Development and validation of the patient-reported outcome for older people living with HIV/AIDS in China (PROHIV-OLD).

BACKGROUND: The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. METHODS: Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. RESULTS: A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach's alpha coefficient, McDonald's ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. CONCLUSIONS: The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

High-mobility spin-polarized two-dimensional electron gas at the interface of EuTiO3/SrTiO3heterostructures.

Spin polarization of two-dimensional electron gas (2DEG) at the interface of EuTiO3/SrTiO3(STO) heterostructures has been theoretical predicted and experimentally observed via x-ray magnetic circular dichroism and polarized x-ray absorption spectroscopy, which, however, is lack of magnetotransport evidence. Here, we report the fabrication of high-quality EuTiO3/STO heterostructures by depositing antiferromagnetic insulating EuTiO3thin films onto STO substrates. Shubnikov-de Haas oscillation, Hall, and magnetoresistance (MR) measurements show that the interface is not only highly conducting, with electron mobility up to5.5×103cm2V-1s-1at 1.8 K, but also shows low-field hysteretic MR effects. MR of ∼9% is observed at 1.8 K and 20 Oe, which is one order of magnitude higher than those observed in other spin-polarized 2DEG oxide systems. Moreover, the heterostructures show ferromagnetic hysteresis loops. These results demonstrate that the high-mobility 2DEG is spin polarized, whose origin is attributed to the interfacial Ti3+-3dstates due to oxygen deficiency and the exchange interactions between interfacial Eu spins and itinerant Ti-3delectrons.

Enhancing Cross-Lingual Entity Alignment in Knowledge Graphs through Structure Similarity Rearrangement.

Cross-lingual entity alignment in knowledge graphs is a crucial task in knowledge fusion. This task involves learning low-dimensional embeddings for nodes in different knowledge graphs and identifying equivalent entities across them by measuring the distances between their representation vectors. Existing alignment models use neural network modules and the nearest neighbors algorithm to find suitable entity pairs. However, these models often ignore the importance of local structural features of entities during the alignment stage, which may lead to reduced matching accuracy. Specifically, nodes that are poorly represented may not benefit from their surrounding context. In this article, we propose a novel alignment model called SSR, which leverages the node embedding algorithm in graphs to select candidate entities and then rearranges them by local structural similarity in the source and target knowledge graphs. Our approach improves the performance of existing approaches and is compatible with them. We demonstrate the effectiveness of our approach on the DBP15k dataset, showing that it outperforms existing methods while requiring less time.

A weakly supervised method for named entity recognition of Chinese electronic medical records.

The field of Chinese medical natural language processing faces a significant challenge in training accurate entity recognition models due to the limited availability of high-quality labeled data. In response, we propose a joint training model, MCBERT-GCN-CRF, which achieves high performance in identifying medical-related entities in Chinese electronic medical records. Additionally, we introduce CM-NER, a 5-step framework that effectively mitigates the effects of noise in weakly labeled data and establishes a principled connection between supervised and weakly supervised named entity recognition. We demonstrate significant improvements in recall rate and accuracy. Our approach outperforms traditional fully supervised pre-training models and other state-of-the-art methods by suppressing noise in weakly labeled data. Our proposed framework achieves an F1 score of 86.29% on the CCKS-2019 dataset, significantly higher than pre-trained model baselines ranging from 74.17 to 83.06%, and higher than the top-performing named entity recognition supervised learning models in the CCKS-2019 competition. Our results demonstrate the effectiveness of our proposed framework and highlight the potential of leveraging unlabeled data to train accurate models for named entity recognition in Chinese medical natural language processing. This research has significant implications for advancing natural language processing techniques in the medical domain and improving patient care.

Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.

A case report of Gitelman syndrome in children.

RATIONALE: Giltelman syndrome (GS) is an autosomal recessive infectious disease, which is caused by the mutation of SLC12A3 gene encoding thiazide diuretic sensitive sodium chloride cotransporter located in the distal convoluted tubule of the kidney. PATIENT CONCERNS: A 7-year-old and 3-month-old male patient has poor appetite, slow growth in height and body weight since the age of 3, body weight: 16 kg (-3 standard deviation), height: 110 cm (-3 standard deviation), normal exercise ability and intelligence. One year ago, he was diagnosed with hypokalemia. After potassium supplement treatment, the blood potassium returned to normal. The patient developed abdominal pain, vomiting, limb weakness, and tetany 1 day before admission. DIAGNOSES: After admission examination, the patient was found to have hypokalemia (2.27-2.88 mmol/L), hypomagnesemia (0.47 mmol/L), hypophosphatemia (1.17 mmol/L), hypocalcemia (1.06 mmol/24 hours), and metabolic alkalosis (PH 7.60). The blood pressure is normal, and the concentration of aldosterone is 791.63 pg/mL. The adrenocorticotropic hormone and cortisol detected at 8 am are 4.95 pmol/L and 275.09 nmol/L, respectively. Twenty-four hours of urine potassium is 32.52 mmol. Gene sequencing results showed 2 pathogenic variants in the GS-related SLC12A3 gene, which are related to the phenotype of the subject. INTERVENTIONS: After admission, the patients were given potassium and magnesium supplements, as well as oral spironolactone. The symptoms of limb weakness and tetany were significantly relieved. After discharge, the patients continued to maintain treatment to keep the blood potassium at more than 3.0 mmol/L, and the blood magnesium at more than 0.6 mmol/L. OUTCOMES: Follow-up at 1 month after discharge, in the patient's self-description, he had no symptoms such as limb weakness and tetany, and his height was increased by 1 cm and the body weight increased by 1.5 kg. LESSONS: For patients with hypokalemia, hypomagnesemia, and metabolic alkalosis, the possibility of GS should be given priority. After the diagnosed by gene sequencing of SLC12A3 gene, potassium and magnesium supplementation could significantly improve symptoms.

Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films.

High-quality Mn2-xCrxSb (x = 0.01, 0.04, and 0.1) epitaxial thin films were grown on SrTiO3 (STO) (001) single-crystal substrates using molecular beam epitaxy. Magnetotransport and magnetic measurements reveal that the x = 0.01 sample undergoes a quasi-ferrimagnetic (I) [Q-FIM(I)]-to-ferrimagnetic (II) [FIM(II)] spin reorientation (SR) transition and a giant magnetoresistance (MR) associated first-order ferrimagnetic(II)-to-antiferromagnetic (AFM) phase transition upon cooling, resulting in the AFM ground state with a weak in-plane net moment. Upon increasing the doping level from x = 0.01 to 0.1, both the SR transition and the first-order magnetic transition are suppressed. For x = 0.1, the former transition is suppressed, leaving only the Q-FIM(I)-to-AFM transition within the whole temperature region. TAFM-FIM shows almost similar changes upon the application of either in-plane or out-of-plane magnetic fields. TAFM-FIM values of the x = 0.01 and 0.04 samples are much higher than those of the Mn2-xCrxSb bulk with similar doping levels, which can be understood by the clamping effect from STO substrates. For each thin-film sample, the MR effect is observed near TAFM-FIM and disappears in the high temperature Q-FIM(I) phase and low temperature AFM phase, indicating that MR is related to the spin-dependent electron scattering during the first-order magnetic phase transition. Based on the magnetotransport and magnetic data, a magnetic phase diagram is established for the Mn2-xCrxSb films in the low doping level region.

Delayed Chronic Acidic Postconditioning Improves Poststroke Motor Functional Recovery and Brain Tissue Repair by Activating Proton-Sensing TDAG8.

Acidic postconditioning by transient CO2 inhalation applied within minutes after reperfusion has neuroprotective effects in the acute phase of stroke. However, the effects of delayed chronic acidic postconditioning (DCAPC) initiated during the subacute phase of stroke or other acute brain injuries are unknown. Mice received daily DCAPC by inhaling 5%/10%/20% CO2 for various durations (three cycles of 10- or 20-min CO2 inhalation/10-min break) at days 3-7, 7-21, or 3-21 after photothrombotic stroke. Grid-walk, cylinder, and gait tests were used to assess motor function. DCAPC with all CO2 concentrations significantly promoted motor functional recovery, even when DCAPC was delayed for 3-7 days. DCAPC enhanced the puncta density of GAP-43 (a marker of axon growth and regeneration) and synaptophysin (a marker of synaptogenesis) and reduced the amoeboid microglia number, glial scar thickness and mRNA expression of CD16 and CD32 (markers of proinflammatory M1 microglia) compared with those of the stroke group. Cerebral blood flow (CBF) increased in response to DCAPC. Furthermore, the mRNA expression of TDAG8 (a proton-activated G-protein-coupled receptor) was increased during the subacute phase of stroke, while DCAPC effects were blocked by systemic knockout of TDAG8, except for those on CBF. DCAPC reproduced the benefits by re-expressing TDAG8 in the peri-infarct cortex of TDAG8-/- mice infected with HBAAV2/9-CMV-TDAG8-3flag-ZsGreen. Taken together, we first showed that DCAPC promoted functional recovery and brain tissue repair after stroke with a wide therapeutic time window of at least 7 days after stroke. Brain-derived TDAG8 is a direct target of DCAPC that induces neuroreparative effects.

Correction: Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films.

Correction for 'Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films' by Ting-Wei Chen et al., Phys. Chem. Chem. Phys., 2023, 25, 5785-5794, https://doi.org/10.1039/D2CP05442F.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential.

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

16S rRNA gene sequencing reveals an altered composition of gut microbiota in children with Mycoplasma pneumoniae pneumonia treated with azithromycin.

Mycoplasma pneumoniae is one of the most important pathogens causing community acquired pneumonia in children, and the pathogenic mechanism of M. pneumoniae infection is complex. Azithromycin is an effective agent for treating the acquired lower respiratory tract infection and urogenital tract infection with slight adverse reactions. This study aimed to compare the intestinal microflora before (PP1) and after azithromycin intervention (PP2) in children with pneumonia caused by M. pneumoniae, combined with body fluid biochemical analysis to determine the intestinal flora affecting the progress of the disease. Fifteen children diagnosed with M. pneumoniae pneumonia were recruited. The fecal samples and clinical biochemical data were collected. 16S rRNA gene amplicon sequencing and bioinformatics analysis were conducted by the Beijing Genomics Institute. The operational taxonomic unit abundance analysis showed significant differences between the two groups. The species richness analysis showed differences in class, family, genus, order, species, and phylum. The abundance of Haemophilus, Pasteurellales, and Pasteurellaceae was found to be significantly higher in the PP1 group. The Pearson correlation analysis showed that the microbes strongly correlated with the clinical features. 16S rRNA gene sequencing data revealed altered composition of gut microbiota in children with M. pneumoniae pneumonia treated with azithromycin. The altered expression of microbes correlated with clinical features, which might help diagnose and treat the disease.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma / 中华内科杂志

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2<PRC≤4 mU/L. PRC was not suppressed (PRC>8.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

The Effects of Urban Green Space on Depressive Symptoms of Mid-Aged and Elderly Urban Residents in China: Evidence from the China Health and Retirement Longitudinal Study.

The aim of this study is to assess the impacts of urban green space on depressive symptoms among Chinese urban residents aged 45 and older. In total, 7397 urban respondents were included in this study. Each respondent participated in the China Health and Retirement Longitudinal Study Wave 3 (2015). Environmental-level variables were retrieved from the National Bureau of Statistics database. Both unadjusted and adjusted methods were used in the multilevel regression analysis. Almost one-third of the sample population suffered from depressive symptoms (31.20%). The multilevel logistic regression model showed that green coverage ratio of city-built districts is negatively associated with the prevalence of depressive symptoms among urban mid-aged (OR = 0.79, p < 0.05) and elderly (OR = 0.75, p < 0.05) residents, and the public recreational green space helps to reduce elderly people's depressive symptoms (OR = 0.77, p < 0.05). This study adds insights about the impact of green space and other environmental factors on depressive symptoms among mid-aged and elderly urban dwellers. It is important to provide enough and accessible overall urban green spaces; additionally, attention should also be paid to specific green space forms such as public recreational green space.

Assessment of Food Quality in School Canteens: A Comparative Quantitative Study between Primary and Secondary Schools in Malaysia.

Schools are an important food environment to cultivate and promote healthy food choices and practices among children and adolescents. The aim of the present study was to assess the type and quality of food and beverages sold in school canteens in public primary and secondary schools in Kelantan, Malaysia. Eligible schools were randomly selected from the list of all schools and detailed information of all food and beverage items sold in the school canteens were collected during school days. Food and beverages were classified based on food groups derived from the Malaysian Food Dietary Guideline and the Recommended Foods for Healthy Cafeteria Guideline. An assessment of the traffic-light nutrition food-labelling system of the total sugar content in all pre-packaged foods was also undertaken. A total of 568 food items were identified, with secondary school canteens selling a greater proportion of food items than the primary schools (55.5% vs. 44.5%). In terms of the main food groups, grains and cereal products represented the largest food group served (33-36%), followed by beverages (21-25%) and confectionary and sweet foods (12-13%). In contrast, the vegetable and fruit group represented the smallest proportion of food items sold (1-3%). Comparisons between primary and secondary schools showed a similar trend and pattern of food types and quality of foods sold, except for animal-based foods. A greater percentage of food items in this category was found among secondary schools (12.1%) versus primary schools (6.7%). When total sugar content of all pre-packaged foods was quantified based on the traffic-light nutrition-labelling system, almost one-third of foods and beverages were classified as high (29.1%). Confectionary (19.1%) and flavoured milk and fruit drinks (10.0%) both exceeded the recommended sugar levels of >22.5 g per 100 g and >11.25 mL per 100 m L, respectively. Only one of these packaged foods and beverages (0.9%) was classified as a healthy food choice. About a quarter of the food items available in school canteens were classified as prohibited based on a new revised list of prohibited food and beverage items. These findings indicate that, despite the Guidelines, a large number of unhealthy food items are being sold in school canteens. Hence, interventions such as sustainable healthy school canteen menus should be implemented to promote healthy food choices amongst school-aged children.

[Clinical effects between cannulated screw and bone plate internal fixation for humeral tuberosity fracture:a Meta analysis].

OBJECTIVE: To compare clinical effect of cannulated screw and bone plate for the treatment of humeral fracture of greater tuberosity. METHODS: From January 2010 to January 2020, clinical trial literatures on the treatment of humeral tuberosity fractures with cannulated screw and bone plate were searched by PubMed, EMbase, Cochrane Library, Wanfang, CNKI, CBM Database, VIP Database and other databases. Independent literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Revman5.2 software was used to perform Meta analysis. RESULTS: Totally 5 clinical randomized controlled trials and 12 cohort studies were selected, including 1 068 patientsin which 559 patients were treated by cannulated screw internal fixation and 509 patients treated by bone plate internal fixation. Meta analysis resluts showed that there were satistical differences in operation time[MD=-23.03, 95% CI(-29.69, -16.36), P<0.000 1], blood loss[MD=-36.39, 95% CI(-53.73, -19.04), P<0.000 1], hospital stay[MD=-1.86, 95%CI(-3.09, -0.64), P=0.003], fracture healing time [MD=-2.23, 95% CI (-4.27, -0.18), P=0.03], postoperative incidence of infection [OR=0.17, 95%CI (0.03, 0.97), P=0.05], failure rate of internal fixation [OR=3.56, 95% CI (1.29, 9.81), P=0.01] bwteen two groups. While there were no differences in postoperative visual analogue scale (VAS)[MD=-1.34, 95% CI (-2.77, 0.09), P=0.07], American Shoulder and Elbow Surgeons(ASES)[MD=0.26, 95% CI(-6.43, 6.96), P=0.94], Constant shoulder score [MD=-4.05, 95% CI(-8.51, 0.42), P=0.08], excellent rate of Constant shoulder score[MD=-1.30, 95% CI(0.46, 3.72), P=0.62], excellent rate of Neer shoulder joint score[OR=2.04, 95% CI(0.97, 4.28), P=0.06], total complication rate[OR=1.50, 95% CI (0.42, 5.35), P=0.53], incidence of postoperative pain[OR=0.74, 95% CI(0.04, 14.49), P=0.84] and incidence of postoperative acromion syndrome [OR=0.88, 95% CI (0.02, 40.63), P=0.95] between two groups. CONCLUSION: Compared with bone plate, cannulated screw for the treatment of humeral fracture of greater tuberosity has advantages of shorter opertaion time, less blood loss, shorter hospital stay, lower incidence rate of postopertaive infection, and more benefit for fracture healing.

CT Radiomics for Distinction of Human Epidermal Growth Factor Receptor 2 Negative Gastric Cancer.

RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the role of computed tomography (CT) radiomics for the prediction of the human epidermal growth factor 2 (HER2) status in patients with gastric cancer. METHODS: One hundred and thirty two consecutive patients with advanced gastric cancer undergoing radical gastrectomy were retrospectively reviewed. All patients received preoperative contrast CT examination, and immunohistochemistry results of their HER2 status were available. All the subjects were randomly divided into a training cohort (n = 90) and a test cohort (n = 42). Arterial phase (AP) and portal phase (PP) contrast CT images were retrieved for tumor segmentation and feature extraction. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate the performance of the radiomics classifiers. RESULTS: Among the 132 patients, a total of 99 patients were HER2 negative, and the remaining 33 patients were border line or positive. The AP radiomics model could distinguish HER2-negative cases with an AUC of 0.756 (95% confidence interval [CI]: 0.656-0.840) in the training cohort, which was confirmed in the test cohort with AUC of 0.830 (95% CI: 0.678-0.930). The PP radiomics model showed AUCs of 0.715 (95% CI: 0.612-0.804) and 0.718 (95% CI: 0.554-0.849) in the training and test cohort for distinction of negative HER2 cases, respectively. CONCLUSION: Radiomics models based on standard-of-care CT images hold promise for distinguishing HER2-negative gastric cancer.

ALICE: a hybrid AI paradigm with enhanced connectivity and cybersecurity for a serendipitous encounter with circulating hybrid cells.

A fully automated and accurate assay of rare cell phenotypes in densely-packed fluorescently-labeled liquid biopsy images remains elusive. Methods: Employing a hybrid artificial intelligence (AI) paradigm that combines traditional rule-based morphological manipulations with modern statistical machine learning, we deployed a next generation software, ALICE (Automated Liquid Biopsy Cell Enumerator) to identify and enumerate minute amounts of tumor cell phenotypes bestrewed in massive populations of leukocytes. As a code designed for futurity, ALICE is armed with internet of things (IOT) connectivity to promote pedagogy and continuing education and also, an advanced cybersecurity system to safeguard against digital attacks from malicious data tampering. Results: By combining robust principal component analysis, random forest classifier and cubic support vector machine, ALICE was able to detect synthetic, anomalous and tampered input images with an average recall and precision of 0.840 and 0.752, respectively. In terms of phenotyping enumeration, ALICE was able to enumerate various circulating tumor cell (CTC) phenotypes with a reliability ranging from 0.725 (substantial agreement) to 0.961 (almost perfect) as compared to human analysts. Further, two subpopulations of circulating hybrid cells (CHCs) were serendipitously discovered and labeled as CHC-1 (DAPI+/CD45+/E-cadherin+/vimentin-) and CHC-2 (DAPI+ /CD45+/E-cadherin+/vimentin+) in the peripheral blood of pancreatic cancer patients. CHC-1 was found to correlate with nodal staging and was able to classify lymph node metastasis with a sensitivity of 0.615 (95% CI: 0.374-0.898) and specificity of 1.000 (95% CI: 1.000-1.000). Conclusion: This study presented a machine-learning-augmented rule-based hybrid AI algorithm with enhanced cybersecurity and connectivity for the automatic and flexibly-adapting enumeration of cellular liquid biopsies. ALICE has the potential to be used in a clinical setting for an accurate and reliable enumeration of CTC phenotypes.

Delayed metformin treatment improves functional recovery following traumatic brain injury via central AMPK-dependent brain tissue repair.

Accumulating evidence suggests that chronic metformin posttreatment offers potent neuroreparative effects against acute brain injury. However, in previous studies, metformin was not initially administered beyond 24 h postinjury, and the effects of delayed metformin treatment in traumatic brain injury (TBI) and other types of acute brain injury and the related mechanisms are unclear. To test this, male C57BL/6 mice received once daily metformin treatment (20, 50 or 100 mg/kg/d, i.p.) at day 1-14, day 1-2, day 1-10, day 3-10, day 5-12 or day 5-28 after cryogenic TBI (cTBI). The results showed that 100 mg/kg/d metformin administered at day 1-14 postinjury significantly promoted motor functional recovery in the beam walking and gait tests and reduced the infarct volume. Metformin (100 mg/kg/d) administered at day 1-10 or day 3-10 but not day 1-2 or day 5-12 after cTBI significantly improved motor functional outcomes at day 7 and 14, and reduced the infarct volume at day 14. Interestingly, the therapeutic time window was further expanded when the duration of metformin treatment starting at day 5 postinjury was extended to 2 weeks. Furthermore, compared with cTBI, the administration of metformin at day 3-10 or day 5-28 after cTBI significantly elevated the expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and growth associated protein 43 (an axonal regeneration marker) and the number of vascular branch points and decreased the area of glial scar and the number of amoeboid microglia in the peri-infarct area at day 14 or 28 postinjury. The above beneficial effects of metformin were blocked by the intracerebroventricular injection of the AMPK inhibitor compound C (40 µg/mouse/d). Our data provide the first evidence that metformin has a wide therapeutic time window for at least 5 days after cTBI, during which it can improve functional recovery by promoting tissue repair and inhibiting glial scar formation and microglial activation in a central AMPK-dependent manner.

[Risk factors for cow's milk protein allergy in infants: a multicenter survey].

OBJECTIVE: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study. METHODS: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA. RESULTS: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors. CONCLUSIONS: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.