Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunomodulatory proteins from hookworms reduce cardiac inflammation and modulate regulatory responses in a mouse model of chronic Trypanosoma cruzi infection

Introduction: Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4 + Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased production of inflammatory cytokines. There are no current antiparasitic drugs that effectively reduce or prevent chronic myocarditis caused by the onset of Chagas disease, thus new therapies are urgently needed. Therefore, the impact of AIP-1 and AIP-2 on myocarditis was investigated in a mouse model of chronic T. cruzi infection. Methods: Female BALB/c mice infected with bioluminescent T. cruzi H1 strain trypomastigotes for 70 days were treated once daily for 7 days with 1mg/kg AIP-1 or AIP-2 protein by intraperitoneal injection. Control mice were left untreated or treated once daily for 14 days with 25mg/kg aspirin in drinking water. At 84 days of infection, splenocytes, cardiac tissue and serum were collected for evaluation. Results: Treatment with both AIP-1 and AIP-2 proteins significantly reduced cardiac cellular infiltration, and reduced cardiac levels of IFNγ, IL-6 and IL-2. AIP-2 treatment reduced cardiac expression of COX-2. Further, while incubation with AIP-1 and AIP-2 proteins did not induce a significant upregulation of an immunoregulatory phenotype in dendritic cells (DC), there was a modest upregulation of CD11c +CD11b+MHCII+SIRPα+ expression, suggesting a regulatory phenotype. Ex-vivo stimulation of splenocytes from the treatment groups with AIP-1 loaded DC induced reduced levels of cytotoxic and pro-inflammatory T cells, stimulation with AIP-2 loaded DC specifically induced enhanced levels of CD4+CD25+Foxp3+ regulatory T cells among treatment groups. Discussion: All in vivo and in vitro results demonstrate that hookworm-derived AIP-1 and AIP-2 proteins reduce T. cruzi induced cardiac inflammation, possibly through multiple anti-inflammatory mechanisms.
The Effects of Zingiber Officinale and Propolis supplementation on Hospitalized Covid-19 Patients' Oxygen Saturation

Antiviral, anti-inflammatory, and supportive therapy are required in the Covid-19 management, whilst there is no available specific antiviral for Covid-19 patients. Zingiber officinale and Propolis were reported to suppress the pro-inflammatory cytokines and their safety profiles were considered in several toxicity studies. However, their efficacy in hospitalized Covid-19 patients has not been clarified yet. This study explored the activity of Z. officinale and Propolis in modulating the clinical signs and hematology parameters in hospitalized Covid-19 patients. A total of 22 subjects were divided into a control group (standard therapy), and a treatment group (standard therapy and supplemented with the combination of Z. officinale 500 mg/day and Propolis 1000 mg/day). We analyzed the differences in demographic characteristics, clinical signs, and hematology parameters at pre and post-treatment in both groups. The increased oxygen saturation in control and treatment groups were 0.45 ± 0.45 and 3.45 ± 1.16, respectively (p = 0.011). Moreover, the high-fluorescent lymphocyte count (HFLC) and mean platelet volume (MPV) in the treatment group tend to be lower compared to the control, although it is not statistically significant. The supplementation of Z. officinale and Propolis has beneficial effects in alleviating clinical signs of Covid-19 disease, especially in the enhancement of oxygen saturation, and tend to restore the hematological parameters.
The Impact of Anxiety and Depression on Individuals with Smoking Habit

Anxiety and depressive disorder is a prevalent mental health disorder on a global scale, often exhibiting a high comorbidity rate with smoking behavior. This present review offers a comprehensive narrative synthesis of the latest scholarly studies pertaining to the influence of anxiety and depression on the onset, perpetuation, and cessation of smoking behavior. The existing literature exhibits variability in terms of the evidence supporting the association between anxiety or anxious symptoms and smoking behavior. The findings consistently indicate a significant association between anxiety and smoking, suggesting a high comorbidity rate between these two illnesses. The existing literature on the association between anxiety, depression and various factors such as onset, severity indicators, and cessation outcomes has yielded inconsistent findings. While there exists compelling data supporting the association between smoking and anxiety, notable distinctions may be observed regarding the specific impact of anxiety on the beginning, severity, and quitting outcomes of smoking. In the future, it will be necessary to employ more advanced approaches in order to ascertain causative relationships, as well as potential moderators and mediators, within the association between anxiety, depression and smoking habit.
MTH1 Inhibition Alleviates Immune Suppression and Enhances the Efficacy of Anti-PD-L1 Immunotherapy in Experimental Mesothelioma

Simple Summary The role of MTH1 in the tumor-related immune responses in mesothelioma remains unknown. We hypothesized that MTH1 regulates immune responses and enhances the efficacy of anti-PD-L1 immunotherapy. We focused on central immune players such as tumor-associated macrophages. MTH1 inhibition enhances M1 macrophage polarization, stimulates CD8 fitness and promotes the activation of DC. Combining anti-PD-L1 immunotherapy with MTH1 inhibitor impairs mesothelioma tumor growth and mesothelioma-associated pleural effusion accumulation more effectively compared to each monotherapy. Abstract Background: MTH1 protects tumor cells and their supporting endothelium from lethal DNA damage triggered by oxidative stress in the tumor microenvironment, thus promoting tumor growth. The impact of MTH1 on the tumor-related immune compartment remains unknown. We hypothesized that MTH1 regulates immune fitness and therefore enhances the activity of currently used immunotherapeutic regimens. Methods: Our hypotheses were validated in two syngeneic murine mesothelioma models using the clinically relevant MTH1 inhibitor, karonudib. We also examined the effect of combined MTH1 and PD-L1 blockade in mesothelioma progression, focusing on the main immune players. Results: Karonudib administration enhances M1 macrophage polarization, stimulates CD8 expansion and promotes the activation of DC and T cells. Combined administration of PD-L1 and MTH1 inhibitors impairs mesothelioma tumor growth and mesothelioma-associated pleural effusion accumulation more effectively compared to each monotherapy. Conclusions: Combined MTH1 and PD-L1 inhibition holds promise for the successful clinical management of mesothelioma.
Impact of Safinamide on Patient-Reported Outcomes in Parkinson’s Disease

Introduction Parkinson’s disease (PD) is a chronic and progressive neurodegenerative condition due to the degeneration of nigral dopaminergic cells. Both motor and non-motor symptoms (NMS) of PD produce a marked impairment in PD patients’ quality of life (QoL), but contrary to motor features, NMS do not improve with dopamine replacement. Novel therapeutic interventions for PD have successfully controlled most motor manifestations of PD, but the management of NMS is still challenging. Since NMS have a negative impact on the QoL of PD patients, researchers are currently looking for drugs that can modulate the activity of neurotransmitter systems other than dopamine in the hope that can alleviate NMS in PD. Among the recently approved drugs for patients experiencing fluctuations in motor symptoms, safinamide stands out as an effective add-on therapy to levodopa. Safinamide is a monoamine oxidase type-B inhibitor (MAOB-I), with proven efficacy in reducing motor fluctuations. Its distinctive mechanism of action impacts dopaminergic pathways via MAOB inhibition and glutamatergic pathways by blocking sodium and calcium channels. Findings from Phase III clinical trials, meta-analysis, post-hoc analysis, and real-life experiences indicate that safinamide benefits motor symptoms such as tremor, bradykinesia, rigidity, and gait. Additionally, it shows promise for improving NMS like fatigue, pain, mood, and sleep disturbances in patients with PD. Areas Covered In this article, the authors explore the impact of safinamide on patient-reported outcomes in PD. A thorough search was conducted on PubMed focusing on studies published between 2018 and 2023 in English. The inclusion criteria encompassed clinical trials, randomized controlled trials, systematic reviews, meta-analyses, and reviews. The search strategy revolved around the implementation of MeSH terms related to safinamide and its impact on the quality of life in PD. Conclusion Our data strongly support the improving effect on QoL, reducing the disabling NMS reported in patients with PD.
Dispersion modeling of particulate matter containing hexavalent chromium during high winds in southern Iraq

The aim of this paper is to describe a scientific methodology (i.e., the combination of different well-established modeling techniques) and its application to a real case scenario of contaminated dust emissions in high winds. This scenario addresses potential air pollution problems at the water treatment plant (WTP) at Qarmat-Ali, Basra, Iraq, during 2003. Workplace practices at the WTP before 2003 resulted in sodium dichromate contamination in the area. Looting at the site in early 2003 also contributed to this contamination. Individuals who were assigned to provide security at the site in 2003 have claimed adverse health effects caused by exposure to dust containing hexavalent chromium [Cr(VI)]. This report presents our modeling study with respect to these claims in relation to (1) amount of Cr(VI) present in the soil, (2) wind erosion episodes, and (3) possible long-term (e.g., annual average) Cr(VI) concentrations inhaled by different people while at the site. Our modeling approach included (1) the analysis of Cr(VI) soil measurements to assess the degree of contamination in different areas of the plant at different times; (2) the use of DUSTRAN model equations to calculate the emission rate of particulate matter (PM) less than 10 µm in diameter (PM10) during high-wind episodes; (3) the use of the U.S. Environmental Protection Agency (EPA) AERMOD modeling system to estimate Cr(VI) concentrations at the site; and (4) the calculation of modeling results in the form of both contour lines of average Cr(VI) concentrations at the site, and specific concentration values for selected individuals, based upon their recollection of their visits to the site. Implications: The assessment of individual exposure to contaminated dust during high-wind episodes requires a combination of modeling tools and the calculation of concentration impacts at precise locations and times. We have combined several state-of-the art simulation algorithms to provide a credible methodology for assessing individual exposure. The methodology has been applied to an actual case where exposure was claimed by individuals.
Geochronology of the North American Midcontinent rift in western Lake Superior and implications for its geodynamic evolution

Volcanism in the Midcontinent rift system lasted between 1108 and 1086 Ma. Rates of flood-basalt eruption and subsidence in the western Lake Superior region appear to have been greatest at the beginning of recorded activity (estimated 5 km/Ma subsidence rate at 1108 Ma) and rapidly waned over a period of 1–3 Ma during a magnetically reversed period. The age of the paleomagnetic polarity reversal is now constrained to be between 1105 ± 2 and 1102 ± 2 Ma. A resurgence of intense volcanism began at 1100 ± 2 Ma in the North Shore Volcanic Group and lasted until 1097 ± 2 Ma. This group contains a ca. 7 Ma time gap between magnetically reversed and normal volcanic sequences. A similar disconformity appears to exist in the upper part of the Powder Mill Group. The average subsidence rate during this period was approximately 3.7 km/Ma. Latitude variations measured from paleomagnetism on dated sequences indicate that the North American plate was drifting at a minimum rate of 22 cm/year during the early history of t.
Dendrochemistry of White Mountain bristlecone pines: An investigation via Synchrotron Radiation Scanning X‐Ray Fluorescence Microscopy

Synchrotron Radiation Scanning X‐Ray Fluorescence Microscopy (SXFM) was used for the first spatially/temporally resolved investigation of the multielemental chemistry of bristlecone pine (Pinus longaeva D.K. Bailey). A new protocol was designed to apply this nondestructive method of analysis to this unique palaeoclimatological resource, extracting previously inaccessible dendrochemical information at subannual resolution from tree rings ranging from 1400 to 40 μm. The potential of Pinus longaeva was assessed for the reconstruction of multicentennial annual resolution sequences of elemental change, with specific focus on the identification of multielemental markers for major, climatically effective volcanic eruptions. Increases in calcium (Ca), strontium (Sr), manganese (Mn), and zinc (Zn) were identified in association with frost rings around AD1601, following the eruption of Huaynaputina, Peru, but these could not be directly attributed to volcanogenic changes in environmental chemistry. Elemental patterns for 500 years from five trees demonstrated little agreement indicating that, for the elements detected, this species may be unsuitable for temporal reconstructions of external chemistry. Further development of SXFM dendrochemical technique, however, offers much potential for future work.
Analysis of Technology Adoption by SMEs Using Technology Organization Environment Model

The increasing existence of Micro, Small and Medium Enterprises (MSMEs) in the era of disruption or global change with intense competition between contestants, makes it imperative for MSMEs to be able to find solutions to these constraints or challenges such as looking for new opportunities, innovating a product, and technological prowess as well as seeking markets with a very wide range of coverage. MSMEs as a support for the Indonesian economy still show a low export contribution so scientific studies are needed to produce a policy for MSME management in managing their business to increase competitiveness, especially exports by taking into account the factors resulting from the theoretical analysis of digital technology adoption. This research intends to identify the contribution of digital technology, based on factors in the Technology, Organization, and Environment (TOE) framework, to increase the competitiveness of export-oriented SMEs in Indonesia. The method used is to analyze the variabels in the TOE framework employing SEM-PLS analysis (Structural Equation Model-Partial Least Square). The outcomes of the TOE model are that the environmental, organizational, technology dimension has a direct positive and significant effect on technology adoption. The technology dimension is supported by relative advantage, trialability with a high significant value and complexity, compatibility, and observability indicators with a lower significance value. The organizational dimension is supported by the variable information processing needs, knowledge competence with a high significant value, and company size having a lower significance value. Lastly, the environmental dimension is supported by government support, uncertain environment, and competitive pressure variables which have a high significant value. The practical implications derived from these results, especially the indicators of complexity, suitability, observability and rigor, are to recommend a policy especially for MSME owners and managers as well as regulatory stakeholders in Indonesia so that they continue to support increased development in the areas of human resource knowledge
On the definition of El Niño and associated seasonal average U.S. weather anomalies

A new NOAA definition of El Niño identifies a number of additional El Niño seasons beyond those conventionally agreed. These additional seasons are characterized by SST anomalies primarily in the western central equatorial Pacific. We show here that the seasonal weather anomalies over the U.S. associated with these additional Dateline El Niño seasons are substantially different from those associated with conventional El Niño seasons. Although some regions have similar associated anomalies, most of the major regional anomalies are quite different. Treating the two as a single phenomenon yields weaker overall seasonal weather associations and does not take advantage of the stronger associations available when the two are treated separately.
Using Instagram as Rate of Reaction Learning Media Based on PjBL to Increase Students’ Motivation and Creative Thinking Ability

This study aims to determine the impact of learning with the Project-Based Learning (PjBL) integrated with Instagram social media in increasing learning motivation and students’ creative thinking abilities in chemical material reaction rate. The research was carried out using a quasi-experimental method. Sampling was taken using a random sampling technique involving two XI classes at State High School 1 Singosari, namely 29 students for the class of control and 33 students for the class of experiment. Data analysis used qualitative and quantitative descriptive tests with independent sample t-tests and N-Gain. Results of the qualitative analysis conducted, the increase in learning motivation in the experimental class (71%) was greater when compared to the control class (64%). The results of HA can be accepted refers on the independent t-test with a value of <0.05. The results of the study show, that the PjBL integrated with social media Instagram can improve students’ creative thinking skills and learning motivation in the matter of reaction rate. Percentage value of the N-gain test is 66.6% and is in the sufficient category to increase students’ creative thinking ability.
Microscopic Analysis of Heterochromatin, Euchromatin and Cohesin in Cancer Cell Models and under Anti-Cancer Treatment

The spatial organization of euchromatin (EC) and heterochromatin (HC) appears as a cell-type specific network, which seems to have an impact on gene regulation and cell fate. The spatial organization of cohesin should thus also be characteristic for a cell type since it is involved in a TAD (topologically associating domain) formation, and thus in gene regulation or DNA repair processes. Based on the previous hypotheses and results on the general importance of heterochromatin organization on genome functions in particular, the configurations of these organizational units (EC represented by H3K4me3-positive regions, HC represented by H3K9me3-positive regions, cohesins) are investigated in the cell nuclei of different cancer and non-cancerous cell types and under different anti-cancer treatments. Confocal microscopic images of the model cell systems were used and analyzed using analytical processes of quantification created in Fiji, an imaging tool box well established in different fields of science. Human fibroblasts, breast cancer and glioblastoma cells as well as murine embryonal terato-carcinoma cells were used as these cell models and compared according to the different parameters of spatial arrangements. In addition, proliferating, quiescent and from the quiescent state reactivated fibroblasts were analyzed. In some selected cases, the cells were treated with X-rays or azacitidine. Heterogeneous results were obtained by the analyses of the configurations of the three different organizational units: granulation and a loss of H3K4me3-positive regions (EC) occurred after irradiation with 4 Gy or azacitidine treatment. While fibroblasts responded to irradiation with an increase in cohesin and granulation, in breast cancer cells, it resulted in decreases in cohesin and changes in granulation. H3K9me3-positive regions (HC) in fibroblasts experienced increased granulation, whereas in breast cancer cells, the amount of such regions increased. After azacitidine treatment, murine stem cells showed losses of cohesin and granulation and an increase in the granulation of H3K9me3-positive regions. Fibroblasts that were irradiated with 2 Gy only showed irregularities in structural amounts and granulation. Quiescent fibroblasts contained less euchromatin-related H3K4me3-positive signals and cohesin levels as well as higher heterochromatin-related H3K9me3-positive signals than non-quiescent ones. In general, fibroblasts responded more intensely to X-ray irradiation than breast cancer cells. The results indicate the usefulness of model cell systems and show that, in general, characteristic differences initially existing in chromatin and cohesin organizations result in specific responses to anti-cancer treatment.
A massif‐type (~1.86 Ga) anorthosite complex in the Yeongnam Massif, Korea: late‐orogenic emplacement associated with the mantle delamination in the North China Craton

To unravel the petrogenesis of a massif‐type anorthosite in terms of the crust‐mantle geodynamics, we dated zircons separated from six samples from the Sancheong‐Hadong (SH) complex, Korea, using a sensitive high‐resolution ion microprobe. The weighted mean 207Pb/206Pb age of two anorthosites is 1862 ± 2 Ma, whereas the ages of the hornblende gabbro and granitic gneiss are 1873 ± 4 Ma and 1875 ± 5 Ma respectively. Zircon rims from mafic granulite and migmatitic gneiss yielded ages of 1860 ± 5 Ma and 1858 ± 4 Ma, respectively, implying that the granulite facies metamorphism and anatexis are associated with anorthosite emplacement. Our results, together with available Re–Os data, are compatible with the ~1.9–1.86 Ga collisional orogeny prevalent in the North China Craton and the Korean Peninsula, and suggest that orogenesis was accompanied by mantle delamination beneath the craton. It is thus likely that the SH anorthositic rocks are a product of late‐orogenic magmatism during the post‐collisional extension‐dominated phase of orogeny.