Faculty Bibliography
Searched for:
in-biosketch:yes
person:leep05
Total Results:
221
Investigating the analytical robustness of the social and behavioural sciences
The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science1-3. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses4. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.
PMID: 41922703
ISSN: 1476-4687
CID: 6041172
Clear cell adenocarcinoma of the urinary bladder: a case report and review of literature [Case Report]
The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.
PMCID:10461038
PMID: 37645618
ISSN: 2330-1910
CID: 5618312
The most effective but largely ignored target for prostate cancer early detection and intervention [Editorial]
Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate has increased in nearly all Asian and African countries, (3) the proportion of advanced cancers at the diagnosis has increased to 8.2% from 3.9% in the USA, (4) the worldwide use of PSA testing and digital rectal examination have failed to reduce the prostate cancer mortality, and (5) there is still no effective preventive method to significantly reduce the development, invasion, and metastasis of prostate cancer… Together, these facts strongly suggest that the global efforts during the past appear to be not in a correlated target with markedly inconsistent basic research and clinic outcomes. The most likely cause for the inconsistence appears due to the fact that basic scientific studies are traditionally conducted on the cell lines and animal models, where it is impossible to completely reflect or replicate the in vivo status. Thus, we would like to propose the human prostate basal cell layer (PBCL) as "the most effective target for the early detection and intervention of prostate cancer". Our proposal is based on the morphologic, immunohistochemical and molecular evidence from our recent studies of normal and cancerous human prostate tissues with detailed clinic follow-up data. We believe that the human tissue-derived basic research data may provide a more realistic roadmap to guide the clinic practice and to avoid the potential misleading from in vitro and animal studies.
PMCID:9608211
PMID: 36313040
ISSN: 1837-9664
CID: 5358422
Caregiver burden and its associated factors among family caregivers of persons with dementia in Shanghai, China: a cross-sectional study
OBJECTIVE:To assess the level of caregiver burden and factors associated with it among family caregivers of persons with dementia (PWD) living in communities of Shanghai, China. DESIGN:Cross-sectional study. SETTING:Communities in Hongkou District of Shanghai, China. PARTICIPANTS:A random sample of 109 older adults with dementia and their primary family caregivers. MAIN OUTCOME MEASURE:Caregiver burden measured by the Caregiver Burden Inventory (CBI), and the Caregivers' depressive symptom measured by the simplified Chinese version of Self-rating Depression Scale was the outcome variable of the study. The independent variables, including the cognitive function (measured by Montreal Cognitive Assessment (MoCA), sleep quality assessed by the Pittsburgh Sleep Quality Index, abilities of daily life assessed by the Activities of Daily Living Scale, and behavioural and psychological symptoms assessed by the Neuropsychiatric Inventory of PWDs, the community service utilisation (measured by the Community Service Utilisation Measurement), perceived social support (assessed by three questions), positive aspects of caregiving (PAC) (assessed by the PAC) of dementia caregivers, were analysed. Multivariate linear regression was employed to determine the factors related to caregiver burden. RESULTS:The average level of CBI was 65.92±16.74. The score of MoCA, PAC and perceived social support of caregivers were negatively associated with caregiver burden (β=-0.84, p<0.001, β=-3.61, p=0.03 and β=-1.22, p=0.001, respectively). Community service utilisation was positively associated (β=3.46, p<0.001) with caregiver burden. Perceived social support by the caregiver moderated the relationship between caregiver burden and caregivers' depression symptoms. CONCLUSION:Dementia caregivers experienced a high level of caregiver burden. The cognitive function of PWD, PAC, social support and community service utilisation were factors associated with caregiver burden. Strengthening social support, providing more high-quality home care services, promoting PAC are imperative to reduce caregiver burden.
PMID: 35613751
ISSN: 2044-6055
CID: 5249552
Identification of novel biomarkers differentially expressed between African-American and Caucasian-American prostate cancer patients
Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.
PMCID:9077070
PMID: 35530298
ISSN: 2156-6976
CID: 5214062
Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial
OBJECTIVE:To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. METHODS:We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. RESULTS:Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. CONCLUSION/CONCLUSIONS:Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.
PMID: 33779064
ISSN: 2326-5205
CID: 4910222
Zhongguo gu shang = China journal of orthopaedics & traumatology. 2021:34(4):382-8.DOI: 10.12200/j.issn.1003-0034.2021.04.018
[Research progress on bone defect repair materials]
In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.
PMID: 33896142
ISSN: 1003-0034
CID: 4882422
Metastasis and immune evasion from extracellular cGAMP hydrolysis
Cytosolic DNA is characteristic of chromosomally unstable metastatic cancer cells, resulting in constitutive activation of the cGAS-STING innate immune pathway. How tumors co-opt inflammatory signaling while evading immune surveillance remains unknown. Here we show that the ectonucleotidase ENPP1 promotes metastasis by selectively degrading extracellular cGAMP, an immune stimulatory metabolite whose breakdown products include the immune suppressor, adenosine. ENPP1 loss suppresses metastasis, restores tumor immune infiltration, and potentiates response to immune checkpoint blockade in a manner dependent on tumor cGAS and host STING. Conversely, overexpression of wildtype ENPP1, but not an enzymatically weakened mutant, promotes migration and metastasis, in part, through the generation of extracellular adenosine, and renders otherwise sensitive tumors completely resistant to immunotherapy. In human cancers, ENPP1 expression correlates with reduced immune cell infiltration, increased metastasis, and resistance to anti-PD1/PD-L1 treatment. Thus, cGAMP hydrolysis by ENPP1 enables chromosomally unstable tumors to transmute cGAS activation into an immune suppressive pathway.
PMID: 33372007
ISSN: 2159-8290
CID: 4731712
INS-fOCT: a label-free, all-optical method for simultaneously manipulating and mapping brain function
PMCID:7108754
PMID: 32258220
ISSN: 2329-423x
CID: 5835762
DNA-Functionalized Metal-Organic Framework Nanoparticles for Intracellular Delivery of Proteins
Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular transfection, nucleic acid-metal organic framework nanoparticle (MOF NP) conjugates have been designed and synthesized from NU-1000 and PCN-222/MOF-545, respectively, and phosphate-terminated oligonucleotides. They have been characterized structurally and with respect to their ability to enter mammalian cells. The MOFs act as protein hosts, and their densely functionalized, oligonucleotide-rich surfaces make them colloidally stable and ensure facile cellular entry. With insulin as a model protein, high loading and a 10-fold enhancement of cellular uptake (as compared to that of the native protein) were achieved. Importantly, this approach can be generalized to facilitate the delivery of a variety of proteins as biological probes or potential therapeutics.
PMCID:8212418
PMID: 30669839
ISSN: 1520-5126
CID: 5860742
