Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study.

AIMS: Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic. METHODS: By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions. RESULTS: A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021. CONCLUSIONS: Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study.

Background: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials. Methods: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis. Findings: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]). Interpretation: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD. Funding: National Institutes of Health, United States Department of Veterans Affairs.

Sixfold Way of Traversable Wormholes in the Sachdev-Ye-Kitaev Model.

In the infrared limit, a nearly anti-de Sitter spacetime in two dimensions (AdS_{2}) perturbed by a weak double trace deformation and a two-site (q>2)-body Sachdev-Ye-Kitaev (SYK) model with N Majoranas and a weak 2r-body intersite coupling share the same near-conformal dynamics described by a traversable wormhole. We exploit this relation to propose a symmetry classification of traversable wormholes depending on N, q, and r, with q>2r, and confirm it by a level statistics analysis using exact diagonalization techniques. Intriguingly, a time-reversed state never results in a new state, so only six universality classes occur-A, AI, BDI, CI, C, and D-and different symmetry sectors of the model may belong to distinct universality classes.

Complete coding genome sequence of a Teschovirus A genotype strain.

This study reports the complete coding genome sequence of a novel Teschovirus A genotype strain, SG2, isolated from the fecal sample of an infected indigenous pig in western Jiangxi, China.

Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM.

Objective: To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin. Design: Federated pharmacoepidemiological evaluation in LEGEND-T2DM. Setting: 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021. Participants: 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments. Exposure: The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort. Main outcomes measures: The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated. Results: 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease. Conclusions: Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.

Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.

Rates of Antipsychotic Drug Prescribing Among People Living With Dementia During the COVID-19 Pandemic.

Importance: Concerns have been raised that the use of antipsychotic medication for people living with dementia might have increased during the COVID-19 pandemic. Objective: To examine multinational trends in antipsychotic drug prescribing for people living with dementia before and during the COVID-19 pandemic. Design, Setting, and Participants: This multinational network cohort study used electronic health records and claims data from 8 databases in 6 countries (France, Germany, Italy, South Korea, the UK, and the US) for individuals aged 65 years or older between January 1, 2016, and November 30, 2021. Two databases each were included for South Korea and the US. Exposures: The introduction of population-wide COVID-19 restrictions from April 2020 to the latest available date of each database. Main Outcomes and Measures: The main outcomes were yearly and monthly incidence of dementia diagnosis and prevalence of people living with dementia who were prescribed antipsychotic drugs in each database. Interrupted time series analyses were used to quantify changes in prescribing rates before and after the introduction of population-wide COVID-19 restrictions. Results: A total of 857 238 people with dementia aged 65 years or older (58.0% female) were identified in 2016. Reductions in the incidence of dementia were observed in 7 databases in the early phase of the pandemic (April, May, and June 2020), with the most pronounced reduction observed in 1 of the 2 US databases (rate ratio [RR], 0.30; 95% CI, 0.27-0.32); reductions were also observed in the total number of people with dementia prescribed antipsychotic drugs in France, Italy, South Korea, the UK, and the US. Rates of antipsychotic drug prescribing for people with dementia increased in 6 databases representing all countries. Compared with the corresponding month in 2019, the most pronounced increase in 2020 was observed in May in South Korea (Kangwon National University database) (RR, 2.11; 95% CI, 1.47-3.02) and June in the UK (RR, 1.96; 95% CI, 1.24-3.09). The rates of antipsychotic drug prescribing in these 6 databases remained high in 2021. Interrupted time series analyses revealed immediate increases in the prescribing rate in Italy (RR, 1.31; 95% CI, 1.08-1.58) and in the US Medicare database (RR, 1.43; 95% CI, 1.20-1.71) after the introduction of COVID-19 restrictions. Conclusions and Relevance: This cohort study found converging evidence that the rate of antipsychotic drug prescribing to people with dementia increased in the initial months of the COVID-19 pandemic in the 6 countries studied and did not decrease to prepandemic levels after the acute phase of the pandemic had ended. These findings suggest that the pandemic disrupted the care of people living with dementia and that the development of intervention strategies is needed to ensure the quality of care.

Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines: international network cohort study from five European countries and the US.

OBJECTIVE: To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. DESIGN: International network cohort study. SETTING: Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. PARTICIPANTS: Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. MAIN OUTCOME MEASURES: Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. RESULTS: Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. CONCLUSIONS: In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Proteolysis of γ-tubulin small complex proteins is mediated by the ubiquitin-proteasome system.

Microtubule nucleation is mainly mediated by the γ-tubulin ring complex (γTuRC), whose core components are γ-tubulin and γ-tubulin complex proteins GCP2-6. A substantial fraction of γ-tubulin also exists with GCP2 and GCP3 in a tetramer called the γ-tubulin small complex (γTuSC). To date, the mechanisms underlying the turnover of γ-tubulin and GCPs have remained unclear. Here, we show that γ-tubulin, GCP2, and GCP3 are proteolyzed by the ubiquitin-proteasome system, and we identify cullin 1, cullin 4A, and cullin 4B as the E3 ligases that mediate the ubiquitination and, consequently, the degradation of γ-tubulin. Notably, we found that γTuSC disassembly promotes the degradation of γ-tubulin, GCP2, and GCP3, which indicates a role for γTuSCs in the stabilization of its components.

A dry electroencephalogram electrode for applications in steady-state visual evoked potential-based brain-computer interface systems.

High-efficiency electroencephalogram (EEG) dry electrodes are a key component of brain-computer interface (BCI) technology because of their direct contact with the scalp. In this study, a semi-flexible polydopamine (PDA)/Pt-TiO2 electrode is prepared for the dry-contact acquisition of EEG signals. The PDA biofilm adheres strongly to the scalp and maintains a dynamic balance of water and ions. The Pt nanoparticles and TiO2 nanotube array together result in fast electron transfer. Therefore, the interface impedance between the dry PDA/Pt-TiO2 electrode and scalp is as low as 19.63-24.53 kΩ. The spontaneous EEG signal collected simultaneously using the dry PDA/Pt-TiO2 and wet Ag/AgCl electrodes had a correlation coefficient of up to 99.9%. In a steady-state visual evoked potential (SSVEP)-based BCI system, the dry electrode was used to collect EEG feedback signals for stimulations at 27 different frequencies in the range of 7-19.25 Hz. For these feedback signals, O1, Oz, and O2 channels in the occipital area exhibited high signal-to-noise ratios of 11.3, 11.8, and 11 dB, respectively. A volunteer wore an EEG headband with three PDA/Pt-TiO2 dry electrodes and successfully controlled the robotic arm of the SSVEP-BCI system in the untrained mode. The dry PDA/Pt-TiO2 electrode-based EEG cap is comfortable to wear, the identification signals of the SSVEP paradigm are accurate, and it is suitable for controlling external devices including a keyboard in the SSVEP-BCI system.

Development of a Real-Time TaqMan PCR Method for Absolute Quantification of the Biocontrol Agent Esteya vermicola.

Esteya vermicola has been used as an effective biocontrol agent for the management of the pinewood nematode, Bursaphelenchus xylophilus. Tools for monitoring the colonization and parasitism patterns of E. vermicola are required for the development of highly effective biocontrol strategies. Because the TaqMan PCR technique is effective for quantification of species in environmental samples, a real-time PCR-based methodology was developed for absolute quantification of E. vermicola via internal standard addition and extrapolation of DNA quantity to hyphal length. Primers and a probe for the 28S ribosomal RNA gene of E. vermicola were designed, and nested TaqMan real-time PCR-based quantification was performed. In addition, internal standard-based yield measurement was correlated to the absolute quantity of target genomic DNA. Moreover, an extrapolation curve obtained by optical microscopy and image analysis of the mycelia was constructed for the measurement of fungal hyphal length. The absolute quantification method developed in the present study provides a sensitive and accurate technique to quantify fungal density in either wood or other substrate samples and can be used as an effective tool for future studies of biocontrol agents.

In vivo infection of Bursaphelenchus xylophilus by the fungus Esteya vermicola.

BACKGROUND: As the causal agent of pine wilt disease, Bursaphelenchus xylophilus, is a serious pathogen of forest pine trees. Esteya vermicola is a nematophagous fungus of B. xylophilus and exhibits great potential as a biological control agent. However, the in vivo infection mechanism of E. vermicola on B. xylophilus is unclear. Experiments were conducted to study the colonization of host plant and infection of B. xylophilus by E. vermicola inside pine tree xylem. RESULTS: A green fluorescent protein (GFP)-tagged E. vermicola transformant was constructed as a biomarker to study the in vivo colonization and infection of B. xylophilus in pine trees. The in vitro infection of B. xylophilus by E. vermicola was observed through GFP expression. The bacilloid conidia produced by trophic hyphae in the body of the nematode are described. Additionally, the monitoring of in vivo colonization by GFP-tagged E. vermicola showed the germination and hyphal extension of this fungus after inoculation. Moreover, B. xylophilus infected by this biocontrol agent were extracted from healthy seedlings and observed in the xylem of trees that were wilting due to pine wilt disease. CONCLUSION: Evidence of fungal colonization and infection of B. xylophilus by E. vermicola is provided to improve our understanding of the in vivo infection mechanisms used by this nematophagous fungus against B. xylophilus. The infection of B. xylophilus by E. vermicola was inferred to begin with the implantation of propagules, and this inference will require future investigation. The colonization of Esteya vermicola in host pine tree xylem and the in vivo infection of pinewood nematode by E. vermicola were investigated using the green fluorescence protein transformant. © 2020 Society of Chemical Industry.

Overexpression of ICAM-1 Predicts Poor Survival in High-Grade Serous Ovarian Carcinoma: A Study Based on TCGA and GEO Databases and Tissue Microarray.

Intercellular cell adhesion molecule-1 (ICAM-1), an important adhesion molecule in the immunoglobulin superfamily, is expressed on many cell types. Recent studies have identified ICAM-1 as a potential oncogene that promotes the development of epithelial ovarian cancer (EOC); it was also found to be associated with poor survival. However, the clinical significance of its expression in high-grade serous ovarian carcinoma (HGSOC) is unclear. Thus, this study aimed to investigate the significance of ICAM-1 expression in HGSOC. Data on ICAM1 expression and mutations in serous ovarian carcinoma (SOC) were obtained from the Cancer Genome Atlas (TCGA), and ICAM1 mRNA expression data in HGSOC were obtained from the Gene Expression Omnibus (GEO) database. ICAM-1 expression was evaluated by immunohistochemistry in HGSOC and normal fallopian tube tissues microarray. In TCGA data, amplification/mutation of ICAM1 was identified in 12% of serous ovarian carcinoma samples, and overexpression of ICAM1 mRNA predicted reduced overall survival in SOC. From TCGA and GEO data, SOC patients with ICAM1 mRNA overexpression treated with chemotherapeutic drugs that contained taxol or taxol and platin together had significantly reduced progression-free survival. According to GEO data, ICAM1 mRNA expression was found significantly higher in HGSOC than in control samples. In our study, ICAM-1 overexpression was observed in 63.1% (65/103) of HGSOCs. As a prognostic biomarker, overexpression of ICAM-1 predicted reduced recurrence-free and overall survival and is an independent risk factor for poor prognosis. These findings suggest that overexpression of ICAM-I is an independent indicator of poor prognosis for HGSOC and that it can serve as an effective clinical prognostic biomarker for this disease.

Start-Up of a Biofilter in a Full-Scale Groundwater Treatment Plant for Iron and Manganese Removal.

In recent years, biological purification technology has been widely developed in the process of iron and manganese removal from groundwater. The cultivation and maturation of the biological filter layer are key for biological iron and manganese removal processes. The time needed for maturation varies significantly with the water quality, filter and filter media conditions and operation parameters; sometimes it takes only one or two months, sometime more than half a year. In this paper, the feasibility of adopting an intermittent operation for the cultivation of biofilter was investigated with productive filters in a groundwater treatment plant, and the comparative test of the filter column was conducted. The results showed that the intermittent operation had little effect on the cultivation of the biofilter because dissolved oxygen would be gradually exhausted during the filter-suspension process, making the filter layer anaerobic, thus possibly inhibiting the growth and reproduction of IMOB (Iron and Manganese Oxidizing Bacteria). At the same time, the test shows that when the mature biological filter needs the suspension operation, the emptying method should be considered to avoid the destruction of the biological layer.

A pine wood sample preparation method for high target and quality DNA extraction for detection of Esteya vermicola by PCR from living pine.

Esteya vermicola is an endophytic fungus of pine wood nematode with demonstrated biocontrol efficacy. At present, the methods for detection of this fungus from pine wood is still inconvenient and inefficient such as thin-section microscopic observations. In the present study, a simple protocol was developed for wood sample preparation for effective extraction of fungal DNA from wood samples for PCR detection. The protocol of preparation of the sample involves washing in sterile water overnight on a shaking table followed by filtration and centrifugation to obtain the extracted DNA. The result indicates that with this sample preparation protocol, any proper DNA extraction method can be effectively used for the rapid and reliable detection of E. vermicola from pine wood. This method can provide valuable support for follow-up studies with practical applications, such as investigation of the growth rate of E. vermicola and how long it remains viable inside a pine tree.

Primary Cervical Malignant Melanoma: 2 Cases and a Literature Review.

Primary cervical malignant melanoma (MM) is an extremely rare tumor, and we are only aware of 44 reported cases. Further information is needed with regard to this disease's clinicopathologic features. Two patients (55 and 81 yr old) with postmenopausal vaginal bleeding were diagnosed with primary cervical MM on the basis of hematoxylin-eosin staining and immunohistochemistry findings. Our literature review revealed that the average age in cases of primary cervical MM was 59 yr (range, 34-81 yr); 93% of patients presented with vaginal bleeding, and 82% of patients were diagnosed at an early clinical stage (International Federation of Gynecology and Obstetrics stages I-II). Primary cervical MM is an extremely rare cervical tumor and is associated with a poor prognosis. Histologic morphology and immunohistochemistry are very important considerations for diagnosing this disease, which must be differentiated from cervical undifferentiated carcinoma, leiomyosarcoma, and malignant peripheral schwannoma.

[Arsenic(â ¤) Removal by Granular Adsorbents Made from Backwashing Residuals from Biofilters for Iron and Manganese Removal].

Granular adsorbents for arsenic removal (GA) made from the backwashing residuals from iron and manganese removal biofilters for groundwater were characterized and examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy, X-ray diffraction (XRD), and BET surface area measurement. The results showed that the GA had rough surfaces, developed pores, and were mainly amorphous, with small fractions of crystalline quartz and hematite. The surface area of the GA, which consists of many mesopores, was 43.8 m2·g-1. The kinetic studies revealed that arsenate adsorption on the GA was described by a pseudo-second-order kinetic equation, and the Freundlich isotherm equation fit the arsenate adsorption well (R2=0.994). The maximum adsorption capacity calculated by the Langmuir isotherm equation for As(Ⅴ) was 5.05 mg·g-1. Further studies showed that the GA operated well for As(Ⅴ) removal over a broad range in pH from 1.1 to 9.5. The coexistence of HCO3- and SO42- had no great influence on arsenic adsorption, while the H2PO4- and SiO32- showed negative effects. The GA can be regenerated well, and 82% of the original adsorption capacity was maintained after three regeneration cycles.

Ovarian microcystic stromal tumor with undetermined potential: case study with molecular analysis and literature review.

Ovarian microcystic stromal tumor is a relatively rare tumor type. This tumor is characterized by a unique microcyst structure, and essentially all tumors show benign biological behavior. Here, we report a case with a primary ovarian microcystic stromal tumor that experienced recurrence. Pathological findings showed that the original tumor, relapsed tumor in the ovary, and the recurrent tumor in the iliac fossa presented similar histologic features. The tumor mainly consisted of microcysts, solid cellular regions, and a fibrous stroma. Immunohistochemically, the tumor cells were positive for ß-catenin, CD10, vimentin, and WT-1. Mutational analysis revealed a missense mutation (c.1590C>T; pG530E) in exon 15 of the APC gene and another missense mutation (c.740G>A; pA247V) in exon 1 of the KRAS gene. We also reviewed other published cases to evaluate the prognosis and treatment. This is the first report to describe a microcystic stromal tumor of the ovary presenting with undetermined biological potential.

Electronic Health Record Driven Prediction for Gestational Diabetes Mellitus in Early Pregnancy.

Gestational diabetes mellitus (GDM) is conventionally confirmed with oral glucose tolerance test (OGTT) in 24 to 28 weeks of gestation, but it is still uncertain whether it can be predicted with secondary use of electronic health records (EHRs) in early pregnancy. To this purpose, the cost-sensitive hybrid model (CSHM) and five conventional machine learning methods are used to construct the predictive models, capturing the future risks of GDM in the temporally aggregated EHRs. The experimental data sources from a nested case-control study cohort, containing 33,935 gestational women in West China Second Hospital. After data cleaning, 4,378 cases and 50 attributes are stored and collected for the data set. Through selecting the most feasible method, the cost parameter of CSHM is adapted to deal with imbalance of the dataset. In the experiment, 3940 samples are used for training and the rest 438 samples for testing. Although the accuracy of positive samples is barely acceptable (62.16%), the results suggest that the vast majority (98.4%) of those predicted positive instances are real positives. To our knowledge, this is the first study to apply machine learning models with EHRs to predict GDM, which will facilitate personalized medicine in maternal health management in the future.

Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y1 Receptor.

The human P2Y1 receptor (P2Y1R) is a purinergic G-protein-coupled receptor (GPCR) that functions as a receptor for adenosine 5'-diphosphate (ADP). An antagonist of P2Y1R might potentially have antithrombotic effects, whereas agonists might serve as antidiabetic agents. On the basis of the antagonist-bound MRS2500-P2Y1R crystal structure, we constructed computational models of apo-P2Y1R and the agonist-receptor complex 2MeSADP-P2Y1R. We then performed conventional molecular dynamics (cMD) and accelerated molecular dynamics (aMD) simulations to study the conformational dynamics after binding with agonist/antagonist as well as the P2Y1R activation mechanism. We identified a new agonist-binding site of P2Y1R that is consistent with previous mutagenesis data. This new site is deeper than those of the agonist ADP in the recently simulated ADP-P2Y1R structure and the antagonist MRS2500 in the MRS2500-P2Y1R crystal structure. During P2Y1R activation, the cytoplasmic end of helix VI shifts outward 9.1 Å, the Ser1463.47-Tyr2375.58 hydrogen bond breaks, a Tyr2375.58-Val2626.37 hydrogen bond forms, and the conformation of the χ1 rotamer of Phe2696.44 changes from parallel to perpendicular to helix VI. The apo-P2Y1R system and the MRS2500-P2Y1R system remain inactive. The newly identified agonist binding site and activation mechanism revealed in this study may aid in the design of P2Y1R antagonists/agonists as antithrombotic/antidiabetic agents, respectively.