Miracle-dz/UniFAR-FTUs huggingface dataset:
Chalcones as Scavengers of HOCl and Inhibitors of Oxidative Burst: Structure-Activity Relationship Studies.

AIMS Evaluate the ability of chalcones to scavenge hypochlorous acid (HOCl) and modulate oxidative burst. BACKGROUND The chemistry of chalcones has long been a matter of interest to the scientific community due to the phenolic groups often present and to the various replaceable hydrogens that allow the formation of a broad number of derivatives. Due to this chemical diversity, several biological activities have been attributed to chalcones, namely anti-diabetic, anti-inflammatory and antioxidant. OBJECTIVES Evaluate the ability of a panel of 34 structurally related chalcones to scavenge HOCl and/or suppress its produc-tion through the inhibition of human neutrophils' oxidative burst, followed by the establishment of the respective structure-activity relationships. METHODS The ability of chalcones to scavenge HOCl was evaluated by fluorimetric detection of the inhibition of dihydro-rhodamine 123 oxidation. The ability of chalcones to inhibit neutrophils' oxidative burst was evaluated by chemiluminomet-ric detection of the inhibition of luminol oxidation. RESULTS It was observed that the ability to scavenge HOCl depends on the position and number of hydroxy groups on both aromatic rings. Chalcone 5b was the most active with an IC50 value of 1.0 ± 0.1 μM. The ability to inhibit neutrophils' oxi-dative burst depends on the presence of a 2'-hydroxy group on A-ring and on other substituents groups, e.g. methoxy, hy-droxy, nitro and/or chlorine atom(s) at C-2, C-3 and/or C-4 on B-ring, as in chalcones 2d, 2f, 2j, 2i, 4b, 2n and 1d, which were the most actives with IC50 values ranging from 0.61 ± 0.02 μM to 1.7 ± 0.2 μM. CONCLUSION The studied chalcones showed high activity at a low micromolar range, indicating their potential as antioxidant agents and to be used as a molecular structural scaffold for the design of new anti-inflammatory compounds.
The statistics and dynamics of confined or entangled stiff polymers

The statistics of a wormlike chain of persistence length P and contour length L trapped in a cylindrical pore of diameter D can be understood if a length scale X N D2/3P*/3 is introduced ( P >> D). If L 5 A, it is a good approximation to view the chain as being completely rigid. Whenever L >> A, it is convenient to regard the stiff coil as a sequence of rigid links, each of length A. The free energy involved in forcing a stiff chain into a pore is calculated by scaling arguments. When the chain is confined in a network of mesh size A, we again have X N A2I3P1J3. If L 5 A, i t is reasonable to approximate the chain as a completely stiff rod in its reptational and reorientational motion. Whenever X 5 L 5 P, a new region emerges in between the rigid rod and flexible chain limits. Then, the rotational diffusion coefficient scales as L-2 instead of L-5 as in the rigid rod case. The usual L-3 dependence (flexible coil limit) is recovered if L 2 P.
Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use.
Clinicopathologic characteristics, survival, and treatments for gastric adenosquamous carcinoma: a population-based study.

Background Gastric adenosquamous carcinoma (gasc) is a rare entity with distinctive characteristics that are not fully understood. In the present study, we evaluated the characteristics of this rare disease. Methods The U.S. Surveillance, Epidemiology, and End Results program database was searched to determine the clinicopathologic features, prognostic factors, and treatments for 246 patients with gasc and 42,735 patients with gastric adenocarcinoma (gac). Results Relative to gac, gasc is associated with higher proportions of cardia involvement, high-grade tumours, deep tumour invasion, metastatic lymph nodes, and chemotherapy treatment. In patients who underwent potentially curative surgery (pcs), gasc was associated with a higher proportion of radiotherapy use and poorer overall survival (p < 0.001), although no significant difference (p = 0.802) was observed after propensity score matching (psm). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were TNM stage [hazard ratio (hr): 1.512; p = 0.021] and regional nodes examined (hr: 0.588; p = 0.02). In patients with advanced disease, no significant difference in survival between gasc and gac was observed (p = 0.212), although survival was significantly poorer for gasc after psm (p = 0.019). Multivariate analysis after psm revealed that the independent prognostic factors for gasc were invasion depth (hr: 1.303; p = 0.036) and chemotherapy (hr: 0.444; p < 0.001). Conclusions Relative to gac, gasc was associated with more aggressive features, although survival outcomes were similar after pcs. Chemotherapy remains a mainstay of treatment for patients with advanced gasc, but its role remains unclear for patients who are undergoing pcs.
GSK3 Restrains Germinal Center B Cells to Form Plasma Cells

Key Points GSK3–c-Myc–IRF4 regulatory axis induces CD138+ Ab-secreting cell formation. GSK3 inactivation facilitated the LZ to DZ transition via increasing Foxo1. Spatiotemporal control of GSK3 activity may be a key regulator of the GC reaction. Visual Abstract B cells in the germinal center (GC) are programmed to form plasma cells (PCs) or memory B cells according to signals received by receptors that are translated to carry out appropriate activities of transcription factors. However, the precise mechanism underlying this process to complete the GC reaction is unclear. In this study, we show that both genetic ablation and pharmacological inhibition of glycogen synthase kinase 3 (GSK3) in GC B cells of mice facilitate the cell fate decision toward PC formation, accompanied by acquisition of dark zone B cell properties. Mechanistically, under stimulation with CD40L and IL-21, GSK3 inactivation synergistically induced the transcription factors Foxo1 and c-Myc, leading to increased levels of key transcription factors required for PC differentiation, including IRF4. This GSK3-mediated alteration of transcriptional factors in turn facilitated the dark zone transition and consequent PC fate commitment. Our study thus reveals the upstream master regulator responsible for interpreting external cues in GC B cells to form PCs mediated by key transcription factors.
African Americans’ and Black Caribbeans’ Religious Coping for Psychiatric Disorders

ABSTRACT This study investigates the use of religious coping among African Americans and Black Caribbeans with 12-month DSM-IV psychiatric disorders. Data from the National Survey of American Life is used to examine three indicators of religious coping: 1) using prayer and other spiritual practices for mental health problems, 2) the importance of prayer in stressful situations, and 3) looking to God for strength. Three out of four respondents who had a mental health problem reported using prayer as a source of coping. Agoraphobia and drug abuse disorder were associated with the importance of prayer during stress. Individuals with generalized anxiety disorder were more likely to report that prayer was important during stressful experiences and that they looked to God for strength. These findings contribute to the limited, but growing body of research on the ways that African Americans and Black Caribbeans cope with psychiatric disorders.
Awareness on sun protection behavior among melanoma and nonmelanoma skin cancer patients: An Italian tertiary cancer center experience

Dear Editor, Incidence of skin cancer is increasing worldwide faster than other malignant neoplasms given to inappropriate sun exposure. Several studies showed that ultraviolet radiation (UVR) is responsible for more than 65% of melanoma cases and 99% of basal cell and squamous cell carcinoma cases. We read with great interest the article written by Tas et al regarding the awareness on melanoma and the preventive measures to adopt in Turkish patients and we want also to share the experience recently conducted in our center, to assess the awareness on skin cancer and the adoption of preventive measures in Italian patients, extending it to melanoma and nonmelanoma skin cancer patients. This study was conducted on adult patients with a diagnosis of melanoma and non-melanoma skin cancer attending our outpatient clinic visits. Patients were asked by their physician to fill in a health questionnaire, which took approximately 5 min to complete, when attending their follow-up visit. The linguistic and cultural adaptation of the questionnaire for the current study was created by a team of experts. The adapted questionnaire was self-administered and consisted of two parts: one to fill in with all socio-demographic and familiarity data and another one composed of multiple-choice answers regarding patients' awareness on skin cancer, their sun protection policies and practices. All data were collected anonymously in accordance with data protection laws. A total of 287 valid responses were received (164 men and 123 women); the median age was 61.3 years (range 31-88). 48 (16.7%) had a diagnosis of melanoma, 118 (41.1%) of basal cell carcinoma, 92 (32%) of actinic keratoses, and 29 (10.2%) patients were diagnosed with squamous cell carcinomas of any differentiation grade (Table 1). Almost the third part of patients (95, 33%) had information about skin cancer prevention and sun protection policy prior to diagnosis. As in the article of Tas et al, higher education was found to be linked with higher awareness; also having another member of the family with a previous diagnosis of skin cancer was related to major awareness on sunscreening and measures to adopt. Moreover, patients with melanoma and actinic keratosis were observed to have better knowledge of sun exposure rules to follow. The majority of patients did not use sunscreen while in the water (74%) and they did not take care of the hottest hours of the day when sunbathing (68%). Interestingly, hat behavior was more enforced in patients with actinic keratosis. All data are reported in Table 2. According to the results the main informative sources prior to the visit were ordered as follows: media and internet, family and patients relatives, physicians. The only patients that did a self-examination were those with melanoma diagnosis. To date, several studies investigating the awareness on skin cancer prevention habits have been conducted
Depression symptoms, HIV testing, linkage to ART, and viral suppression among women in a high HIV burden district in KwaZulu-Natal, South Africa: A cross-sectional household study

Achieving the UNAIDS 90-90-90 targets by 2020 is contingent on identifying and addressing mental health challenges that may affect HIV testing and treatment-related behaviors. This study is based on survey data from KwaZulu-Natal, South Africa (2014–2015). HIV positive women who reported higher depression scores had a lower odds of having tested previously for HIV (15–25 years: AOR = 0.90, 95% CI [0.83, 0.98]; 26–49 years: AOR = 0.90, 95% CI [0.84, 0.96]). Because HIV testing behavior represents a gateway to treatment, the findings suggest mental health may be one challenge to attaining the UNAIDS 90-90-90 targets.
Relational counselling as a psychosocial intervention for dementia: Qualitative evidence from people living with dementia and family members

Counselling and other psychotherapeutic interventions can be offered to people with dementia and their caregivers, to treat specific conditions or symptoms (e.g. affective disorders such as depression). Psychotherapeutic interventions also offer the opportunity for individuals with dementia and their families/caregivers to engage in psychological support for a wide range of presentations. However, little is known about how those within this demographic who receive these interventions perceive the experience. This study aimed to understand the experiences of individuals with dementia or caring for someone with dementia, before and after a 12-week relational counselling intervention delivered through a third sector organisation within England. Semi-structured interviews were completed with participants (29 pre-intervention and 25 post-intervention). Framework analysis was conducted, with four main themes identified; expectations and outcomes of counselling, emotional impact of life with dementia, appraisals of identity and importance of therapeutic relationship. Participants reported that counselling interventions addressed a range of needs and concerns that they had, enabling them to reassess and reconsider these. Specific training is needed before therapists deliver therapeutic interventions with people with dementia, to ensure that appropriate support is provided for those with more severe cognitive impairment or who may have fluctuating capacity. Future research should explore the experiences of people with dementia and their caregivers, across different counselling modalities, to establish the appropriateness and effectiveness of relational counselling.
[Fractalkine inhibits lipopolysaccharide-induced M1 polarization of macrophages by activating Wnt/β-catenin signaling pathway].

OBJECTIVE To explore the mechanism by which fractalkine (CX3CL1; FKN) inhibits lipopolysaccharide (LPS)-induced immunological response in RAW264.7 cells. METHODS A RAW264.7 cell model overexpressing FKN was established by transfection with the lentiviral vector CX3CL1. The effects of LPS, ICG-001 (a Wnt/β-catenin signaling pathway inhibitor), either alone or in combination, on M1 polarization of na? ve and FKN-overexpressing RAW264.7 cells were evaluated by detecting of intereukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) using ELISA. The protein expressions of the inflammatory factors (iNOS, TNF-α, and IL-6), FKN, Wnt-4, and β-catenin were detected by Western blotting. The subcellular localization of IL-6 in the cells was detected by immunofluorescence assay. RESULTS The RAW264.7 cell model of FKN overexpression was successfully established. In na? ve RAW264.7 cells, treatment with both ICG-001 and LPS, as compared with LPS alone, significant promoted TNF-α and IL-6 secretions, increased intracellular levels of TNF-α, IL-6 and iNOS (P < 0.05), and reduced intracellular FKN, Wnt-4 and β-catenin levels (P < 0.01). In FKN-overexpressing RAW264.7 cells, LPS treatment significantly reduced the secretion of TNF-α and IL-6 and intracellular levels of TNF-α, IL-6 and iNOS (P < 0.01), increased intracellular FKN, Wnt-4 and β-catenin protein contents (P < 0.01), and inhibited IL-6 localization in the cytoplasm; compared with LPS, the combined treatment with ICG-001 and LPS obviously enhanced IL-6 localization in the cytoplasm of the cells. CONCLUSIONS FKN overexpression suppresses LPS-induced M1 type polarization of RAW264.7 cells by activating Wnt/β-catenin signaling pathway.
Expression of PD-L1 for predicting response to immune checkpoint inhibitors in metastatic urothelial carcinoma: a systematic review and meta-analysis.

Background We conducted this meta-analysis and systematic literature review to study the ability of PD-L1 to predict objective response in patients with urothelial cancer treated with PD-1/PD-L1 inhibitors. Methods Relevant studies of PD-1 or PD-L1 inhibitors in urothelial cancer that reported objective response rate (orr) based on PD-L1 expression status in PubMed, embase, and the Cochrane Library were retrieved. Efficacy of PD-L1 expression status in predicting orr and the efficacy, safety of PD-1 and PD-L1 drugs were analyzed. Results Studies were divided into ≥1%, ≥5%, and ≥25% based on PD-L1 positivity threshold, and the patients were grouped into PD-L1 positive and negative. In all 3 expression thresholds, patients with positive PD-L1 expression were more likely to experience an objective response [≥1% threshold odds ratio (or): 1.74; 95% confidence interval (ci): 1.20 to 2.53; ≥5% threshold or: 2.74; 95% ci: 2.01 to 3.724; ≥25% threshold or: 7.13; 95% ci: 2.38 to 21.40] in comparison with patients with negative PD-L1 expression. Of the 3 thresholds, the ≥25% threshold was better in predicting orr (1.74 vs. 2.93 vs. 7.13; p < 0.0001). The ≥1% PD-L1 threshold had a relatively high sensitivity in predicting orr; the ≥5% PD-L1 threshold was better for specificity. Sensitivity was higher at the ≥25% threshold than at the other two thresholds, but specificity was lower. Further, we found that there is no statistically significant difference in efficacy between PD-1 and PD-L1 drugs. Conclusions Urothelial cancer patients with PD-L1 positive expression responded better than PD-L1 negative patients did, and a threshold of ≥5% or greater for PD-L1 expression might predict positive clinical response.
Quantitative serum PCR argues against long‐term persistence of HHV‐6 viremia after umbilical cord blood transplantation

Human herpes virus-6 (HHV-6) reactivates in ~75% of cord blood transplant (CBT) recipients at a median of 2-3 weeks post-transplant1-3 . This contrasts with peripheral blood or bone marrow allografts where HHV-6 reactivation is uncommon4 . In a previous study of 23 CBT recipients, 52% of patients had detectable HHV-6 by whole blood qPCR at a median of 3.9y (range 1.3-7.1) post-transplant5 . Because whole blood qPCR can be positive with both latent virus and viremia, these results do not distinguish between the two scenarios. While long-term intracellular persistence of the latent virus is expected, persistent viremia (i.e., extracellular virus) may suggest the graft's inability to clear viremia. We report our long-term findings using serum, rather than whole blood, to distinguish latent from replicating HHV-6.
Premixed Turbulent Combustion Controlled by Complex Chemical Kinetics

Abstract The combustion of a turbulent homogeneous mixture of propane and air within a duct having a stationary one-dimensional mean flow is modelled. Under the conditions chosen for the study, chemical kinetics factors are important and a relatively detailed chemical model is needed. A semi-global model for the combustion of hydrocarbon is used and simplifying assumptions are made which reduce the system of independent variables to that of temperature and CO2 mass fraction. A two-dimensional probability density function is introduced to close the mean chemical production terms. The required equations for Favre averaged temperature, CO2 mass fraction, turbulence kinetic energy and the mean square fluctuation of the temperature are solved numerically. Predictions are made of the profiles of mean quantities through the combustion zone under different initial temperature, turbulence intensities and dissipation length scales.
Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity

Abstract Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 32 factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X1) and sonication time (X2) on the responses for dependent variables, particle size (Y1) and time to 90% release of LUF (t90) (Y2). Optimized formulation (F3) has shown to possess lowest particle size (95.34 nm) with minimum t90 value (⁓3 mins), which was lyophilized to obtain the dry powder form of the nanosuspension. The characterization parameters confirmed the amorphous form of LUF with good stability and no chemical interactions of the drug with the incorporated components. Further, saturation solubility study revealed increased solubility of the LUF nanosuspension (1670 µg/mL) when compared to the pure drug (212.33 µg/mL). Further, rate of dissolution of LUF from the nanosuspension formulations were found to be significantly (p < 0.05) higher when compared to the pure drug. Fabricated lyophilized nanosuspension was found to be stable at 25 ± 2 °C/60 ± 5% RH and 40 ± 2 °C/75 ± 5% RH for the duration of three months. In conclusion, lyophilized nanosuspension showed ∼8-folds increase in drug release, which indicated a better way to offer higher release of LUF in controlling malaria. GRAPHICAL ABSTRACT SEM images of Lyophilization of LUF nanosuspension formulation
Factors influencing lithium versus valproate prescription preference in the maintenance treatment of bipolar patients: a report from the Italian Early Career Psychiatrists (SOPSI-GG)

Abstract Background Objective of the present manuscript is to investigate, among Italian early career psychiatrists (ECPs), prescriber and patient-related factors associated with lithium or valproate preference to treat patients affected by Bipolar Disorder (BD). Methods An on-line survey was carried out among 252 ECPs, investigating their prescription patterns in relation to lithium and the differences with prescription of valproate. Collected data were compared according to lithium or valproate prescription preference in the long-term treatment of BD by χ 2 tests for qualitative variables. Results Over two thirds of ECPs preferred lithium over valproate for the maintenance treatment of BD. Less than half of the sample used lithium as first-line agent for mania or major depression, and less than one third for mixed episodes. Factors associated with lithium preference as first-line maintenance treatment include perception of having a good knowledge of lithium (p < 0.001) and complete satisfaction with education on lithium (p < 0.001). One of the main factors to prefer valproate was the concern about long-term side effects of lithium (p < 0.001). Conclusions Type of education, source of information, clinical experience and safety concerns influence the choice of lithium versus valproate in the long-term treatment of BD. Present findings may guide educational training of ECPs. KEY POINTS Lithium has been less prescribed in the last years for long-term treatment of Bipolar Disorder. Educational and clinical factors seem to influence the attitude to prescribe lithium. Only half of the Italian early career psychiatrists declare to have at least an adequate knowledge of lithium. Residency program in psychiatry should consider the implementation of education on lithium.