year students. There were no studies including fifth-year students. The most frequently used assessment method was the Readiness for Interprofessional Learning Scale (RIPLS) (n = 6, 26%). About half of study outcomes showed a significant increase in positive attitudes towards interprofessional education after interventions across all medical years. CONCLUSIONS: This systematic review showed some evidence of a post-intervention change of attitudes towards IPE across different medical years studied. IPE was successfully introduced both in pre-clinical and clinical years of the medical curriculum. With respect to changes in attitudes to IPE, we could not demonstrate a difference between interventions delivered in early and later years of the curriculum. TRIAL REGISTRATION: PROSPERO registration number:  CRD42020160964 .

Lightweight and Resource-Constrained Learning Network for Face Recognition with Performance Optimization.

Despite considerable progress in face recognition technology in recent years, deep learning (DL) and convolutional neural networks (CNN) have revealed commendable recognition effects with the advent of artificial intelligence and big data. FaceNet was presented in 2015 and is able to significantly improve the accuracy of face recognition, while also being powerfully built to counteract several common issues, such as occlusion, blur, illumination change, and different angles of head pose. However, not all hardware can sustain the heavy computing load in the execution of the FaceNet model. In applications in the security industry, lightweight and efficient face recognition are two key points for facilitating the deployment of DL and CNN models directly in field devices, due to their limited edge computing capability and low equipment cost. To this end, this paper provides a lightweight learning network improved from FaceNet, which is called FN13, to break through the hardware limitation of constrained computational resources. The proposed FN13 takes the advantage of center loss to reduce the variations of the between-class features and enlarge the difference of the within-class features, instead of the triplet loss by using FaceNet. The resulting model reduces the number of parameters and maintains a high degree of accuracy, only requiring few grayscale reference images per subject. The validity of FN13 is demonstrated by conducting experiments on the Labeled Faces in the Wild (LFW) dataset, as well as an analytical discussion regarding specific disguise problems.