Exploration of potential biomarkers for prurigo nodularis based on plasma-metabolome analysis.

Prurigo nodularis (PN) is a chronic and debilitating skin disease with severe itching that negatively impacts patients' quality of life and mental state. However, the treatment options for PN remain limited. Global metabolomics analysis can offer effective information on energy metabolism, pathogenesis and potential diagnostic biomarkers. No study on metabolomic analysis of PN has been reported. To further understand the mechanisms of PN and analyse the plasma metabolite profiles in patients with PN. Targeted-metabolome analysis of 306 metabolites in plasma from 18 patients with PN and 19 healthy controls was performed using Liquid Chromatography-tandem Mass Spectrometer analysis. We identified 31 differential metabolites. Most acylcarnitines, long-chain fatty acids, alpha-aminobutyric acid, hydroxybutyric acid and lactic acid among these metabolites were up-regulated in patients with PN; in contrast, glucaric acid, suberic acid, bile acid derivatives and most amino acids were down-regulated. Positive correlations exist between glucaric acid and itching severity and acylcarnitines and insomnia. Suberic acid and the Investigator's Global Assessment (IGA) scores correlate negatively. Metabolite variation reflects the dysregulation of energy metabolism and chronic systematic inflammation in PN. Several metabolites, such as glucaric acid, suberic acid and acylcarnitines, merit further study as potential biomarkers of disease severity in PN.

New insight into prurigo nodularis: Proadrenomedullin N-terminal 20 peptide mediates mouse mast cell activation via Mrgprb2.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disorder that is characterized by extremely itchy nodules. Proadrenomedullin N-terminal 20 (PAMP) activates mast cell degranulation via Mas-related G protein-coupled receptor X2 (MRGPRX2), which is associated with pruritus in allergic contact dermatitis. However, the mechanisms underlying the action of PAMP and MRGPRX2 in PN remain unclear. OBJECTIVE: To determine the role of PAMP-induced mast cell activation via MRGPRX2 (mouse homologous Mrgprb2) in PN. METHODS: The expression of PAMP and the number of MRGPRX2-expressing mast cells in the skin biopsies of patients with PN, atopic dermatitis (AD), and healthy participants were analyzed using immunohistochemistry and immunofluorescence, respectively. The biphasic response of PAMP9-20 mediated by Mrgprb2 in mouse peritoneal mast cells (PMC) was validated in vitro using qRT-PCR, ELISA, flow cytometry, and siRNA techniques. RESULTS: PAMP expression and the number of MRGPRX2+ mast cells in lesional PN skin, but not in AD, were elevated compared to healthy skin. PAMP9-20 mediates the immediate and delayed phase responses of PMC, such as degranulation, histamine and ß-hexosaminidase release, and secretion of inflammatory factors such as CCL2, TNF-α, and GM-CSF. These effects were inhibited when Mrgprb2 expression was silenced. Silencing Mrgprb2 did not affect the biphasic response of PMC that was induced by IgE-FcεRI activation. CONCLUSIONS: The results show that PAMP mediates mouse mast cell activation via Mrgprb2, which may be involved in the pathogenesis of PN. The PAMP/ Mrgprb2 pathway, independent of classical IgE signaling, could be developed as a candidate drug target for treating PN.

A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.

We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.

RNA sequencing reveals the transcriptome profile of the atopic prurigo nodularis with severe itching.

Prurigo nodularis (PN), characterized by inevitable chronicity and severe pruritus, is most frequently associated with atopy compared with other origins. However, the skin transcriptomic profiling of PN arising from atopic dermatitis (AD), so-called atopic PN (APN), remains unclear. We sought to explore the cutaneous transcriptome of APN with severe pruritus and compare it with classic AD. RNA sequencing was performed on the lesional skin from 13 APN to 11 AD patients with severe pruritus (itch numerical rating scale score ≥ 7) and normal skin from 11 healthy subjects. Quantitative real-time polymerase chain reaction and immunochemistry were used for validation. We detected 1085 and 1984 differentially expressed genes (DEGs) in lesional APN skin and lesional AD skin versus normal skin, respectively. In total, 142 itch/inflammation-related DEGs were identified. Itch/inflammation-related DEGs, such as IL-6, IL-10, IL-13, oncostatin M, and IL-4 receptor, had elevated gene transcript levels in both diseases. The itch/inflammation-related DEGs that increased only in APN were mainly neuroactive molecules, while many inflammatory mediators such as T helper 22-related genes were found to be increased only in AD. Both disorders showed mixed Th1/Th2/Th17 polarisation and impaired skin barrier. In contrast to AD, M1/M2 macrophage activation, tumor necrosis factor production, fibrosis, revascularization and neural dysregulation are unique features of APN. The study findings broaden our understanding of the pathogenesis underlying APN, which provides insights into novel pathogenesis with potential therapeutic implications.

Racial and ethnic differences in neuropsychiatric symptoms and progression to incident cognitive impairment among community-dwelling participants.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are a risk factor for dementia; however, their prevalence and severity among ethnoracial groups are poorly understood. METHODS: We used data from the National Alzheimer's Coordinating Center (NACC) (n = 6958; ≥50 years old). Cognitively normal participants at baseline, without any NPS or dementia diagnosis, had at least one follow-up. Survival analyses assessed the hazard ratio for 12 NPS models and progression to cognitive impairment. Propensity score weighting (PSW) matched participants on age, sex, education, and race/ethnicity. RESULTS: All 12 NPS were significantly associated with progression to cognitive impairment. In the PSW models, compared to whites, Black/African Americans were more likely to progress to cognitive impairment across all 12 NPS models, followed by Hispanic, and then Asian participants. DISCUSSION: PSW minimized selection bias to provide robust risk estimates. There is a higher risk of progressing to cognitive impairment for ethnoracial groups with NPS. Tailored screening of NPS and cognitive impairment should incorporate patient and caregiver reports.

Negative Pressure Wound Therapy for Patients With Complicated Mucocutaneous Separation Following Ileal Conduit Urinary Diversion: A Case Series.

BACKGROUND: Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion. CASES: We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications. CONCLUSION: Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion.

Contrast-Enhanced Ultrasound Features of Adult Xp11.2 Translocation Renal Cell Carcinoma: Differential Diagnosis With Three Main Renal Cell Carcinoma Subtypes.

OBJECTIVES: To investigate the sonographic features in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) using both conventional ultrasound (US) and contrast-enhanced US (CEUS) and evaluate the usefulness of sonographic imaging characteristics to differentiate between Xp11.2 tRCC and the three common RCC subtypes. METHODS: Thirty-four adult Xp11.2 tRCC patients who preoperatively underwent both conventional US and CEUS and had solitary renal lesions and pathological confirmation after surgery were enrolled. Control matched patients included 131 with clear cell RCC (ccRCC), 48 with papillary RCC (pRCC), and 35 with chromophobe RCC (chRCC). Conventional US and CEUS data of all patients were retrospectively analyzed and compared. RESULTS: Xp11.2 tRCC was more common in young women. The echogenicity of Xp11.2 tRCC lesions was hypo- and isoechoic relative to the adjacent renal cortex. A higher frequency of calcification within tumors was detected in Xp11.2 tRCC, but the presence of color flow signal (26.5%, 9/34) was much lower. Regarding CEUS features relative to the adjacent renal cortex, synchronous wash-in (61.8%, 21/34), iso-enhancement at peak (55.9%, 19/34), and fast wash-out (50.0%, 17/34) were more common in Xp11.2 tRCC. Moreover, an integrated variables model based on these features could differentiate Xp11.2 tRCC from ccRCC, pRCC, and chRCC (area under the curve, sensitivity, and specificity: 0.934, 92.0%, and 86.0%; 0.907, 88.0%, and 87.0%; and 0.808, 65.0%, and 99.0%, respectively). CONCLUSIONS: Combining conventional US and CEUS lesion features with clinical information may provide a feasible and effective method to differentiate Xp11.2 tRCC from ccRCC, pRCC, and chRCC.

The complex relationship between depression and progression to incident cognitive impairment across race and ethnicity.

INTRODUCTION: We examined baseline differences in depression and antidepressant use among cognitively normal older adults in five ethnoracial groups and assessed whether depression predicted a faster progression to incident cognitive impairment across groups. METHODS: Data from the National Alzheimer's Coordinating Center (n = 8168) were used to examine differences between non-Hispanic Whites (nHW), African Americans (AA), Hispanics, Asians, and American Indian and Alaskan Natives in cross-sectional and longitudinal models. RESULTS: AA had a lower risk of depression compared to nHW at baseline. No statistical interactions were noted between ethnoracial groups and depression. However, depression independently predicted a faster progression to incident cognitive impairment. Hispanics and Asian participants had a higher hazard for progression compared to nHW. DISCUSSION: Previously established risk factors between depression and dementia were not found among AA and nHW participants. The relationship between depression and ethnoracial groups is complex and suggests differential effects on progression from cognitive normality to impairment.

[Detection of clinically significant prostate cancer in lesions of PI-RADS score 3 in different histological zones of the prostate and MRI/TRUS fusion prostate biopsy].

Objective: To investigate the detection rate of clinically significant PCa (CSPCa) in lesions of prostate imaging-reporting and data system (version 2) (PI-RADS v2) score 3 in different histological zones of the prostate, the value range of clinical parameters, and the possibility of improving the detection rate by MRI/TRUS fusion prostate biopsy. METHODS: This retrospective study included 297 patients with prostatic lesions of PI-RADS v2 score 3 undergoing transperineal prostate biopsy in Nanjing Drum Tower Hospital from January to December 2019. We analyzed their clinical data, the detection rate of CSPCa in the four histological zones of the prostate and the value range of the clinical parameters. RESULTS: The detection rates of CSPCa in the peripheral zone, transitional zone, central zone and anterior fibromuscular stroma were 23.8%, 11.2%, 40.0% and 50.0%, respectively. In comparison with conventional biopsy, additional MRI/TRUS image fusion biopsy improved the detection rate of CSPCa in the four zones, though with no statistically significant difference. The patients with CSPCa, compared with those in the non-CSPCa group, showed a lower value of free PSA/total PSA (fPSA/tPSA) (0.12 ± 0.05 vs 0.18 ± 0.07) but a higher tPSA level (ï¼»13.06 ± 10.07ï¼½ vs ï¼»8.61 ± 5.86ï¼½ µg/L) and PSA density (PSAD) (ï¼»0.35 ± 0.34ï¼½ vs ï¼»0.16 ± 0.11ï¼½ µg/L2). CONCLUSIONS: In prostate lesions of PI-RADS v2 score 3, the detection rate of CSPCa was higher in the peripheral zone, even higher in the central zone and anterior fibromuscular stroma, than in the transitional zone. Prostatic biopsy is strongly recommended for patients with fPSA/tPSA < 0.12 or PSAD > 0.35 µg/L2, and additional MRI/TRUS image fusion biopsy is preferable for the lesions in the transitional or central zone.

Photopatch testing in Chinese patients: A 5-year experience.

BACKGROUND: In 2015, a Chinese expert consensus on photopatch testing (PPT) was established, based on European consensus methodology. OBJECTIVES: To update current information on the prevalence of photoallergic contact dermatitis (PACD) to 20 photoallergens and their clinical relevance in the Chinese context. METHODS: A retrospective analysis of 2372 patients who performed PPT in a tertiary referral center in China between 2015 and 2019 was completed. A total of 1208 PACD reactions were observed in 897 (37.8%) patients, and 413 reactions were of current or past relevance. RESULTS: The proportion of reactions of current or past relevance was 34.2%. The most frequent photoallergens were chlorpromazine, thimerosal, potassium dichromate, and formaldehyde. The ultraviolet absorbers, benzophenone and Para-aminobenzoic acid, showed opposite gender distribution to PACD. Twenty-five patients (1.9%) developed PACD reactions to a newly added photoallergen preparation - fragrance mix I. Patients with chronic actinic dermatitis, widespread exposed-site or generalized dermatitis, and older age were more likely to have PACD. CONCLUSIONS: This study is the first to profile PACD reactions with clinical relevance in China. The prevalence of PACD to culprit photoallergens was affected by regional peculiarities. Attention needs to be paid to the age, body-site distribution, and known diagnoses of patients for the identification of PACD.

Nanoinstabilities of Cu2O porous nanostructured films as driven by nanocurvature effect and thermal activation effect.

In this work, the instabilities at the nanoscale (i.e. nanoinstabilities) of triangular pyramids-like Cu2O porous nanostructured films (PNFs) are studied by heating treatments under different atmosphere and temperature. It is found that the nanoscale building triangular pyramids turn round preferentially at the sharp angles and/or coalesce with their contacting ones by directional diffusion and plastic flow of atoms, which are driven by the nonuniformly-distributed surface nanocurvature. As a result, the triangular pyramids become quasi-sphere shape and the PNF evolves into a big, dense particles film. It is also observed that the heating or thermal activation effect efficiently promotes the reduction or oxidation of Cu2O pyramids and the crystallization or growth of the as-achieved Cu or CuO grains. The above physical and chemical instabilities or changes at the nanoscale of Cu2O PNFs can be well accounted for by the combined mechanism of nanocurvature effect and thermal activation effect. The nanocurvature effect can lower the energy barrier for the atom diffusion or plastic flow and lower the activation energy for the chemical reactions, while the thermal activation effect can supply the required kinetic energy or activation energy and make the atomic transportations and reactions kinetically possible. The findings reveal the evolution laws of morphology, crystal structure and composition of triangular pyramids-like Cu2O PNF during heating treatments, which can further be extended to other types of Cu2O PNFs. Also, the findings have important implications for the nanoinstabilities of Cu2O PNFs-based devices, especially those working at a high temperature.

Cu2O porous nanostructured films fabricated by positive bias sputtering deposition.

In this work, the authors fabricated Cu2O porous nanostructured films (PNFs) on glass slide substrates by the newly developed positive bias deposition approach in a balanced magnetron sputtering (MS) system. It was found that the surface morphology, crystal structure and optical property of the as-deposited products were greatly dependent on the applied positive substrate bias. In particular, when the substrate was biased at +50 and +150 V, both of the as-prepared Cu2O PNFs exhibited a unique triangular pyramids-like structure with obvious edges and corners and little gluing, a preferred orientation of (111) and a blue shift of energy band gap at 2.35 eV. Quantitative calculation results indicated that the traditional bombardment effects of electrons and sputtering argon ions were both negligible during the bias deposition in the balanced MS system. Instead, a new model of tip charging effect was further proposed to account for the controllable formation of PNFs by the balanced bias sputtering deposition.

Leptin suppresses microRNA-122 promoter activity by phosphorylation of foxO1 in hepatic stellate cell contributing to leptin promotion of mouse liver fibrosis.

Adipocytokine leptin promotes hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and was demonstrated to inhibit liver fibrosis and reduced HSC proliferation. Our previous study revealed that leptin reduced miR-122 level in HSCs. This study was aimed to investigate whether leptin affected miR-122 promoter and the underlying mechanisms in HSCs. Results showed that leptin inhibited miR-122 promoter activity. Forkhead box protein O1(FoxO1) bound to miR-122 promoter at a site around - 56 and thus promoted miR-122 promoter activity, which could be suppressed by leptin-induced phosphorylation of FoxO1 at serine 256. The PI3K/Akt signaling pathway was involved in leptin-induced phosphorylation of FoxO1 and the effect of leptin on miR-122 expression. Furthermore, FoxO1 increased miR-122 and pri-miR-122 (primary miR-122) levels in HSCs in vivo, and reduced leptin-induced HSC activation and liver fibrosis in ob/ob mouse (leptin deficient) model. In conclusion, leptin suppressed microRNA-122 expression by PI3K/Akt/foxO1 axis in HSCs. These results have potential implications for clarifying the mechanisms for liver fibrogenesis in obese patients with hyperleptinaemia.

LGC-DBP: the method of DNA-binding protein identification based on PSSM and deep learning.

The recognition of DNA Binding Proteins (DBPs) plays a crucial role in understanding biological functions such as replication, transcription, and repair. Although current sequence-based methods have shown some effectiveness, they often fail to fully utilize the potential of deep learning in capturing complex patterns. This study introduces a novel model, LGC-DBP, which integrates Long Short-Term Memory (LSTM), Gated Inception Convolution, and Improved Channel Attention mechanisms to enhance the prediction of DBPs. Initially, the model transforms protein sequences into Position Specific Scoring Matrices (PSSM), then processed through our deep learning framework. Within this framework, Gated Inception Convolution merges the concepts of gating units with the advantages of Graph Convolutional Network (GCN) and Dilated Convolution, significantly surpassing traditional convolution methods. The Improved Channel Attention mechanism substantially enhances the model's responsiveness and accuracy by shifting from a single input to three inputs and integrating three sigmoid functions along with an additional layer output. These innovative combinations have significantly improved model performance, enabling LGC-DBP to recognize and interpret the complex relationships within DBP features more accurately. The evaluation results show that LGC-DBP achieves an accuracy of 88.26% and a Matthews correlation coefficient of 0.701, both surpassing existing methods. These achievements demonstrate the model's strong capability in integrating and analyzing multi-dimensional data and mark a significant advancement over traditional methods by capturing deeper, nonlinear interactions within the data.

Is Multidimensional Poverty Associated to Dementia Risk? The Case of Older Adults in Pakistan.

Background and Objectives: Multidimensional poverty is associated with dementia. We aimed at establishing this association in Pakistan. Research Design and Methods: A cross-sectional study was conducted in Punjab and Sindh, Pakistan, between March 30, 2002, and August 22, 2022, among adults aged 50 and older. Multidimensional poverty measures were composed of 6 dimensions and 15 indicators. Poverty was compared between adults with and without dementia using the Rowland Universal Dementia Assessment Scale, adjusting for sex, age, marital status, and household size. Associations between dementia and poverty were investigated using a multivariate logistic regression model. Results: We found that 594 (72.7%), 171 (20.9%), and 52 (6.4%) had no, mild, and moderate-to-severe dementia, respectively. More women than men had dementia (11.4% vs 2.9%). Approximately 40.4% of adults with dementia were found to be deprived in 4 or more dimensions compared to 8.9% without dementia, and the difference in multidimensional poverty between them was 348.6%. Education, health, living conditions, and psychological well-being were the main contributors to poverty. Poverty in 4 or more dimensions was strongly associated with dementia (odds ratio [OR], 5.02; 95% confidence interval [CI], 2.07-12.16) after adjusting for sex, marital status, age, and household size, with greater odds for older women (OR, 2.02; 95% CI, 1.41-2.90). Discussion and Implications: Our findings suggest that early improvement in social determinants of health through targeted structural policies may prevent dementia later in life. Improving access to free, quality education, health care including mental health care and basic living standards, and employment should reduce the collective risk of dementia.

Traumatic Brain Injury, Seizures, and Cognitive Impairment Among Older Adults.

Importance: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups. Objective: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association. Design, Setting, and Participants: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer's Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer's Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype. Exposure: Health history of TBI, seizures, or both conditions. Main Outcomes and Measures: Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0. Results: Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk. Conclusions and Relevance: This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.

Corrigendum to "Multidimensional poverty is associated with dementia among adults in Afghanistan" [eClinicalMedicine 58(2023) 101906].

[This corrects the article DOI: 10.1016/j.eclinm.2023.101906.].

Identifying Gaps and Barriers in Alzheimer's Disease and Related Dementia Research and Management in Low- and Middle-Income Countries: A Survey of Health Professionals and Researchers.

Background: The significant increase in Alzheimer's disease and related dementia prevalence is a global health crisis, acutely impacting low- and lower-middle and upper-middle-income countries (LLMICs/UMICs). Objective: The objective of this study is to identify key barriers and gaps in dementia care and research in LLMICs and UMICs. Methods: We conducted an international, cross-sectional survey among clinicians and healthcare professionals (n = 249 in 34 countries) across LLMICs and UMICs, exploring patient demographics, use of clinical diagnosis, dementia evaluation, screening/evaluation tools, and care and treatment. Results: Significant disparities were found in diagnostic practices, access to assessments, and access to care. On average, clinicians in LLMICs saw more patients, had less time for evaluations, lower use of formal screening and tools, and less access to biomarkers. They were also under-resourced compared to UMICs. Conclusions: The findings provide insights for policymakers, healthcare organizations, and researchers to address the complex challenges associated with dementia care in diverse settings. Addressing these challenges requires a multipronged approach involving local, national, and international stakeholders.

Recruiting a prospective community cohort to study Alzheimer's disease and structural and social determinants of health among adults racialized as Black: The ARCHES cohort.

INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study. METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop. RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking engagements were the most effective. DISCUSSION: The systemic underrepresentation of Black participants in AD research impacts the ability to generalize research findings and determine the effectiveness and safety of disease-modifying treatments. Research to slow, stop, or prevent AD remains a top priority but requires diversity in sample representation. Highlights: Provide flexible appointments in the evening or weekends, offering transportation assistance, and allowing participants to complete study visits at alternative locations, such as senior centers or community centers.Continuously monitor and analyze recruitment data to identify trends, challenges, and opportunities for improvement.Implement targeted strategies to recruit participants who are underrepresented based on sex, gender, or education to increase representation.Diversify the research team to include members who reflect the racial and cultural backgrounds of the target population, to enhance trust and rapport with prospective participants.

Clinical and pathological heterogeneity of four common fusion subtypes in Xp11.2 translocation renal cell carcinoma.

Background: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a group of rare and highly heterogeneous renal cell carcinoma (RCC). The translocation involving TFE3 and different fusion partners lead to overexpression of the chimeric protein. The purpose of this study is to explore the clinicopathological features of Xp11.2 tRCC with four common fusion subtypes. Methods: We screened out 40 Xp11.2 tRCC patients from January 2007 to August 2021 in our institution. The diagnosis was initially confirmed by TFE3 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assay and their fusion partners were verified by RNA sequencing. Then the 40 cases were divided into two groups (DBHS family and non-DBHS family group) and a clinical comparison among the four common fusion subtypes was performed. Results: Among the 40 cases, 11 cases with SFPQ-TFE3 gene fusion and 7 cases with NONO-TFE3 gene fusion were classified in DBHS group, the remaining cases with ASPL-TFE3 (11 cases) or PRCC-TFE3 (11 cases) gene fusion were classified in non-DBHS group. Lymph node (LN) metastasis (P=0.027) and distant metastasis (P=0.009) were more common seen in non-DBHS family group than DBHS family group and cases in DBHS family group have better progressive-free survival (PFS) (P=0.02). In addition, ASPL-TFE3 fusion was associated with worse outcome (P=0.03) while NONO-TFE3 fusion (P=0.04) predicted a better prognosis. Conclusions: Different fusion partner genes may play a functional role in various morphology, molecular and biological features of Xp11.2 tRCCs. The impact of fusion partners on clinical characteristics of Xp11.2 tRCCs deserves further exploration.