Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Multistage Linear Genomic Selection Indices To Predict the Net Genetic Merit in Plant Breeding

A combined multistage linear genomic selection index (CMLGSI) is a linear combination of phenotypic and genomic estimated breeding values useful for predicting the individual net genetic merit, which in turn is a linear combination of the true unobservable breeding values of the traits weighted by their respective economic values. The CMLGSI is a cost-saving strategy for improving multiple traits because the breeder does not need to measure all traits at each stage. The optimum (OCMLGSI) and decorrelated (DCMLGSI) indices are the main CMLGSIs. Whereas the OCMLGSI takes into consideration the index correlation values among stages, the DCMLGSI imposes the restriction that the index correlation values among stages be zero. Using real and simulated datasets, we compared the efficiency of both indices in a two-stage context. The criteria we applied to compare the efficiency of both indices were that the total selection response of each index must be lower than or equal to the single-stage combined linear genomic selection index (CLGSI) response and that the correlation of each index with the net genetic merit should be maximum. Using four different total proportions for the real dataset, the estimated total OCMLGSI and DCMLGSI responses explained 97.5% and 90%, respectively, of the estimated single-stage CLGSI selection response. In addition, at stage two, the estimated correlations of the OCMLGSI and the DCMLGSI with the net genetic merit were 0.84 and 0.63, respectively. We found similar results for the simulated datasets. Thus, we recommend using the OCMLGSI when performing multistage selection.
Influence of variation in the volumetric moisture content of the substrate on irrigation efficiency in early potato varieties

Potato is a plant with high water requirements. This factor affects not only the weight of potato tubers but also their quality parameters. In order to achieve quantity and quality goal, it is helpful if we apply the principles of precision agriculture, which also contributes to sustainable management of environmental resources. Accurate identification of the water requirements of crops is the basis for determining optimal irrigation doses and dates. After their application, it is possible to assess the effectiveness of irrigation treatments and their impact on the air-water conditions in soil with a root system. The aim of the presented study was to analyse the influence of volumetric soil moisture diversity on the vegetation of early potato varieties. Two potato varieties were subject to investigation: Denar and Julinka. Pot experiments were carried out at the Department of Horticulture of Wroclaw University of Environmental and Life Sciences. Three variants were analysed: one with a low water content in the soil (pF 2.7), one with the optimal water content (pF 2.5) and one with a high water content (pF 2.2). The basis for the selection of the frequency and application rate of water doses was soil moisture measured with an SM150-Kit set. Volumetric moisture was measured with a TDR apparatus. It was found that the water requirements of both potato varieties differ and increase along with the development of the aboveground and underground parts. Moreover, it was shown that the irrigation requirements of cv. Julinka are higher than those of Denar (31.4–33.0% higher), depending on the adopted variant. The research also showed that the most effective method of potato cultivation is to maintain soil moisture at a lower level. This should be taken into account in regions where the cultivation of this species uses supplementation of the water requirements by irrigation.
Epidemiology and Prognosis of Intensive Care Unit–Acquired Bloodstream Infection

Abstract. Intensive care unit–acquired bloodstream infections (ICU-BSI) are frequent and are associated with high morbidity and mortality rates. We conducted this study to describe the epidemiology and the prognosis of ICU-BSI in our ICU and to search for factors associated with mortality at 28 days. For this, we retrospectively studied ICU-BSI in the ICU of the Cayenne General Hospital, from January 2013 to June 2019. Intensive care unit–acquired bloodstream infections were diagnosed in 9.5% of admissions (10.3 ICU-BSI/1,000 days). The median delay to the first ICU-BSI was 9 days. The ICU-BSI was primitive in 44% of cases and secondary to ventilator-acquired pneumonia in 25% of cases. The main isolated microorganisms were Enterobacteriaceae in 67.7% of patients. They were extended-spectrum beta-lactamase (ESBL) producers in 27.6% of cases. Initial antibiotic therapy was appropriate in 65.1% of cases. Factors independently associated with ESBL-producing Enterobacteriaceae (ESBL-PE) as the causative microorganism of ICU-BSI were ESBL-PE carriage before ICU-BSI (odds ratio [OR]: 7.273; 95% CI: 2.876–18.392; P < 0.000) and prior exposure to fluoroquinolones (OR: 4.327; 95% CI: 1.120–16.728; P = 0.034). The sensitivity of ESBL-PE carriage to predict ESBL-PE as the causative microorganism of ICU-BSI was 64.9% and specificity was 81.2%. Mortality at 28 days was 20.6% in the general population. Factors independently associated with mortality at day 28 from the occurrence of ICU-BSI were traumatic category of admission (OR: 0.346; 95% CI: 0.134–0.894; P = 0.028) and septic shock on the day of ICU-BSI (OR: 3.317; 95% CI: 1.561–7.050; P = 0.002). Mortality rate was independent of the causative organism.
Etudes structurale et fonctionnelle de protéines impliquées dans la virulence chez S. pneumoniae et P. aeruginosa

Cette these est composee de deux parties : Le premiere partie rend compte de l'etude structurale de la proteine RrgA. RrgA est associee au pilus du pathogene Streptococcus pneumoniae et participe aux premieres etapes de colonisation chez l'hote en se liant a plusieurs composes de la Matrice Extra Cellulaire. Nous avons resolu la structure de cette proteine a 1.9 A par cristallographie aux rayons-X. RrgA possede une structure allongee formee de quatre domaines alignes d'origine eucaryote et procaryote. En effet, trois domaines ayant des similarites structurales avec les IgG et le domaine Cna-B semblent servir de piedestal pour orienter et presenter le domaine fonctionnel de type Integrine. Nous avons confirme la formation de deux ponts isopeptidiques stabilisateurs par spectrometrie de masse. De plus, le domaine integrine possede deux insertions particulieres dont la presence pourrait etre impliquee dans la reconnaissance des divers substrats par RrgA. La deuxieme partie de cette these est axee sur l'etude structurale du complexe ATPase et de ExsB, la pilotine presumee du systeme de secretion de type III chez Pseudomonas aeruginosa, bacterie opportuniste et jouant un role majeur dans l'infection des patients atteints de mucoviscidose. Pour la premiere fois, nous avons mis au point un protocole d'expression et de purification sous forme soluble de l'ATPase PscN en complexe avec une proteine partenaire, PscL. Des cristaux de ce complexe ont ete obtenus au robot du PSB. Par ailleurs, nous avons confirme l'expression de la lipoproteine ExsB chez P. aeruginosa que nous avons localisee au sein de la membrane externe. De plus, nous avons resolu la structure de cette proteine qui presente un nouveau repliement et qui etablie les bases structurales pour l'etude des pilotines pour tous les systemes de secretion de type III de la famille Ysc.
Identification of UAP1L1 as tumor promotor in gastric cancer through regulation of CDK6

Gastric cancer (GC) is one of the most commonly diagnosed malignancies in digestive tract and its underlying molecular mechanism is still not clear, so we aimed to reveal the relationship between GC and UDP-GlcNAc pyrophosphorylase-1 like 1 (UAP1L1). The detection of UAP1L1 expression in GC tumor and normal tissues was accomplished by immunohistochemistry and demonstrated the upregulation of UAP1L1 in GC, which was statistically associated with tumor grade. GC cell models constructed via transfection of UAP1L1-silencing/overexpressing lentiviruses were employed for evaluating the effects of UAP1L1 knockdown/overexpression on GC in vitro and in vivo. The results indicated that UAP1L1 played important role in development of GC through regulating cell proliferation, colony formation, cell apoptosis and cell migration. Subsequently, CDK6 was identified as a potential target in UAP1L1 induced regulation of GC, downregulation of which exhibited similar inhibition effects on GC with UAP1L1. Moreover, it was demonstrated that the promotion of GC by UAP1L1 overexpression could be significantly attenuated or even reversed by simultaneously silencing CDK6. In conclusion, UAP1L1 was reported to be a tumor promotor in the development and progression of GC which may exert its role through regulating CDK6 and may act as a candidate of therapeutic target in treatment.
Leptin: Less Is More

The successful use of leptin for the treatment of individuals with lipodystrophy and leptin deficiency is well established. However, pharmacological approaches of leptin therapy for the treatment of diet-induced obesity have been ineffective. There is ample room for a better understanding of the much famed “leptin resistance” phenomenon. Our recent data in this area prompt us to call for a conceptual shift. This shift entails a model in which a reduction of bioactive leptin levels in the context of obesity triggers a high degree of leptin sensitization and improved leptin action, both centrally and peripherally. Put another way, hyperleptinemia per se causes leptin resistance and associated metabolic disorders. In this perspective, we briefly discuss the underlying conceptual steps that led us to explore partial leptin reduction as a viable therapeutic avenue. We hope this discussion will contribute to potential future applications of partial leptin reduction therapy for the treatment of obesity and type 2 diabetes.
Emerging pharmacotherapies for elderly acute myeloid leukemia patients

ABSTRACT Introduction Acute myeloid leukemia (AML) is a disease mainly seen in the elderly, for which treatment is undergoing rapid changes. Although recent studies have supported the survival benefit of induction chemotherapy in fit patients and that of hypomethylating agents (HMAs) in non-induction candidates, treatment of this patient age population remains a significant challenge for the treating oncologist. Areas covered In this review, we will examine effectiveness and safety outcomes of upcoming novel treatment strategies in elderly (≥60 years old) patients with AML, highlight the current literature and ongoing trials able to maximize therapeutic options in this heterogeneous patient population. Expert opinion Current developments including new chemotherapeutic strategies and combinations of HMAs with novel drugs targeting epigenetic or immunomodulatory pathways are underway to improve patient survival and quality of life.
Microbial community overlap between the phyllosphere and rhizosphere of three plants from Yongxing Island, South China Sea

Phyllosphere and rhizosphere are unique and wide‐ranging habitats that harbor various microbial communities, which influence plant growth and health, and the productivity of the ecosystems. In this study, we characterized the shared microbiome of the phyllosphere and rhizosphere among three plants (Ipomoea pes‐caprae, Wedelia chinensis, and Cocos nucifera), to obtain an insight into the relationships between bacteria (including diazotrophic bacteria) and fungi, present on these host plants. Quantitative PCR showed that the abundances of the microbiome in the soil samples were significantly higher than those in the phyllosphere samples, though there was an extremely low abundance of fungi in bulk soil. High‐throughput sequencing showed that the alpha‐diversity of bacteria and fungi was higher in the rhizosphere than the phyllosphere samples associated with the same plant, while there was no obvious shift in the alpha‐diversity of diazotrophic communities between all the tested phyllosphere and soil samples. Results of the microbial composition showed that sample‐specific bacteria and fungi were found among the phyllosphere and rhizosphere of the different host plants. About 10%–27% of bacteria, including diazotrophs, and fungi overlapped between the phyllosphere and the rhizosphere of these host plants. No significant difference in microbial community structure was found among the tested rhizosphere samples, and soil properties had a higher influence on the soil microbial community structures than the host plant species.
The indirect paths to cascading effects of extinctions in mutualistic networks.

Biodiversity loss is a hallmark of our times, but predicting its consequences is challenging. Ecological interactions form complex networks with multiple direct and indirect paths through which the impacts of an extinction may propagate. Here we show that accounting for these multiple paths connecting species is necessary to predict how extinctions affect the integrity of ecological networks. Using an approach initially developed for the study of information flow, we estimate indirect effects in plant-pollinator networks and find that even those species with several direct interactions may have much of their influence over others through long indirect paths. Next, we perform extinction simulations in those networks and show that while traditional connectivity metrics fail in the prediction of coextinction patterns, accounting for indirect interaction paths allows predicting species' vulnerability to the cascading effects of an extinction event. Embracing the structural complexity of ecological systems contributes towards a more predictive ecology, which is of paramount importance amid the current biodiversity crisis.
Landscape mapping of shared antigenic epitopes and their cognate TCRs of tumor-infiltrating T lymphocytes in melanoma

HLA-restricted T cell responses can induce antitumor effects in cancer patients. Previous human T cell research has largely focused on the few HLA alleles prevalent in a subset of ethnic groups. Here, using a panel of newly developed peptide-exchangeable peptide/HLA multimers and artificial antigen-presenting cells for 25 different class I alleles and greater than 800 peptides, we systematically and comprehensively mapped shared antigenic epitopes recognized by tumor-infiltrating T lymphocytes (TILs) from eight melanoma patients for all their class I alleles. We were able to determine the specificity, on average, of 12.2% of the TILs recognizing a mean of 3.1 shared antigen-derived epitopes across HLA-A, B, and C. Furthermore, we isolated a number of cognate T cell receptor genes with tumor reactivity. Our novel strategy allows for a more complete examination of the immune response and development of novel cancer immunotherapy not limited by HLA allele prevalence or tumor mutation burden.
Evaluation of Surgical and Audiological Outcomes of Push-Through Myringoplasty and Underlay Cartilage Tympanoplasty in Repairing Anterior Tympanic Membrane Perforations.

INTRODUCTION Endoscopic push-through myringoplasty (PTM) that could be performed by the endoscopic transcanal approach is a minimally invasive procedure in repairing anterior quadrant perforations of the tympanic membrane. Push-through myringoplasty does not require any skin incision rather than graft harvesting and also does not require tympanomeatal flap elevation. OBJECTIVE The purpose of the current study was to compare the surgical and audiological outcomes of PTM and conventional retroauricular underlay cartilage tympanoplasty (UCT) in the treatment of patients with anterior tympanic membrane (TM) perforation. METHODS This clinical trial was conducted on total of 71 subjects with anterior TM perforation who underwent PTM (n = 32) and UCT (n = 39). Graft uptake rates, audiological outcomes, duration of surgery (DoS), and complications were analyzed and compared between groups. RESULTS Graft uptake rates of the PTM and UCT group were 90.6% and 89.7%, respectively (P = 0.512). According to pure tone audiometry measurements at postoperative month 6, the air-bone gap (ABG) values remarkably improved in both PTM and UCT groups without any significant difference (P = 0.654). The average DoS was shorter in the PTM (29.7 ± 5.7 minutes) group relative to the UCT (48.7 ± 11.3 minutes) group, and the difference was extremely significant (P < 0.0001). CONCLUSIONS Push-through myringoplasty yielding shorter DoS and fewer postoperative complication and morbidity may serve as an efficient alternative to conventional microscopic UCT in treatment of anterior TM perforations, with comparable graft uptake rates and audiological outcomes.
A multi‐institutional comparison of mitoxantrone, etoposide, and cytarabine vs high‐dose cytarabine and mitoxantrone therapy for patients with relapsed or refractory acute myeloid leukemia

Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC) and mitoxantrone and high‐dose Ara‐C (Ara‐C couplets). We analyzed 155 patients treated at three academic institutions between 1998 and 2017; 87 patients received MEC and 68 received Ara‐C couplets. The primary endpoint was overall response (OR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and nonhematologic toxicities, and success in proceeding to alloSCT. Baseline characteristics of the cohorts were well matched, though patients receiving Ara‐C couplets had more co‐morbidities (48.5% vs 33%; P = .07). OR was achieved in 43.7% of MEC and 54.4% of Ara‐C couplets patients (P = .10). Ara‐C couplets patients also trended towards a longer OS and PFS, more frequently proceeded to alloSCT (31% vs 54.4%; P = .003), and experienced less febrile neutropenia (94% vs 72%; P < .001) and grade 3/4 gastrointestinal toxicities (17.2% vs 2.94%; P = .005). No significant differences in other toxicities or median duration of hospitalization were noted. This is the first multi‐institutional study directly comparing these regimens in a racially diverse population of R/R AML patients. Although these regimens have equivalent efficacy in terms of achieving OR, Ara‐C couplets use is associated with significant reductions in toxicities, suggesting it should be used more frequently in these patients.
Systemic Hypertension: An Over View Of Various Cardiovascular Risk Factors And Multiple Treatments

Systemic hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double-blind, randomized, placebo-controlled trials have found that antihypertensive drug therapy reduces cardiovascular events in patients aged younger than 80 years and in patients aged 80 years and older in the Hypertension in the Very Elderly Trial. Although the optimal blood pressure treatment goal has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic blood pressure goal should be <140/90 mm Hg in patients younger than 80 years and a systolic blood pressure of 140-145 mm Hg if tolerated in patients aged 80 years and older. Nonpharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in patients with hypertension. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers, and diuretics have all reduced cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost.
Weak interactions in higher-order chromatin organization

Abstract The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are involved in their establishment and maintenance have been characterized. Generally, protein–protein and protein–DNA interactions underlie the spatial genome organization in eukaryotes. However, it is becoming increasingly evident that weak interactions, which exist in biological systems, also contribute to the 3D genome. Here, we provide a snapshot of our current understanding of the role of the weak interactions in the establishment and maintenance of the 3D genome organization. We discuss how weak biological forces, such as entropic forces operating in crowded solutions, electrostatic interactions of the biomolecules, liquid-liquid phase separation, DNA supercoiling, and RNA environment participate in chromosome segregation into structural and functional units and drive intranuclear functional compartmentalization.