Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved chemotherapy modeling with RAG-based immune deficient mice

We have previously characterized an acute myeloid leukemia (AML) chemotherapy model for SCID-based immune deficient mice (NSG and NSGS), consisting of 5 days of cytarabine (AraC) and 3 days of anthracycline (doxorubicin), to simulate the standard 7+3 chemotherapy regimen many AML patients receive. While this model remains tractable, there are several limitations, presumably due to the constitutional Pkrdcscid (SCID, severe combined immune deficiency) mutation which affects DNA repair in all tissues of the mouse. These include the inability to combine preconditioning with subsequent chemotherapy, the inability to repeat chemotherapy cycles, and the increased sensitivity of the host hematopoietic cells to genotoxic stress. Here we attempt to address these drawbacks through the use of alternative strains with RAG-based immune deficiency (NRG and NRGS). We find that RAG-based mice tolerate a busulfan preconditioning regimen in combination with either AML or 4-drug acute lymphoid leukemia (ALL) chemotherapy, expanding the number of samples that can be studied. RAG-based mice also tolerate multiple cycles of therapy, thereby allowing for more aggressive, realistic modeling. Furthermore, standard AML therapy in RAG mice was 3.8-fold more specific for AML cells, relative to SCID mice, demonstrating an improved therapeutic window for genotoxic agents. We conclude that RAG-based mice should be the new standard for preclinical evaluation of therapeutic strategies involving genotoxic agents.
Targeting histone acetylation in pulmonary hypertension and right ventricular hypertrophy

Epigenetic mechanisms, including DNA methylation and histone post‐translational modifications (PTMs), have been known to regulate chromatin structure and lineage‐specific gene expression during cardiovascular development and disease. However, alterations in the landscape of histone PTMs and their contribution to the pathogenesis of incurable cardiovascular diseases such as pulmonary hypertension (PH) and associated right heart failure (RHF) remain largely unexplored. This review focusses on the studies in PH and RHF that investigated the gene families that write (histone acetyltransferases), read (bromodomain‐containing proteins) or erase (histone deacetylases [HDACs] and sirtuins [SIRT]) acetyl moieties from the ε‐amino group of lysine residues of histones and non‐histone proteins. Analysis of cells and tissues isolated from the in vivo preclinical models of PH and human pulmonary arterial hypertension not only confirmed significant alterations in the expression levels of multiple HDACs, SIRT1, SIRT3 and BRD4 proteins but also demonstrated their strong association to proliferative, inflammatory and fibrotic phenotypes linked to the pathological vascular remodelling process. Due to the reversible nature of post‐translational protein acetylation, the therapeutic efficacy of numerous small‐molecule inhibitors (vorinostat, valproic acid, sodium butyrate, mocetinostat, entinostat, tubastatin A, apabetalone, JQ1 and resveratrol) have been evaluated in different preclinical models of cardiovascular disease, which revealed the promising therapeutic benefits of targeting histone acetylation pathways in the attenuation of cardiac hypertrophy, fibrosis, left heart dysfunction, PH and RHF. This review also emphasizes the need for deeper molecular insights into the contribution of epigenetic changes to PH pathogenesis and therapeutic evaluation of isoform‐specific modulation in ex vivo and in vivo models of PH and RHF.
Population history and the selective landscape shape patterns of osmoregulatory trait divergence in tidal marsh Savannah sparrows (Passerculus sandwichensis)

A persistent challenge in making associations between phenotypic and environmental variation is understanding how ecological factors and demographic history interact to shape adaptive outcomes. Evaluating the degree to which conspecific populations exposed to similar environmental pressures respond in parallel provides a powerful framework for addressing this challenge. We took this comparative approach with multiple populations of Savannah sparrows (Passerculus sandwichensis) found in tidal marshes along the Pacific coast of North America. The high salinities characterizing tidal marshes select for increased osmoregulatory performance and salinity tolerance. We collected data on physiological traits associated with osmoregulatory performance from 10 tidal marsh and three freshwater‐adapted interior populations to evaluate the degree of parallel divergence across populations. All traits showed differences in the magnitude of divergence, but only total evaporative water loss (TEWL) showed differences in the direction of divergence. The drivers of these differences in both the magnitude and direction of divergence varied among traits. For kidney morphology and TEWL, patterns of divergence were best explained by variation in immigration rate from interior populations. Maximum temperature was the best predictor of variation in urine excretion ability, and both gene flow and temperature contributed to variation in plasma osmolality. Finally, analysis of multitrait divergence patterns indicated that differences in the direction of divergence were best explained by population genetic structure, whereas differences in the magnitude of divergence were explained by environmental differences. Together these results show that the influences of demography and the selective landscape can manifest themselves differently across functionally integrated traits.
Estimating and differentiating maternal feeding practices in a country ranked first in childhood obesity

Abstract Objective: Mexico ranks first in childhood obesity worldwide. However, little is known about the factors influencing maternal feeding practices. The present study aimed to estimate the prevalence of feeding practices and explore associations between weight concern, weight perception, sociodemographic characteristics and those feeding practices. Design: Cross-sectional. Setting: North-eastern Mexico. Participants: Mothers aged ≥18 years who were in charge of feeding a singleton child aged 2–6 years with no endocrine disease or visible genetic malformations (n 507). Information on six maternal feeding practices, concern and perception of the child’s weight and demographics were collected by interview. The mother’s and child’s height and weight were measured. The feeding practices questionnaire was subject to content, construct and convergent validity analysis. Then, mean feeding scores were obtained and prevalence and 95 % CI were determined for scores ≥3; multivariate logistic regression was performed. Results: Not modelling (63·5 %; 95 % CI 59·2, 67·8 %) and pressuring to eat (55·6 %; 95 % CI 51·2, 60·0 %) were the most frequent feeding practices, followed by easy access to unhealthy foods (45·4 %; 95 % CI 40·9, 49·8 %) and child control (43·2 %; 95 % CI 38·8, 47·6 %). They prevailed despite concern about the child’s excess weight or a perception of the child as overweight/obese. Education was associated with the highest number of practices (educated mothers used more pressuring to eat, less regulation and less easy access; or monitoring was less absent). Conclusions: The frequency of certain feeding practices needs to be improved. Emphasis on the child’s weight concern, obesity perception and maternal education is essential for optimizing intervention planning.
Do the Quality and Quantity of Honey Bee-Collected Pollen Vary Across an Agricultural Land-Use Gradient?

Abstract Pollen is the source of protein for most bee species, yet the quality and quantity of pollen is variable across landscapes and growing seasons. Understanding the role of landscapes in providing nutritious forage to bees is important for pollinator health, particularly in areas undergoing significant land-use change such as in the Northern Great Plains (NGP) region of the United States where grasslands are being converted to row crops. We investigated how the quality and quantity of pollen collected by honey bees (Apis mellifera L. [Hymenoptera: Apidae]) changed with land use and across the growing season by sampling bee-collected pollen from apiaries in North Dakota, South Dakota, and Minnesota, USA, throughout the flowering season in 2015–2016. We quantified protein content and quantity of pollen to investigate how they varied temporally and across a land-use gradient of grasslands to row crops. Neither pollen weight nor crude protein content varied linearly across the land-use gradient; however, there were significant interactions between land use and sampling date across the season, particularly in grasslands. Generally, pollen protein peaked mid-July while pollen weight had two maxima in late-June and late-August. Results suggest that while land use itself may not correlate with the quality or quantity of pollen resources collected by honey bees among our study apiaries, the nutritional landscape of the NGP is seasonally dynamic, especially in certain land covers, and may impose seasonal resource limitations for both managed and native bee species. Furthermore, results indicate periods of qualitative and quantitative pollen dearth may not coincide.
Novel missense alteration in LRP4 gene underlies Cenani–Lenz syndactyly syndrome in a consanguineous family

Syndactyly is a clinical feature of split‐hand foot malformation (SHFM), ectodermal‐dysplasia‐syndactyly (EDSS1) and Cenani–Lenz syndactyly syndromes (CLSS). In EDSS1, only cutaneous syndactyly is observed, with sparse hair, abnormal nails and dentition. In SHFM, bony syndactyly may vary from hypoplasia of one phalanx to aplasia of central digits, extending to complete fusion of all fingers and toes in CLSS. Several genes have been assigned to these syndromes. Performing a single step molecular diagnostics becomes a challenge when a phenotype has overlaps with several syndromes or when some of the clinical features are not fully expressed in patients.
Early Warning of Suspected Doping from Biological Passport Based on Multivariate Trends

Abstract The indirect identification of doping in sports can be performed by assessing athletesʼ hematological perturbations from the analysis of blood collected on different occasions. Because prosecution for doping based on this information requires expensive and time-consuming interpretation of blood analysis results by various expert hematologists, mathematical data screening is performed to decide which cases should be forwarded to hematologists. The current Bayesian and univariate screening of data does not process the multivariate trends of blood parameters or take the time interval between samplings into account. This work presents a computational tool that overcomes these limitations by calculating a single score, the hematological perturbation index (HPIx), for which a threshold is defined above which hematologists should be asked to assess the athleteʼs biological passport. The doping detection from this index, normalized for days difference between samplings based on 3, 4 or 5 consecutive samplings, is associated with true positive result rates (TP) not below 98% and false positive result rates (FP) less than 0.9%. Therefore, this tool can be useful as an early warning system of hematological perturbations to decide which athletes should be more closely monitored and which biological passports should be forwarded to hematologists for medical interpretation of data.
Traumatic Stress in the 21st Century

Objective: The introduction to a series of articles on traumatic stress aims to examine the ambivalent relationship between traumatic stress and psychiatry. It provides an outline to the very significant contribution that this field made before the conceptualisation of posttraumatic stress disorder (PTSD) and how the research and theoretical thinking in this field can provide many insights into the relationship between environmental factors and psychological health. It focuses on the relevance of this field to general psychiatry. Result: Posttraumatic stress disorder has emerged as the most common anxiety disorder in women. As well, there are high rates discovered in a range of chronically ill psychiatric patient populations. In particular, strategies for dealing with the issues of childhood abuse and neglect are not often considered by adult psychiatric services for the chronically and severely mentally ill, despite there being important predictors of suicidal behaviour, hospitalisation and prolonged disability. An effective consideration of the available evidence is often complicated by concerns about the impact of financial compensation on the presentation of psychopathology. This is a complex social dialectic whose impact is important to the practise of psychiatry. Equally, this field in itself must avoid becoming excessively rigid in its clinical definitions and the particular interventions which are espoused. Conclusions: The impact of traumatic events on long-term psychological adjustment and physical health have been under estimated. Identification of those at risk is an important issue given that effective treatments are now available. This is an area in which further conceptual thinking is required. It also provides particular opportunities to explore the biological processes of, and interaction between, the environment and the underlying genetic and neurobiological processes which are critical to the modulation of psychopathology.
Electrical properties of graphene/In2O3 bilayer with remarkable uniformity as transparent conducting electrode

A graphene/In2O3 bilayer (termed as GI-bilayer) is proposed as a transparent conducting electrode with remarkably improved areal-uniformity. To fabricate this new structure, an In2O3 layer with a thickness of less than 50 nm was grown by atomic layer deposition and then a graphene layer was grown by chemical vapor deposition and subsequently transferred onto the as-grown In2O3 layer. Electrical and optical properties of the GI-bilayer were systematically studied to verify effects of the underlying In2O3 layer. Hall measurements and following analysis showed a conductance enhancement of the GI-bilayer owing to p-type doping of graphene. Specifically, Raman analysis and ultraviolet photoelectron spectroscopy were performed to prove p-type doping of the graphene in the GI-bilayer. In addition, the GI-bilayer exhibited the significantly improved uniformity of the sheet resistance compared to that of a conventional monolayer of graphene. There was a duality on the role of the In2O3 underlayer in the GI-bilayer. It acted as a dopant layer to the graphene and lowered the sheet resistance from 863 to 510 Ω/sq as well as compensated microscale defects on graphene. More importantly, the In2O3 underlayer resulted in the extremely reduced standard deviation of sheet resistance from 150 to 7.5 Ω/sq over the area of 49 cm2.
The knowledge of, attitudes to, and beliefs concerning cancer of the prostate among a selected group of Jamaican males aged 45 years and over

The annual incidence of prostate cancer has increased dramatically during the last ten years in the United States; the number of cases in the Caribbean, including Jamaica, have also been increasing. Various reasons have been suggested for the increased rates, among them are heightened patient awareness, improved diagnostic tools enabling early detection of prostate cancer, and improved accuracy in reporting new cases. A cross-sectional survey among males, 45 years and over, was conducted among professional, skilled and unskilled workers of the University of Technology and the University of the West Indies, to determine their knowledge, attitudes, and beliefs as they relate to signs and symptoms, risk factors, screening methods, treatment, and susceptibility to prostate cancer. The main findings were that: i)Over 50 percent of the males lacked knowledge in all aspects of signs and symptoms, risk factors, screening methods and treatment of prostate cancer; ii)there was a moderately positive attitude to the principle of early testing to detect for postate cancer, and to the digital rectal examination; iii) there was a trend towards over consumption of foods high in fat; iv)there was a positive family history of cancer which meant that about 25 percent of the respondents were susceptible to postate cancer. The main conclusion was that the respondents were deficient in knowledge about the pertinent aspect of postate cancer e.g. risk factors, but they had a positive attitude to screening for early detection of the disease; there was a small group that was susceptible to prostate cancer because of their family history and the majority of the sample were placing themselves at risk because of their improper dietary practices(AU)
Expression patterns of cofilin and scinderin in breast cancer and their association with clinicopathological features in Iranian patients

Background: Cofilin-1 (CLF1) and scinderin (SCIN) are significant actin-binding proteins that are involved in the regulation of the actin polymerization dynamics. Overexpression of CLF1 and SCIN has been associated with aggressive and tumorigenesis characteristics of various cancer types. The aim of the present study was to investigate the expression of CFL1 and SCIN genes in breast cancer cells and their association with clinicopathological features. Materials and Methods: In this study, 65 breast cancer tissues were randomly selected, and quantitative real-time polymerase chain reaction was performed to measure the expression level of CFL1 and SCIN genes in breast tumors. Then, the association of CFL1 and SCIN expression level with clinicopathological features was assessed using Prism 5 software. Results: Overexpression of CFL1 and SCIN was observed to be statistically significantly associated with tumor stage and lymph node involvement (P < 0.05). However, no association was found between the expression of the mentioned genes and tumor grade, tumor size, and patient age. Conclusion: The results of this study suggest that as CFL1 and SCIN genes may play a role in the development of breast cancer; they have the potential to be examined as new biomarkers to predict the progression of the mentioned disease.
A Brønsted Acid Catalyzed Tandem Pinacol-Type Rearrangement for the Synthesis of α-(3-Indolyl) Ketones by Using α-Hydroxy Aldehydes.

A Brønsted acid catalyzed Pinacol-type rearrangement pathway is reported here to synthesize various substituted α-(3-indolyl) ketones by employing unprotected indoles and α-hydroxy aldehydes as coupling partners. Utilization of economic and readily available Brønsted acid catalyst and use of simple starting precursors exemplifies the economic viability of this method. Under this developed protocol, selective migration of aryl over alkyl or a second aryl group is observed depending upon the migratory aptitude of the substituents. Applicability of this method was further demonstrated by synthesizing highly substituted carbazoles through a simple extension of this method to one-pot cascade annulation strategy.
Physical Activity: Impact on Survival in Gynecologic Cancer.

Importance Physical activity has many important health benefits. There is also growing evidence that physical activity plays a role in the prevention and prognosis of multiple cancers, including gynecologic malignancies. Despite the many benefits of physical activity, the number of individuals meeting physical activity recommendations remains low. Objective To examine the role that physical activity plays in the prevention, treatment, and prognosis of gynecologic malignancies and to review the feasibility of physical activity interventions among gynecologic cancer survivors. Evidence Acquisition A PubMed search was performed using relevant terms to identify journal articles related to the proposed subject. The websites of multiple national and international organizations were also used to obtain up-to-date guidelines and recommendations. Results Physical activity appears to decrease the risk of ovarian, endometrial, and cervical cancer, with the strongest evidence of this association seen in endometrial cancer. Although the literature is scarce, participation in physical activity is feasible during active treatment for gynecologic cancers and may decrease symptom burden and increase chemotherapy completion rates. Gynecologic cancer survivors are motivated to increase physical activity, and lifestyle intervention programs are feasible and well received among this population. Conclusions and Relevance Health care providers caring for women with gynecologic malignancies must counsel patients regarding the importance of physical activity. This should include a discussion of the health benefits and, specifically, the cancer-related benefits. A personalized approach to physical activity intervention is essential.
Bacterial cellulose synthesized with apple pomace enhanced by ionic liquid pretreatment

Abstract Apple pomace was explored as alternative feedstock for producing bacterial cellulose (BC) by Gluconacetobacter xylinus following a cellulase saccharification performed after pretreatment of 1-allyl-3-methylimidazolium chloride ([AMIM]Cl). The dissolving process of apple pomace cellulose was observed by polarized light microscopy (PLM). As FT-IR and XRD results demonstrated, the IL pretreatment proved to be a physical process and no changes in the crystalline structure occurred during the pretreatment. However, the SEM result showed that more fissures and breakages appeared on the surface of pomace microfibers after IL-pretreating, which increased the contact area with cellulase and improved the enzymatic hydrolysis efficiency. An enhancing effect on the BC yield has been observed, 27% higher yield of BC obtained from hydrolysate as compared to sucrose-based medium indicates efficiency of IL-treated apple pomace to serve as high quality feedstock in BC production.
Delivery of pemetrexed by magnetic nanoparticles: design, characterization, in vitro and in vivo assessment

Abstract Drug-loaded magnetic nanoparticles have been developed because of the advantages of specific drug targeting in cancer treatment. Pemetrexed (PEM) is a multi-targeting antifolate agent that is effective for the treatment of many cancers, for example, non-small cell lung cancer. Here, PEM loaded magnetic O-carboxymethyl chitosan (O-CMC) nanoparticles were prepared to deliver PEM on tumor tissue with an external magnetic field. The modification of chitosan to O-CMC was confirmed by FTIR analysis. Nanoparticle synthesis was performed via ionic gelation method. The diameter of magnetic O-CMC nanoparticles (MCMC) was found to be 130.1 ± 22.96 nm. After PEM loading, diameter was found to be 123.9 ± 11.42 nm. The drug release of PEM loaded MCMC (PMCMC) was slower in physiological medium than in acidic medium. A549-luc-C8 and CRL5807 cell lines were used for MTT test which showed that IC50 values of nanoparticles were lower than PEM. The antitumor efficiency of PMCMC in xenograft tumor model was examined with in vivo imaging system (IVIS) and caliper and with hematological analyses. In vivo studies revealed that PMCMC had targeted antitumor activity in A549-luc-C8-tumor-bearing mice compared to PEM. As a result, it was suggested that PMCMC have great potential for the treatment of non-small cell lung cancer.