Miracle-dz/UniFAR-FTUs huggingface dataset:
Redefining Plant-Necrotroph Interactions: The Thin Line Between Hemibiotrophs and Necrotrophs

Fungal pathogens are a heterogeneous group of organisms which differ in many important traits such as mode of nutrition, type of reproduction, and dispersal mechanisms. Traditional classification of fungal pathogens has relied on their mode of nutrition to classify them into three broad categories viz. biotrophs, necrotrophs, and hemibiotrophs. Biotrophs derive nutrients and energy from living cells, while necrotrophs derive their energy from dead or dying cells. Hemibiotrophs initially invade live cells prior to transitioning to a necrotrophic lifestyle to obtain nutrients from killing the host cells. Necrotrophic pathogens have traditionally been perceived as “unsophisticated brutes” that employ a “Kill and feed” approach with the use of a battery of secreted toxins and cell-wall degrading enzymes (CWDEs). However, the perception of necrotrophic pathogens has undergone rapid changes in the last two decades. The experimental evidences that has changed the definition of a typical necrotrophic lifestyle are discussed below. Further, I propose that older definitions and classification of necrotrophs should be revisited in light of these evidences.
Roles of Anxiety and Depression in Predicting Cardiovascular Disease Among Patients With Type 2 Diabetes Mellitus: A Machine Learning Approach

Cardiovascular disease (CVD) is a major complication of type 2 diabetes mellitus (T2DM). In addition to traditional risk factors, psychological determinants play an important role in CVD risk. This study applied Deep Neural Network (DNN) to develop a CVD risk prediction model and explored the bio-psycho-social contributors to the CVD risk among patients with T2DM. From 2017 to 2020, 834 patients with T2DM were recruited from the Department of Endocrinology, Affiliated Hospital of Harbin Medical University, China. In this cross-sectional study, the patients' bio-psycho-social information was collected through clinical examinations and questionnaires. The dataset was randomly split into a 75% train set and a 25% test set. DNN was implemented at the best performance on the train set and applied on the test set. The receiver operating characteristic curve (ROC) analysis was used to evaluate the model performance. Of participants, 272 (32.6%) were diagnosed with CVD. The developed ensemble model for CVD risk achieved an area under curve score of 0.91, accuracy of 87.50%, sensitivity of 88.06%, and specificity of 87.23%. Among patients with T2DM, the top five predictors in the CVD risk model were body mass index, anxiety, depression, total cholesterol, and systolic blood pressure. In summary, machine learning models can provide an automated identification mechanism for patients at CVD risk. Integrated treatment measures should be taken in health management, including clinical care, mental health improvement, and health behavior promotion.
Post-ischemic Myocardial Inflammatory Response: A Complex and Dynamic Process Susceptible to Immunomodulatory Therapies

Following acute occlusion of a coronary artery causing myocardial ischemia and implementing first-line treatment involving rapid reperfusion, a dynamic and balanced inflammatory response is initiated to repair and remove damaged cells. Paradoxically, restoration of myocardial blood flow exacerbates cell damage as a result of myocardial ischemia–reperfusion (MI-R) injury, which eventually provokes accelerated apoptosis. In the end, the infarct size still corresponds to the subsequent risk of developing heart failure. Therefore, true understanding of the mechanisms regarding MI-R injury, and its contribution to cell damage and cell death, are of the utmost importance in the search for successful therapeutic interventions to finally prevent the onset of heart failure. This review focuses on the role of innate immunity, chemokines, cytokines, and inflammatory cells in all three overlapping phases following experimental, mainly murine, MI-R injury known as the inflammatory, reparative, and maturation phase. It provides a complete state-of-the-art overview including most current research of all post-ischemic processes and phases and additionally summarizes the use of immunomodulatory therapies translated into clinical practice.
Non-medical Use of Prescription Gabapentinoids (Gabapentin and Pregabalin) in Five European Countries

Background: Non-medical use (NMU) of prescription GABA analogs (pregabalin and gabapentin) has been reported especially in opiate dependent persons. However, by now the prevalence of NMU of gabapentinoids in the general population has not been sufficiently evaluated. The aim of this research paper is to determine the prevalence of prescription GABA analog NMU and associated demographics in five European countries with special detail of Spain. Methods: The RADARS Survey of Non-Medical Use of Prescription Drugs Program (NMURx) is a harmonized series of contemporaneous cross-sectional surveys of adults conducted in multiple countries. NMURx collects data from the general population in each participating country about NMU of prescription drugs, illicit drugs, and associated demographics. NMU was defined as “using a medication without a doctor's prescription or for any reason other than what was recommended by their doctor. ” Responses from Spain (4Q2017, n=10,062) were analyzed in detail. Comparative data were available from France, Germany, Italy, and UK. Responses were collected using non-probability quota sampling and post-stratification population weighting was applied to reflect the national distributions of adults, based on age, gender, and census region. Rates of NMU and associated demographics were reported as rate of past 90-day NMU per 100,000 adult population with 95% confidence intervals. Results: Germany (1,197 per 100,000 adult population [95% CI: 1,004.3–1,379.1]) and United Kingdom (1,067 per 100,000 adult population [95% CI: 851.3–1,283.2]) presented the highest prevalence of gabapentinoids NMU. In Spain the prevalence of past 90 days GABA analog NMU was: 344.4, 95% (CI 204.8–484.0), with male predominance. Those who non-medically use GABA analogs had a higher prevalence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse treatment. In Spain, 20% of respondents who ever have used gabapentinoids, reported a lifetime NMU; the prevalence was higher for pregabalin 624 (6.2%) than for gabapentin 444 (4.4%). The main reasons for use were to self-treat pain and other medical conditions. Conclusions: The risk of NMU of gabapentinoids should not be neglected. Subjects with a history of chronic pain and lifetime substance use disorders had an increased risk of NMU of gabapentinoids.
Prediction of the Minimum Film Boiling Temperature of Quenching Vertical Rods in Water Using Random Forest Machine Learning Algorithm

A great amount of research is focused, nowadays, on experimental, theoretical, and numerical analysis of transient pool boiling. Knowing the minimum film boiling temperature (Tmin) for rods with different substrate materials that are quenched in distilled water pools at various system pressures is known to be a complex and highly non-linear process. This work aims to develop a new correlation to predict the Tmin in the above process: Random forest machine learning technique is applied to predict the Tmin. The approach trains a machine learning algorithm using a set of experimental data collected from the literature. Several parameters such as liquid subcooling temperature (Tsub), fluid to the substrate material thermophysical properties (βf/βw), and system saturated pressure (Psat) are collected and used as inputs, whereas Tmin is measured and used as the output. Computational results show that the algorithm achieves superior results compared to other correlations reported in the literature.
Radiation-Induced Soft Tissue Injuries in Patients With Advanced Mandibular Osteoradionecrosis: A Preliminary Evaluation and Management of Various Soft Tissue Problems Around Radiation-Induced Osteonecrosis Lesions

Objectives Radiation-induced soft-tissue injuries (STIs) in mandibular osteoradionecrosis (ORN) are not well studied regarding their correlations with nearby bone lesions. The aim of this study is to investigate the severity of radiation-induced STIs in advanced mandibular ORN and its relationship with hard-tissue damage and postoperative outcomes. Methods A retrospective study was performed in our institution from January 2017 to December 2019. Aside from demographic factors, the associations between the triad ORN variables (irradiation doses, ORN stages, ORN sizes) and radiation-related STI factors, vascular characteristics, and postoperative functional recovery were assessed. In addition, the severity of STI was also compared with treatment outcomes. Such correlations were established via both univariate and multivariable analyses. Results A total number of 47 patients were included. The median follow-up reached 27 months. Nasopharyngeal cancer was the histology type among most patients (n = 21, 44.7%). The median irradiation doses reached 62 Gy (range, 40–110 Gy). For STI, the symptom scoring equaled an average of 5.4 (range from 1 to 12), indicative of the severity of STI problems. During preoperative MRI examinations, signs of hypertrophy or edema (n = 41, 87.2%) were frequently discerned. Most patients (n = 23, 48.9%) also had extensive muscular fibrosis and infection, which required further debridement and scar release. Surprisingly, most STI factors, except cervical fibrosis (p = 0.02), were not in parallel with the ORN levels. Even the intraoperative soft-tissue defect changes could not be extrapolated by the extent of ORN damage (p = 0.096). Regarding the outcomes, a low recurrence rate (n = 3, 6.9%) was reported. In terms of soft tissue-related factors, we found a strong correlation (p = 0.004) between symptom scores and recurrence. In addition, when taking trismus into consideration, both improvements in mouth-opening distance (p < 0.001) and facial contour changes (p = 0.004) were adversely affected. Correlations were also observed between the intraoperative soft-tissue defect changes and complications (p = 0.024), indicative of the importance of STI evaluation and management. Conclusions The coexistence of hard- and soft-tissue damage in radiation-induced advanced mandibular ORN patients reminds surgeons of the significance in assessing both aspects. It is necessary to take the same active measures to evaluate and repair both severe STIs and ORN bone lesions.
Vascular Access Perspectives in Patients After Kidney Transplantation

Introduction: More attention has been paid to the influence of arteriovenous fistula (AVF) on the cardiovascular system. In renal transplant recipients, some beneficial effect of an elective vascular access (VA) ligation was observed in patients with a high AVF flow. However, this strategy is not widely accepted and is in contradiction to the rule of vasculature preservation for possible future access. The aim of our study is to elucidate the vascular access function and VA perspective in the kidney transplantation (KTx) population. Materials and Methods: KTx patients with a stable graft function were recruited to participate in this single center observational study (NCT04478968). The measurement of VA flow and vessel mapping for future vascular access was performed by a color Doppler ultrasound. The study group included 99 (63%) males and 58 (37%) females; the median age was 57 (IQR 48–64) years. The median time from the transplantation to the baseline visit was 94 (IQR 61–149) months. Median serum creatinine concentration was 1.36 (IQR 1.13–1.67) mg/dl. Results: Functioning VA was found in 83 out of 157 (52.9%) patients. The sites were as follows: snuffbox in six (7.2%), wrist in 41 (49.4%), distal forearm in 18 (21.7%), middle or proximal forearm in eight (9.6%), upper-arm AV graft in one (1.2%), and upper-arm AVFs in nine (10.8%) patients, respectively. Blood flow ranged from 248 to 7,830 ml/min; the median was 1,134 ml/min. From the transplantation to the study visit, 66 (44.6%) patients experienced access loss. Spontaneous thrombosis was the most common, and it occurred in 60 (90.9%) patients. The surgical closure of VA was performed only in six (4%) patients of the study group with a functioning VA at the time of transplantation. Access loss occurred within the 1st year after KTx in 33 (50%) patients. Majority (50 out of 83, 60.2%) of the patients with an active VA had options to create a snuffbox or wrist AVF on the contralateral extremity. In a group of 74 patients without a functioning VA, the creation of a snuffbox or wrist AVF on the non-dominant and dominant extremity was possible in seven (9.2%) and 40 (52.6%) patients, respectively. In 10 (13.1%) patients, the possibilities were limited only to the upper-arm or proximal forearm VA on both sides. Access ligation was considered by 15 out of 83 (18.1%) patients with a patent VA. Conclusions: In the majority of the patients, vascular access blood flow was below the threshold of the negative cardiovascular effect of vascular access. Creation of a distal AVF is a protective measure to avoid a high flow and preserve the vessels for future access. The approach to VA should be individualized and adjusted to the patient's profile.
Role of PARP1 in oligodendrocyte differentiation during developmental myelination and remyelination after myelin damage

The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remain enigmatic. Here we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a novel PARylated target which we show controls OPC differentiation through PARylation-modulated de-repression of myelin protein expression. Furthermore, PARP1’s enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.
rDNA nascent transcripts promote a unique spatial organization during mouse early development

During the first cell cycles of the early development, the chromatin of the embryo is highly reprogrammed alongside that embryonic genome starts its own transcription. The spatial organization of the genome is a major process that contributes to regulating gene transcription in time and space, however, it is poorly studied in the context of early embryos. To study the cause and effect link between transcription and spatial organization in embryos, we focused on the ribosomal genes, that are first silent and begin to transcribe during the 2-cell stage in mouse. We demonstrated that ribosomal sequences are spatially organized in a very peculiar manner from the 2-cell to the 16-cell stage with transcription and processing of ribosomal RNAs excluding mutually. Using drugs inhibiting the RNA polymerase I, we show that this organization, totally different from somatic cells, depends on an active transcription of ribosomal genes and induces a unique chromatin environment that favors major satellite sequences transcription after the 4-cell stage.
Microbial genomic trait evolution is dominated by frequent and rare pulsed evolution

On the macroevolutionary timescale, does trait evolution proceed gradually or by rapid bursts (pulses) separated by prolonged periods of stasis or slow evolution? Although studies have shown pulsed evolution is prevalent in animals, our knowledge about the tempo and mode of evolution across the tree of life is very limited. This long-standing debate calls for a test in bacteria and archaea, the most ancient and diverse forms of life with unique population genetic properties (asexual reproduction, large population sizes, short generation times, high dispersal rates and extensive lateral gene transfers). Using a likelihood-based framework, we analyzed evolutionary patterns of four microbial genomic traits (genome size, genome GC%, 16S rRNA GC% and the nitrogen use in proteins) on a broad macroevolutionary timescale. Our model fitting of phylogenetic comparative data shows that pulsed evolution is not only present, but also prevalent and predominant in microbial genomic trait evolution. Interestingly, for the first time, we detected two distinct types of pulsed evolution (small frequent and large rare jumps) that are predicted by the punctuated equilibrium and quantum evolution theories. Our findings suggest that major bacterial lineages could have originated in quick bursts and pulsed evolution is a common theme across the tree of life despite the drastically different population genetic properties of bacteria, archaea and eukaryotes.
Perceptual Asymmetries and Auditory Processing of Estonian Quantities

Similar to visual perception, auditory perception also has a clearly described “pop-out” effect, where an element with some extra feature is easier to detect among elements without an extra feature. This phenomenon is better known as auditory perceptual asymmetry. We investigated such asymmetry between shorter or longer duration, and level or falling of pitch of linguistic stimuli that carry a meaning in one language (Estonian), but not in another (Russian). For the mismatch negativity (MMN) experiment, we created four different types of stimuli by modifying the duration of the first vowel [ɑ] (170, 290 ms) and pitch contour (level vs. falling pitch) of the stimuli words (‘SATA,’ ‘SAKI’). The stimuli were synthesized from Estonian words (‘SATA,’ ‘SAKI’) and follow the Estonian language three-way quantity system, which incorporates tonal features (falling pitch contour) together with temporal patterns. This made the meaning of the word dependent on the combination of both features and allows us to compare the relative contribution of duration and pitch contour in discrimination of language stimuli in the brain via MMN generation. The participants of the experiment were 12 Russian native speakers with little or no experience in Estonian and living in Estonia short-term, and 12 Estonian native speakers (age 18–27 years). We found that participants’ perception of the linguistic stimuli differed not only according to the physical features but also according to their native language, confirming that the meaning of the word interferes with the early automatic processing of phonological features. The GAMM and ANOVA analysis of the reversed design results showed that the deviant with longer duration among shorter standards elicited a MMN response with greater amplitude than the short deviant among long standards, while changes in pitch contour (falling vs. level pitch) produced neither strong MMN nor asymmetry. Thus, we demonstrate the effect of language background on asymmetric perception of linguistic stimuli that aligns with those of previous studies (Jaramillo et al., 2000), and contributes to the growing body of knowledge supporting auditory perceptual asymmetry.
FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

Background As an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM. Methods In this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders. Results The serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall (P < 0.001), with similar results observed between the corresponding BMI subgroups (P < 0.05). The 2nd (OR 1.224, 95% CI 0.603–2.485), 3rd (OR 2.478, 1.229–5.000), and 4th (OR 3.419, 95% CI 1.626–7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments. Conclusions The serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.
Redundant neural circuits regulate olfactory masking

Olfactory masking is a complex olfactory response found in humans. However, the mechanisms whereby the presence of one odorant masks the sensory and behavioral responses elicited by another odorant are poorly understood. Here, we report that Caenorhabditis elegans displays olfactory masking and that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly masks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde that signals food. Using a forward genetic screen, we found that several genes, osm-5, osm-1, and dyf-7, known to regulate the structure and function of sensory neurons played a critical role in olfactory masking. Loss of these genes mildly reduces the response to 2-nonanone and disrupts the masking effect of 2-nonanone. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue olfactory masking. AWB is activated by the removal of 2-nonanone stimulation or the onset of IAA; however, the mixture of 2-nonanone and IAA stimulates AWB similarly as 2-nonanone alone, masking the cellular effect of IAA. The latency of the AWB response is critical for the masking effect. Thus, our results identify redundant neural circuits that regulate the robust masking effect of a repulsive odorant and uncover the neuronal and cellular basis for this complex olfactory task. AUTHOR SUMMARY In their natural environment, animals, including humans, encounter complex olfactory stimuli. However, regardless how complex the stimuli are, the behavioral output can only be one. Thus, how the brain processes multiple sensory cues to generate a coherent behavioral output is critical for the survival of the animal. In the present study, we combined molecular cellular genetics, optical physiology and behavioral analysis to study olfactory masking, a common olfactory phenomenon in which the presence of one odorant masks the stimulation of another odorant. Our results show that olfactory masking is regulated by redundant neuronal circuits, a mechanism that likely ensures the robust behavioral response to the sensory cue representing information critical for the survival.