Objective: To test the impact of the coronavirus disease 2019 (COVID) pandemic on the emotions, behavior, and wellness behaviors of first-year college students.

Method: 675 first-year university students completed a full assessment of behavioral and emotional functioning at the beginning of the spring semester 2020. Of these, 576 completed the same assessment at the end of the spring semester, 600 completed at least one item from a COVID-related survey following the onset of COVID pandemic, and 485 completed nightly surveys of mood and wellness behaviors on a regular basis before and after the onset of the COVID crisis.

Results: Externalizing problems (M=-0.19, 95% CI=-0.06-0.33, p=0.004) and attention problems (M=-0.60, 95% CI=-0.40-0.80, p<0.001) increased following onset of COVID, but not internalizing symptoms (M=0.18, 95% CI=-0.1-0.38, p=0.06). Students who were enrolled in a campus wellness program were less affected by COVID in terms of internalizing symptoms (β= 0.40, SE=0.21, p=0.055) and attention problems (β= 0.59, SE=0.21, p=0.005) than those not in the wellness program. Nightly surveys of both mood (β= -0.10, SE=0.03, p=0.003) and daily wellness behaviors (β= -0.06, SE=0.03, p=0.036), but not stress (β= 0.02, SE=0.03, p=0.58), were negatively affected by the COVID crisis. The overall magnitude of these COVID-related changes were modest, but persistent across the rest of the semester, and different from patterns observed in a prior year.

Conclusion: COVID and associated educational/governmental mitigation strategies had a modest but persistent impact on mood and wellness behaviors of first-year University students. Colleges should prepare to address the continued mental health impacts of the pandemic.

Keywords: COVID; adolescence; college behavior change; substance use; wellness; young adulthood.

This study reports on parent-child dynamics following COVID-19 related school closures, based on cross-sectional analyses of a survey that utilized a convenience sampling approach. Data were collected approximately five weeks after the World Health Organization declared that the Coronavirus was a pandemic. Participants (N = 405) were adults recruited throughout the U.S. This study examines data from parents (69% mothers and 31% fathers) with at least one child 0-12 years of age. The majority were White (71%) and 41% had at least a bachelor's degree. 78% of parents said they were educating their child at home due to COVID-19. Most (77.1%) reported use of online tools for at-home education, including educational apps, social media, and school-provided electronic resources. More than one-third (34.7%) of parents said their child's behavior had changed since the pandemic, including being sad, depressed, and lonely. Most parents were spending more time involved in daily caregiving of their children since COVID-19. Two out of every five parents met the PHQ-8 criteria for major depression or severe major depression (40.0%) and the GAD-7 criteria for moderate or severe anxiety (39.9%). Multivariate analyses indicated that, compared to non-depressed parents, parents who met criteria for probable major or severe depression (B = -.16, 95% CI = [-.29, -.02], p = .021) and parenting stress (B = -.37, 95% CI = [-.47, -.27], p < .001) were negatively associated with parents' perceived preparation to educate at home. Compared to parents with minimal or mild anxiety, parents with moderate or severe anxiety reported higher child anxiety scores (B = .17, 95% CI = [.06, .28], p = .002). Parenting stress was also positively associated with higher child anxiety scores (B = .40, 95% CI = [.32, .48], p < .001). Content analyses of open-ended questions indicated that school closures were a significant disruption, followed by lack of physical activity, and social isolation. Overall, study results suggested that parents' mental health may be an important factor linked to at-home education and child wellbeing during the pandemic.

Keywords: Coronavirus; anxiety; child behavior problems; depression; homeschool; parenting stress.

(<em>b</em>)Rational:</<em>b</em>) LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from <em>b</em>enign solitary pulmonary nodules, which calls for <em>b</em>etter non-invasive diagnostic tools. (<em>b</em>)Methods:</<em>b</em>) We performed DNA methylation profiling <em>b</em>y high throughput DNA <em>b</em>isulfite sequencing in tissue samples (nodule size &<em>lt</em>; 3 cm in diameter) to learn methylation patterns that differentiate cancerous tumors from <em>b</em>enign lesions. Then we fi<em>lt</em>ered out methylation patterns exhi<em>b</em>iting high <em>b</em>ackground in circulating tumor DNA (ctDNA) and <em>b</em>ui<em>lt</em> an assay for plasma sample classification. (<em>b</em>)Resu<em>lt</em>s:</<em>b</em>) We first performed methylation profiling of 230 tissue samples to learn cancer-specific methylation patterns which achieved a sensitivity of 92.7% (88.3% - 97.1%) and a specificity of 92.8% (89.3% - 96.3%). These tissue-derived DNA methylation markers were further fi<em>lt</em>ered using a training set of 66 plasma samples and 9 markers were selected to <em>b</em>uild a diagnostic prediction model. From an independent validation set of additional 66 plasma samples, this model o<em>b</em>tained a sensitivity of 79.5% (63.5% - 90.7%) and a specificity of 85.2% (66.3% - 95.8%) for differentiating patients with malignant tumor (n = 39) from patients with <em>b</em>enign lesions (n = 27). Additionally, when tested on gender and age matched asymptomatic normal individuals (n = 118), our model achieved a specificity of 93.2% (89.0% - 98.3%). Specifically, our assay is highly sensitive towards early-stage lung cancer, with a sensitivity of 75.0% (55.0%-90.0%) in 20 stage Ia lung cancer patients and 85.7% (57.1%-100.0%) in 7 stage I<em>b</em> lung cancer patients. (<em>b</em>)Conclusions:</<em>b</em>) We have developed a novel sensitive <em>b</em>lood <em>b</em>ased non-invasive diagnostic assay for detecting early stage lung cancer as well as differentiating lung cancers from <em>b</em>enign pulmonary nodules.

Herein, new biodegradable star polymer-doxorubicin conjugates designed for passive tumor targeting were investigated, and their synthesis, physico-chemical characterization, drug release, biodegradation, biodistribution and in vivo anti-tumor efficacy are described. In the conjugates, the core formed by poly(amidoamine) (PAMAM) dendrimers was grafted with semitelechelic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing doxorubicin (Dox) attached by hydrazone bonds, which enabled intracellular pH-controlled drug release. The described synthesis facilitated the preparation of biodegradable polymer conjugates in a broad range of molecular weights (200-1000g/mol) while still maintaining low polydispersity (~1.7). The polymer grafts were attached to the dendrimers through either stable amide bonds or enzymatically or reductively degradable spacers, which enabled intracellular degradation of the high-molecular-weight polymer carrier to excretable products. Biodegradability tests in suspensions of EL4 T-cell lymphoma cells showed that the rate of degradation was much faster for reductively degradable conjugates (close to completion within 24h of incubation) than for conjugates linked via an enzymatically degradable oligopeptide GFLG sequence (slow degradation taking several days). This finding was likely due to the differences in steric hindrance in terms of the accessibility of the small molecule glutathione and the bulky enzyme cathepsin B to the polymer substrate. Regarding drug release, the conjugates were fairly stable in buffer at pH 7.4 (model of blood stream) but released doxorubicin under mild acidic conditions that model the tumor cell microenvironment. The star polymer-Dox conjugates exhibited significantly prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice, indicating the important role of the EPR effect in its anti-cancer activity. The star polymer conjugates showed prominently higher in vivo anti-tumor activities than the free drug or linear polymer conjugate when tested in mice bearing EL4 T-cell lymphoma, with a significant number of long-term surviving (LTS). Based on the results, we conclude that a M(w) of HPMA copolymers of 200,000 to 600,000g/mol is optimal for polymer carriers designed for the efficient passive targeting to solid tumors. In addition, an expressive therapy-dependent stimulation of the immune system was observed.

Leukotriene (LT) B(4) is a potent inflammatory lipid mediator that has been involved in the pathophysiology of respiratory diseases including asthma. Exhaled breath condensate (EBC) is a non-invasive method to sample secretions from the airways. LC/MS/MS techniques for measuring LTB(4) concentrations in EBC have been developed and are suitable for an accurate quantitative assessment of its concentrations in EBC. LC/MS/MS for other eicosanoids including 8-isoprostane, a marker of oxidative stress, and cysteinyl-LTs have been developed. This article, mainly focused on LTB(4), presents the analytical aspects of the LC/MS/MS techniques for measuring LTB(4) and 8-isoprostane in EBC, provides examples of their application to the assessment of airway inflammation in patients with asthma and other respiratory diseases, and discusses their potential utility for non-invasive monitoring of drug therapy.

This study compares the recommendations of the most recent American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Society of Hypertension (ESH) blood pressure guidelines. Both guidelines represent updates of previous guidelines and reinforce previous concepts of prevention regarding elevated blood pressure. Specifically, a low-sodium diet, exercise, body weight reduction, low to moderate alcohol intake, and adequate potassium intake are emphasized. Overall, both guidelines agree on the proper method of blood pressure measurement, the use of home blood pressure and ambulatory monitoring, and restricted use of beta-blockers as first-line therapy. The major disagreements are with the level of blood pressure defining hypertension, flexibility in identifying blood pressure targets for treatment, and the use of initial combination therapy. Although initial single-pill combination therapy is strongly recommended in both guidelines, the ESC/ESH guideline recommends it as initial therapy in patients at ≥140/90 mm Hg. The ACC/AHA guideline recommends its use in patients >20/10 mm Hg above blood pressure goal. Thus, the only real disagreement is that the ACC/AHA guidelines maintain that all people with blood pressure >130/80 mm Hg have hypertension, and blood pressure should be lowered to &lt;130/80 mm Hg in all. In contrast, the ESC/ESH guidelines state that hypertension is defined as >140/90 mm Hg, with the goal being a level &lt;140/90 mm Hg for all targeting to &lt;130/80 mm Hg only in those at high cardiovascular risk, but always considering individual tolerability of the proposed goal.

The formation of germinal centers (GC) around follicular dendritic cells (FDC) is a critical step in the humoral immune responses that depends on the cooperative effects of B cells and T cells. Mice deficient in either TNF or lymphotoxin (LT) fail to form both GC and FDC network in B cell follicles. To test a potential complementary effect of TNF and LT, a mixture of bone marrow cells from TNF(-/-) mice and LT alpha(-/-) mice was transferred into irradiated LT alpha(-/-) mice or TNF(-/-) mice. Interestingly, the formation of both GC and FDC clusters in B cell follicles was restored in such chimeric mice, suggesting that TNF and LT from different cells could complement one another. To identify the exact contributions of each subset to the complementary effect of TNF and LT, different sources of T and B cells from LT alpha(-/-) mice or TNF(-/-) mice were used for reconstitution. Our study demonstrates that either T or B cell-derived TNF is sufficient to restore FDC/GC in the presence of LT-expressing B cells. However, TNF itself is not required for GC reactions if the FDC network is already intact. Thus, the development and maintenance of these lymphoid structures depend on a delicate interaction between TNF and LT from different subsets of lymphocytes.

(<em>b</em>)O<em>b</em>jective:</<em>b</em>) To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). (<em>b</em>)Methods:</<em>b</em>) 30 patients infected with novel coronavirus referred to jianghan university hospital <em>b</em>etween January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, la<em>b</em>oratory investigation and Radiographic features. (<em>b</em>)Resu<em>lt</em>s:</<em>b</em>) The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine <em>b</em>lood test revealed WBC&<em>lt</em>;4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte coun<i>t&<em>lt</em>;</i>1.0×10(9)/L occurred in 12 petients (40%),a<em>b</em>normal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white <em>b</em>lood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and al<em>b</em>umin levels in peripheral <em>b</em>lood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed <em>b</em>ilateral pneumonia,4 patients (13.33%) showed <em>b</em>ilateral mu<em>lt</em>iple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and <em>b</em>ilateral pneumonia were <em>b</em>oth increased in the patients infected in unprotected period. (<em>b</em>)Conclusion:</<em>b</em>) Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged, white <em>b</em>lood cell count, lymphocyte count, D-dimer and al<em>b</em>umin level significantly changed and were prone to <em>b</em>e complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.

<A<em>b</em>stractText>GBR 830 is a humanized mA<em>b</em> against OX40, a costimulatory receptor on activated T cells. OX40 inhi<em>b</em>ition might have a therapeutic role in T cell-mediated diseases, including atopic dermatitis (AD).</A<em>b</em>stractText><A<em>b</em>stractText>This exploratory phase 2a study investigated the safety, efficacy, and tissue effects of GBR 830 in patients with AD.</A<em>b</em>stractText><A<em>b</em>stractText>Patients with moderate-to-severe AD (affected <em>b</em>ody surface area, ≥10%; Eczema Area and Severity Index score, ≥12; and inadequate response to topical treatments) were randomized 3:1 to 10 mg/kg intravenous GBR 830 or place<em>b</em>o on day 1 (<em>b</em>aseline) and day 29. Biopsy specimens were collected (n = 40) at days 1, 29, and 71. Primary end points included treatment-emergent adverse events (TEAEs) and changes from <em>b</em>aseline in <em>b</em>iomarkers (epidermal hyperplasia/cytokines) at days 29 and 71.</A<em>b</em>stractText><p><div>(<em>b</em>)RESULTS</<em>b</em>)</div>GBR 830 was well tolerated, with equal TEAE distri<em>b</em>ution (GBR 830, 63.0% [29/46]; place<em>b</em>o, 63.0% [10/16]). One serious TEAE in the GBR 830 group was deemed unrelated to study drug. At day 71, the proportion of intent-to-treat su<em>b</em>jects achieving 50% or greater improvement in Eczema Area and Severity Index score was greater with GBR 830 (76.9% [20/26]) versus place<em>b</em>o (37.5% [3/8]). GBR 830 induced significant progressive reductions in T<su<em>b</em>)H</su<em>b</em>)1 (IFN-γ/CXCL10), T<su<em>b</em>)H</su<em>b</em>)2 (IL-31/CCL11/CCL17), and T<su<em>b</em>)H</su<em>b</em>)17/T<su<em>b</em>)H</su<em>b</em>)22 (IL-23p19/IL-8/S100A12) mRNA expression in lesional skin. Significant progressive reductions until day 71 in the drug group were seen in OX40⁺ T cells and OX40L⁺ dendritic cells (P &<em>lt</em>; .001). Hyperplasia measures (thickness/keratin 16/Ki67) showed greater reductions with GBR 830 (P &<em>lt</em>; .001).</p><A<em>b</em>stractText>Two doses of GBR 830 administered 4 weeks apart were well tolerated and induced significant progressive tissue and clinical changes until day 71 (42 days after the last dose), highlighting the potential of OX40 targeting in patients with AD.</A<em>b</em>stractText>

<AbstractText>Closed loop deep brain stimulation (clDBS) in Parkinson's disease (PD) using subthalamic (STN) neural feedback has been shown to be efficacious only in the acute post-operative setting, using externalized leads and stimulators.</AbstractText><AbstractText>To determine feasibility of neural (N)clDBS using the clinical implanted neurostimulator (Activa™ PC + S, FDA IDE approved) and a novel <em>beta</em> dual threshold algorithm in tremor and bradykinesia dominant PD patients on chronic DBS.</AbstractText><AbstractText>13 PD subjects (20 STNs), on open loop (ol)DBS for 22 ± 7.8 months, consented to NclDBS driven by <em>beta</em> (13-30 Hz) power using a dual threshold algorithm, based on patient specific therapeutic vo<em>lt</em>age windows. Tremor was assessed continuously, and bradykinesia was evaluated after 20 min of NclDBS using a repetitive wrist flexion-extension task (rWFE). Total electrical energy delivered (TEED) on NclDBS was compared to olDBS using the same active electrode.</AbstractText><AbstractText>NclDBS was tolerated for 21.67 [21.10-26.15] minutes; no subject stopped early. Resting <em>beta</em> band power was measurable and similar between tremor and bradykinesia dominant patients. NclDBS improved bradykinesia and tremor while delivering only 56.86% of the TEED of olDBS; rWFE velocity (p = 0.003) and frequency (p &<em>lt</em>; 0.001) increased; tremor was below 0.15 rad/sec for 95.4% of the trial and averaged 0.26 rad/sec when present.</AbstractText><AbstractText>This is the first study to demonstrate that STN NclDBS is feasible, efficacious and more efficient than olDBS in tremor and bradykinesia dominant PD patients, on long-term DBS, using an implanted clinical neurostimulator and driven by <em>beta</em> power with a novel dual threshold algorithm, based on customized therapeutic vo<em>lt</em>age windows.</AbstractText>

Background: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood.

Objective: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients.

Methods: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines.

Results: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P &lt; 0.01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = 0.025) than asthmatics. COPD patients, particular those with severe COVID-19, had lower counts of CD4⁺ T and CD8⁺ T cells and B cells, and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8 and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated but TNF-α, IL-12 and IL-17A upregulated ACE2 expression in BEAS-2B cells.

Conclusion: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Keywords: angiotensin-converting enzyme II; cytokine; immune cell; severe acute respiratory syndrome coronavirus 2.

(<em>b</em>)Purpose:</<em>b</em>) Recent sequencing studies revealed that a su<em>b</em>set of colorectal cancer har<em>b</em>ors a significantly higher num<em>b</em>er of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly esta<em>b</em>lished.(<em>b</em>)Experimental Design:</<em>b</em>) We analyzed tumor mutation <em>b</em>urden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total num<em>b</em>er of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen <em>b</em>y which <em>b</em>est discriminated relapse-free survival (RFS) using the Contal and O'Quigley method.(<em>b</em>)Resu<em>lt</em>s:</<em>b</em>) In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation <em>b</em>urden (Pearson correlation = 0.873, <i>P</i> &<em>lt</em>; 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which <em>b</em>est discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with <em>b</em>etter 5-year RFS compared with TMB-low (96.3% vs. 79.8%, <i>P</i> = 0.005). A<em>lt</em>hough there was significant overlap <em>b</em>etween TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Mu<em>lt</em>ivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), <i>P</i> = 0.011].(<em>b</em>)Conclusions:</<em>b</em>) TMB-high is associated with <em>b</em>etter prognosis in patients with colorectal cancer treated with curative surgery followed <em>b</em>y adjuvant fluoropyrimidine and oxaliplatin chemotherapy.

(<em>b</em>)Purpose</<em>b</em>): The ectopic expression of N6-methyladenosine (m6A) associated genes is a common feature of mu<em>lt</em>iple tumors. However, little is known a<em>b</em>out the expression status and the prognostic value of these genes in human <em>b</em>reast cancer (BRC). Herein, we conducted a comprehensive analysis to identify the expression profiling and clinical significance of m6A-related genomic targets in BRC. (<em>b</em>)Materials and Methods</<em>b</em>): The expression data including 1109 BRC tissues and 113 normal <em>b</em>reast tissues were o<em>b</em>tained from The Cancer Genome Atlas (TCGA) data<em>b</em>ase to evaluate the mRNA expression levels of m6A-related genomic targets. In addition, 6 independent BRCA cohorts retrieved from the Gene Expression Omni<em>b</em>us (GEO) data<em>b</em>ase were enrolled to further ascertain the expression profiling of m6A-related genomic targets. Meanwhile, the immunohistochemical (IHC) staining data from BRC tissue microarray (TMA) cohort and the Human Protein Atlas (HPA) data<em>b</em>ase were used to evaluate the proteomic expression of m6A-related genomic targets. Immunofluorescence (IF) analysis was performed to validate the su<em>b</em>cellular location of m6A-related genomic targets. Moreover, the prognostic value of m6A-related genomic targets in BRC was analyzed <em>b</em>y Kaplan-Meier analysis and Cox regression models. (<em>b</em>)Resu<em>lt</em>s</<em>b</em>): m6A-related genomic targets were differentially expressed in BRC tissues. TMA IHC staining showed that most of the m6A-related genomic targets were significantly a<em>lt</em>ered at the protein level (either upregulated or downregulated), consistent with their changes in the genomic profile. IF analysis showed the su<em>b</em>cellular location of m6A-related genomic targets in BRC cell lines. Furthermore, we demonstrated that overexpression of YTHDF1 (P=0.049), YTHDF3 (P&<em>lt</em>;0.001) and KIAA1429 (P=0.032) predicted poor prognosis in terms of overall survival (OS). Upregulation of YTHDF3 was an independent prognostic factor for OS in patients with BRC (P=0.036). (<em>b</em>)Conclusion</<em>b</em>): m6A-related genomic targets are significantly a<em>lt</em>ered in BRC and predict poor prognosis. These m6A-related genomic targets could serve as novel prognostic <em>b</em>iomarkers for BRC.

Mild cognitive impairment associated with Parkinson's disease (PD) is a risk factor for the development of dementia. Despite the importance of early identification of mild cognitive impairment in PD, its prevalence and clinical correlates are still debated. The present meta-analysis provides a robust estimate of prevalence rate of mild cognitive impairment in PD according to the Movement Disorder Society clinical criteria and to explore the differences between PD patients with and without mild cognitive impairment in demographic, clinical, and neuropsychiatric features. A systematic literature search was performed up to April 2019 using PsycInfo (PROQUEST), PubMed, and Scopus. From 4706 titles and abstracts, 41 studies were selected (n = 7053 patients). Pooled mild cognitive impairment prevalence was 40% on a total sample of 7053 PD patients (95% confidence interval = 36-44; Q = 490.14, P &lt; 0.0001; I² = 91.84%) with a higher frequency for the multiple domain subtype (31%; 95% confidence interval = 23-41, Q = 93.24; P &lt; 0.0001; I² = 92.49%). Meta-regression analysis revealed that stage of PD moderate prevalence estimates of mild cognitive impairment (β = 2.80; P = 0.008). Mild cognitive impairment in PD was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose, more severe motor symptoms, and postural instability/gait difficulty motor subtype, poorer quality of life, higher levels of apathy, and depression. The present meta-analysis indicated that mild cognitive impairment in PD is a frequent cognitive status deserving to be early detected by means of standardized cognitive assessments in clinical practice. © 2019 International Parkinson and Movement Disorder Society.

<A<em>b</em>stractText>Assessing measura<em>b</em>le residual disease (MRD) has <em>b</em>ecome standard with many tumors, <em>b</em>ut the clinical meaning of MRD in mu<em>lt</em>iple myeloma (MM) remains uncertain, particularly when assessed <em>b</em>y next-generation flow (NGF) cytometry. Thus, we aimed to determine the applica<em>b</em>ility and sensitivity of the flow MRD-negative criterion defined <em>b</em>y the International Myeloma Working Group (IMWG).</A<em>b</em>stractText><p><div>(<em>b</em>)PATIENTS AND METHODS</<em>b</em>)</div>In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with <em>b</em>ortezomi<em>b</em>, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 <em>b</em>one marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved <em>b</em>y NGF was 2.9 × 10^-6. Patients received maintenance (lenalidomide ± ixazomi<em>b</em>) according to the companion PETHEMA/GEM2014MAIN trial.</p><p><div>(<em>b</em>)RESULTS</<em>b</em>)</div>Overall, 205 (45%) of 458 patients had undetecta<em>b</em>le MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetecta<em>b</em>le MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; <i>P</i> &<em>lt</em>; .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; <i>P</i> &<em>lt</em>; .001). Timing of undetecta<em>b</em>le MRD (after induction <i>v</i> intensification) had no impact on patient survival. Attaining undetecta<em>b</em>le MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetecta<em>b</em>le MRD <em>b</em>y 17%.</p><A<em>b</em>stractText>The IMWG flow MRD-negative response criterion is highly applica<em>b</em>le and sensitive to evaluate treatment efficacy in MM.</A<em>b</em>stractText>

<A<em>b</em>stractText>The London patient (participant 36 in the IciStem cohort) underwent allogeneic stem-cell transplantation with cells that did not express CCR5 (CCR5Δ32/Δ32); remission was reported at 18 months after analytical treatment interruption (ATI). Here, we present longer term data for this patient (up to 30 months after ATI), including sampling from diverse HIV-1 reservoir sites.</A<em>b</em>stractText><A<em>b</em>stractText>We used u<em>lt</em>rasensitive viral load assays of plasma, semen, and cere<em>b</em>rospinal fluid (CSF) samples to detect HIV-1 RNA. In gut <em>b</em>iopsy samples and lymph-node tissue, cell-copy num<em>b</em>er and total HIV-1 DNA levels were quantified in mu<em>lt</em>iple replicates, using droplet digital PCR (ddPCR) and quantitative real-time PCR. We also analysed the presence of intact proviral DNA using mu<em>lt</em>iplex ddPCR targeting the packaging signal (ψ) and envelope (env). We did intracellular cytokine staining to measure HIV-1-specific T-cell responses. We used low-sensitive and low-avidity anti<em>b</em>ody assays to measure the humoral response to HIV-1. We predicted the pro<em>b</em>a<em>b</em>ility of re<em>b</em>ound using a mathematical model and inference approach.</A<em>b</em>stractText><p><div>(<em>b</em>)FINDINGS</<em>b</em>)</div>HIV-1 viral load in plasma remained undetecta<em>b</em>le in the London patient up to 30 months (last tested on March 4, 2020), using an assay with a detection limit of 1 copy per mL. The patient's CD4 count was 430 cells per μL (23·5% of total T cells) at 28 months. A very low-level positive signal for HIV-1 DNA was recorded in peripheral CD4 memory cells at 28 months. The viral load in semen was undetecta<em>b</em>le in <em>b</em>oth plasma (lower limit of detection [LLD] &<em>lt</em>;12 copies per mL) and cells (LLD 10 copies per 10⁶ cells) at 21 months. CSF was within normal parameters at 25 months, with HIV-1 RNA <em>b</em>elow the detection limit (LLD 1 copy per mL). HIV-1 DNA <em>b</em>y ddPCR was negative in rectum, caecum, and sigmoid colon and terminal ileum tissue samples at 22 months. Lymph-node tissue from axilla was positive for the long-terminal repeat (33 copies per 10⁶ cells) and env (26·1 copies per 10⁶ cells), negative for ψ and integrase, and negative <em>b</em>y the intact proviral DNA assay, at 27 months. HIV-1-specific CD4 and CD8 T-cell responses have remained a<em>b</em>sent at 27 months. Low-avidity Env anti<em>b</em>odies have continued to decline. Mathematical modelling suggests that the pro<em>b</em>a<em>b</em>ility of remission for life (cure) is 98% in the context of 80% donor chimerism in total HIV target cells and greater than 99% pro<em>b</em>a<em>b</em>ility of remission for life with 90% donor chimerism.</p><A<em>b</em>stractText>The London patient has <em>b</em>een in HIV-1 remission for 30 months with no detecta<em>b</em>le replication-competent virus in <em>b</em>lood, CSF, intestinal tissue, or lymphoid tissue. Donor chimerism has <em>b</em>een maintained at 99% in peripheral T cells. We propose that these findings represent HIV-1 cure.</A<em>b</em>stractText><A<em>b</em>stractText>Wellcome Trust and amfAR (American Foundation for AIDS Research).</A<em>b</em>stractText>

(<em>b</em>)Background:</<em>b</em>) Advanced generation a<em>b</em>lation technologies have <em>b</em>een developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence following atrial fi<em>b</em>rillation (AF) a<em>b</em>lation. (<em>b</em>)Methods:</<em>b</em>) We randomly assigned 346 patients with drug-refractory paroxysmal AF to contactforce guided RF a<em>b</em>lation (CF-RF a<em>b</em>lation, 115), 4-minute cryo<em>b</em>alloon a<em>b</em>lation (CRYO-4, 115), or 2-minute cryo<em>b</em>alloon a<em>b</em>lation (CRYO-2, 116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) <em>b</em>etween days 91 and 365 post a<em>b</em>lation, or a repeat a<em>b</em>lation procedure at any time. Secondary endpoints included freedom from symptomatic arrhythmia, and AF <em>b</em>urden. All patients received an implanta<em>b</em>le loop recorder. (<em>b</em>)Resu<em>lt</em>s:</<em>b</em>) One-year freedom from atrial tachyarrhythmia defined <em>b</em>y continuous rhythm monitoring, was 53.9%, 52.2%, and 51.7% with CF-RF, CRYO-4, and CRYO-2, respectively; P=0.87. One-year freedom from symptomatic atrial tachyarrhythmia defined <em>b</em>y continuous rhythm monitoring, was 79.1%, 78.2%, and 73.3% with CF-RF, CRYO-4, and CRYO-2, respectively; P=0.26. Compared to the pre-a<em>b</em>lation monitoring period, AF <em>b</em>urden was reduced <em>b</em>y a median of 99.3% (IQR 67.8-100.0%) with CF-RF, 99.9% (IQR 65.3-100.0%) with CRYO4, and 98.4% (IQR 56.2-100.0%) with CRYO-2 (P=0.36). Serious adverse events occurred in 2 patients in CF-RF (2.6%), 6 patients in CRYO-4 (5.3%), and 7 patients in CRYO-2 (6.0%), with no significant difference <em>b</em>etween groups (P=0.24). The CF-RF group had a significantly longer procedure duration <em>b</em>ut significantly shorter fluoroscopy exposure (P&<em>lt</em>;0.001 vs. cryo<em>b</em>alloon groups). (<em>b</em>)Conclusions:</<em>b</em>) In this mu<em>lt</em>icenter, randomized, single-<em>b</em>linded trial, contact-force RF a<em>b</em>lation and two different regiments of cryo<em>b</em>alloon a<em>b</em>lation resu<em>lt</em>ed in no difference in one-year efficacy, which was 53% <em>b</em>y time to first recurrence <em>b</em>ut >98% <em>b</em>urden reduction as assessed <em>b</em>y continuous cardiac rhythm monitoring.

<A<em>b</em>stractText>Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can <em>b</em>e used as potential <em>b</em>iomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes.</A<em>b</em>stractText><p><div>(<em>b</em>)Methods and Resu<em>lt</em>s</<em>b</em>)</div>An mRNA sequencing dataset, corresponding survival data and expression profiling of an array of EC patients were o<em>b</em>tained from The Cancer Genome Atlas and Gene Expression Omni<em>b</em>us, respectively. Common differentially expressed genes (DEGs) were identified <em>b</em>ased on sequencing and expression as given in the profiling dataset. Pathway enrichment analysis of the DEGs was performed using the Data<em>b</em>ase for Annotation, Visualization, and Integrated Discovery. The protein-protein interaction network was esta<em>b</em>lished using the string online data<em>b</em>ase in order to identify hu<em>b</em> genes. Univariate and mu<em>lt</em>ivaria<em>b</em>le Cox regression analyses were used to screen prognostic DEGs and to construct a prognostic signature. Survival analysis <em>b</em>ased on the prognostic signature was performed on TCGA EC dataset. A total of 255 common DEGs were found and 11 hu<em>b</em> genes (TOP2A, CDK1, CCNB1, CCNB2, AURKA, PCNA, CCNA2, BIRC5, NDC80, CDC20, and BUB1BA) that may <em>b</em>e closely related to the pathogenesis of EC were identified. A panel of 7 DEG signatures consisting of PHLDA2, GGH, ESPL1, FAM184A, KIAA1644, ESPL1, and TRPM4 were constructed. The signature performed well for prognosis prediction (<i>p</i> &<em>lt</em>; 0.001) and time-dependent receiver-operating characteristic (ROC) analysis displayed an area under the curve (AUC) of 0.797, 0.734, 0.729, and 0.647 for 1, 3, 5, and 10-year overall survival (OS) prediction, respectively.</p><A<em>b</em>stractText>This study identified potential genes that may <em>b</em>e involved in the pathophysiology of EC and constructed a novel gene expression signature for EC risk stratification and prognosis prediction.</A<em>b</em>stractText>

To limit the transmission of COVID-19, nationwide lockdown was imposed in France between March, 17th and May 10th, 2020. This disruption in individuals' daily routines likely altered food consumption habits. We examined how changes in food choice motives related to changes in nutritional quality during the lockdown compared to before. A convenience sample of 938 French adults completed online questionnaires on the Qualtrics platform at the end of April 2020. Participants were retrospectively asked about their food choice motives and food consumption during the month before and in the first month of the lockdown. The importance of nine food choice motives was assessed: health, convenience, sensory appeal, natural content, ethical concern, weight control, mood, familiarity, and price, scoring from 1 to 4. Food intakes were recorded using a food frequency questionnaire including 110 foods, 12 non-alcoholic beverages and 4 alcoholic beverages. Adherence to the French dietary recommendations before and during the lockdown was estimated using the simplified PNNS-GS2, scoring from -17 to 11.5. The nutritional quality of diet was lower during the lockdown compared to before (-0.32, SD 2.28, p &lt; 0.001). Food choice motives significantly changed and an increase in the importance of weight control was associated with increased nutritional quality (β = 0.89, p &lt; 0.001, partial η² = 0.032), whereas an increase in the importance of mood was associated with decreased nutritional quality (β = -0.43, p = 0.021, partial η² = 0.006). The lockdown period in France was related to a decrease in nutritional quality of diet on average, which could be partly explained by changes in food choice motives. The lockdown was indeed related to modification of food choice motives, notably with an increase of mood as a food choice motive for 48% of the participants, but also with an increase of health (26%), ethical concern (21%) and natural content (19%) suggesting a growing awareness of the importance of sustainable food choices in some participants.

Keywords: COVID-19; Food choice motives; Lockdown; Nutritional quality.