Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Serum Trefoil Factor-3 to Endoscopy in Diagnosing Helicobacter Pylori Associated Gastric Ulcer

Background and aim of the work: Helicobacter pylori-associated gastric ulcer (H.pylori-GU) is a serious condition, not only because H.pylori is identified as a grade 1 carcinogen but also because GU is a precancerous condition. Identification and treatment of H.pylori-GU may prevent the sequential progression of dysplasia to carcinoma. Trefoil factor 3 (Tf3) has been implicated in gastric mucosal repair. We compared serum Tf3 to gastric endoscopy in diagnosing H.pylori-GU. Subjects and methods: The study included eighty patients suffering from H.pylori induced gastritis, forty of which presented with GU. Gastric endoscopy with slide urease test was used to diagnose H.pylori-GU. Serum Tf3 level was determined using an enzyme immunoassay in all patients as well as thirty healthy volunteers. Results: Serum Tf3 showed a significant stepwise decrease among the studied groups. It was significantly lower in patients compared to the control group (p<0.001). Furthermore, it was lower in those with GU compared to those without GU (p=0.023). Based on a receiver operating characteristic curve generated cut off value of 2.4 ng/mL, the diagnostic performance of serum Tf3 as a biomarker of H.pylori-GU revealed a diagnostic specificity of 42.5%, sensitivity of 67.5%, positive and negative predictive values of 54% and 56.67% respectively. Conclusion: Although serum Tf3 showed significant variation in H.pylori-GU, further studies are warranted to confirm its role in the pathogenesis of gastric ulcers.
Immunophenotyping of Rhesus CMV‐Specific CD8 T‐Cell Populations

A vaccine to ameliorate cytomegalovirus (CMV)‐related pathogenicity in transplantation patients is considered a top priority. A therapeutic vaccine must include components that elicit both neutralizing antibodies, and highly effective CD8 T‐cell responses. The most important translational model of vaccine development is the captive‐bred rhesus macaque (Macaca mulatta) of Indian origin. There is a dearth of information on rhesus cytomegalovirus (rhCMV)‐specific CD8 T cells due to the absence of well‐defined CD8 T‐cell epitopes presented by classical MHC‐I molecules. In the current study, we defined two CD8 T‐cell epitopes restricted by high‐frequency Mamu alleles: the Mamu‐A1*002:01 restricted VY9 (VTTLGMALY aa291‐299) epitope of protein IE‐1, and the Mamu‐A1*008:01 restricted NP8 (NPTDRPIP aa96‐103) epitope of protein phosphoprotein 65‐2. We developed tetramers and determined the level, phenotype, and functional capability of the two epitope‐specific T‐cell populations in circulation and various tissues. We demonstrated the value of these tetramers for in situ tetramer staining. Here, we first provided critical reagents and established a flow cytometric staining strategy to study rhCMV‐specific T‐cell responses in up to 40% of captive‐bred rhesus macaques. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.
Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4·8%), 149 (10%), 200 (13·2%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo‐γ) and normal Ig levels (γ‐normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment‐free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels.
Comparing taxonomic and geographic scales in the morphologic disparity of Ordovician through Early Silurian Laurentian crinoids

Abstract Interpretations of morphologic radiations and macroevolutionary patterns are dependent on a priori choices of taxonomic and geographic scales of study. The results of disparity analysis at varying taxonomic (species and genus) and geographic (regional, biofacies, and community) scales are examined in a study of Ordovician though Early Silurian crinoids. Using discrete morphologic characters, we examined the disparity of 421 crinoids from 65 Laurentian biofacies. Crinoid disparity differs when analyzed at the regional and biofacies levels. Regardless of fluctuations in regional crinoid disparity, average within-biofacies disparity was static throughout the Ordovician, deviating only during the Silurian because of the proliferation of the morphologically aberrant myelodactylid crinoids. The choice of taxonomic level does not have an effect at the biofacies level. However, at the regional level, the two taxonomic scales (genus and species) can produce different results because of variation in the number of species per genus through time and the amount of morphologic variation within individual genera. Weighting disparity by abundance provides a metric combining morphology and community structure. Average weighted disparity at the community level showed patterns similar to that of the biofacies-level disparity curve, but this metric has a greater degree of variation between biofacies. Biofacies with a low ratio of weighted to unweighted disparity display the distinctive community structure (based on aerosol filtration theory) that is often reported in crinoid assemblages.
24‐Dehydrocholesterol reductase promotes the growth of breast cancer stem‐like cells through the Hedgehog pathway

Cholesterol is a risk factor for breast cancer. However, it is still unclear whether the cholesterol biosynthesis pathway plays any significant role in breast carcinogenesis. 24‐Dehydrocholesterol reductase (DHCR24) is a key enzyme in the cholesterol synthesis pathway. Although DHCR24 is reported to have different functions in different cancers, it is not clear whether DHCR24 is involved in breast cancer. In this study, we found that DHCR24 expression was higher in breast cancer especially in luminal and HER2 positive breast cancer tissues compared with normal breast. Changes in DHCR24 expression altered cellular cholesterol content without affecting the adherent growth of breast cancer cells. However, DHCR24 knockdown reduced whereas DHCR24 overexpression enhanced breast cancer stem‐like cell populations such as mammosphere and aldehyde dehydrogenase positive cell numbers. In addition, DHCR24 overexpression increased the expression of the Hedgehog pathway‐regulated genes. Treating DHCR24 overexpressing breast cancer cell lines with the Hedgehog pathway inhibitor GANT61 blocked DHCR24‐induced mammosphere growth and increased mRNA levels of the Hedgehog regulated genes. Furthermore, expression of a constitutively activated mutant of Smoothened, a key hedgehog signal transducer, rescued the decreases in mammosphere growth and Hedgehog regulated gene expression induced by knockdown of DHCR24. These results indicate that DHCR24 promotes the growth of breast cancer stem‐like cells in part through enhancing the Hedgehog signaling pathway. Our data suggest that cholesterol contribute to breast carcinogenesis by enhancing Hedgehog signaling and cancer stem‐like cell populations. Enzymes including DHCR24 involved in cholesterol biosynthesis should be considered as potential treatment targets for breast cancer.
Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Abstract Context L-DOPA is the first-line drug for Parkinson’s disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. Objectives This study determined changes in terms of neurodegeneration, locomotion and mechanosensation in Caenorhabditis elegans (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. Materials and methods Neurodegeneration was monitored via fluorescence microscopy of GFP-tagged dopaminergic neurons in the head and tail regions of C. elegans. Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60 mM), caffeine (10 mM) or 60 mM L-DOPA + 10 or 20 mM caffeine (60LC10 and 60LC20) treatments were scored for 3 days (n = 20). Results L-DOPA (60 mM) reduced CEP and ADE neurons by 4.3% on day 3, with a concomitant decrease in fluorescence by 44.6%. This correlated with reductions in gentle head (−35%) and nose touch (−40%) responses, but improved locomotion (20–75%) compared with vehicle alone. CEP and ADE neuron counts were preserved with caffeine (10 mM) or 60LC10 (98–100%), which correlated with improved mechanosensation (10–23%) and locomotion (18–76%). However, none of the treatments was able to preserve PDE neuron count, reducing the basal slowing response. Discussion and conclusions Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.
Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis.

Importance It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. Design, Setting, and Participants In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. Exposures The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Main Outcomes and Measures Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Results Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. Conclusions and Relevance In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.
Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase‐1

Loss of ovarian function results in increased fat mass, leading to the accumulation of adipose tissue macrophages that participate in chronic inflammation. We hypothesized that ovariectomy (OVX)‐induced increases in body weight and fat mass are associated with decreased adipose tissue (AT) browning due to estrogen (E2) deficiency. In mice, OVX decreased AT browning along with increased body weight, fat mass, and size of lipid droplets 12 weeks after surgery. Exogenous E2 recovered the OVX‐induced changes. AT browning was enhanced by M2 macrophages induced by exogenous E2. E2‐induced M2 polarization occurred due to the increased expression of heme oxygenase‐1 (HO‐1) in macrophages, leading to decreased reactive oxygen species levels. Collectively, we demonstrated that E2 enhances AT browning via M2 polarization mediated by HO‐1.
National drug shortages worsen during COVID-19 crisis: Proposal for a comprehensive model to monitor and address critical drug shortages

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
Construction of mathematical models for the estimation of signal strength at the input to the 802.11 standard receiver in a 5 GHz band

The paper proposes mathematical models for the spatial estimation of signal strength at the input of the receiver for the 802.11x family of standards in a 5 GHz range. The models were constructed based on the experimental research into signal distribution for the angular and central location of an access point. A special feature of these models is taking the main energy parameter into consideration under a real-time mode, and accounting for the maximally possible number of impact factors. In addition, the permissible limits have been determined for these models, which exert a minimal influence on the effective data transfer rate. It was established that for the 802.11 standard, in a 5 GHz frequency range, the rather significant signal fluctuations exist. Depending on the extent to which premises are filled with various objects, the level of fluctuations can amount to δ=±4.8 dBm, subject to the MIMO system availability. The greatest concentration of radiation energy is observed directly at the transmitting antenna at a distance of up to two meters; it subsequently fades on 10.20 dBm. It has been established that the presence of MIMO technology introduces a certain heterogeneity to spatial distribution. In this case, there are zones with a lower signal level, as well as zone-bands with a higher level in the presence of multiple antennas. The effectiveness of such a system is maximal in the plane of the arrangement of antennas. The advantages of the derived models for the spatial signal distribution include: the estimation of a signal level in space for any premises; taking into consideration fluctuations in the primary energy parameter, as well as parameters for the transmission medium; accounting for the parameters of premises, as well as the extent to which space is filled with objects. Such models are most effective for application in methods to diagnose and control wireless networks and channels in the 802.11x family of standards
Pathologically Proven Gadolinium-enhanced MRI Lesions in the Bilateral Corticospinal Tracts in Lymphomatosis Cerebri

A 78-year-old woman in complete remission of mass-forming primary central nervous system lymphoma (PCNSL) showed diffuse leukoencephalopathy as well as corticospinal tract lesions with intense gadolinium enhancement on magnetic resonance imaging (MRI). She died 3 months later. In line with the MRI findings, pathological examination revealed dense infiltration of atypical lymphoid cells, consistent with a diagnosis of lymphomatosis cerebri (LC)-type PCNSL. This is the first report of LC in which the corticospinal tracts demonstrated robust contrast enhancement directly corresponding to the neuropathological findings, and it is also a rare instance in which LC presented as a recurrence of typical PCNSL.
Operationalizing patient‐centered cancer care: A systematic review and synthesis of the qualitative literature on cancer patients' needs, values, and preferences

Efficiently addressing patient priorities and concerns remains a challenge in oncology. Systematic operationalization of patient‐centered care (PCC) can support improved assessment and practice of PCC in this unique care setting. This review aimed to synthesize the qualitative empirical literature exploring the National Academy of Medicine (NAM)'s PCC constructs of values, needs, and preferences among patients' during their cancer treatment experiences.
The Big Five and subjective wellbeing: The mediating role of optimism.

BACKGROUND Previous literature has shown that personality is one of the most important predictors of Subjective Wellbeing. However, the mechanisms through which basic personality dispositions contribute to wellbeing have scarcely been explored. Therefore, in this study we examined the mediating role of Optimism in the relationship between the Big Five personality model (both factors and facets) and Subjective Wellbeing. Additionally, we assessed whether the results varied by sex. METHOD A sample of 611 Spanish adolescents completed self-report measures of BFQ, LOT-R, and SHS. We conducted structural equation modeling to test the proposed mediating models. RESULTS Optimism completely mediated the relationship between Extraversion and Emotional Stability factors and Subjective Wellbeing. Likewise, Optimism mediated the relationship between the personality facets Politeness, Perseverance, Emotion control, Impulse control, and Dynamism and Subjective Wellbeing. The findings were invariant by sex. CONCLUSIONS These results provide help in identifying the possible mechanisms through which basic dispositions of personality contribute to wellbeing. These findings can be used to develop interventions that target the promotion of greater Subjective Wellbeing through Optimism, and thereby improve adolescents' adjustment.
Coronary artery bypass grafting versus percutaneous coronary intervention in patients with diabetes.

As percutaneous coronary intervention (PCI) continues to evolve, comparative outcomes for PCI versus coronary artery bypass grafting (CABG) remain relevant in diabetic patients. All revascularization procedures in patients with coronary artery disease and diabetes mellitus from 2010-2018 were included. Propensity matching was used to identify equivalent cohorts to compare revascularization strategies. Primary outcomes included 30-day, 1-year, and 5-year mortality. Multivariable analysis was used to define factors associated with major adverse cardiovascular and cerebrovascular events (MACCE). A total of 2869 patients with diabetes were divided into PCI (n=653) and CABG (n=2216) cohorts. Propensity matching yielded a 1:1 match consisting of 552 patients in each cohort (CABG vs PCI). Total median follow-up was 3.28 years (range: 1.83-5.00). Following propensity matching in patients with no prior PCI (1:1; n=279), mortality remained significantly higher in the PCI cohort at 1-year (13.98% vs 7.53%; p=0.014) and 5-year (26.88% vs 16.85%; p<0.004). Hospital readmissions were higher for PCI patients at 1-year (16.49% vs 9.32%; p<0.0122) and 5-years (19.71% vs 11.83%; p=0.011). MACCE occurred more frequently in the PCI cohort (32.97% vs 21.51%; p=0.002). Need for subsequent revascularization (6.45% vs 2.51%; p=0.024) were significantly higher in the PCI cohort and time interval to revascularization was significantly longer in the CABG cohort [3.48 (2.11-5.17) vs 2.62 (1.33-4.25) years; p<0.001]. The current study reports improved survival, fewer long-term hospital readmissions, and reduced MACCE and need for repeat revascularization in the CABG cohort. Given these data, patients with diabetes mellitus my fare better with surgical revascularization, compare to PCI.
Nocturnal whey protein ingestion impairs post-prandial glucose tolerance at breakfast

Abstract Poor post-prandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so the present study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised crossover design, fifteen adults (seven males, eight females; age, 22 (sd 3) years; BMI, 24·0 (sd 2·8) kg/m2; fasting blood glucose, 4·9 (sd 0·5) mmol/l) woke at 04.00 (sd 1) hours to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate/kg body mass, 2356 (sd 435) kJ), 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental AUC) to breakfast by 43·5 (sd 55·5) mmol × 120 min/l (P = 0·009, d = 0·94). Consistent with this effect, individual peak blood glucose concentrations were 0·6 (sd 1·0) mmol/l higher following breakfast when protein had been ingested (P = 0·049, d = 0·50). Immediately prior to breakfast, rates of lipid oxidation were 0·02 (sd 0·03) g/min higher (P = 0·045) in the protein condition, followed by an elevated post-prandial energy expenditure (0·38 (sd 0·50) kJ/min, P = 0·018). Post-prandial appetite and energy intake were similar between conditions. The present study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing post-prandial energy expenditure.
Negative pressure pyrolysis induced highly accessible single sites dispersed on 3D graphene frameworks for enhanced oxygen reduction.

The surface structure of supports is related to the properties of catalytic sites and their spatial structure also plays a dominant role in the mass transfer during catalysis process. Herein, we report a negative pressure pyrolysis to access dense single metal sites (Co, Fe, Ni etc.) with high accessibility dispersed on three-dimensional (3D) graphene frameworks (GFs), during which the differential pressure between inside and outside of metal-organic frameworks (MOFs) promotes the cleavage of the derived-carbon layers and gradual expansion of mesopores. In situ transmission electron microscopy and Brunauer-Emmett-Teller tests reveal the formed 3D GFs possess an enhanced mesoporosity and external surface area, which greatly favor the mass transport and utilization of metal sites. This contributes to an excellent oxygen reduction reaction (ORR) activity (with a half-wave potential of 0.901 V vs. RHE). Theoretical calculations verify that selective carbon cleavage near Co centers can efficiently lower the overall ORR theoretical overpotential in comparison with intact atomic configuration. This work discovers the structure-property correlations that provides an idea of designing highly accessible catalysts for practical applications.