Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Apathy With Risk of Incident Dementia: A Systematic Review and Meta-analysis

Importance Fear of dementia is pervasive in older people with cognitive concerns. Much research is devoted to finding prognostic markers for dementia risk. Studies suggest apathy in older people may be prodromal to dementia and could be a relevant, easily measurable predictor of increased dementia risk. However, evidence is fragmented and methods vary greatly between studies. Objective To systematically review and quantitatively synthesize the evidence for an association between apathy in dementia-free older individuals and incident dementia. Data Sources Two reviewers conducted a systematic search of Medline, Embase, and PsychINFO databases. Study Selection Inclusion criteria were (1) prospective cohort studies, (2) in general populations or memory clinic patients without dementia, (3) with clear definitions of apathy and dementia, and (4) reporting on the association between apathy and incident dementia. Data Extraction and Synthesis PRISMA and MOOSE guidelines were followed. Data were extracted by 1 reviewer and checked by a second. Main Outcomes and Measures Main outcomes were pooled crude risk ratios, maximally adjusted reported hazard ratios (HR), and odds ratios (OR) using DerSimonian-Laird random effects models. Results The mean age of the study populations ranged from 69.2 to 81.9 years (median, 71.6 years) and the percentage of women ranged from 35% to 70% (median, 53%). After screening 2031 titles and abstracts, 16 studies comprising 7365 participants were included. Apathy status was available for 7299 participants. Studies included populations with subjective cognitive concerns (n = 2), mild cognitive impairment (n = 11), cognitive impairment no dementia (n = 1), or mixed cognitive and no cognitive impairment (n = 2). Apathy was present in 1470 of 7299 participants (20.1%). Follow-up ranged from 1.2 to 5.4 years. In studies using validated apathy definitions (n = 12), the combined risk ratio of dementia for patients with apathy was 1.81 (95% CI, 1.32-2.50; I2 = 76%; n = 12), the hazard ratio was 2.39 (95% CI, 1.27-4.51; I2 = 90%; n = 7), and the odds ratio was 17.14 (95% CI, 1.91-154.0; I2 = 60%; n = 2). Subgroup analyses, meta-regression, and individual study results suggested the association between apathy and dementia weakened with increasing follow-up time, age, and cognitive impairment. Meta-regression adjusting for apathy definition and follow-up time explained 95% of heterogeneity in mild cognitive impairment. Conclusions and Relevance Apathy was associated with an approximately 2-fold increased risk of dementia in memory clinic patients. Moderate publication bias may have inflated some of these estimates. Apathy deserves more attention as a relevant, cheap, noninvasive, and easily measureable marker of increased risk of incident dementia with high clinical relevance, particularly because these vulnerable patients may forgo health care.
You Will Know That Despite Being HIV Positive You Are Not Alone: Qualitative Study to Inform Content of a Text Messaging Intervention to Improve Prevention of Mother-to-Child HIV Transmission

Background Prevention of mother-to-child HIV transmission (PMTCT) relies on long-term adherence to antiretroviral therapy (ART). Mobile health approaches, such as text messaging (short message service, SMS), may improve adherence in some clinical contexts, but it is unclear what SMS content is desired to improve PMTCT-ART adherence. Objective We aimed to explore the SMS content preferences related to engagement in PMTCT care among women, male partners, and health care workers. The message content was used to inform an ongoing randomized trial to enhance the PMTCT-ART adherence. Methods We conducted 10 focus group discussions with 87 HIV-infected pregnant or postpartum women and semistructured individual interviews with 15 male partners of HIV-infected women and 30 health care workers from HIV and maternal child health clinics in Kenya. All interviews were recorded, translated, and transcribed. We analyzed transcripts using deductive and inductive approaches to characterize women’s, partners’, and health care workers’ perceptions of text message content. Results All women and male partners, and most health care workers viewed text messages as a useful strategy to improve engagement in PMTCT care. Women desired messages spanning 3 distinct content domains: (1) educational messages on PMTCT and maternal child health, (2) reminder messages regarding clinic visits and adherence, and (3) encouraging messages that provide emotional support. While all groups valued reminder and educational messages, women highlighted emotional support more than the other groups (partners or health care workers). In addition, women felt that encouraging messages would assist with acceptance of their HIV status, support disclosure, improve patient-provider relationship, and provide support for HIV-related challenges. All 3 groups valued not only messages to support PMTCT or HIV care but also messages that addressed general maternal child health topics, stressing that both HIV- and maternal child health–related messages should be part of an SMS system for PMTCT. Conclusions Women, male partners, and health care workers endorsed SMS text messaging as a strategy to improve PMTCT and maternal child health outcomes. Our results highlight the specific ways in which text messaging can encourage and support HIV-infected women in PMTCT to remain in care, adhere to treatment, and care for themselves and their children. Trial Registration ClinicalTrials.gov NCT02400671; https://clinicaltrials.gov/ct2/show/NCT02400671 (Archived by WebCite at http://www.webcitation.org/70W7SVIVJ)
Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2

Cellular senescence is a key driver of ageing, influenced by age-related changes to the regulation of alternative splicing. Hydrogen sulfide (H2S) has similarly been described to influence senescence, but the pathways by which it accomplishes this are unclear. We assessed the effects of the slow release H2S donor Na-GYY4137 (100 µg/ml), and three novel mitochondria-targeted H2S donors AP39, AP123 and RT01 (10 ng/ml) on splicing factor expression, cell proliferation, apoptosis, DNA replication, DNA damage, telomere length and senescence-related secretory complex (SASP) expression in senescent primary human endothelial cells. All H2S donors produced up to a 50% drop in senescent cell load assessed at the biochemical and molecular level. Some changes were noted in the composition of senescence-related secretory complex (SASP); IL8 levels increased by 24% but proliferation was not re-established in the culture as a whole. Telomere length, apoptotic index and the extent of DNA damage were unaffected. Differential effects on splicing factor expression were observed depending on the intracellular targeting of the H2S donors. Na-GYY4137 produced a general 1.9 – 3.2-fold upregulation of splicing factor expression, whereas the mitochondria-targeted donors produced a specific 2.5 and 3.1-fold upregulation of SRSF2 and HNRNPD splicing factors only. Knockdown of SRSF2 or HNRNPD genes in treated cells rendered the cells non-responsive to H2S, and increased levels of senescence by up to 25% in untreated cells. Our data suggest that SRSF2 and HNRNPD may be implicated in endothelial cell senescence, and can be targeted by exogenous H2S. These molecules may have potential as moderators of splicing factor expression and senescence phenotypes.
Cancer Site–Specific Disparities in New York, Including the 1945–1965 Birth Cohort's Impact on Liver Cancer Patterns

Background: Analyses of cancer patterns by detailed racial/ethnic groups in the Northeastern United States are outdated. Methods: Using 2008–2014 death data from the populous and diverse New York State, mortality rates and regression-derived ratios with corresponding 95% confidence intervals (CIs) were computed to compare Hispanic, non-Hispanic white (NHW), non-Hispanic black (NHB), Asian populations, and specific Hispanic and NHB subgroups: Puerto Rican, Dominican, South American, Central American, U.S.-born black, and Caribbean-born black. Special analyses on liver cancer mortality, given the higher prevalence of hepatitis C infection among the 1945–1965 birth cohort, were performed. Results: A total of 244,238 cancer-related deaths were analyzed. Mortality rates were highest for U.S.-born blacks and lowest for South Americans and Asians. Minority groups had higher mortality from liver and stomach cancer than NHWs; Hispanics and NHBs also had higher mortality from cervical and prostate cancers. Excess liver cancer mortality among Puerto Rican and U.S.-born black men was observed, particularly for the 1945–1965 birth cohort, with mortality rate ratios of 4.27 (95% CI, 3.82–4.78) and 3.81 (95% CI, 3.45–4.20), respectively. Conclusions: U.S.-born blacks and Puerto Ricans, who share a common disadvantaged socioeconomic profile, bear a disproportionate burden for many cancers, including liver cancer among baby boomers. The relatively favorable cancer profile for Caribbean-born blacks contrasts with their U.S.-born black counterparts, implying that race per se is not an inevitable determinant of higher mortality among NHBs. Impact: Disaggregation by detailed Hispanic and black subgroups in U.S. cancer studies enlightens our understanding of the epidemiology of cancer and is fundamental for cancer prevention and control efforts. Cancer Epidemiol Biomarkers Prev; 27(8); 917–27. ©2018 AACR.
Chronic Scapholunate Interosseous Ligament Disruption: A Systematic Review and Meta-Analysis of Surgical Treatments

Background: Although many techniques have been described, there is no clear optimal surgical treatment for chronic scapholunate interosseous ligament (SLIL) disruption. Methods: We identified 255 articles reporting outcomes of SLIL reconstruction. Of these, 40 studies (978 wrists) met eligibility requirements and reported sufficient data on radiographic outcomes to be included in the study. The mean and standard deviation of preoperative and follow-up assessments including scapholunate gap (SLG) and scapholunate angle (SLA) were used to calculate pooled standardized mean differences (SMD) with 95% confidence intervals (CIs). For other radiographic or clinical outcomes, there were not enough reported data to calculate a pooled effect size, and pooled nonstandardized comparisons were made. Results: The SMD between preoperative and postoperative SLA in tenodesis reconstruction was 0.7 (CI, 0.29 to 1.11, P = .001) and 0.04 (CI, –0.27 to 0.38, P = .8) for capsulodesis reconstruction. For SLG, tenodesis demonstrated an SMD of 1.1 (CI, 0.6 to 1.55, P < .001) compared with 0.1 (CI, –0.36 to 0.59, P = .6) for capsulodesis reconstruction. Tenodesis had a significant improvement compared with capsulodesis in SLA (P = .01) and SLG (P = .005). Tenodesis also showed improvement in grip strength and Disabilities of the Arm, Shoulder and Hand scores. Conclusions: Comparing preoperative and postoperative radiographic measurements, tenodesis reconstruction demonstrated significantly improved SLG and SLA relative to capsulodesis. Interpreted in the context of the limitations, existing data demonstrates some benefit of tenodesis reconstruction.
Colon cleansing efficacy and safety with 1 L NER1006 versus sodium picosulfate with magnesium citrate: a randomized phase 3 trial

Abstract Background Polyethylene glycol (PEG) bowel preparations are widely used for precolonoscopy bowel cleansing. This phase 3 trial assessed the efficacy, safety, and tolerability of the novel 1 L PEG-based NER1006 vs. sodium picosulfate plus magnesium citrate (SP + MC) in day-before dosing. Methods Patients requiring colonoscopy were randomized (1 : 1) to receive NER1006 or SP + MC. Cleansing was assessed on the Harefield Cleansing Scale (HCS) and Boston Bowel Preparation Scale (BBPS) using central readers. Two primary end points were assessed: overall colon cleansing success and high-quality cleansing of the right colon. Intention-to-treat (modified full analysis set [mFAS]) and per protocol (PP) analyses were performed. Results Of 515 patients, efficacy was analyzed in 501 (NER1006, n = 250; SP + MC, n = 251) and 379 patients (NER1006, n = 172; SP + MC, n = 207) in the mFAS and PP analyses, respectively. Non-inferiority of NER1006 vs. SP + MC was established in the mFAS for both overall cleansing (62.0 % vs. 53.8 %; P = 0.04) and high-quality cleansing in the right colon (4.4 % vs. 1.2 %; P = 0.03). Superiority of NER1006 was demonstrated using HCS in the PP set for overall cleansing success (68.0 % vs. 57.5 %; P = 0.02) and right colon high-quality cleansing (5.2 % vs. 1.0 %; P = 0.02) and using BBPS in the mFAS for overall cleansing success (58.4 % vs. 45.8 %; P = 0.003) and right colon high-quality cleansing (4.0 % vs. 0.8 %; P = 0.02). Mean segmental scores for 4/5 segments were higher with NER1006 (P ≤ 0.04). Both treatments were well tolerated, with more mild adverse events for NER1006 (17.0 % vs. 10.0 %; P = 0.03). Conclusions Colon cleansing with NER1006 vs. SP + MC was non-inferior (mFAS) and superior (PP), with acceptable safety. European Clinical Trials Database (EudraCT) 2014-002186-30 TRIAL REGISTRATION: Multicenter, randomized, parallel group, phase 3 study 2014-002186-30 at https://eudract.ema. europa.eu/
Mini‐review: Phytoplankton‐derived polysaccharides in the marine environment and their interactions with heterotrophic bacteria

Within the wealth of molecules constituting marine dissolved organic matter, carbohydrates make up the largest coherent and quantifiable fraction. Their main sources are from primary producers, which release large amounts of photosynthetic products - mainly polysaccharides - directly into the surrounding water via passive and active exudation. The organic carbon and other nutrients derived from these photosynthates enrich the 'phycosphere' and attract heterotrophic bacteria. The rapid uptake and remineralization of dissolved free monosaccharides by heterotrophic bacteria account for the barely detectable levels of these compounds. By contrast, dissolved combined polysaccharides can reach high concentrations, especially during phytoplankton blooms. Polysaccharides are too large to be taken up directly by heterotrophic bacteria, instead requiring hydrolytic cleavage to smaller oligo- or monomers by bacteria with a suitable set of exoenzymes. The release of diverse polysaccharides by various phytoplankton taxa is generally interpreted as the deposition of excess organic material. However, these molecules likely also fulfil distinct, yet not fully understood functions, as inferred from their active modulation in terms of quality and quantity when phytoplankton becomes nutrient limited or is exposed to heterotrophic bacteria. This minireview summarizes current knowledge regarding the exudation and composition of phytoplankton-derived exopolysaccharides and acquisition of these compounds by heterotrophic bacteria.
Step-Down Task Identifies Differences in Ankle Biomechanics Across Functional Activities

Abstract Currently, there is no clinical exam to evaluate ankle frontal plane kinematics. The purpose of this study was to determine whether individuals identified as “lateral” landing during a video-recorded step-down task have differences in ankle inversion as measured with 3-dimensional motion capture during walking, step-down, and jump-landing tasks compared to individuals identified as “non-lateral”. Fifty-seven recreationally active adults completed the descriptive laboratory study. During walking, step-down, and jump-landing tasks, participants had their ankle frontal plane kinematics measured using a 3-dimensional motion capture system. In addition, during the step-down task, participants had a posterior view video of their foot recorded using a commercial camera. Following testing, a blinded-investigator scored the step-down video of all participants by classifying them as ”lateral” landing or ”non-lateral” landing. Ankle frontal plane kinematics during the walking, step-down, and jump-landing tasks were compared between the two groups (lateral (N=24) and non-lateral (N=33) using a binary logistic regression and time-series confidence interval analysis. During walking, stepping-down, and jump-landing, the lateral group had significantly more inversion at initial contact and during various other phases specific to each task. This study found that a clinical screening tool could identify individuals who have significantly more inversion during three tasks.
Chronic stress causes protein kinase C epsilon-aldehyde dehydrogenase 2 signaling pathway perturbation in the rat hippocampus and prefrontal cortex, but not in the myocardium

Chronic stress is strongly associated with the occurrence and development of depression and cardiovascular disease. Stress can induce altered mitochondrial function and activation of apoptosis in the cardio-cerebral system. However, it is unknown whether the protein kinase C ε (PKCε)-aldehyde dehydrogenase 2 (ALDH2) pathway is altered under chronic stress, and this study sought to address this question. A rat model of depression was established using a chronic unpredictable mild stress (CUMS) protocol. After experiencing CUMS for 4 weeks, the sucrose preference test and the forced swim test verified depressive-like behaviors. Enzyme linked immunosorbent assays showed that ALDH2 activity was decreased in the rat hippocampus and prefrontal cortex, but was not altered in the myocardium. Western blot assays demonstrated reduced levels of ALDH2 and PKCε, but increased levels of 4-hydroxy-2-nonenal (4HNE) adducts. Caspase-3 expression did not obviously alter, but active forms of caspase-3 were increased in the hippocampus and prefrontal cortex. In the myocardium, expression of ALDH2, PKCε and 4HNE adducts did not remarkably alter; while caspase-3 expression was reduced and the active forms of caspase-3 were upregulated. Pearson’s correlation test demonstrated that expression of 4HNE adducts was positively correlated with levels of the active forms of caspase-3 in the hippocampus and prefrontal cortex, but not in the myocardium. In conclusion, chronic stress can damage the PKCε-ALDH2 signaling pathway in the hippocampus and prefrontal cortex, but not in the myocardium. Moreover, 4HNE is associated with active forms of caspase-3 in the hippocampus and prefrontal cortex.
PD-L1+ tumor-associated macrophages and PD-1+ tumor-infiltrating lymphocytes predict survival in primary testicular lymphoma

Primary testicular lymphoma is a rare and aggressive lymphoid malignancy, most often representing diffuse large B-cell lymphoma histologically. Tumor-associated macrophages and tumor-infiltrating lymphocytes have been associated with survival in diffuse large B-cell lymphoma, but their prognostic impact in primary testicular lymphoma is unknown. Here, we aimed to identify macrophages, their immunophenotypes and association with lymphocytes, and translate the findings into survival of patients with primary testicular lymphoma. We collected clinical data and tumor tissue from 74 primary testicular lymphoma patients, and used multiplex immunohistochemistry and digital image analysis to examine macrophage markers (CD68, CD163, and c-Maf), T-cell markers (CD3, CD4, and CD8), B-cell marker (CD20), and three checkpoint molecules (PD-L1, PD-L2, and PD-1). We demonstrate that a large proportion of macrophages (median 41%, range 0.08–99%) and lymphoma cells (median 34%, range 0.1–100%) express PD-L1. The quantity of PD-L1+ CD68+ macrophages correlates positively with the amount of PD-1+ lymphocytes, and a high proportion of either PD-L1+ CD68+ macrophages or PD-1+ CD4+ and PD-1+ CD8+ T cells translates into favorable survival. In contrast, the number of PD-L1+lymphoma cells or PD-L1− macrophages do not associate with outcome. In multivariate analyses with IPI, PD-L1+ CD68+ macrophage and PD-1+ lymphocyte contents remain as independent prognostic factors for survival. In conclusion, high PD-L1+ CD68+ macrophage and PD-1+ lymphocyte contents predict favorable survival in patients with primary testicular lymphoma. The findings implicate that the tumor microenvironment and PD-1 – PD-L1 pathway have a significant role in regulating treatment outcome. They also bring new insights to the targeted thera py of primary testicular lymphoma.
Prevalence and Pattern of Chronic Kidney Disease and its Associated Risk Factors in a Rural Community in South Western Nigeria.

BACKGROUND Chronic kidney disease (CKD) has now become a disease of public health importance. The increased prevalence in the population of patients with end stage renal disease (ESRD) is partly related to the failure of early detection of the pre-clinical stages of the disease and its associated risk factors. This study aimed to determine the prevalence of chronic kidney disease and its associated risk factors in Aiyepe community in Ogun state, south western Nigeria as well as determining the awareness level of the population about CKD. MATERIALS AND METHODS It was a cross-sectional community-based study involving 456 participants recruited through cluster and simple random sampling techniques.Participants were screened for urinary albumin by dipstick and/or albumin creatinine ratio. Serum creatinine, fasting blood sugar and serum lipid profile were determined while glomerular filtration rate was estimated using Cockroft and Gault formula from serum creatinine. RESULTS The mean age ± standard deviation (SD) of the study population was 48.09(±15.7) years, and the age range was 18-80 years. Hypertension was seen in 28.9% of studied participants while only 4.2% were diabetic. The mean waist-hip ratio (WHR) of the participants was 0.94(±0.55). The mean BMI of the participants was 26.62(±6.0) kg/m2 with a range of 15.04 to 48.68 kg/m2. The prevalence of overweight and obesity was found to be 24.4% and 30% respectively. The prevalence of proteinuria was 16.3% while 3.7% of the participants had history of haematuria. The prevalence of CKD was 27.6%. Age (OR-1.080, CI-95%, 1.059-1.102), female gender (OR-0.550, CI-95%, 0.320-0.945), BMI (OR-0.832, CI-95%, 0.785-0.882) and dyslipidaemia (OR-1.007, CI-95%, 0.978-1.037) were found to be predictive of CKD in this study. CONCLUSION The prevalence of CKD and its associated risk factors is high in Aiyepe community in Ogun state, south western Nigeria. If this is true for other rural communities generally, it will pose huge challenges on the available healthcare resources.