Miracle-dz/UniFAR-FTUs huggingface dataset:
One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis

Objective: The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. Design: Historical cohort analyses of de-identified electronic medical records. Subjects: In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. Main outcome measures: Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (#5.5 mg/dL) and mean number of PB pills/day. Results: Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P <.0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P <. 0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women). Conclusion: Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.
Noncommercial US Funders’ Policies on Trial Registration, Access to Summary Results, and Individual Patient Data Availability

Key Points Question What are the current policies for clinical trial registration, summary results sharing, and individual patient data sharing among the top 10 noncommercial US health research funders? Findings In this review study, 6 of 9 (67%) of the top US funders have a publicly available written policy addressing all 3 major trial transparency domains. However, fewer US funders require specific transparency actions in these domains (11%-56%) or monitor compliance with their policies (56%-67%). Meaning More work remains to be done to ensure timely implementation and enforcement of clinical trial transparency initiatives to reduce waste and realize public value from clinical research investments.
Association of accumulated advanced glycation end‐products with a high prevalence of sarcopenia and dynapenia in patients with type 2 diabetes

Advanced glycation end‐products (AGEs), which are a major cause of diabetic vascular complications, accumulate in various tissues under chronic hyperglycemic conditions, as well as with aging in patients with diabetes. The loss of muscle mass and strength, so‐called sarcopenia and dynapenia, has recently been recognized as a diabetic complication. However, the influence of accumulated AGEs on muscle mass and strength remains unclear. The present study aimed to evaluate the association of sarcopenia and dynapenia with accumulated AGEs in patients with type 2 diabetes.
Associations of Harsh Physical Punishment and Child Maltreatment in Childhood With Antisocial Behaviors in Adulthood

Key Points Question Are harsh physical punishment in the absence of child maltreatment and child maltreatment with and without harsh physical punishment in childhood associated with antisocial behaviors in adulthood? Findings In this cross-sectional study using nationally representative data on 36 309 adults, harsh physical punishment in the absence of child maltreatment and child maltreatment that they had experienced were associated with antisocial behavior. Together, these issues are estimated to account for 45.5% and 47.3% of antisocial behaviors among men and women, respectively, in the United States. Meaning Preventing harsh physical punishment and child maltreatment may be associated with decreases in adult antisocial behaviors in the general population.
The core pattern of Chinese herbal formulae and drug–herb concurrent usage in patients with dementia

Abstract More than 40% dementia patients received traditional Chinese Medicine treatment. However, the prescription pattern of Chinese herbal formulae (CHF) for treating neurocognitive or behavioral disorders in patients with dementia has not been elucidated. This large-scale survey aimed is to evaluate core patterns of CHF and drug–herb concurrent use in patients with dementia. We analyzed patients with a diagnosis of dementia from one million cohorts of the Longitudinal Health Insurance Database in the National Health Insurance Research Database, between 1997 and 2008. Of 18,141 newly diagnosed dementia patients, 3471 patients received CHF for mental and nervous system diseases. There were 13,254 outpatient visits, with 60,968 formulae prescriptions. We calculate the frequency and proportion of combined use, identify drug–herb concurrent usage, and determine core prescription patterns. Also, we drew network graphs of co-prescription pairs which occurred more than 200 times. Chinese medicine prescription patterns changed as dementia progressed. During the first 3 years after the diagnosis of dementia, Jia-Wei-Xiao-Yao-San, Gan-Mai-Da-Zao-Tang, and Ban-Xia-Bai-Zhu-Tian-Ma-Tang were the core CHF prescribed for mental and nervous system disorders. However, during the later stages of dementia, Suan-Zao-Ren-Tang, Gui-Pi-Tang, Jia-Wei-Xiao-Yao-San, and Wen-Dan-Tang were the core CHF prescribed. Benzodiazepines were the most common sedative drugs combined with traditional Chinese formulae. The results of this study suggest that TCM prescription were different in various stages of dementia, and indicated the frequently combined use of the TCM formulae and Benzodiazepines in dementia care.
The macrophage-specific V-ATPase subunit ATP6V0D2 restricts inflammasome activation and bacterial infection by facilitating autophagosome-lysosome fusion

ABSTRACT Macroautophagy/autophagy is a conserved ubiquitous pathway that performs diverse roles in health and disease. Although many key, widely expressed proteins that regulate autophagosome formation followed by lysosomal fusion have been identified, the possibilities of cell-specific elements that contribute to the autophagy fusion machinery have not been explored. Here we show that a macrophage-specific isoform of the vacuolar ATPase protein ATP6V0D2/subunit d2 is dispensable for lysosome acidification, but promotes the completion of autophagy via promotion of autophagosome-lysosome fusion through its interaction with STX17 and VAMP8. Atp6v0d2-deficient macrophages have augmented mitochondrial damage, enhanced inflammasome activation and reduced clearance of Salmonella typhimurium. The susceptibility of atp6v0d2 knockout mice to DSS-induced colitis and Salmonella typhimurium-induced death, highlights the in vivo significance of ATP6V0D2-mediated autophagosome-lysosome fusion. Together, our data identify ATP6V0D2 as a key component of macrophage-specific autophagosome-lysosome fusion machinery maintaining macrophage organelle homeostasis and, in turn, limiting both inflammation and bacterial infection. Abbreviations: ACTB/β-actin: actin, beta; ATG14: autophagy related 14; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); ATP6V0D1/2: ATPase, H+ transporting, lysosomal V0 subunit D1/2; AIM2: absent in melanoma 2; BMDM: bone marrow-derived macrophage; CASP1: caspase 1; CGD: chronic granulomatous disease; CSF1/M-CSF: colony stimulating factor 1 (macrophage); CTSB: cathepsin B; DSS: dextran sodium sulfate; IL1B: interleukin 1 beta; IL6: interleukin 6; IRGM: immunity-related GTPase family M member; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; LC3: microtubule-associated protein 1 light chain 3; LPS: lipo-polysaccaride; NLRP3: NLR family, pyrin domain containing 3; PYCARD/ASC: PYD and CARD domain containing; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SNAP29: synaptosomal-associated protein 29; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TLR: toll-like receptor; TNF: tumor necrosis factor ; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1; VAMP8: vesicle-associated membrane protein 8; WT: wild type; 3-MA: 3-methyladenine
Efficacy and safety of laparoscopic holmium laser lithotripsy in the treatment of complicated biliary calculus

Backgroud: The aim of this study was to assess the efficacy and safety of laparoscopic holmium laser lithotripsy (LHLL) in the treatment of complicated biliary calculus. Methods: We systematically searched the electronic database (PubMed, EMBASE, Cochrane library, Web of science, and Chinese Biomedical Literature Database) up to May 2018 to identify case-controlled studies that compared LHLL with laparoscopic bile duct exploration (LBDE) for complicated biliary calculus. Results: Five case-controlled studies were included, with 541 patients (273 in the LHLL group and 268 in the LBDE group). Compared with LBDE, LHLL was associated with shorter operative time (weighted mean difference [WMD] = -40.04, P < .001) and lower estimated blood loss (EBL) (WMD = -56.42, P < .001), lesser duration of hospitalization (WMD = -3.93, P < .001) and lower rate of residual stone (OR = 0.13, P < .001). There was no statistically significant differences in bile leakage (OR = 0.48, P = .23) and hemobilia (OR = 0.49, 0.41). Conclusion: Current evidence suggests that the efficacy of LHLL is superior to that of LBDE but they are similarly safe for the treatment of complicated biliary calculus. Limited by the quantity and quality of the studies included, these conclusions need to be verified by more high-quality studies.
Association between vaginal washing and vaginal bacterial concentrations

Vaginal washing is a common practice associated with adverse outcomes including bacterial vaginosis (BV) and HIV infection. Prior studies have not examined the associations between vaginal washing and individual vaginal bacteria, or whether these associations are independent of the effect of vaginal washing on BV. The purpose of this study was to characterize the association between vaginal washing and the presence and concentrations of vaginal bacteria associated with optimal and sub-optimal vaginal states. The analysis utilized data from participants in the placebo arm of the Preventing Vaginal Infections trial, which enrolled HIV-uninfected women from the United States and Kenya. Detection of bacterial taxa associated with BV was compared between visits with versus without reported vaginal washing. The effect of vaginal washing on a number of vaginal bacteria differed substantially (p<0.05) between the US and Kenya, so results were stratified by country. In US women, vaginal washing was associated with a significantly higher likelihood of detection of BV associated bacterium 1 (BVAB1) (relative risk [RR] 1.55, 95% confidence interval [CI] 1.15–2.09, p = 0.004), BVAB2 (RR 1.99, 95%CI 1.46–2.71, p<0.001), Mageeibacillus indolicus (RR 2.08, 95%CI 1.46–2.96, p<0.001), Atopobium vaginae (RR 1.34, 95%CI 1.13–1.59, p = 0.001), Leptotrichia/Sneathia species (RR 1.66, 95% CI 1.33–2.09, p<0.001), Megasphaera species (RR 1.78, 95%CI 1.34–2.37, p<0.001) and Gardnerella vaginalis (RR 1.08, 95%CI 1.01–1.16, p = 0.02). No significant association between vaginal washing and bacterial detection was found in Kenyan women. Adjustment for bacterial vaginosis diagnosed by Gram stain did not alter these results. This study provides evidence that the association between vaginal washing and detection of individual bacterial taxa can vary regionally. For some vaginal bacteria, the association with vaginal washing may be independent of the effect on Gram stain detection of BV. Larger prospective studies in diverse geographic settings should explore whether eliminating vaginal washing impacts the presence and concentrations of key vaginal bacteria.
Adaptive Auto-Regressive Proportional Myoelectric Control

In proportional myographic control, one can control either position or velocity of movement. Here, we propose to use adaptive auto-regressive filters, so as to gradually adjust between the two. We implemented this in an adaptive system with closed-loop feedback, where both the user and the machine simultaneously attempt to follow a cursor on a 2-D arena. We tested this on 15 able-bodied and three limb-deficient participants using an eight-channel myoelectric armband. The human–machine pairs learn to perform smoother cursor movements with a larger range of motion when using the auto-regressive filters, as compared with our previous effortswithmoving-average filters. Importantly, the human–machine system converges to an approximate velocity control strategy resulting in faster and more accuratemovements with lessmuscle effort. The method is not specific tomyoelectriccontroland could be used equally well for motion control using high-dimensional signals from reinnervatedmuscles or direct brain recordings.
Understanding the Mechanism of Antidepressant-Related Sexual Dysfunction: Inhibition of Tyrosine Hydroxylase in Dopaminergic Neurons after Treatment with Paroxetine but Not with Agomelatine in Male Rats

Antidepressant-related sexual dysfunction is a frequent adverse event caused by serotonergic activation that intensely affects quality of life and adherence in depressed patients. The dopamine system has multiple effects promoting sexual behavior, but no studies have been carried out to confirm dopaminergic changes involved in animal models after antidepressant use. Methods: The sexual behavior-related dopaminergic system in the rat was studied by comparing two different antidepressants and placebo for 28 days. The antidepressants used were paroxetine (a serotonergic antidepressant that causes highly frequent sexual dysfunction in humans) and agomelatine (a non-serotonergic antidepressant without associated sexual dysfunction). The tyrosine hydroxylase immunoreactivity (THI) in the substantia nigra pars compacta, the ventral tegmental area, the zona incerta, and the hypothalamic arcuate nucleus, as well as the dopaminergic projections to the striatum, hippocampus, cortex, and median eminence were analyzed. Results: The THI decreased significantly in the substantia nigra and ventral tegmental area after treatment with paroxetine, and the labeling was reduced drastically in the zona incerta and mediobasal hypothalamus. The immunoreactive axons in the target regions (striatum, cortex, hippocampus, and median eminence) almost disappeared only in the paroxetine-treated rats. Conversely, after treatment with agomelatine, a moderate reduction in immunoreactivity in the substantia nigra was found without appreciable modifications in the ventral tegmental area, zona incerta, and mediobasal hypothalamus. Nevertheless, no sexual or copulatory behavior was observed in any of the experimental or control groups. Conclusion: Paroxetine but not agomelatine was associated with important decreased activity in dopaminergic areas such as the substantia nigra and ventral tegmental areas that could be associated with sexual performance impairment in humans after antidepressant treatment.
Neurovascular Response to Pressure in Patients With Diabetic Foot Ulcer

Diabetic foot ulcer (DFU) is a problem worldwide, and prevention is crucial. We hypothesized that the inability of the skin to respond to pressure is involved in DFU pathogenesis and could be an important predictive factor to take into account. We included 29 patients with DFU and 30 patients with type 2 diabetes without DFU. Neuropathy and skin blood flow at rest were assessed in response to acetylcholine, sodium nitroprusside, local heating (42°C), and to nonnoxious locally applied pressure. Results were compared with those obtained from 10 healthy age-matched control subjects. Vasodilatation in response to pressure was significantly impaired in both groups with diabetes compared with healthy subjects. The vasodilator capacity to pressure was significantly lower in patients with DFU compared with those without DFU, despite the absence of significant difference in cutaneous pressure perception threshold and vascular reactivity to acetylcholine, sodium nitroprusside, and heat. This pronounced alteration of neurovascular response to pressure in patients with DFU is a good marker of skin vulnerability and could be used to better predict individuals at risk.
Phenolic Compounds of Catalpa speciosa, Taxus cuspidata, and Magnolia acuminata have Antioxidant and Anticancer Activity

Tree bark represents an important source of medicinal compounds that may be useful for cancer therapy. In the current study, high-performance liquid chromatography with diode-array detection (HPLC-DAD) was used to determine the profile of the phenolic compounds of Catalpa speciosa, Taxus cuspidata, and Magnolia acuminata bark extracts. The antioxidant and anticancer bioactivities against different cancer cell lines were investigated. M. acuminata exerted significantly higher antioxidant activities in the diphenyl picrylhydrazine and β-carotene-linoleic acid assays than the other species. In C. speciosa, novel profiles of phenolic acids (ferulic acid was the predominant compound) and catechin were detected. In T. cuspidata, six phenolic acids were detected; the predominant compounds were hydroxycaffeic acid and protocatechuic acid. In M. acuminata, two phenolic acids and three catechins were detected; catechin was the predominant compound. The three species exerted clear anticancer activity against MCF-7, HeLa, Jurkat, T24, and HT-29 cells, with the strongest activity found in the extracts from M. acuminata. No antiproliferative activity against normal cells was found. Flow cytometry revealed greater accumulation of necrotic and early/late apoptotic cells in various treated cancer cells than in untreated control cells, and protocatechuic acid induced a similar accumulation of necrotic cells to that of the bark extracts. Caspase-3 and -7 activity was increased in cancer cells treated with different bark extracts; the highest activity was found in the M. acuminata treatment. Our results suggested that the treatment of cancer cells with bark extracts of M. acuminata, C. speciosa, and T. cuspidata, and protocatechuic acid induced apoptosis, suggesting an association between anticancer activities and individual phenolic compounds.
Exploring Disparities in Maternal Residential Proximity to Unconventional Gas Development in the Barnett Shale in North Texas

Background: This study explores sociodemographic disparities in residential proximity to unconventional gas development (UGD) among pregnant women. Methods: We conducted a secondary analysis using data from a retrospective birth cohort of 164,658 women with a live birth or fetal death from November 2010 to 2012 in the 24-county area comprising the Barnett Shale play, in North Texas. We considered both individual- and census tract-level indicators of sociodemographic status and computed Indexes of Concentration at the Extremes (ICE) to quantify relative neighborhood-level privilege/disadvantage. We used negative binomial regression to investigate the relation between these variables and the count of active UGD wells within 0.8 km of the home during gestation. We calculated count ratios (CR) and 95% confidence intervals (CI) to describe associations. Results: There were fewer wells located near homes of women of color living in low-income areas compared to non-Hispanic white women living in more privileged neighborhoods (ICE race/ethnicity + income: CR = 0.51, 95% CI = 0.48–0.55). Conclusions: While these results highlight a potential disparity in residential proximity to UGD in the Barnett Shale, they do not provide evidence of an environmental justice (EJ) issue nor negate findings of environmental injustice in other regions.
Facilitators and barriers to the novice nurse practitioner workforce transition in primary care.

BACKGROUND AND PURPOSE Little is known about the facilitators and barriers to the workforce transition of novice nurse practitioners (NPs) in primary care. This research aimed to identify factors contributing and detracting from a successful initial workforce transition for novice NPs in the primary care setting. METHODS A descriptive, cross-sectional study was conducted via online survey administered to a national sample of 177 NPs who graduated from an accredited NP program and were practicing in a primary care setting for 3-12 months. Open-ended responses were analyzed using the Krippendorff content analysis method. CONCLUSIONS This study demonstrated that facilitators of the novice NP transition are the presence of mentorship and social support, finding meaning in their work, job satisfaction, and work-life balance. Barriers to the novice NP transition are lack of support and respect, role ambiguity, and workload. IMPLICATIONS FOR PRACTICE More mentorship, support, role clarity, and respect are needed to facilitate the novice NP workforce transition. More research is needed on interventions that can be implemented by health care organizations to improve the facilitators of role transition identified in this study.
The metastasis suppressor NDRG1 down-regulates the epidermal growth factor receptor via a lysosomal mechanism by up-regulating mitogen-inducible gene 6

The metastasis suppressor, N-Myc downstream-regulated gene-1 (NDRG1) inhibits a plethora of oncogenic signaling pathways by down-regulating the epidermal growth factor receptor (EGFR). Herein, we examined the mechanism involved in NDRG1-mediated EGFR down-regulation. NDRG1 overexpression potently increased the levels of mitogen-inducible gene 6 (MIG6), which inhibits EGFR and facilitates its lysosomal processing and degradation. Conversely, silencing NDRG1 in multiple human cancer cell types decreased MIG6 expression, demonstrating the regulatory role of NDRG1. Further, NDRG1 overexpression facilitated MIG6–EGFR association in the cytoplasm, possibly explaining the significantly (p <0.001) increased half-life of MIG6 from 1.6 ± 0.2 h under control conditions to 7.9 ± 0.4 h after NDRG1 overexpression. The increased MIG6 levels enhanced EGFR co-localization with the late endosome/lysosomal marker, lysosomal-associated membrane protein 2 (LAMP2). An increase in EGFR levels after MIG6 silencing was particularly apparent when NDRG1 was overexpressed, suggesting a role for MIG6 in NDRG1-mediated down-regulation of EGFR. Silencing phosphatase and tensin homolog (PTEN), which facilitates early to late endosome maturation, decreased MIG6, and also increased EGFR levels in both the presence and absence of NDRG1 overexpression. These results suggest a role for PTEN in regulating MIG6 expression. Anti-tumor drugs of the di-2-pyridylketone thiosemicarbazone class that activate NDRG1 expression also potently increased MIG6 and induced its cytosolic co-localization with NDRG1. This was accompanied by a decrease in activated and total EGFR levels and its redistribution to late endosomes/lysosomes. In conclusion, NDRG1 promotes EGFR down-regulation through the EGFR inhibitor MIG6, which leads to late endosomal/lysosomal processing of EGFR.