Vulture: cloud-enabled scalable mining of microbial reads in public scRNA-seq data.

The rapidly growing collection of public single-cell sequencing data has become a valuable resource for molecular, cellular, and microbial discovery. Previous studies mostly overlooked detecting pathogens in human single-cell sequencing data. Moreover, existing bioinformatics tools lack the scalability to deal with big public data. We introduce Vulture, a scalable cloud-based pipeline that performs microbial calling for single-cell RNA sequencing (scRNA-seq) data, enabling meta-analysis of host-microbial studies from the public domain. In our benchmarking experiments, Vulture is 66% to 88% faster than local tools (PathogenTrack and Venus) and 41% faster than the state-of-the-art cloud-based tool Cumulus, while achieving comparable microbial read identification. In terms of the cost on cloud computing systems, Vulture also shows a cost reduction of 83% ($12 vs. ${\$}$70). We applied Vulture to 2 coronavirus disease 2019, 3 hepatocellular carcinoma (HCC), and 2 gastric cancer human patient cohorts with public sequencing reads data from scRNA-seq experiments and discovered cell type-specific enrichment of severe acute respiratory syndrome coronavirus 2, hepatitis B virus (HBV), and Helicobacter pylori-positive cells, respectively. In the HCC analysis, all cohorts showed hepatocyte-only enrichment of HBV, with cell subtype-associated HBV enrichment based on inferred copy number variations. In summary, Vulture presents a scalable and economical framework to mine unknown host-microbial interactions from large-scale public scRNA-seq data. Vulture is available via an open-source license at https://github.com/holab-hku/Vulture.

Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). RESULTS: We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). CONCLUSIONS: While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.

Attrition and non-compliance in secondary stroke prevention trials.

BACKGROUND: Attrition and non-compliance of subjects in secondary stroke prevention trials due to study drug-induced adverse events and loss to follow-up could lead to bias and loss of information, thus affecting the analysis of study results. METHODS: We reviewed results from ten antiplatelet stroke prevention clinical trials: CAN TIA, DUTCH TIA, SWED ASA, SALT, UK TIA, CATS, TASS, ESPS, ESPS-2, and CAPRIE to tabulate the frequencies for total subject discontinuation, voluntary withdrawal, and loss to follow-up. RESULTS: Forty thousand seven hundred and thirty (40,730) subjects participated in the aforementioned secondary stroke prevention trials. The range of outcomes was 11.8-52.0% for subjects discontinued for any reason (n = 9 trials); 3.0-20.9% for study drug-induced adverse events (n = 9 trials), and 4.2-7.8% for voluntary withdrawal (n = 10 trials). CONCLUSION: There is a substantial discrepancy (up to 20%) between the frequencies of total subject discontinuation for any reason and the sum of study drug-induced adverse events, voluntary withdrawal and loss to follow-up. Underestimation of these important outcomes may limit the ability of clinicians to translate results from clinical trials into medical practice.

The influence of maternal child-rearing attitudes and teaching behaviors on preschoolers' delay of gratification.

This study was an exploratory examination of the influence of mothers' teaching behaviors, strategies, and child-rearing attitudes on their children's ability to delay gratification. In an externally imposed delay of gratification situation, 30 mothers from a rural university community taught their children strategies that could help them refrain from touching a brightly wrapped present when the mothers left the room. Results showed that mothers of children who did not delay gratification exhibited teaching behaviors and child-rearing attitudes consistent with a permissive parenting style, whereas mothers of children who did delay gratification exhibited teaching behaviors and child-rearing attitudes consistent with an authoritative parenting style. The results of this study are discussed with respect to the development of children's self-control and self-regulatory abilities.

The recruitment triangle: reasons why African Americans enroll, refuse to enroll, or voluntarily withdraw from a clinical trial. An interim report from the African-American Antiplatelet Stroke Prevention Study (AAASPS).

Recruitment and retention of study subjects are key to the success of a clinical trial. In the case of minority patients, this may be challenging as minority patients have been underserved by the medical health-care system. Furthermore, minority patients are more likely to experience barriers to entry into a clinical trial such as mistrust of the medical system, economic disadvantages, lack of awareness of study programs, and communication barriers. An open-ended questionnaire was used to determine reasons why subjects in the African-American Antiplatelet Stroke Prevention Study (AAASPS) remained in the study or voluntarily withdrew in the absence of an adverse event. Potential enrollees who refused to participate in the AAASPS also were queried. Enrollees who remained in the program consistently stated that they participated to reduce the risk of stroke recurrence and to help others by finding a "cure" for stroke. Those who withdrew or refused to participate consistently stated that they were afraid of being used as "guinea pigs." A "recruitment triangle" emerged that might predict a patient's likelihood of participation in a clinical trial. The sides of the triangle include the patient, key family members and friends, and the primary medical doctor and other medical personnel. The organizers of a clinical trial need to be aware of the "recruitment triangle" and establish strategies to heighten and maintain its integrity.

African American antiplatelet stroke prevention study: Clinical trial design.

BACKGROUND AND PURPOSE: African Americans are about two times more likely than European Americans to die of cerebrovascular disease or to experience stroke. Although this disparity exists, African Americans have been underrepresented in clinical trials. The African American Antiplatelet Stroke Prevention Study (AAASPS) is a multi-center, randomized, double-blind, clinical trial to compare the effect of ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, and vascular death in African Americans with recent, noncardioembolic ischemic stroke. TRIAL DESIGN: There will be 1,800 African American noncardioembolic ischemic stroke patients at 40 sites nationally randomized to receive ticlopidine (500 mg/d) or aspirin (650 mg/d) at least 7 days but no more than 90 days after the qualifying event. Complete blood count and platelet count are monitored every 2 weeks during the first 3 months of active treatment to monitor for neutropenia and thrombocytopenia. Patients with transient cerebral ischemia, recent active peptic ulcer disease or lower gastrointestinal bleeding, bleeding diathesis, and women of childbearing potential are excluded. Study patients will be followed-up for a total of 2 years for occurrence of the primary outcome endpoint cluster of recurrent stroke, myocardial infarction, and vascular death. Safety analyses will focus on the incidence of severe adverse events such as neutropenia, thrombocytopenia, gastrointestinal bleeding, and liver dysfunction. Analyses for key endpoints will use the intention-to-treat principle and time-to-event data will be analyzed using Mantel-Haenszel and various regression methods. CONCLUSION: African Americans have a survival disadvantage that substantially relates to the occurrence of stroke. AAASPS is the first secondary stroke prevention study exclusively for African Americans and promises to provide important information to guide recurrent stroke prevention treatment for this high-risk group.

Establishing a community network for recruitment of African Americans into a clinical trial. The African-American antiplatelet stroke Prevention Study (AAASPS) experience.

A major aspect of a clinical trial is the ability to successfully recruit patients. There is a paucity of information concerning the nuances of recruiting study patients, especially those from minority communities. As minorities generally have been underrepresented in the health-care system, they may be less likely to participate in clinical trials or other studies. Thus, a strategy is needed to overcome this potential shortfall. One of our solutions has been the development of a community network to help disseminate information about our program. We believe that a key aspect has been the involvement of community members during pre-trial planning, community awareness programs, and our Community Advisory Panel. We also believe that it may be a major error to bring a health-care initiative unannounced into a targeted community without extensive pre-program planning in cooperation with that community. As our community awareness scheme suggests (Figure), there are many possible avenues to heighten awareness about a health-care program. While the church remains an important institution for religious and cultural activities in the African-American community, we have found that the news, television, and radio media also can be a powerful source for spreading awareness. Thus, we recommend creating awareness about an initiative through a "grassroots" approach of church and community organizations, along with a global approach through news, television, and radio media. As part of the awareness promotion campaign, it must be emphasized that the study is safe and provides benefits to enrollees. The success of health programs is largely dependent on community acceptance, which must be established in the pre-program planning stages of the initiative. This concept of obtaining community approval and acceptance prior to program initiation is not a new one, nor does it exclusively apply to the African-American community. Community leaders and members need to have a vested interest in such a program and a sense of empowerment. Through this type of communication, patient enrollment and community satisfaction can be substantial. Such success can serve as a springboard for other targeted health-care studies or programs in high-risk communities.

Why African Americans may not be participating in clinical trials.

African Americans have been underrepresented in clinical trials. This study was designed to determine factors that may help explain the low participation rate of African Americans in clinical trials. A historical review documented past medical experimentation and other practices on blacks that were often brutal and unethical. These experiences may have served to fortify the legacy of African-American mistrust in the medical system and culminated in the infamous Tuskegee Syphilis Study. Four major barriers to participation in clinical trials were identified: lack of awareness about trials, economic factors, communication issues, and mistrust. These barriers, as well as others, can be surmounted with proper pretrial planning, patient education, genuine commitment and concern by study staff, and hard work to overcome deficiencies.

Neuroepidemiology of vascular and Alzheimer's dementia among African-American women.

To better understand risk factors for Alzheimer's disease and vascular dementia, demographic, medical, and other epidemiological factors were compared for 83 African-American women with Alzheimer's disease and 46 with vascular dementia. Overall, the risk-factor profiles for Alzheimer's disease and vascular dementia were similar to those in other studies. However, Alzheimer's patients had a high frequency of hypertension and a relatively high frequency of diabetes mellitus. The presence of such risk factors raises the possibility that there is a vascular component to the dementia in these African-American women with Alzheimer's disease. Neuropathological studies are needed to help answer this question.

CT and MRI findings among African-Americans with Alzheimer's disease, vascular dementia, and stroke without dementia.

We compared CT and MRI findings among 78 Alzheimer's disease (AD), 66 vascular dementia (VaD), and 41 stroke without dementia (SWD) African-American patients to identify possible neuroimaging indicators of dementia. The patients with AD and VaD were generally older and less educated than those with SWD. VaD and SWD patients had a higher frequency of cardiovascular disease risk factors than those with AD. In multivariate analysis, the CT data showed that the presence of white matter lesions, nonlacunar infarcts, and left subcortical infarcts were predictors of VaD when compared with AD, whereas atrophy of the third ventricle and equal distribution of white matter lesions distinguished VaD from SWD. On MRI, atrophy of the temporal sulci, temporal horns, and the third ventricle, and right hemisphere infarcts, distinguished AD from VaD, while atrophy of the third ventricle differentiated VaD from SWD. These data suggest that atrophy, especially at the level of the third ventricle, presence of infarcts, and white matter lesions may be useful predictors of dementia subtype. Furthermore, the qualitative CT and MRI findings among our African-American patients were similar to those reported in other dementia studies.

Psychiatric symptoms in dementia associated with stroke: a case-control analysis among predominantly African-American patients.

As part of a case-control study, the psychiatric symptoms and behavioral problems of 61 multi-infarct dementia (MID) cases and 86 multi-infarct controls without dementia were compared to determine the prevalence of psychiatric symptoms and to clarify psychiatric predictors of dementia associated with cerebral infarcts. Ninety-two percent of the cases and 85% of the controls were African American. Cases were generally older, less well educated, and had a greater number of strokes and more neurologic deficits than controls. The most frequent psychiatric symptoms as reported by caregivers of patients with MID were irritability (57.3%), apathy (44.4%), insomnia (43.6%), agitation (40.7%), impatience (37%), and emotional lability (28.3%). In multivariate analysis, apathy and irritability were independent predictors of dementia associated with cerebral infarcts unless tests of cognitive function were added to the model. Our findings suggest that psychiatric symptoms are common in African-American vascular dementia patients, and cognitive impairment may be associated with psychiatric symptoms, behavioral problems, and personality changes. As there is a paucity of information about the prevalence of psychiatric symptoms in African Americans with vascular dementia, additional studies are needed to validate these findings. A better understanding of psychiatric symptoms in vascular dementia could lead to improved diagnosis and treatment of this disorder.

Epidemiology of vascular and Alzheimer's dementia among African Americans in Chicago, IL: baseline frequency and comparison of risk factors.

We compared demographic, medical, and other epidemiologic factors among 113 African-American Alzheimer's disease (AD) patients and 79 African-American vascular dementia (VaD) patients. The typical background profile of our AD and VaD patients who entered into the study was that of women who were born and raised on farms in the southeastern United States, currently lived in an apartment or home in Chicago with other family members, and were retired, widowed, and had some form of medical insurance. The following distinct patient profiles emerged: (1) African-American AD patients were generally older than their VaD counterparts, more likely to have a family history of AD, Parkinson's disease and dementia, a history of head injury with loss of consciousness and hip fracture, and more severe cognitive impairment and difficulty with instrumental activities of daily living. (2) African-American VaD patients had a higher frequency of cardiovascular disease risk factors and focal neurologic findings, more difficulty with activities of daily living, and a higher frequency of medication use. Differences in risk-factor profile may help explain differential susceptibility by dementia subtype. Since ethnic minorities will constitute a higher proportion of the United States population in the future, targeted epidemiologic research to better understand etiology and risk factors for the dementias of middle and later life among minorities is needed.

Comparison of dementia criteria: sensitivity and specificity testing among African American patients.

We compared the sensitivity and specificity of recently proposed general dementia, vascular dementia, and Alzheimer's disease criteria using the DSM III-R as the 'gold standard' among 61 elderly African American patients. There were 10 patients with vascular dementia, 20 with Alzheimer's disease and 31 controls. Comparison of the sensitivity and specificity of the various criteria showed that with few exceptions, the results were similar. Additional studies of this kind among different populations, and among mild dementia patients, are needed to cross-validate the results.

Risk factors for dementia associated with multiple cerebral infarcts. A case-control analysis in predominantly African-American hospital-based patients.

OBJECTIVE: To clarify risk factors for dementia associated with cerebral infarction. DESIGN: Case-control study. SETTING: The study was conducted in a hospital setting. PATIENTS: The subjects were consecutive patients with acute stroke with multiple cerebral infarctions who were admitted to the hospital between November 1, 1987, and December 1, 1990. They were predominantly elderly African Americans. Index cases met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, for multi-infarct dementia, whereas control subjects were patients with multiple infarcts who did not have dementia. There were 61 multi-infarct disease index cases and 86 controls without cognitive impairment. MAIN OUTCOME MEASURES: Demographic and cardiovascular disease risk factor variables. RESULTS: Index cases were older (mean [+/- SD] age, 75.5 +/- 9.7 vs 69.6 +/- 9.1 years), were less well educated (odds ratio, 4.37; confidence interval, 2.12 to 9.04), had lower annual incomes (odds ratio, 8.82; confidence interval, 2.38 to 32.70), more frequently had a family history of dementia (odds ratio, 3.61; confidence interval, 1.09 to 11.96) and laboratory evidence of proteinuria (odds ratio, 3.66; confidence interval, 1.54 to 8.71), had lower scores on neuropsychological tests, had more neurologic signs and symptoms, and were more functionally impaired in activities of daily living. Multiple logistic regression analysis showed that advanced age, lower educational attainment, history of myocardial infarction, and recent cigarette smoking were positively associated with case status and systolic blood pressure level was negatively associated with case status. CONCLUSIONS: Cardiovascular disease risk factors may be modifiable predictors of dementia associated with cerebral infarction. Additional well-designed epidemiologic studies are needed to clarify these associations.

Cranial computed tomographic observations in multi-infarct dementia. A controlled study.

BACKGROUND AND PURPOSE: We compared cranial computed tomography findings among 58 multi-infarct dementia index cases and 74 multi-infarct control subjects without cognitive impairment to identify potential determinants of multi-infarct dementia. METHODS: The cranial computed tomography records of acute ischemic stroke patients with a history of multiple cerebral infarcts were compared to determine the number, location, and size of cerebral infarcts; the pattern of infarction; brain volume loss; and the degree of white matter lucency, sulcal enlargement, and ventricular enlargement. Multi-infarct patients were divided into two groups: 1) index cases were defined as those with multi-infarct dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, edition 3 (DSM-III) criteria; and 2) control subjects were defined as those multi-infarct patients without dementia or multi-infarct dementia according to DSM-III criteria. RESULTS: Overall, multi-infarct index cases had more cerebral infarcts, more cortical and subcortical left hemisphere infarcts, higher mean ventricular volume to brain volume ratio, more extensive enlargement of the body of the lateral ventricles and cortical sulci, and a higher prevalence of white matter lucencies. Among multi-infarct cases and control subjects the most frequent site of infarction was the subcortical region, and the most frequent pattern of infarction was lacunar. Stepwise logistic regression analysis examined cranial computed tomography as well as other factors and showed that level of education, stroke severity, left cortical infarction, and diffuse enlargement of the left lateral ventricle were the best overall predictors of multi-infarct dementia. CONCLUSIONS: Level of education, stroke severity, and left hemisphere infarction may be predictors of multi-infarct dementia.

Vascular dementia: a clinical and death certificate study.

We compared the extent of documentation of the diagnoses, vascular dementia and stroke, on inpatient (hospital) medical records and death certificates among 23 multi-infarct dementia index cases and 14 multi-infarct controls without cognitive dysfunction who were enrolled in a hospital-based case-control study and were followed longitudinally. Both the inpatient medical records and the death certificates markedly under-diagnosed vascular dementia when compared to the case-control study diagnosis. Furthermore, the diagnosis of stroke was grossly underdiagnosed on the death certificates. In lieu of the lack of medical record and death certificate documentation of vascular dementia, studies that utilize such information may be in considerable error. Clarification of the criteria for the diagnosis of vascular dementia and greater physician and public awareness of vascular dementia are needed.

A DNA probe for the detection of Mycobacterium paratuberculosis.

A genomic library of DNA extracted from Mycobacterium paratuberculosis was constructed in the expression vector lambda gt 11. The library was screened by plaque hybridization with labelled M. paratuberculosis genomic DNA as probe. Strongly hybridizing plaques were isolated and their DNA extracted and characterised for M. paratuberculosis specificity by hybridization to DNA from other Mycobacteriaceae. A clone was obtained which was specific for M. paratuberculosis. DNA from this clone could detect 7 ng M. paratuberculosis DNA.