Miracle-dz/UniFAR-FTUs huggingface dataset:
Antimicrobial and α-glucosidase inhibitory activities of chemical constituents from Gardenia aqualla (Rubiaceae)

Abstract An aliphatic alkene namely pentapentacontene (4) was isolated for the first time from a natural source, Gardenia aqualla, along with fourteen other compounds including nonacosanol (1), tetratriacontanol (2), octatriacontanol (3), β-sitosterol (5) and stigmasterol (6), daucosanol (7), ursolic acid (8), uvaol (9), 3β,19α,23β,24α-tetrahydroxyurs-12-en-28-oic acid (10), lupenone (11), oleanolic acid (12), vanillin (13), vanillic acid (14) and D-mannitol (15). α-glucosidase inhibitory assay revealed that MeOH and EtOAc extracts of leaves had the best activity with IC50 of 9.65 and 20.03 µg/ml respectively. All the tested compounds showed dose dependent inhibition of α-glucosidase and some of them were found to be comparable to acarbose. Compound 10 was the most potent with IC50 = 1.72 μM. It also showed the most interesting antibacterial activity, against the isolate strain of S. typhi and P. aeruginosa and also exhibited the most significant antifungal activities against all the tested yeasts. GRAPHICAL ABSTRACT
SV40 T antigen helicase domain regions responsible for oligomerisation regulate Okazaki fragment synthesis initiation

The initiation of Okazaki fragment synthesis during cellular DNA replication is a crucial step for lagging strand synthesis, which is carried out by the primase function of DNA polymerase α‐primase (Pol‐prim). Since cellular replication protein A (RPA) prevents primase from starting RNA synthesis on single‐stranded DNA (ssDNA), primase requires auxiliary factors, such as the simian virus 40 (SV40) T antigen (Tag), for the initiation reaction on RPA‐bound ssDNA. Here, we investigated the ability of Tag variants and Tag protein complexes to bind to ssDNA and their resulting effects on the stimulation of Pol‐prim on free and RPA‐bound ssDNA. Atomic force microscopy imaging showed that while Tag131‐627(V350E/P417D) and Tag131‐627(L286D/R567E) (abbreviated as M1 and M2, respectively) could bind to ssDNA as monomers, these monomeric Tags could come together and bind to ssDNA as dimers as well. In a model assay for the initiation of Okazaki fragment synthesis, full‐length Tag SV40 Tag1‐708 and monomeric M2 stimulated DNA synthesis of Pol‐prim on ssDNA and on RPA‐bound ssDNA. In contrast, neither monomeric M1 nor M1‐M2 dimers could stimulate Pol‐prim, on ssDNA or on RPA‐bound ssDNA. Overall, we show that a lack of stimulatory activity of monomeric M1 and M1‐M2 dimers suggests that residues V350 and P417 are not only important for interactions between Tag molecules but also for protein–protein interactions within Okazaki fragment initiation complexes. Thus, we highlight that mutations in M1 are dominant negative with regard to Okazaki fragment initiation.
Spirituality in Occupational Therapy Practice: Where is Our Spirituality Now?

Although occupational therapy (OT) practitioners are well suited to address spirituality within client care, evidence suggests many practitioners feel discomfort or lack of knowledge of this subject. Few studies have delved into OTs’ experiences and encapsulated if and how spirituality has been experienced in practice. This study aimed to gain a deeper and more updated insight into this phenomenon. Utilizing a phenomenological approach with interviews, this study explored OT practitioners’ (n = 15) experiences with spirituality in client care. (a) Losing spirit: the inadequacy of only addressing mind and body, (b) spirituality as a vehicle for reaffirming purpose in both client and therapist, and (c) addressing spirituality through functional and measurable treatments. Although the concept of mind, body, and spirit is not new, occupational therapists often do not consistently address these components simultaneously, leading to missed opportunities in client practice.
Approaches to modeling chemical reaction pathways in radiobiology

Abstract Purpose Recent interest in understanding effects of high dose-rate (‘FLASH’) radiobiology has prompted a number of groups to model the chemical reactions that might be involved, either to estimate radiolytic oxygen consumption in tissues, or the yields and persistence of specific reactive intermediates or products. However, most models have been either not biomimetic and/or inadequately supported by kinetic data. This review summarizes issues which should be addressed in developing models for chemical reactions in radiobiology. Conclusions A model should be based on mechanistic pathways that lead to well-defined chemical and biological endpoints: crucially, the pathways should be plausibly similar in both the model and cells or tissues, and reflect the Law of Mass Action. Complex calculations of radiolytic yields are unnecessary, as reasonable estimates based on experimental data are generally available. Different parts of the intracellular milieu (such as the cytoplasm, nucleus, or phospholipid membranes) should be addressed separately, or with two-compartment models where appropriate. Homogeneous kinetics can be used as a first step in modeling, but the heterogeneity – both of radiolytic damage distribution and of cellular reactants – will need to be addressed. Major problems arise in choosing appropriate rate constants and estimating intracellular concentrations of reactants in the different organelles. It helps to identify and focus on the key reactions, as complex models may mask deficiencies and/or uncertainties; but it is still important to include all reactions and reactants that can have a significant effect on the model, as well as build upon experience in modeling chemical pathways in biology.
Comparison of Proteomic Expression Profiles after Radiation Exposure across Four Different Species

There is a need to identify biomarkers of radiation exposure for use in development of circulating biodosimeters for radiation exposure and for clinical use as markers of radiation injury. Most research approaches for biomarker discovery rely on a single animal model. The current study sought to take advantage of a novel aptamer-based proteomic assay which has been validated for use in many species to characterize changes to the blood proteome after total-body irradiation (TBI) across four different mammalian species including humans. Plasma was collected from C57BL6 mice, Sinclair minipigs, and Rhesus non-human primates (NHPs) receiving a single dose of TBI at a range of 3.3 Gy to 4.22 Gy at 24 h postirradiation. NHP and minipig models were irradiated using a 60Co source at a dose rate of 0.6 Gy/min, the C57BL6 mouse model using an X-ray source at a dose rate of 2.28 Gy/min and clinical samples from a photon source at 10 cGy/min. Plasma was collected from human patients receiving a single dose of 2 Gy TBI collected 6 h postirradiation. Plasma was screened using the aptamer-based SomaLogic SomaScan® proteomic assay technology to evaluate changes in the expression of 1,310 protein analytes. Confirmatory analysis of protein expression of biomarker HIST1H1C, was completed using plasma from C57BL6 mice receiving a 2, 3.5 or 8 Gy TBI collected at days 1, 3, and 7 postirradiation by singleplex ELISA. Summary of key pathways with altered expression after radiation exposure across all four mammalian species was determined using Ingenuity Pathway Analysis (IPA). Detectable values were obtained for all 1,310 proteins in all samples included in the SomaScan assay. A subset panel of protein biomarkers which demonstrated significant (p < 0.05) changes in expression of at least 1.3-fold after radiation exposure were characterized for each species. IPA of significantly altered proteins yielded a variety of top disease and biofunction pathways across species with the organismal injury and abnormalities pathway held in common for all four species. The HIST1H1C protein was shown to be radiation responsive within the human, NHP and murine species within the SomaScan dataset and was shown to demonstrate dose dependent upregulation at 2, 3.5 and 8 Gy at 24 h postirradiation in a separate murine cohort by ELISA. The SomaScan proteomics platform is a useful screening tool to evaluate changes in biomarker expression across multiple mammalian species. In our study, we were able to identify a novel biomarker of radiation exposure, HIST1H1C, and characterize panels of radiation responsive proteins and functional proteomic pathways altered by radiation exposure across murine, minipig, NHP and human species. Our study demonstrates the efficacy of using a multispecies approach for biomarker discovery.
Active Use and Engagement in an mHealth Initiative Among Young Men With Obesity: Mixed Methods Study

Background The effectiveness of mobile health (mHealth) approaches that employ wearable technology to promote physical activity have been the subject of concern due to the declining active use observed in trial settings. Objective To better contextualize active use, this study aimed to identify the barriers and enablers to engagement in a tracker-based mHealth initiative among young men who had recently completed a 19-week residential weight loss program. Methods A mixed methods study was conducted among 167 young men who had voluntarily enrolled in the national steps challenge (NSC), an mHealth physical activity promotion initiative, following a residential weight loss intervention. A subsample of 29 enrollees with a body mass index of 29.6 (SD 3.1) participated in semistructured interviews and additional follow-up assessments. Quantitative systems data on daily step count rates were used to describe active use. Qualitative data were coded and analyzed to elicit barriers and enablers to microlevel engagement in relation to the NSC, focusing on tracker and smartphone use. We further elicited barriers and enablers to macrolevel engagement by exploring attitudes and behaviors toward the NSC. Using triangulation, we examined how qualitative engagement in the NSC could account for quantitative findings on active use. Using integration of findings, we discussed how the mHealth intervention might have changed physical activity behavior. Results Among the 167 original enrollees, active use declined from 72 (47%) in week 1 to 27 (17%) in week 21. Mean daily step counts peaked in week 1 at 10,576 steps per day and were variable throughout the NSC. Barriers to engagement had occurred in the form of technical issues leading to abandonment, device switching, and offline tracking. Passive attitudes toward step counting and disinterest in the rewards had also prevented deeper engagement. Enablers of engagement included self-monitoring and coaching features, while system targets and the implicit prospect of reward had fostered new physical activity behaviors. Conclusions Our study showed that as the NSC is implemented in this population, more emphasis should be placed on technical support and personalized activity targets to promote lasting behavior change.
“Be careful what you recall”: Retrieval-induced forgetting of genuine real-life autobiographical memories

Which episodes from our lives will be remembered and which will be forgotten, and why? This question has still not been answered satisfactorily by research into autobiographical memory. Previous work has shown that retrieval-induced forgetting (RIF) might be a factor responsible for forgetting parts of the autobiographical memory content. However, none of the previous studies assessed RIF in memories for recent, controlled, personal events. We report here the results of an experiment in which autobiographical memories of real-life events were induced in a controlled, but fully naturalistic, manner under the disguise of team-building exercises, while an adapted RIF paradigm was applied to these memories. Results clearly showed the influence of RIF on autobiographical memory retrieval. These findings demonstrate conclusively that RIF occurs in everyday life when remembering personal events.
Predictors of stigma toward alcohol misuse in Latino communities: a path model

Abstract This study explores stigma-related beliefs within the Latino community concerning alcohol misuse. A community-based convenience sample of 251 self-identified Latino adults were recruited to participate in a research study using an experimental vignette methodology. Participants were randomly assigned one of four vignettes about alcohol misuse and asked to share their attitudes and stigma-related beliefs about the problem and the person in the vignette. Sociodemographic characteristics of participants differentially predicted alcohol-related stigma. These data may be used to inform health literacy and stigma reduction interventions within the Latino community.
Mitochondrial biogenesis gene POLG correlates with outcome in pediatric acute myeloid leukemia

Mitochondrial adaptations, including alterations in mitochondrial DNA (mtDNA) copy number, respiratory com-plex activity, and onco-metabolite production, are common in malignancies with possible prognostic impact of mitochondrial D-Loop on prognosis in with myeloid leukemia in mitochondrial biogenesis its is to explore the impact of altered of on disease biology and
The interplay of helminthic neuropeptides and proteases in parasite survival and host immunomodulation

Neuropeptides comprise a diverse and broad group of neurotransmitters in vertebrates and invertebrates, with critical roles in neuronal signal transduction. While their role in controlling learning and memory in the brains of mammals is known, their extra-synaptic function in infection and inflammation with effects on distinct tissues and immune cells is increasingly recognized. Helminth infections especially of the central nervous system (CNS), such as neurocysticercosis, induce neuropeptide production by both host and helminth, but their role in host–parasite interplay or host inflammatory response is unclear. Here, we review the neurobiology of helminths, and discuss recent studies on neuropeptide synthesis and function in the helminth as well as the host CNS and immune system. Neuropeptides are summarized according to structure and function, and we discuss the complex enzyme processing for mature neuropeptides, focusing on helminth enzymes as potential targets for novel anthelminthics. We next describe known immunomodulatory effects of mammalian neuropeptides discovered from mouse infection models and draw functional parallels with helminth neuropeptides. Last, we discuss the anti-microbial properties of neuropeptides, and how they may be involved in host–microbiota changes in helminth infection. Overall, a better understanding of the biology of helminth neuropeptides, and whether they affect infection outcomes could provide diagnostic and therapeutic opportunities for helminth infections.
KAT6A Acetylation of SMAD3 Regulates Myeloid‐Derived Suppressor Cell Recruitment, Metastasis, and Immunotherapy in Triple‐Negative Breast Cancer

In the originally published article, the representative BLI images of treated mice in Figure 6D present the wrong samples (the third in the second row, and the third in the fourth row). The correct Figure 6D is shown below. The authors declare that this correction does not affect the description, interpretation, or the original conclusions of the manuscript. The authors regret the inconvenience this error may have caused.
Multi-omics analyses reveal early metabolic imbalance and mitochondrial stress in neonatal photoreceptors leading to cell death in Pde6brd1/rd1 mouse model of retinal degeneration.

Retinal diseases exhibit extensive genetic heterogeneity and complex etiology with varying onset and severity. Mutations in over 200 genes can lead to photoreceptor dysfunction and/or cell death in retinal neurodegeneration. To deduce molecular pathways that initiate and/or drive cell death, we adopted a temporal multi-omics approach and examined molecular and cellular events in newborn and developing photoreceptors before the onset of degeneration in a widely-used Pde6brd1/rd1 (rd1) mouse, a model of autosomal recessive retinitis pigmentosa caused by PDE6B mutations. Transcriptome profiling of neonatal and developing rods from the rd1 retina revealed early downregulation of genes associated with anabolic pathways and energy metabolism. Quantitative proteomics of rd1 retina showed early changes in calcium signaling and oxidative phosphorylation, with specific partial bypass of complex I electron transfer, which precede the onset of cell death. Concurrently, we detected alterations in central carbon metabolism, including dysregulation of components associated with glycolysis, pentose phosphate and purine biosynthesis. Ex vivo assays of oxygen consumption and transmission electron microscopy validated early and progressive mitochondrial stress and abnormalities in mitochondrial structure and function of rd1 rods. These data uncover mitochondrial over-activation and related metabolic alterations as determinants of early pathology and implicate aberrant calcium signaling as an initiator of higher mitochondrial stress. Our studies thus provide a mechanistic framework with mitochondrial damage and metabolic disruptions as early drivers of photoreceptor cell death in retinal degeneration.
Nutritional status and its association with in-hospital major adverse cardiac events in patients with severe heart failure: a prospective study.

OBJECTIVES this study aimed to evaluate the relationship of Nutritional Risk Screening 2002 (NRS2002) and in-hospital major adverse cardiac events (MACE) in patients with severe heart failure. METHODS an observational study was conducted at the emergency intensive care units (EICU) of Shandong University Qilu Hospital from January 2017 to December 2019. Nutritional screening and assessment were performed at the time of admission to hospital with the NRS2002. RESULTS of the 209 patients included, 16 cases (7.66 %) were not at nutritional risk, and 193 cases (92.34 %) were at risk. Among them, 12 cases (5.74 %) were malnourished, 38 cases (18.18 %) were at high nutritional risk, and 115 cases (55.02 %) were overweight and obese. The differences in prealbumin (PA) and N-terminal B-type natriuretic peptide precursor (NT-proBNP) between the 2 groups were statistically significant (p < 0.05). A total of 134 cases (64.12 %) received nutrition treatment support, of which 39 cases (29.10 %) received enteral nutrition (EN), 77 cases (57.46 %) parenteral nutrition, and 18 cases (13.43 %) enteral nutrition combined with parenteral nutrition (EN + SPN) support treatment. In all, 31 cases (54.39 %) reached 100 % of the target dose. Patients in the EN and EN + SPN groups had 37 MACE (64.91 %) and 31 enteral nutrition complications (54.39 %), with differences between the 3 groups being statistically significant (p < 0.05). CONCLUSION the nutritional risk of patients with severe heart failure is high, and age and heart function are positively correlated with nutritional risk. The complications rate of patients with high nutritional risk is significantly higher than in those with low risk; the higher the nutritional risk, the higher the hospital mortality rate - that is, nutritional risk affects disease outcome.
No association of BMI and body adiposity with cardiometabolic biomarkers among a small sample of reindeer herders of sub-Arctic Finland

ABSTRACT The rising global obesity rate is alarming due to its real health and socioeconomic consequences. Finland, like other circumpolar regions, is also experiencing a rise in obesity . Here we assess BMI, body adiposity, and measures of cardiometabolic health among a small population of reindeer herders in sub-Arctic Finland. We collected anthropometric and biomarker measures at two different time points: October 2018 (N = 20) and January 2019 (N = 21) with a total of 25 unique individuals across the data collection periods (ages 20–64). Anthropometric measures included height, weight, age, and body composition. Biomarkers included measures of cholesterol, fasting glucose, HDL cholesterol, LDL cholesterol, and triglyceride levels. Over 70% of this sample was classified as “overweight” and “obese” as categorised by BMI and 64% classified as “overfat” based on body fat percentage. However, there was no significant relationship between BMI and body fat percentage with any of the measured biomarkers. Although the sample size is small, the results of this study suggest there might not be a strong correlation between BMI, body adiposity, and cardiometabolic health indices within this population – a pattern that has been documented elsewhere. However, further study is needed to confirm this lack of a correlation.
Antiphospholipid antibodies and idiopathic infertility

Objective The aim of our study was to evaluate obstetric outcome of women affected by idiopathic infertility showing persistently positive antiphospholipid antibodies (aPL). Methods : From 2000 consecutive patients undergoing ART, we selected 151 (7.55%) clinical records of patients affected by idiopathic infertility undergoing ICSI and showing positive aPL. Results Persistently positive aPL were found in 64/151 (42.38%) of the patients: in 34/64 (53.12%) at medium/high titers (group A) and in 30/64 (46.87%) at low titers (group B). Primary or secondary antiphospholipid syndrome (APS) was diagnosed in 25% of the patients, whereas 37.5% women showed clinical and/or laboratory features suggestive of APS, but not fulfilling clinical or laboratory classification criteria. Idiopathic infertility was the sole symptom in 31.25%. In 55% of these infertile patients, a history of recurrent failures of assisted reproductive techniques (ART) was also observed. Eighty-eight percent (88.88%) of women became pregnant and 77.77% gave birth. During pregnancy, an increase of aPL values was observed in 29.41% women of group B. Conclusions A careful selection of patients allowed us to confirm that women affected by idiopathic infertility show a high prevalence of aPL, suggesting that these autoantibodies can also affect conception. Considering pregnancy complications and thrombotic risk related to ovarian stimulation, measuring aPL can represent a valid tool to identify among infertile women undergoing ART those at higher risk of pregnancy complications potentially life-threatening for mother and the fetus. In such patients, an accurate diagnosis and an adequate therapy are related to a better ART outcome.