Miracle-dz/UniFAR-FTUs huggingface dataset:
Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.
Cellular Dermatofibroma: Clinicopathologic Review of 218 Cases of Cellular Dermatofibroma to Determine Clinical Recurrence Rate.

BACKGROUND Cellular dermatofibromas, a variant of dermatofibroma, are reported to recur at rates of 26% to 50%. OBJECTIVE To determine whether there are distinct clinical or histological differences between cellular dermatofibromas that recur versus those that do not. To determine recurrence rates in a real-world clinical setting. MATERIALS AND METHODS A retrospective analysis of the medical records and skin biopsies of cellular dermatofibroma in the University of Utah Health system between December 2011 and 2016. Clinical and dermatopathological features were evaluated to find distinct differences between the cellular dermatofibromas that recurred compared with those that did not. RESULTS There were no significant differences in histology between the primary lesions in recurrent and nonrecurrent cases. One factor that seemed to be associated with a greater likelihood of recurrence was an initial lesion size greater than 1 cm. The authors' data suggest that if the margins are involved on initial biopsy, there is a 10% chance of recurrence. This percentage is far less than the 26% to 50% reported in the past literature. CONCLUSION If a patient presents with a cellular dermatofibroma larger than 1 cm and positive margins at initial biopsy, a careful discussion should be had between the provider and patient about the low risk of local recurrence.
Comparison of adipose- and bone marrow-derived stem cells in protecting against ox-LDL-induced inflammation in M1-macrophage-derived foam cells

Adipose-derived stem cells (ADSCs) and bone marrow-derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co-cultured with M1 foam macrophages via treatment with oxidized low-density lipoprotein (ox-LDL) would lead to similar or improved anti-inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox-LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography-quadrupole time-of-flight-mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis-9, trans-11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox-LDL. Overall, 2×106 ADSCs, BMSCs or BMSCs+cis-9, trans-11 were co-cultured with M1 foam macrophages. Anti-inflammatory capability, phagocytic activity, anti-apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis-9, trans-11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti-inflammatory capabilities, phagocytic activity, anti-apoptotic capability activity and cell viability over BMSCs or BMSCs+cis-9, trans-11. Additionally, BMSCs+cis-9, trans-11 also demonstrated marked improvement in anti-inflammatory capability, phagocytic activity, anti-apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis-9, trans-11. This may be an important mechanism to regulate macrophage immune function.
The Food Energy/Protein Ratio Regulates the Rat Urea Cycle but Not Total Nitrogen Losses

Nitrogen balance studies have shown that a portion of the N ingested but not excreted is not accounted for. We compared several diets (standard, high-fat, high-protein, and self-selected cafeteria) to determine how diet-dependent energy sources affect nitrogen handling, i.e., the liver urea cycle. Diet components and rat homogenates were used for nitrogen, lipid, and energy analyses. Plasma urea and individual amino acids, as well as liver urea cycle enzyme activities, were determined. Despite ample differences in N intake, circulating amino acids remained practically unchanged in contrast to marked changes in plasma urea. The finding of significant correlations between circulating urea and arginine-succinate synthase and lyase activities supported their regulatory role of urea synthesis, the main N excretion pathway. The cycle operation also correlated with the food protein/energy ratio, in contraposition to total nitrogen losses and estimated balance essentially independent of dietary energy load. The different regulation mechanisms observed have potentially important nutritional consequences, hinting at nitrogen disposal mechanisms able to eliminate excess nitrogen under conditions of high availability of both energy and proteins. Their operation reduces urea synthesis to allow for a safe (albeit unknown) mechanism of N/energy excess accommodation.
Strategies to Enhance the Efficiency of Endothelial Progenitor Cell Therapy by Ephrin B2 Pretreatment and Coadministration with Smooth Muscle Progenitor Cells on Vascular Function during the Wound-Healing Process in Irradiated or Nonirradiated Condition

Endothelial progenitor cell (EPC) transplantation has beneficial effects for therapeutic neovascularization. We therefore assessed the effect of a therapeutic strategy based on EPC administation in the healing of radiation-induced damage. To improve cell therapy for clinical use, we used pretreatment with ephrin B2-Fc (Eph-B2-Fc) and/or coadministration with smooth muscle progenitor cells. At day 3, EPCs promoted dermal wound healing in both nonirradiated and irradiated mice by 1.2- and 1.15-fold, respectively, compared with animals injected with phosphate-buffered saline. In addition, EPCs also improved skin-blood perfusion and capillary density in both irradiated and nonirradiated mice compared with PBS-injected animals. We also demonstrated that activation with Eph-B2-Fc increased wound closure by 1.6-fold compared with unstimulated EPCs in nonirradiated mice. Interestingly, the beneficial effect of Eph-B2-Fc was abolished in irradiated animals. In addition, we found that Eph-B2-Fc stimulation did not improve EPC-induced vascular permeability or adhesiveness compared to unstimulated EPCs. We hypothesized that this effect was due to high oxidative stress during irradiation, leading to inhibition of EPCs' beneficial effect on vascular function. In this line, we demonstated that, in irradiated conditions, N-acetyl-l-cysteine treatment restored the beneficial effect of EPC stimulation with Eph-B2-Fc in the wound healing process. In conclusion, stimulation by Eph-B2-Fc improved the beneficial effect of EPCs in physiological conditions and irradiated conditions only in association with antioxidant treatment. Additionally, cotherapy was beneficial in pathological conditions.
Interdental cleaning and periodontal pocketing among finnish adults

AIM To investigate the relationship between frequency of interdental cleaning and 11-year change in teeth with periodontal pocketing in Finnish adults. METHODS Data from 1667 dentate adults, aged 30 to 82 years, who participated in the Health 2000 survey and were re-examined in 2004 and/or 2011 were analysed. Participants reported their frequency of interdental cleaning (either dental floss or interdental brush) at baseline. Teeth with periodontal pocketing (PD) ≥4 mm were counted in every survey and treated as a repeated outcome. The association between the frequency of interdental cleaning and the number of teeth with PD ≥4 mm was evaluated in linear mixed effects models, controlling for demographic factors, socioeconomic position, diabetes, smoking status, toothbrushing frequency, dental attendance and number of teeth. RESULTS Twelve per cent of adults reported daily interdental cleaning. Significant inverse linear trends in the number of teeth with PD ≥4 mm were found in every survey according to the frequency of interdental cleaning. However, this association was completely attenuated after adjustment for the full set of confounders. Contrarily, toothbrushing frequency was negatively associated with the baseline number of teeth with PD ≥4 mm and its rate of change over time. CONCLUSION Interdental cleaning was not associated with 11-year change in periodontal pocketing after accounting for other established risk factors for periodontal disease.
Osteopontin in Vascular Disease: Friend or Foe?

Inflammatory cytokines are necessary for an acute response to injury and the progressive healing process. However, when this acute response does not resolve and becomes chronic, the same proteins that once promoted healing then contribute to chronic inflammatory pathologies, such as atherosclerosis. OPN (Osteopontin) is a secreted matricellular cytokine that signals through integrin and CD44 receptors, is highly upregulated in acute and chronic inflammatory settings, and has been implicated in physiological and pathophysiologic processes. Evidence from the literature suggests that OPN may fit within the Goldilocks paradigm with respect to cardiovascular disease, where acute increases are protective, attenuate vascular calcification, and promote postischemic neovascularization. In contrast, chronic increases in OPN are clinically associated with an increased risk for a major adverse cardiovascular event, and OPN expression is a strong predictor of cardiovascular disease independent of traditional risk factors. With the recent finding that humans express multiple OPN isoforms as the result of alternative splicing and that these isoforms have distinct biologic functions, future studies are required to determine what OPN isoform(s) are expressed in the setting of vascular disease and what role each of these isoforms plays in vascular disease progression. This review aims to discuss our current understanding of the role(s) of OPN in vascular disease pathologies using evidence from in vitro, animal, and clinical studies. Where possible, we discuss what is known about OPN isoform expression and our understanding of OPN isoform contributions to cardiovascular disease pathologies.
Role of Krüppel-like Factor 4-p21CIP1 Axis in Breast Cancer Stem-like Cell Inhibition by Benzyl Isothiocyanate

Cancer chemoprevention by benzyl isothiocyanate (BITC), which is derived from cruciferous vegetables like garden cress, in a transgenic mouse model of breast cancer is associated with inhibition of breast cancer stem-like cells (bCSC), but the molecular regulators of this effect remain elusive. This study demonstrates a protective effect of Krüppel-like factor 4 (KLF4)-p21CIP1 axis in bCSC inhibition by BITC. Exposure of human breast cancer cells (MCF-7, MDA-MB-231, and SUM159) to plasma-achievable concentrations of BITC resulted in a robust induction of KLF4 mRNA and its protein expression as determined by qRT-PCR and Western blotting or confocal microscopy. BITC-mediated suppression of bCSC markers, including aldehyde dehydrogenase 1 activity and mammosphere frequency, was significantly augmented by transient or stable knockdown of KLF4. Western blotting and IHC revealed relatively higher levels of KLF4 protein in mammary tumor sections from BITC-treated mice in comparison with controls, but the difference was insignificant. Analysis of the breast cancer RNA-Seq data from The Cancer Genome Atlas indicated significant positive correlation between expression of KLF4 and that of p21CIP1 (CDKN1A) but not β-Catenin (CTNNB1). Knockdown of p21CIP1 protein also amplified BITC-mediated suppression of bCSC. Finally, KLF4 was recruited to the promoter of p21CIP1 as indicated by chromatin immunoprecipitation assay. These results indicate that induction of KLF4–p21CIP1 axis attenuates inhibitory effect of BITC on bCSC self-renewal. Translational implication of these findings is that breast cancer chemoprevention by BITC may be augmented with a combination regimen involving BITC and an inhibitor of KLF4.
Sex differences in employment and supports for adults with autism spectrum disorder

This study explored sex differences in employment, reasons for unemployment, benefits, and supports among a large, international sample of adults with autism spectrum disorder. The sample included 443 adults with autism spectrum disorder (60% female; 74% residing in the United States) who consented to be part of an autism research registry and completed an Internet survey. Outcome variables included current employment status, number of hours working, number of jobs in the past 5 years, reasons for unemployment, as well as the number of benefits received and the amount of financial support currently being received from families of origin. Using multiple regression models, we found that males and females were working at similar rates. Females were more likely than males to say that their unemployment was a result of choosing to withdraw from the labor market. Similar percentages of males and females reported receiving some form of benefits or family support, but of those receiving benefits/family support, males received more than females. These results are consistent with other studies finding subtle, but potentially important sex differences in life-course outcomes of individuals with autism spectrum disorder.
Family Health Support Center: suffering from the perspective of psychodynamics of work.

OBJECTIVE To analyze the work process of the Family Health Support Center and identify the repercussions on professionals' quality of life at work. METHOD A descriptive-exploratory qualitative case study conducted with workers from Family Health Support Centers. The content analysis technique was used to analyze the resulting empirical material in the light of the theoretical reference of Work Psychodynamics. RESULTS Twenty workers participated in the focus groups. This study discusses the category of 'suffering' by the chosen theoretical perspective, which derives from interpersonal relationships and teamwork, the feeling of not belonging, lack of infrastructure for work, violence and vulnerability present in the territory. CONCLUSION Group union and collaborative integration among workers can be strategies for the minimization of suffering at work in the context of the Family Health Strategy.
Outcomes in Older Kidney Transplant Recipients after Prior Non-Kidney Transplants.

BACKGROUND Recipients of non-kidney solid organ transplants (nkSOT) are living longer, and 11-18% will develop ESRD. While our general inclination is to treat nkSOT recipients who develop ESRD with a kidney transplant (KT), an increasing number are developing ESRD at an older age where KT may not be the most appropriate treatment. It is possible that the risk of older age and prior nkSOT might synergize to make KT too risky, but this has never been explored. METHODS To examine death-censored graft loss and mortality for KT recipients with and without prior nkSOT, we used Scientific Registry of Transplant Recipients data to identify 42,089 older (age ≥65) KT recipients between 1995 and 2016. Additionally, to better understand treatment options for these patients and survival benefit of KT, we identified 5,023 older (age ≥65) with prior nkSOT recipients listed for subsequent KT, of whom 863 received transplants. RESULTS Compared to 41,159 older KT recipients without prior nkSOT, death-censored graft loss was similar (aHR: 1.13, 95% CI: 0.93-1.37, P = .2), but mortality (aHR: 1.40, 95%CI: 1.28-1.54, P < .001) was greater for older KT recipients with prior nkSOT. Nonetheless, in a survival benefit model (survival with versus without the transplant), among older prior nkSOT recipients, KT decreased the risk of mortality by more than half (aHR: 0.47, 95%CI: 0.42-0.54, P < .001). CONCLUSIONS Older prior nkSOT recipients who subsequently develop ESRD derive survival benefit from KT, but graft longevity is limited by overall survival in this population. These findings can help guide patient counseling for this challenging population.
Co-Occurrence of Local Binary Patterns Features for Frontal Face Detection in Surveillance Applications

Face detection in video sequence is becoming popular in surveillance applications. The tradeoff between obtaining discriminative features to achieve accurate detection versus computational overhead of extracting these features, which affects the classification speed, is a persistent problem. This paper proposes to use multiple instances of rotational Local Binary Patterns (LBP) of pixels as features instead of using the histogram bins of the LBP of pixels. The multiple features are selected using the sequential forward selection algorithm we called Co-occurrence of LBP (CoLBP). CoLBP feature extraction is computationally efficient and produces a high-performance rate. CoLBP features are used to implement a frontal face detector applied on a 2D low-resolution surveillance sequence. Experiments show that the CoLBP face features outperform state-of-the-art Haar-like features and various other LBP features extensions. Also, the CoLBP features can tolerate a wide range of illumination and blurring changes.
A comparative analysis of the restaurant consumer food environment in Rochester (NY, USA) and London (ON, Canada): assessing children’s menus by neighbourhood socio-economic characteristics

Abstract Objective To assess restaurant children’s menus for content and nutritional quality; and to investigate the relationship between the restaurant consumer food environment for children and neighbourhood-level socio-economic characteristics within and between one Canadian city and one US city. Design Cross-sectional observational study. Setting London, ON, Canada and Rochester, NY, USA. Participants Restaurant children’s menus were assessed, scored and compared using the Children’s Menu Assessment tool. We quantified neighbourhood accessibility to restaurants by calculating 800 m road-network buffers around the centroid of each city census block and created a new Neighbourhood Restaurant Quality Index for Children (NRQI-C) comprising the sum of restaurant menu scores divided by the total number of restaurants within each area. After weighting by population, we examined associations between NRQI-C and neighbourhood socio-economic characteristics using correlations and multiple regression analyses. Results Nutritional quality of children’s menus was greater, on average, in Rochester compared with London. Only one variable remained significant in the regression analyses for both cities: proportion of visible minorities had a positive effect on neighbourhood NRQI-C scores in London, whereas the reverse was true in Rochester. Conclusions Results suggest the presence of a socio-economic disparity within Rochester, where children in more disadvantaged areas have poorer access to better nutritional quality restaurant choices. In London, results suggest an inverse relationship across the city where children in more disadvantaged areas have better access to better nutritional quality restaurant choices. Given these disparate results, research on restaurant nutritional quality for children requires additional consideration.
T lymphocytes in the third trimester decidua in preeclampsia

ABSTRACT Objective: The aim of study was to conduct immunohistochemical quantification of CD3+ and CD8+ decidual lymphocytes in preeclampsia. Methods: A study group included 30 cases of preeclampsia and a control group included 20 healthy pregnant women, all delivered by Cesarean section. Samples of placental bed were analyzed after immunohistochemical staining of CD45+, CD3+ and CD8+ cells. Results: The group with preeclampsia included a significantly higher number of CD3+ (p < 0.01) and CD8+ (p < 0.05) T lymphocytes. Conclusion: It is certain that thebalance dysregulation of T cell of the immune milieu of deciduais of importance in etiopathogenesis and manifestations of preeclampsia.
Hydrothermally Modified Corn Starch Ingestion Attenuates Soccer Skill Performance Decrements in the Second Half of a Simulated Soccer Match.

Hydrothermally modified non-genetically modified organisms corn starch (HMS) ingestion may enhance endurance exercise performance via sparing carbohydrate oxidation. To determine whether similar effects occur with high-intensity intermittent exercise, we investigated the effects of HMS ingestion prior to and at halftime on soccer skill performance and repeated sprint ability during the later stages of a simulated soccer match. In total, 11 male university varsity soccer players (height = 177.7 ± 6.8 cm, body mass = 77.3 ± 7.9 kg, age = 22 ± 3 years, body fat = 12.8 ± 4.9%, and maximal oxygen uptake = 57.1 ± 3.9 ml·kg BM-1·min-1) completed the match with HMS (8% carbohydrate containing a total of 0.7 g·kg BM-1·hr-1; 2.8 kcal·kg BM-1·hr-1) or isoenergetic dextrose. Blood glucose was lower (p < .001) with HMS at 15 min (5.3 vs. 7.7 mmol/L) and 30 min (5.6 vs. 8.3 mmol/L) following ingestion, there were no treatment differences in blood lactate, and the respiratory exchange ratio was lower with HMS at 15 min (0.84 vs. 0.86, p = .003); 30 min (0.83 vs. 0.85, p = .004); and 45 min (0.83 vs. 0.85, p = .007) of the first half. Repeated sprint performance was similar for both treatments (p > .05). Soccer dribbling time was slower with isoenergetic dextrose versus baseline (15.63 vs. 14.43 s, p < .05) but not so with HMS (15.04 vs. 14.43 s, p > .05). Furthermore, during the passing test, penalty time was reduced (4.27 vs. 7.73 s, p = .004) with HMS. During situations where glycogen availability is expected to become limiting, HMS ingestion prematch and at halftime could attenuate the decline in skill performance often seen late in contests.