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Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Background: Multiple frailty screening tools are implemented; however, it is unclear whether they perform in a comparable way for both frailty detection and prediction of perioperative outcomes in patients undergoing lower-extremity revascularization. Methods: Patients undergoing lower-extremity revascularization were identified from the Vascular Quality Initiative (VQI) national database. Two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI). Results: Out of 134,081 patients undergoing PVI, frailty was identified in 67% by mFI-5 and 28% by RAI. Similarly, out of 41,316 patients in the bypass cohort, frailty was identified in 69% by mFI-5 and 16% by RAI. There was little agreement between the two frailty tools for both vascular cohorts (PVI: kappa: 0.17; bypass: kappa: 0.13). In an adjusted analysis, frailty as assessed by mFI-5 and RAI was associated with higher odds of mortality in both cohorts ( p < 0.001). A significant association between frailty and unplanned amputations was only noted in the bypass cohort when RAI was applied (OR: 1.50, p < 0.01). The addition of frailty to traditional PAD risk factors marginally improved model performance to predict mortality and unplanned major amputations. Conclusion: There was significant variation in frailty detection by mFI-5 and RAI. Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited. Future research should focus on designing new frailty screening tools specific to the PAD population.

Amblyopia is the decreased best-corrected visual acuity (BCVA) in one or both eyes caused by the abnormal processing of visual input during development. One common cause of amblyopia is anisometropia, which has attracted widespread attention. Many structural changes occur in the primary and extrastriate visual areas of the cerebral cortex, as well as in the eyes, in patients with anisometropic amblyopia. Understanding these mechanisms has provided a favorable theoretical basis for treating anisometropic amblyopia. This article reviews the functional and anatomical changes and progress toward the treatment of anisometropic amblyopia.

Simulation studies play an important role in evaluating the performance of statistical models developed for analyzing complex survival data such as those with competing risks and clustering. This article aims to provide researchers with a basic understanding of competing risks data generation, techniques for inducing cluster-level correlation, and ways to combine them together in simulation studies, in the context of randomized clinical trials with a binary exposure or treatment. We review data generation with competing and semi-competing risks and three approaches of inducing cluster-level correlation for time-to-event data: the frailty model framework, the probability transform, and Moran’s algorithm. Using exponentially distributed event times as an example, we discuss how to introduce cluster-level correlation into generating complex survival outcomes, and illustrate multiple ways of combining these methods to simulate clustered, competing and semi-competing risks data with pre-specified correlation values or degree of clustering.

In recent years, with the gradual maturation of myopia correction surgery, the changes in binocular visual function after surgery have attracted widespread attention. The accommodation of facility, the amplitude of accommodation, relative accommodation, and accommodation convergence/accommodation assembly are essential parameters for assessing binocular visual function. The changes in these parameters are significant for guiding patients in the design of the preoperative surgical approach and alleviating postoperative visual fatigue. This paper aims to guide the preoperative assessment, design, and postoperative visual training of refractive surgery in myopic patients from the perspective of changes in binocular visual function before and after myopia and surgery, which can improve accommodation and convergence function in patients after refractive surgery.

BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual. Multiple primary cancer always presents as solid cancer or acute myeloid leukemia (AML) secondary to lymphoma. Here, we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment. CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb. Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis. Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen. Pathological biopsy revealed Burkitt lymphoma. After three hyper-CVAD (A + B) regimens, she achieved complete remission. Two years later, lymphadenectasis reoccurred. A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma, which was accompanied by gastrointestinal invasion and hemocytopenia. Meanwhile, bone marrow examination revealed AML. On the second day of scheduled treatment, she developed gastrointestinal bleeding, peptic ulcers, and hemorrhagic shock and was critically ill. She was then discharged from the hospital due to financial concerns. CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.

Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816 and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889 and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323 and rs5741880) and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879 and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single nucleotide polymorphism (SNP) rs1879026 had a higher risk of developing severe cases (GG vs GT: OR=1.875, 95% CI, 1.183-2.971, P=0.007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs CT: OR=0.350, 95% CI, 0.163-0.751, P=0.006; C vs T: OR=0.566, 95% CI, 0.332-0.965, P=0.036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs CT: OR=2.537, 95% CI, 1.108-5.806, P=0.026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs GT: OR=2.076, 95% CI, 1.144-3.768, P=0.016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290 and rs3775291 are associated with the severity of EV-A71-associated HFMD in the Chinese children population. This article is protected by copyright. All rights reserved.

Background/Aim In clinical trials, there is potential for bias from unblinded observers that may influence ascertainment of outcomes. This issue arose in the Strategies to Reduce Injuries and Develop Confidence in Elders trial, a cluster randomized trial to test a multicomponent intervention versus enhanced usual care (control) to prevent serious fall injuries, originally defined as a fall injury leading to medical attention. An unblinded nurse falls care manager administered the intervention, while the usual care arm did not involve contact with a falls care manager. Thus, there was an opportunity for falls care managers to refer participants reporting falls to seek medical attention. Since this type of observer bias could not occur in the usual care arm, there was potential for additional falls to be reported in the intervention arm, leading to dilution of the intervention effect and a reduction in study power. We describe the clinical basis for ascertainment bias, the statistical approach used to assess it, and its effect on study power. Methods The prespecified interim monitoring plan included a decision algorithm for assessing ascertainment bias and adapting (revising) the primary outcome definition, if necessary. The original definition categorized serious fall injuries requiring medical attention into Type 1 (fracture other than thoracic/lumbar vertebral, joint dislocation, cut requiring closure) and Type 2 (head injury, sprain or strain, bruising or swelling, other). The revised definition, proposed by the monitoring plan, excluded Type 2 injuries that did not necessarily require an overnight hospitalization since these would be most subject to bias. These injuries were categorized into those with (Type 2b) and without (Type 2c) medical attention. The remaining Type 2a injuries required medical attention and an overnight hospitalization. We used the ratio of 2b/(2b + 2c) in intervention versus control as a measure of ascertainment bias; ratios > 1 indicated the likelihood of falls care manager bias. We determined the effect of ascertainment bias on study power for the revised (Types 1 and 2a) versus original definition (Types 1, 2a, and 2b). Results The estimate of ascertainment bias was 1.14 (95% confidence interval: 0.98, 1.30), providing evidence of the likelihood of falls care manager bias. We estimated that this bias diluted the hazard ratio from the hypothesized 0.80 to 0.86 and reduced power to under 80% for the original primary outcome definition. In contrast, adapting the revised definition maintained study power at nearly 90%. Conclusion There was evidence of ascertainment bias in the Strategies to Reduce Injuries and Develop Confidence in Elders trial. The decision to adapt the primary outcome definition reduced the likelihood of this bias while preserving the intervention effect and study power.

Rituximab is a mouse and human chimeric CD20 (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD20 antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD20 molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.

While the gold standard for clinical trials is to blind all parties -- participants, researchers, and evaluators -- to treatment assignment, this is not always a possibility. When some or all of the above individuals know the treatment assignment, this leaves the study open to the introduction of post-randomization biases. In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial, we were presented with the potential for the unblinded clinicians administering the treatment, as well as the individuals enrolled in the study, to introduce ascertainment bias into some but not all events comprising the primary outcome. In this manuscript, we present ways to estimate the ascertainment bias for a time-to-event outcome, and discuss its impact on the overall power of a trial versus changing of the outcome definition to a more stringent unbiased definition that restricts attention to measurements less subject to potentially differential assessment. We found that for the majority of situations, it is better to revise the definition to a more stringent definition, as was done in STRIDE, even though fewer events may be observed., Comment: 31 pages, 11 figures; submitted to Statistics in Medicine

While the two-stage randomized design allows us to unbiasedly evaluate the impact of patients’ treatment preference on the outcome of interest, it may not always be practical to implement in clinical practice; patients with a strong preference may not be willing to be randomized. The more pragmatic, partially randomized preference design (PRPD) allows patients who are unwilling to be randomized, but willing to state their preference, to receive their preferred treatment in lieu of the first-stage randomization in the two-stage design, at the cost of potentially introducing bias in estimating the effects of interest. In this article, we consider the application of propensity score stratification (PSS) in a PRPD to recreate a conditional first-stage randomization based on observed covariates, enabling the estimation and inference of the overall treatment, selection and preference effects with minimum bias. We additionally derive a set of closed-form sample size formulas for detecting all three effects of interest in a PSS-PRPD. Simulation studies demonstrate the bias reduction properties of the PSS-PRPD, and validate the accuracy of the proposed sample size formulas. Our results show that 5 to 10 propensity score strata may be needed to correct for biases in effect estimates, and the exact number of strata needed to achieve the best match between the empirical power and formula prediction may depend on the degree of effect heterogeneity. Finally, we demonstrate our proposed formulas by estimating the required sample sizes to detect treatment, selection and preference effects in the context of the Harapan Study.

While statistical methods for analyzing cluster randomized trials with continuous and binary outcomes have been extensively studied and compared, little comparative evidence has been provided for analyzing cluster randomized trials with survival outcomes in the presence of competing risks. Motivated by the Strategies to Reduce Injuries and Develop Confidence in Elders trial, we carried out a simulation study to compare the operating characteristics of several existing population-averaged survival models, including the marginal Cox, marginal Fine and Gray, and marginal multi-state models. For each model, we found that adjusting for the intraclass correlations through the sandwich variance estimator effectively maintained the type I error rate when the number of clusters is large. With no more than 30 clusters, however, the sandwich variance estimator can exhibit notable negative bias, and a permutation test provides better control of type I error inflation. Under the alternative, the power for each model is differentially affected by two types of intraclass correlations—the within-individual and between-individual correlations. Furthermore, the marginal Fine and Gray model occasionally leads to higher power than the marginal Cox model or the marginal multi-state model, especially when the competing event rate is high. Finally, we provide an illustrative analysis of Strategies to Reduce Injuries and Develop Confidence in Elders trial using each analytical strategy considered.

RAB27B is a member of Ras-like small GTPases that plays a role in endocytosis, exocytosis, and vesicle trafficking. We made an attempt to study the impacts of RAB27B on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. The silencing of RAB27B was induced by siRNA for the detection of proliferation, cell cycle, and apoptosis, respectively by Cell Counting Kit-8 (CCK8), flow cytometry, and TUNEL. Related markers were also evaluated by Western blot analysis. The interaction between RAB27B and BDH2 was predicted by bioinformatics analysis and determined by immunoprecipitation. The gain of function of BDH2 was also detected by these functional assays. RAB27B exhibited high levels in AML cells, and RAB27B silencing led to reduced proliferation, increased cell cycle arrest and apoptosis levels. Then, the interaction between RAB27B and BDH2 was confirmed. Moreover, the effects of RAB27B inhibition on the proliferation, cell cycle arrest, and cell apoptosis were abolished after BDH2 overexpression. RAB27B inhibits proliferation and promotes apoptosis of leukemic cells by interacting with BDH2. Targeting RAB27B might be an effective method for the treatment of AML.

Author(s): Jennings, Lee A; Araujo, Katy LB; Meng, Can; Peduzzi, Peter; Charpentier, Peter; Reuben, David B | Abstract: BackgroundBecause of the COVID-19 pandemic, the ongoing D-CARE pragmatic trial of two models of dementia care management needed to transition to all data collection by telephone.MethodsFor the first 1069 D-CARE participants, we determined the feasibility of administering a short 3-item version of the Montreal Cognitive Assessment (MoCA) to persons with dementia by telephone and examined the correlation with the full 12-item version.ResultsThe 3-item version could be administered by telephone in approximately 6nmin and was highly correlated with the full MoCA (rn=n0.78, p l 0.0001).ConclusionsThis brief version of the MoCA was feasible to collect by telephone and could be used as an alternative to the full MoCA, particularly if the purpose of cognitive assessment is characterization of study participants.

Significant improvement in ductility without strength loss is achieved by the hierarchical refinement of the pearlite in hypoeutectoid steels, through two approaches, i.e., the grain refinement and increasing the undercooling degree. The increased undercooling is achieved by a temporary undercooling treatment without austenite decomposition at bainitic temperature before the transformation of pearlite. Further refined colonies with increased misorientation are developed in the undercooled sample, whereas such colonies exhibit thicker ferrite plates and thinner cementite plates than fine-grained sample. The two aspects account for the higher ductility manifested by the undercooled sample, and the thickness ratio of cementite/ferrite plates can therefore be used to evaluate the ductility of lamellar pearlite. In addition, the uniformity of the colonies structure has positive effect on the enhanced ductility. This work provides a new understanding of high-performance fully pearlitic steels, which are expected to be applicable in drawing processes.

Background Research suggests that growth in Black and Hispanic (minority) older adults' nursing home (NH) use may be the result of disparities in access to community-based and alternative long-term services and supports (LTSS). Objective We aimed to determine whether minority groups receiving care in NHs versus the community had fewer differences in their functional needs compared with the differences in nonminority older adults, suggesting a disparity. Methods We identified respondents aged 65 years or above with a diagnosis of Alzheimer disease or dementia in the 2016 Health and Retirement Study who reported requiring LTSS help. We performed unadjusted analyses to assess the difference in functional need between community and NH care. Functional need was operationalized using a functional limitations score and 6 individual activities of daily living. We compared the LTSS setting for minority older adults to White older adults using difference-in-differences. Results There were 186 minority older adults (community=75%, NH=25%) and 357 White older adults (community=50%, NH=50%). Between settings, minority older adults did not differ in education or marital status, but were younger and had greater income in the NH versus the community. The functional limitations score was higher in NHs than in the community for both groups. Functional needs for all 6 activities of daily living for the minority group were greater in NHs compared with the community. Conclusion Functional need for minority older adults differed by setting while demographics varied in unexpected ways. Factors such as familial and financial support are important to consider when implementing programs to keep older adults out of NHs.

To analyze and evaluate the nutritional composition of five main products of freshwater shrimp including crawfish, river prawn, macrobrachium, freshwater shrimp, exopalaemon modestus in Anhui Province.Conventional and biochemical analytical method were used to detect the moisture, ash, crude protein, crude fat, amino acid, fatty acid, minerals and vitamin.The contents of crude protein, crude fat, ash of the five freshwater shrimp were 13. 9-20. 8 g/100 g edible, 0. 6-2. 2 g/100 g edible, 1. 5-4. 1 g/100 g edible, respectively. A total of 18 amino acids were detected, the content of which were 11600-18600 mg/100 g edible. The amount of nine essential amino acid was measured to be 5336-9342 mg/100 g edible. The main restrictive amino acids in the five kinds of shrimps were methionine and cysteine, threonine and valine. The essential amino acid indexes in five kinds of shrimps(EAAI) were 39. 62 and 31. 81, 28. 65, 44. 85, and 33. 48, respectively. Fourteen types of fatty acid were detected. The total content of fatty acid was 287-1851 mg/100 g edible. The monounsaturated fatty acid(MUFA) and the polyunsaturated fatty acid(PUFA) were 12-234 mg/100 g edible, 164-377 mg/100 g edible, respectively. Nine minerals were detected which including five microelements and four microelements. The content of calcium in river prawn, macrobrachium and exopalaemon modestus was higher than that in crawfish and freshwater shrimp. The content of phosphorus, kalium, sodium, magnesium in five freshwater shrimp were 221-296 mg/100 g edible, 196-278 mg/100 g edible, 120. 7-202. 7 mg/100 g edible, 37-95 mg/100 g edible, respectively. The content of iron, manganese, cuprum in crawfish were higher than the others. The content of zinc in river prawn and exopalaemon modestus was high. Moreover, the vitamin B_2 and E were also detected in five freshwater shrimp. The content of vitamin B_2 and E were 0. 02-0. 07 mg/100 g edible and 1. 61-3. 30 mg/100 g edible.Five main products of freshwater shrimp in Anhui belong to super nutritional value food which contained high protein, variety of amino acid, low fat, a certain amount of vitamin B_2 and E, rich in minerals.

Author(s): Gill, Thomas M; Bhasin, Shalender; Reuben, David B; Latham, Nancy K; Araujo, Katy; Ganz, David A; Boult, Chad; Wu, Albert W; Magaziner, Jay; Alexander, Neil; Wallace, Robert B; Miller, Michael E; Travison, Thomas G; Greenspan, Susan L; Gurwitz, Jerry H; Rich, Jeremy; Volpi, Elena; Waring, Stephen C; Manini, Todd M; Min, Lillian C; Teresi, Jeanne; Dykes, Patricia C; McMahon, Siobhan; McGloin, Joanne M; Skokos, Eleni A; Charpentier, Peter; Basaria, Shehzad; Duncan, Pamela W; Storer, Thomas W; Gazarian, Priscilla; Allore, Heather G; Dziura, James; Esserman, Denise; Carnie, Martha B; Hanson, Catherine; Ko, Fred; Resnick, Neil M; Wiggins, Jocelyn; Lu, Charles; Meng, Can; Goehring, Lori; Fagan, Maureen; Correa-de-Araujo, Rosaly; Casteel, Carri; Peduzzi, Peter; Greene, Erich J | Abstract: Background/objectivesIn the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability.DesignPragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries.SettingA total of 86 primary care practices within 10 U.S. healthcare systems.ParticipantsA random subsample of 743 persons aged 75 and older.MeasurementsThe well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument.ResultsParticipants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference.ConclusionsSTRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.

Background: Migration is at an all-time high worldwide, and despite increased focus on international migrants, there is little evidence about internal migrants’ exposures to socioeconomic, occupational, and environmental risk factors in low-and middle-income countries. Objective: The aim of this study was to examine differences in occupational health and access to water, sanitation, and hygiene (WASH) between internal migrants and non-migrants. Methods: A face-to-face survey (n = 937) was conducted in Mandalay, Myanmar. Bivariate and multivariate analysis included traditional social determinants such as education, income, occupation, gender, age, and location in addition to internal migration status. Findings: The majority of internal migrants (23% of the total sample) were labor migrants (67.3%), and while common social determinants (e.g., household income, education, and gender) were not statistically different between migrants and non-migrants, these groups reported different occupational profiles (p < 0.001). Migrants had higher odds of being street vendors (AOR = 2.26; 95% CI 1.33–3.85; p = 0.003) and were less likely to work labor jobs such as in factories or construction (AOR = 0.44; 95% CI 0.19–1.00; p = 0.051) when controlling for age, gender, education, and location. Internal migrants had significantly greater probabilities of experiencing some injuries and illness symptoms, such as cuts, vomiting, coughing, heatstroke, and diarrhea at work (p < 0.001). Compared to non-migrants, migrants’ households were approximately three times more likely (AOR = 3.45; 95% CI 2.17–5.62; p < 0.001) to have an unimproved source of drinking water and twice as likely (AOR = 1.98; 95% CI 1.10–3.58; p < 0.05) to have unimproved sanitation facilities in their homes. Conclusions: The results underscore the importance of considering internal migration as an aspect of social determinants analyses, and the need for targeting appropriate WASH interventions to address inequities.

Author(s): Reuben, David B; Gill, Thomas M; Stevens, Alan; Williamson, Jeff; Volpi, Elena; Lichtenstein, Maya; Jennings, Lee A; Tan, Zaldy; Evertson, Leslie; Bass, David; Weitzman, Lisa; Carnie, Martie; Wilson, Nancy; Araujo, Katy; Charpentier, Peter; Meng, Can; Greene, Erich J; Dziura, James; Liu, Jodi; Unger, Erin; Yang, Mia; Currie, Katherine; Lenoir, Kristin M; Green, Aval-NaʼRee S; Abraham, Sitara; Vernon, Ashley; Samper-Ternent, Rafael; Raji, Mukaila; Hirst, Roxana M; Galloway, Rebecca; Finney, Glen R; Ladd, Ilene; Rahm, Alanna Kulchak; Borek, Pamela; Peduzzi, Peter | Abstract: Background/objectivesAlthough several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown.DesignPragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad.SettingFour clinical trial sites (CTSs) based in academic and clinical health systems.ParticipantsA total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers.InterventionsEighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline.MeasurementsPrimary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales.Secondary outcomesNPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims.ResultsThe results will be reported in the spring of 2024.ConclusionD-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more closely to community resources. It will also assess the effectiveness of both interventions compared with UC and will evaluate the cost effectiveness of each intervention.

BackgroundInjuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined.MethodsWe conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group.ResultsThe demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups.ConclusionsA multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.).

How nitrate (NO3-) fertilization influences ciprofloxacin (CIP) uptake by crops remains unsolved. Here, two Brassica parachinensis cultivars differing in CIP accumulation were cultivated to investigate the effects of NO3- supply on CIP uptake and the underlying mechanism. The results showed that NO3- supply effectively reduced CIP toxicity and accumulation in the two cultivars, especially in the low CIP cultivar. Moreover, NO3- supply induced different mechanisms of coping with CIP stress in the two cultivars through influencing subcellular distribution of CIP. The uptake of CIP by root was demonstrated to be a carrier-mediated, energy-consuming, and proton motive force-dependent influx process. Consequently, a mechanism of nitrate supply decreasing CIP uptake was proposed that uptake of CIP and NO3- into root cell would compete for the proton motive force and share a common energy source provided by plasma membrane H+-ATPase. Besides, regulating the concentration balances of cytoplasmic NO3- and proton by inhibiting the activities of NRase and two tonoplast proton pumps (V-ATPase and V-PPase) led to opposite effect on CIP uptake, further supporting this inference. Our results provide a novel insight into CIP uptake by plant roots, and improve the strategy of minimizing CIP accumulation in crops for food safety by fertilization management.

The study objective was to examine barriers and facilitators of maternal health services utilization in Myanmar with the highest maternal mortality ratio in Southeast Asia. Data for 258 mothers with children under five were extracted from a community health survey administered between 2016 and 2017 in Mandalay, the largest city in central Myanmar, and analyzed for associations between determinants of maternal health care choices and related outcomes. The study showed that late antenatal care was underutilized (41.7%), and antenatal care attendance was significantly associated with geographical setting, household income, education, and access to transportation (p &le, 0.05). Less than one-third of women gave birth at home and 18.5% of them did so without the assistance of traditional birth attendants. Household education level was a significant predictor for home delivery (p &lt, 0.01). Utilization of postnatal care services was irregular (47.9%&ndash, 70.9%) and strongly associated with women&rsquo, s places of delivery (p &lt, 0.01). Efforts geared towards improving maternal health outcomes should focus on supporting traditional birth attendants in their role of facilitating high-quality care and helping women reach traditional health facilities, as well as on maternal health literacy based on culturally appropriate communication.

Introduction: Blood pressure (BP) is an important modifiable parameter after endovascular thrombectomy (EVT). Observational studies have found associations between elevated BP after EVT with hemorrhagic transformation and poor functional outcome. However, blood pressure course after EVT has not been well characterized and optimal hemodynamic management in the immediate post-stroke period remains unresolved. We utilized blood pressure data up to 72 hours after EVT to identify distinct systolic BP (SBP) trajectories and studied their associations with functional outcome. Methods: We retrospectively studied a multicenter cohort of 1060 patients with large-vessel occlusion stroke who underwent EVT. BP was recorded non-invasively recorded at least hourly for the first 72 hours. Functional outcome was assessed using the modified Rankin scale (mRS). Favorable functional outcome was defined as mRS &lt. Latent variable mixture modeling was applied to identify patient subgroups that have comparable SBP trajectories. All analyses were adjusted for age, admission NIHSS, and recanalization status. Results: One thousand sixty patients (mean age 70±15, mean NIHSS 16) were included in the analysis. Five distinct SBP trajectories were identified: (1) low (17%), (2) moderate (38%), (3) moderate-to-high (21%), (4) high-to-moderate (17%), and (5) high (7%) (Figure 1A). SBP trajectory group was an independent predictor of functional outcome at discharge (p=0.001) and 90 days (p=0.010, Figure 1B). Patients with high and high-to-moderate SBP trajectories had a significantly higher odds of an unfavorable outcome at 90 days (adjusted OR 2.3, 95%CI 1.2 - 4.3, p=0.01 and adjusted OR 4, 95% CI 1.5-10.7, p=0.06, respectively) Conclusions: During the first 72 hours after EVT, acute ischemic stroke patients show distinct SBP trajectories, which differ in relation to functional outcome. The findings may help recognize potential candidates for future blood pressure control trials.

Due to biomass burning and coal combustion, heavy fine particulate matter (PM2.5) pollution frequently occurs in Northeast China, threatening the health of more than 117 million inhabitants. Although meteorological conditions have always been considered key factors in the accumulation and dilution of PM2.5 pollution, their exact contribution to particulate pollution in Northeast China is still highly uncertain. Applying multiple regression analysis to observational data, we identify the wind speed, temperature inversion, and height of the planetary boundary layer as the dominant meteorological factors affecting PM2.5 pollution (PM2.5 > 75 µg m–3) in the major cities of Northeast China, with the wind speed and the planetary boundary layer playing the primary roles in Harbin and Shenyang, and Changchun, respectively. Heavy pollution (PM2.5 > 150 µg m–3) in this region typically occurs when the wind speed is less than 20 knots, the planetary boundary layer is below 500 m, and the temperature inversion is greater than 6°C. These results suggest that reducing the PM2.5 pollution requires us to focus not only on anthropogenic emissions but also on special meteorological conditions that can affect the air pollution mechanisms in Northeast China.

Exposure to PM2.5 results in negative effects on human health. However, PM2.5 exposure at the national scale is poorly known for China owing to limited spatial and temporal PM2.5 concentration data. In this study, we present analyses of PM2.5 exposure throughout China using high-resolution temporal and spatial ground-level PM2.5 data from 2015. Our results indicated that the annual mean PM2.5 concentration was 52.81μg/m3, and that the highest annual mean PM2.5 concentrations primarily appeared in the North China Plain. We also found the lowest and highest monthly mean PM2.5 concentrations appeared in August and January, respectively, while the lowest and highest diurnal mean PM2.5 concentrations occurred at 16:00 and 10:00, respectively. Moreover, comparisons to data from 2013 indicated that the annual mean PM2.5 concentrations decreased by 12.31% from 2013 to 2015, which was likely due to the implementation of environmental protection laws in early 2015. Our findings provide new insights, for not only studies of PM2.5 exposure and human health, but also to inform the implementation of national and regional air pollution reduction policies.

Ciprofloxacin (CIP) is one of most used quinolone antibiotics detected frequently in agricultural soils and vegetables. In the present study, variations in microbial community and CIP removal in rhizospheric soils between two cultivars of Brassica parachinensis L. that accumulate higher and lower CIP (Sijiu and Cutai, respectively) were investigated under CIP stress (0mg/kg in CK, 2.94mg/kg in T1, and 67.11mg/kg in T2). The removal rates of CIP in rhizospheric soils of cultivar Sijiu were higher than those of cultivar Cutai, with a significant difference in T2 (48.7%>39.4%, P

Background Acute myeloid leukemia (AML) is one of the most common blood cancers, and is characterized by impaired hematopoietic function and bone marrow (BM) failure. Under normal circumstances, autophagy may suppress tumorigenesis, however under the stressful conditions of late stage tumor growth autophagy actually protects tumor cells, so inhibiting autophagy in these cases also inhibits tumor growth and promotes tumor cell death. Methods AML gene expression profile data and corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, from which prognostic-related genes were screened to construct a risk score model through LASSO and univariate and multivariate Cox analyses. Then the model was verified in the TCGA cohort and GEO cohorts. In addition, we also analyzed the relationship between autophagy genes and immune infiltrating cells and therapeutic drugs. Results We built a model containing 10 autophagy-related genes to predict the survival of AML patients by dividing them into high- or low-risk subgroups. The high-risk subgroup was prone to a poorer prognosis in both the training TCGA-LAML cohort and the validation GSE37642 cohort. Univariate and multivariate Cox analysis revealed that the risk score of the autophagy model can be used as an independent prognostic factor. The high-risk subgroup had not only higher fractions of CD4 naïve T cell, NK cell activated, and resting mast cells but also higher expression of immune checkpoint genes CTLA4 and CD274. Last, we screened drug sensitivity between high- and low-risk subgroups. Conclusion The risk score model based on 10 autophagy-related genes can serve as an effective prognostic predictor for AML patients and may guide for patient stratification for immunotherapies and drugs.

This paper presents a new algorithm to simultaneously retrieve Aerosol Optical Depth (AOD) and land surface Bidirectional Reflectance Distribution Function (BRDF) from Advanced Along-Track Scanning Radiometer (AATSR) by adopting gradient optimization method. Different from traditional method the approach presented here can perform simultaneous retrieval from each individual AATSR swath rather than multiple days. A theoretical sensitivity study proves the proposed method is insensitive to the distortion of initial BRDF. The presented algorithm is tested on AATSR data around four different Aerosol Robotic Network (AERONET) sites representing various types of land surface. Compared with the four selected AERONET sites' AOD and BRDF-derived albedo from AERONET-based Surface Reflectance Validation Network (ASRVN) data in corresponding four AERONET sites, the presented algorithm proves considerable accuracy for various type of land surface with correlation of AOD ranging from 0.647 to 0.911 and correlation of BRDF-derived albedo ranging from 0.483 to 0.944. The intersensor comparison with Moderate Resolution Imaging Spectroradiometer (MODIS) 3 km AOD dark target product reveals high coverage rate of the presented method especially in bright surface or nonvegetation area and the correlation between the two sensors reaches up to 0.967. The improved estimation of BRDF from AATSR retrieval in AERONET Beijing site is compared with MODIS MCD43B1 product. The relative differences in hemispherical albedo calculated from average BRDF shape function parameters between AATSR and MODIS product are 1.33%, 1.52%, 2.60% and 4.28% at 550 nm, 670 nm, 870 nm and 1600 nm respectively.

MYC proteins, a group of transcription factors belonging to bHLH super family, play important roles in regulation of metabolism and plant growth. In this study, a novel MYC gene, DoMYC2 (GeneBank accession KJ649471), was isolated from Dendrobium officinale. The full length of DoMYC2 cDNA contains 2351 bp with an open reading frame of 1971 bp encoding 656 amino acids. BlastP analyses showed that its amino acid sequence was homologous with typical MYC proteins in other plant species. Furthermore, expression of DoMYC2 could be induced by MeJA and chitosan, respectively. Overexpression of DoMYC2 led to a decrease in transcript levels of AtHMGR2, AtFPS1 and AtFPS2 in Arabidopsis. Moreover, DoMYC2 was able to bind to the E-box cis-elements in yeast. These results suggest that DoMYC2 participate in terpenoid indole alkaloid synthesis through regulating the expression of key enzymes in MVA pathway.

Use of mammography screening in the general population has been credited with improvements in the diagnosis of breast cancer. Yet, the proportion of women with invasive breast cancers who are diagnosed at later, distant stages has not been declining. Two statewide data sources were linked to compare mammography screening compliance of female Medicare beneficiaries and stage of breast cancer at diagnosis at a population level. Breast cancer diagnoses were ascertained from the Kansas Cancer Registry. Mammogram use was identified using Medicare claims files and were classified as annual, biennial, less than biennial, or never use. The study included women aged ≥69 years at the time of their primary invasive breast cancer diagnosis between 2011 and 2012 who were continuously enrolled in Medicare parts A and B for at least 4 years prior to diagnosis. This approach enabled demographic comparisons to be made at the population level, providing novel and important insights about how sociocharacteristics of residency affect mammography compliance in an invasive breast cancer population. Of the 915 female Kansans who met the eligibility criteria, 73% (672) had received at least 1 mammography screening during the 4 years prior to their primary invasive breast cancer. The percentages of these women who received annual, biennial, less than biennial, and no screening were 25.8%, 27.5%, 20.1%, and 26.6%, respectively. Women aged ≥74 years, those living in counties with a median income below $42,000, and those living in counties with a higher percentage of individuals without a college degree at the time of diagnosis had higher odds of not having had an annual screening. Linkage of data from the statewide cancer registry with Medicare claims data on mammogram screening may help to identify subgroups of older women to be targeted for promoting breast cancer screening.

Foodborne disease remains a major public health problem worldwide. To understand the epidemiology and changes of foodborne disease in China, data reported to the National Foodborne Disease Outbreak Surveillance System during 2003–2017 were collected. A total of 19,517 outbreaks, which resulted in 235,754 illnesses, 107,470 hospitalizations, and 1,457 deaths, were reported in this period. Of the 13,307 outbreaks with known etiology, 31.8% of outbreaks were caused by poisonous mushrooms, followed by Vibrio parahaemolyticus (11.3%), saponin (8.0%), Salmonella (6.8%), nitrite (6.4%), pesticide (4.8%), Staphylococcus aureus (4.2%) and Bacillus cereus (3.0%). Among 18,955 outbreaks with reported setting, 46.6% were associated with food prepared in a household, followed by 22.5% with food prepared in a restaurant, and 18.4% prepared in a canteen. Of the 13,305 outbreaks associated with a single food category, fungi (mainly poisonous mushroom) were the most commonly implicated food category, followed by meats, vegetables, aquatic animals, condiments, poisonous plants (such as saponin, tung oil or seed, aconite) and grains (such as rice, noodle, rice noodle). Analysis of foodborne disease outbreaks can provide insight into the most important causative agents and sources of foodborne disease, and assist public health agencies determine the high-risk etiology and food pairs, specific points of contamination and settings to reduce foodborne disease illnesses.