Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Chickpea (Cicer arietinum L.) Flour Films: Effects of pH and Plasticizer Concentration

The use of flours as a material for biopolymer-based film preparation has gained interest due to the fact that they are a natural mixture of compatible macromolecules and due to their low cost. Chickpea flour shows a promising composition for the development of edible films. The aim of this study was to characterize and evaluate the properties of chickpea flour films as affected by pH (7 or 10) and plasticizer concentration (1% or 3% w/v) of film-forming solutions. Water vapor permeability, solubility, color, opacity, mechanical properties, thermal stability, structural changes by Fourier transform infrared analysis, and microstructure of the films were determined. Glycerol content and pH influenced chickpea flour film properties, microstructure and structural organization; interactions were also observed. The 1% glycerol films showed lower water vapor permeability, thickness, radical scavenging capacity, elongation at break and puncture deformation, and higher dry matter content, swelling, opacity, elastic modulus, and tensile and puncture strengths than 3% glycerol films. Film-forming solutions at pH 10 produced films with higher thickness and swelling, and were greener than those from solutions at neutral pH. The changes were more intense in 1% glycerol films. Glycerol concentration and pH could be combined in order to obtain chickpea flour films with different properties according to different food packaging requirements.
METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes

ABSTRACT N6-methyladenosine (m6A) mRNA modifications play critical roles in various biological processes. However, no study addresses the role of m6A in macroautophagy/autophagy. Here, we show that m6A modifications are increased in H/R-treated cardiomyocytes and ischemia/reperfusion (I/R)-treated mice heart. We found that METTL3 (methyltransferase like 3) is the primary factor involved in aberrant m6A modification. Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes. However, overexpression of METTL3 or inhibition of the RNA demethylase ALKBH5 has an opposite effect, suggesting that METTL3 is a negative regulator of autophagy. Mechanistically, METTL3 methylates TFEB, a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3ʹ-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. Further experiments show that autophagic flux enhanced by METTL3 deficiency is TFEB dependent. In turn, TFEB regulates the expression levels of METTL3 and ALKBH5 in opposite directions: it induces ALKBH5 and inhibits METTL3. TFEB binds to the ALKBH5 promoter and activates its transcription. In contrast, inhibition of METTL3 by TFEB does not involve transcriptional repression but rather downregulation of mRNA stability, thereby establishing a negative feedback loop. Together, our work uncovers a critical link between METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease. Abbreviations: ACTB, actin beta; ALKBH5, alkB homolog 5, RNA demethylase; ANXA5, annexin A5; ATG, autophagy-related; BafA, bafilomycin A1; CASP3, caspase 3; ELAVL1, ELAV like RNA binding protein 1; FTO, FTO, alpha-ketoglutarate dependent dioxygenase; GFP, green fluorescent protein; GST, glutathione S-transferase; HNRNPD, heterogeneous nuclear ribonucleoprotein D; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LAD, left anterior descending; m6A, N6-methyladenosine; MEFs, mouse embryo fibroblasts; Mer, mutated estrogen receptor domains; METTL3, methyltransferase like 3; METTL14, methyltransferase like 14; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin kinase complex 1; NMVCs, neonatal mouse ventricular cardiomyocytes; PCNA, proliferating cell nuclear antigen; PE, phosphatidylethanolamine; PI, propidium iodide; PTMs, post-translational modifications; PVDF, polyvinylidenedifluoride; RIP, RNA-immunoprecipitation; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TUBA: tublin alpha; WTAP, WT1 associated protein; YTHDF, YTH N6-methyladenosine RNA binding protein
Development and Validation of Markers for the Fertility Restorer Gene Rf1 in Sunflower

Hybrid breeding in sunflowers based on CMS PET1 requires development of restorer lines carrying, in most cases, the restorer gene Rf1. Markers for marker-assisted selection have been developed, but there is still need for closer, more versatile, and co-dominant markers linked to Rf1. Homology searches against the reference sunflower genome using sequences of cloned markers, as well as Bacterial Artificial Chromosome (BAC)-end sequences of clones hybridizing to them, allowed the identification of two genomic regions of 30 and 3.9 Mb, respectively, as possible physical locations of the restorer gene Rf1 on linkage group 13. Nine potential candidate genes, encoding six pentatricopeptide repeat proteins, one tetratricopeptide-like helical domain, a probable aldehyde dehydrogenase 22A1, and a probable poly(A) polymerase 3 (PAPS3), were identified in these two genomic regions. Amplicon targeted next generation sequencing of these nine candidate genes for Rf1 was performed in an association panel consisting of 27 maintainer and 32 restorer lines and revealed the presence of 210 Single Nucleotide Polymorphisms (SNPs) and 67 Insertions/Deletions (INDELs). Association studies showed significant associations of 10 SNPs with fertility restoration (p-value < 10−4), narrowing Rf1 down to three candidate genes. Three new markers, one co-dominant marker 67N04_P and two dominant markers, PPR621.5R for restorer, and PPR621.5M for maintainer lines were developed and verified in the association panel of 59 sunflower lines. The versatility of the three newly developed markers, as well as of three existing markers for the restorer gene Rf1 (HRG01 and HRG02, Cleaved Amplified Polymorphic Sequence (CAPS)-marker H13), was analyzed in a large association panel consisting of 557 accessions.
Uniform Widespread Nuclear Phosphorylation of Histone H2AX Is an Indicator of Lethal DNA Replication Stress

Phosphorylated histone H2AX (γ-H2AX), a central player in the DNA damage response (DDR), serves as a biomarker of DNA double-strand break repair. Although DNA damage is generally visualized by the formation of γ-H2AX foci in injured nuclei, it is unclear whether the widespread uniform nuclear γ-H2AX (called pan-nuclear) pattern occurring upon intense replication stress (RS) is linked to DDR. Using a novel monoclonal antibody that binds exclusively to the phosphorylated C-terminus of H2AX, we demonstrate that H2AX phosphorylation is systematically pan-nuclear in cancer cells stressed with RS-inducing drugs just before they die. The pan-nuclear γ-H2AX pattern is abolished by inhibition of the DNA-PK kinase. Cell death induction of cancer cells treated with increasing combinations of replication and kinase (ATR and Chk1) inhibitory drugs was proportional to the appearance of pan-nuclear γ-H2AX pattern. Delivery of labeled anti-γ-H2AX Fabs in stressed cells demonstrated at a single cell level that pan-nuclear γ-H2AX formation precedes irreversible cell death. Moreover, we show that H2AX is not required for RS-induced cell death in HeLa cells. Thus, the nuclear-wide formation of γ-H2AX is an incident of RS-induced cell death and, thus, the pan nuclear H2AX pattern should be regarded as an indicator of lethal RS-inducing drug efficacy.
A paradise for parasites? Seven new haemogregarine species infecting lizards from the Canary Islands

Abstract Oceanic islands are hotspots of biodiversity due to their high levels of endemism, with the Canary Islands being a notable example. A previous molecular study on the biogeography and host associations of haemogregarines (Apicomplexa: Adeleorina) infecting lizards from this archipelago detected seven parasite haplogroups. These haplogroups exhibited high host-specificity and geographical structure, suggesting that they might correspond to distinct biological identities. In this study, along with sequencing a longer fragment of the 18S rRNA, we further explore the distinctiveness of these parasites by analysing their morphology, effects on host erythrocytes and parasitaemia levels. These lines of evidence together with their genetics, host associations, frequency of occurrence and geographical distribution support them as different biological entities. As such, we describe seven new species: Karyolysus canariensis sp. nov., Karyolysus galloti sp. nov., Karyolysus stehlini sp. nov., Karyolysus gomerensis sp. nov., Karyolysus atlanticus sp. nov., Karyolysus tinerfensis sp. nov. and Karyolysus makariogeckonis sp. nov. These new taxa are further examples of endemic diversity in the Canarian archipelago. They also contribute to clarify the taxonomy within the Apicomplexa, a phylum estimated to have one of the lowest percentages of described species.
Endogenous Neurostimulation and Physiotherapy in Cluster Headache: A Clinical Case

Objective: The aim of this paper is to describe the progressive changes of chronic cluster headaches (CHs) in a patient who is being treated by a multimodal approach, using pharmacology, neurostimulation and physiotherapy. Subject: A male patient, 42 years of age was diagnosed with left-sided refractory chronic CH by a neurologist in November 2009. In June 2014, the patient underwent a surgical intervention in which a bilateral occipital nerve neurostimulator was implanted as a treatment for headache. Methods: Case report. Results: Primary findings included a decreased frequency of CH which lasted up to 2 months and sometimes even without pain. Besides this, there were decreased levels of anxiety, helplessness (PCS subscale) and a decreased impact of headache (HIT-6 scale). Bilateral pressure pain thresholds (PPTs) were improved along with an increase in strength and motor control of the neck muscles. These improvements were present at the conclusion of the treatment and maintained up to 4 months after the treatment. Conclusions: A multimodal approach, including pharmacology, neurostimulation and physiotherapy may be beneficial for patients with chronic CHs. Further studies such as case series and clinical trials are needed to confirm these results.
HIV-related tuberculosis: mortality risk in persons without vs. with culture-confirmed disease.

BACKGROUND Tuberculosis (TB) diagnosis in human immunodeficiency virus (HIV) positive persons is difficult, particularly in resource-limited settings. The relationship between TB culture status and mortality in HIV-positive persons treated for TB is unclear. METHODS We evaluated HIV-positive adults treated for TB at or after their first HIV clinic visit in Argentina, Brazil, Chile, Honduras, Mexico or Peru from 2000 to 2015. Anti-tuberculosis treatment included 2 months of isoniazid, rifampicin (RMP)/rifabutin (RBT), pyrazinamide ± ethambutol, followed by continuation phase treatment with isoniazid + RMP/RBT. RESULTS Of 759 TB-HIV patients, 238 (31%) were culture-negative, 228 (30%) had unknown culture status or did not undergo culture and 293 (39%) were culture-positive. The median CD4 at TB diagnosis was 96 (interquartile range 40-228); 636 (84%) received concurrent antiretroviral therapy (ART) and anti-tuberculosis treatment. There were 123 (16%) deaths: 90/466 (19%) with TB culture-negative, unknown or not performed vs. 33/293 (11%) who were TB culture-positive (P = 0.005). In Kaplan-Meier analysis, mortality in TB patients without culture-confirmed disease was higher (P = 0.002). In a Cox model adjusted for age, sex, CD4, ART timing, disease site and stratified by study site, mortality in persons without culture-confirmed TB was not significantly increased compared to those with culture-positive TB (hazard ratio 1.39, 95%CI 0.89-2.16, P = 0.15). CONCLUSION Most HIV-positive patients treated for TB did not have culture-confirmed TB, and mortality tended to be higher in patients without culture-confirmed disease, although the association was not statistically different after adjusting for other variables. Accurate TB diagnosis in HIV-positive persons is crucial.
Pathogenesis of and major animal models used for nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) and its pathologically more severe form, nonalcoholic steatohepatitis (NASH), have become prevalent worldwide and carry an increased risk of developing hepatocellular carcinoma and other metabolic diseases. Diverse animal models have been proposed to replicate particular characteristics of NAFLD and NASH and have provided significant clues to the critical molecular targets of NASH treatment. In this review, we summarize the histopathology, pathogenesis, and molecular basis of NAFLD progression and discuss the benchmark animal models of NAFLD/NASH.
Anthracycline Cardiotoxicity.

The discovery of anthracyclines in the 1960s was a major breakthrough in oncology. And although the field of cancer therapeutics has undergone dramatic changes over subsequent decades, anthracyclines remain the cornerstone of contemporary chemotherapeutic regimens for a variety of cancers. Although very effective, the use of anthracyclines has been limited by significant dose-dependent cardiotoxicity. In the contemporary cohort of 2625 anthracycline-treated patients, who were followed for a median time of 5.2 years after chemotherapy, the incidence of cardiotoxicity was 9% (cardiotoxicity was defined as reduction in left ventricular [LV] ejection fraction >10% from baseline and <50%). 1 Although anthracycline-induced cardiotoxicity was initially thought to be irreversible,2 there is increasing evidence of myocardial recovery after anthracycline-induced damage. In the study of 201 patients with anthracycline-induced cardiomyopathy (LV ejection fraction <45%), treatment with enalapril and carvedilol within 2 months after the completion of chemotherapy was associated with normalization of the LV ejection fraction in 64% of the patients.3 In contrast, LV ejection fraction did not normalize in any of the patients who started treatment later than 6 months after the completion of chemotherapy.3 Understanding the biological mechanisms underlying anthracycline-induced cardiac toxicity is critical to developing successful strategies for prevention, early detection, and treatment. Previously, anthracycline-induced cardiotoxicity was primarily attributed to iron-dependent generation of reactive oxygen species and subsequent oxidative damage.4 More recent data indicate that anthracycline-induced generation of reactive oxygen species is dependent on topoisomerase-2β. 5 Doxorubicin-bound topoisomerase-2β suppresses transcription of antioxidative and electron transport genes, leading to marked increase in reactive oxygen species and defective mitochondrial biogenesis. Mice with a cardiac-specific deletion of Top2b are protected against doxorubicin-related cardiomyopathy.5 Many recent clinical studies indicated that LV mass reduction is seen early in the course of anthracycline-induced cardiotoxicity. In a study by Jordan et al,6 76 patients receiving chemotherapy were evaluated by a cardiac magnetic resonance imaging (CMR) before and 6 months after receiving chemotherapy. Patients who received anthracyclines demonstrated a 5% reduction in LV mass, which was not seen among patients receiving other types of chemotherapy. In another CMR-based study of 91 patients with anthracycline-induced cardiomyopathy decrease in LV mass index correlated with the cumulative dose of anthracycline.7 Moreover, LV mass index was a strong predictor of major adverse cardiac events, composed of death, heart failure admissions, and appropriate defibrillator therapy.7 This reduction in LV mass may be caused by apoptosis as well as myocyte atrophy. In a CMR-based imaging study of EDITORIAL
Vehicle yielding probability estimation model at unsignalized midblock crosswalks in Shanghai, China

The vehicle-pedestrian encounter at midblock crosswalks in urban centers is inevitable but the challenge to urban transportation planners is in achieving a balance between traffic flow efficiency and pedestrian safety. Vehicles are expected to yield to pedestrians who have a right of way at the midblock unsignalized crosswalks but, failure to yield causes conflicts that at times are fatal. This study investigated the effect of macroscopic factors on the vehicle yielding. Six environmental factors are considered: temporal gap size, number of traffic lanes, number of waiting pedestrians, position of pedestrian (whether on street kerb or median), traffic flow direction and presence (or absence) of monitoring ePolice. Video Data on six observed variables that influenced vehicle yielding was collected from 13 uncontrolled crosswalk locations in Shanghai city in the Peoples Republic of China. A Logit model with a 95.9% accuracy was developed to describe the vehicle yielding behavior. The results showed that gap size and number of traffic lanes had the highest influence on driver yielding decision and that drivers were more likely to yield if ePolice was present. The sensitivity analysis was conducted and appropriate recommendations on improving the pedestrians crossing safety were proposed accordingly.
The Plant Circadian Oscillator

It has been nearly 300 years since the first scientific demonstration of a self-sustaining circadian clock in plants. It has become clear that plants are richly rhythmic, and many aspects of plant biology, including photosynthetic light harvesting and carbon assimilation, resistance to abiotic stresses, pathogens, and pests, photoperiodic flower induction, petal movement, and floral fragrance emission, exhibit circadian rhythmicity in one or more plant species. Much experimental effort, primarily, but not exclusively in Arabidopsis thaliana, has been expended to characterize and understand the plant circadian oscillator, which has been revealed to be a highly complex network of interlocked transcriptional feedback loops. In addition, the plant circadian oscillator has employed a panoply of post-transcriptional regulatory mechanisms, including alternative splicing, adjustable rates of translation, and regulated protein activity and stability. This review focuses on our present understanding of the regulatory network that comprises the plant circadian oscillator. The complexity of this oscillatory network facilitates the maintenance of robust rhythmicity in response to environmental extremes and permits nuanced control of multiple clock outputs. Consistent with this view, the clock is emerging as a target of domestication and presents multiple targets for targeted breeding to improve crop performance.
Micromanagement of Developmental and Stress-Induced Senescence: The Emerging Role of MicroRNAs

MicroRNAs are short (19–24-nucleotide-long), non-coding RNA molecules. They downregulate gene expression by triggering the cleavage or translational inhibition of complementary mRNAs. Senescence is a stage of development following growth completion and is dependent on the expression of specific genes. MicroRNAs control the gene expression responsible for plant competence to answer senescence signals. Therefore, they coordinate the juvenile-to-adult phase transition of the whole plant, the growth and senescence phase of each leaf, age-related cellular structure changes during vessel formation, and remobilization of resources occurring during senescence. MicroRNAs are also engaged in the ripening and postharvest senescence of agronomically important fruits. Moreover, the hormonal regulation of senescence requires microRNA contribution. Environmental cues, such as darkness or drought, induce senescence-like processes in which microRNAs also play regulatory roles. In this review, we discuss recent findings concerning the role of microRNAs in the senescence of various plant species.
Current Advances in Palliative & Hospice Care: Problems and Needs of Relatives and Family Caregivers During Palliative and Hospice Care—An Overview of Current Literature

Palliative and hospice care aims to improve quality of life of patients’ relatives, but still little is known about their specific problems and needs. We present a comprehensive literature update. Narrative review to present an expert overview of peer-reviewed, English-written original research publications and reviews on psychosocial and existential problems, supportive needs as well as interventions for relatives during the patients’ disease trajectory published between January 2017 and November 2018. A total of 64 publications were included. Relatives report high rates of psychological and existential distress, burden and psychological morbidity during the total disease trajectory of the patient. In addition, relatives report an alarmingly high number of unmet needs with information being the central issue. Relatives’ problems and needs are part of complex systems influenced by various socio-demographic factors and patient–relatives-interactions and dependency between different psychological phenomena. First support interventions for relatives during disease trajectory have proven feasible and secondary data from randomized studies suggest beneficial effects of providing early palliative care also for relatives. Relatives should be addressed to a still larger extent in the daily practice of palliative and hospice care, thus further research to reveal more detailed systematic information is needed to improve relatives’ psychological burden and quality of life.
Time trends in US cannabis use and cannabis use disorders overall and by sociodemographic subgroups: a narrative review and new findings

ABSTRACT Background: Due to significant comorbidity and impairment associated with cannabis use and cannabis use disorder, understanding time trends in cannabis use and cannabis use disorder is an important public health priority. Objectives: To identify trends in cannabis use and cannabis use disorder overall, and by sociodemographic subgroup. Methods: Narrative review of published findings on trends in cannabis use and cannabis use disorders in data from repeated cross-sectional US general population surveys. In addition, in National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2002–2002) and NESARC-III (2012–2013) data, logistic regression was used to examine whether trends differed between subgroups of adults. Results: The review showed that in adults, cannabis use increased over the past decade overall and within sociodemographic subgroups (gender, age, race/ethnicity, income, education, marital status, urbanicity, region, pregnancy status, disability status), with greater increases in men and disabled adults. Most sources also indicated significant increases in cannabis use disorders. New analysis showed significantly greater increases in adult cannabis use and cannabis use disorder in men (p ≤ .0001); young adults (p < .05); Blacks (vs. Whites, p < .01); low income groups (p < .001); never-married p ≤ . 0001), and urban residents (p < .05). In adolescents, cannabis use generally decreased, although recent increases were observed in older and non-White adolescents. Conclusion: Cannabis use and cannabis use disorder are increasing in adults, with specific sociodemographic groups at higher risk, and may be increasing in some adolescent subgroups. Studies should determine mechanisms for differential trends to provide information to policymakers and enable informed decisions on cannabis legalization and service planning.