Miracle-dz/UniFAR-FTUs huggingface dataset:
External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry

Introduction Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators. Methods We evaluated incident patients from the French PAH Registry and applied a four-stratum risk method at baseline and at first reassessment. We applied refined cut-points for three variables: World Health Organization functional class, 6-min walk distance and N-terminal pro-brain natriuretic peptide. We used Kaplan–Meier survival analyses and Cox proportional hazards regression to assess survival according to three-stratum and four-stratum risk approaches. Results At baseline (n=2879), the four-stratum approach identified four distinct risk groups and performed slightly better than a three-stratum method for predicting mortality. Four-stratum model discrimination was significantly higher than the three-stratum method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease and portopulmonary hypertension. Using the four-stratum approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the three-stratum approach. Those who achieved or maintained a low risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high risk. Conclusions The four-stratum risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the three-stratum approach. A four-stratum risk assessment method with low, intermediate-low, intermediate-high and high risk categories was better at discriminating survival in pulmonary arterial hypertension than a three-stratum method with low, intermediate and high risk groups https://bit.ly/3mA6kj7
In-cell structures of conserved supramolecular protein arrays at the mitochondria–cytoskeleton interface in mammalian sperm

Significance Spatial organization of mitochondria is vital for cellular function. In many specialized cell types, mitochondria are immobilized at specific subcellular loci through interactions with the cytoskeleton. One of the most striking mitochondrial configurations occurs in mammalian sperm, where mitochondria wrap around the flagellum. Malformation of the mitochondrial sheath causes infertility, but the molecular structures underlying this intricate arrangement are unknown. Here, we analyzed the mitochondrial sheath in sperm from three mammalian species. We find that although mitochondrial dimensions and cristae architecture vary across species, molecular assemblies mediating intermitochondria and mitochondria–cytoskeleton interactions are conserved. These findings yield important insight into sperm physiology and evolution and are relevant for other polarized cell types, such as muscles, neurons, photoreceptors, and hair cells. Mitochondria–cytoskeleton interactions modulate cellular physiology by regulating mitochondrial transport, positioning, and immobilization. However, there is very little structural information defining mitochondria–cytoskeleton interfaces in any cell type. Here, we use cryofocused ion beam milling-enabled cryoelectron tomography to image mammalian sperm, where mitochondria wrap around the flagellar cytoskeleton. We find that mitochondria are tethered to their neighbors through intermitochondrial linkers and are anchored to the cytoskeleton through ordered arrays on the outer mitochondrial membrane. We use subtomogram averaging to resolve in-cell structures of these arrays from three mammalian species, revealing they are conserved across species despite variations in mitochondrial dimensions and cristae organization. We find that the arrays consist of boat-shaped particles anchored on a network of membrane pores whose arrangement and dimensions are consistent with voltage-dependent anion channels. Proteomics and in-cell cross-linking mass spectrometry suggest that the conserved arrays are composed of glycerol kinase-like proteins. Ordered supramolecular assemblies may serve to stabilize similar contact sites in other cell types in which mitochondria need to be immobilized in specific subcellular environments, such as in muscles and neurons.
The Holmes-Adie Syndrome in the Mona Lisa of Leonardo da Vinci (1452-1519)

The literature describes that the renowned artwork of the genius of human anatomy, Leonardo da Vinci (1452-1519), known as Mona Lisa (1503-1506), is among one of the most enigmatic artworks in the History of Art. In this context, many details inserted on the composition of this artwork, including those related to Mona Lisa physical aspects’ (anatomy) are controversial. The few known descriptions that provide some thorough indications about the woman who served as the model for this work, were written by Giorgio Vasari (1511-1574) in 1550. According to Vasari, the Mona Lisa is a portrait of Lisa del Giocondo (1479-1542) and although he has given a detailed description concerning Lisa’s physical characteristics, some are not fully understood so far. In this context, the unequal size of her pupils stands out, a clinical condition known as anisocoria. On this detail, this Letter presents unprecedented pieces of evidence that the anisocoria represented in Mona Lisa may be an indicator that Lisa del Giocondo had a neurological disorder known as Holmes-Adie Syndrome, which could have been caused by an endocrine disruption of the thyroid hormones. Thus, the pieces of information presented on this Letter are essential for further studies once, through them, it is possible to know more about the physical characteristics and also about the probable health condition of the renowned character of one of the most famous artworks of history. (www.actabiomedica.it).
The Role of Enemy-Mediated Competition in Determining Fitness of a Generalist Herbivore

Abstract. The influence of indirect competition on insect communities is not well understood. We studied how the fitness of a gregarious lepidopteran species, fall webworm, Hyphantria cunea (Drury), is affected by another gregarious caterpillar species, western tent caterpillar, Malacosoma californicum (Packard). Fall webworm and tent caterpillars both feed on chokecherry, Prunus virginiana L. , and create silken structures in which they reside until just prior to pupation. Preliminary observations suggested that predators and parasitoids reside in tent caterpillar tents after tents have been abandoned by the caterpillars, thus increasing the presence of enemies near tents. We hypothesized that when reared near tent caterpillar tents, fall webworms are less fit because of increased predation from nearby enemies (enemy-mediated competition). We tested our hypothesis at two field sites by placing fall webworm larvae in the field with or without a tent caterpillar tent nearby. We compared differences in survival rates, parasitism rates, and fitness between the larvae reared with and without tents nearby. At one field site, webworm larvae near tent caterpillar tents disappeared ∼30% faster than did larvae without tents nearby. Although survival or fitness did not differ significantly between larvae reared with or without tents nearby, distance separating fall webworm larvae from a tent caterpillar tent might be important. Our results suggested that enemy-mediated competition might affect the fitness of fall webworm larvae and should be investigated further.
The toxicology of microcystins and its implication on human health.

Eutrophication is a widely recognized problem of water quality deterioration. Discharge of urban, industrial and agricultural waste has increased the quantum of various chemicals that enter the receiving waters, and alters the physicochemical characteristic. The exploiding human population demanding more and more food, thereby pressing for more use of chemical fertilizers, and the residue of these chemicals reaches into fresh water reservoirs. The increasing nutrients results into prevalence of algal blooms in fresh waters, placing greater pressure on uses of water for both drinking and recreational purposes. Cyanobacterial blooms consisting Microcystis aeroginosa found in several parts of the world causes lethal poisoning to human, livestocks, wildlife and aquatic animals. Microcystin enters in the food chain through zooplankton, fish and aquatic animals. Microcystins toxins are naturally produced poisons stored in the cells of cyanobacterium M. aeroginosa. Human are affected with water related exposure of microcystins with range of symptoms including stomach cramps, vomiting, nausea, diarrhoea, fever, headache, muscle pain, flirtter of the mouth and liver damage. In addition, microcystins causes protein phosphatase inhibition and the cells suffers from oxidative stress. Thus, cyanotoxin phytotoxicity and zootoxicity strongly suggests a need for the surveillance ofcyanoharmful algal bloom and the monitoring of water quality for drinking as well as for other purposes.
Genome sequencing identifies three molecular diagnoses including a mosaic variant in the COL2A1 gene in an individual with Pol III–related leukodystrophy and Feingold syndrome

Undiagnosed genetic disease imposes a significant burden on families and health-care resources, especially in cases with a complex phenotype. Here we present a child with suspected leukodystrophy in the context of additional features, including hearing loss, clinodactyly, rotated thumbs, tapered fingers, and simplified palmar crease. Trio genome sequencing (GS) identified three molecular diagnoses in this individual: compound heterozygous missense variants associated with polymerase III (Pol III)–related leukodystrophy, a 4-Mb de novo copy-number loss including the MYCN gene associated with Feingold syndrome, and a mosaic single-nucleotide variant associated with COL2A1-related disorders. These variants fully account for the individual's features, but also illustrate the potential for superimposed and unclear contributions of multiple diagnoses to an individual's overall presentation. This report demonstrates the advantage of GS in detection of multiple variant types, including low-level mosaic variants, and emphasizes the need for comprehensive genetic analysis and detailed clinical phenotyping to provide individuals and their families with the maximum benefit for clinical care and genetic counseling.
A prognostic fibroblast-related risk signature in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the world. The accessibility of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data allows the prognostic evaluation of CRC. Fibroblasts play a key role in the development and progression of tumors while fibroblast-related risk signature in CRC patients has rarely been mentioned. In this study, TCGA data was classified into high-fibroblast and low-fibroblast groups according to the median of fibroblast content. Among 3845 differentially expressed genes between two groups, 14 prognostic genes commonly expressed in GSE39582 and TCGA were identified by LASSO-COX analysis. Then we established a fibroblast-related risk signature in TCGA training group and validated in the GSE39582 testing group. The risk score was significantly associated with the overall survival (OS), and the poor prognosis of patients in high-risk group might relate to the immune cell infiltration in the tumor microenvironment, epithelial-mesenchymal transition, and extracellular matrix related processes. Overall, we proved that the fibroblast-related signature could predict the prognosis of patients which might shed light on the treatment of CRC.
Första chefsrollen och personlig utveckling

En sammanfattning av uppsatsen pa maximalt 8000 tecken. Syftet med foreliggande arbete ar att fa kannedom om personlig utveckling hos relativt nyblivna chefer och darigenom fa fordjupad forstaelse av forsta chefsrollens innebord och processen av chefsblivande.Teorier som belyser personliga processer i ledar- och chefskap, vilket innebar teorier om emotionell intelligens och hur ledare skapas, ligger till grund for uppsatsens undersokningsomrade. En kvalitativ forskningsansats med narrativ teori och metod samt intervju for insamling av data, har tillampats. Sju teman framkom under bearbetningen av det empiriska materialet och askadliggor gemensamma upplevelser av forsta chefskapet: chefsrollen – ensamhet och satt att hantera den – arbetsbelastning: granssattning, prioritering och delegering – personlighet, sjalvmedvetenhet och utveckling – mellanmanskligt samspel – lar- och insiktsprocesser – fa stod. Dartill har vi under rubriken ”Ovrigt” valt att belysa ytterligare nagra teman for att fanga skillnader i upplevelser. For samtliga har chefsrollen inneburit okad sjalvinsikt och satt igang en utvecklingsprocess hos dem sjalva kopplat till personlighet och behoven i arbetet, aven om sattet att uttrycka sig om och kanslorna infor detta varierar. Det verkar som att chefskap innebar insikter och larande pa ett personligt plan. Det framkommer att forsta chefsrollen innebar flera element som chefer maste forhalla sig till. For det forsta handlar det om att hantera ett flertal uppgifter: att engagera, att stodja, att coacha, att fatta beslut, att kommunicera och att ge feedback. For det andra handlar det om att positionen som chef i manga fall medfor kanslor av ensamhet och ett byte av referensgrupp. For det tredje handlar det om en hog arbetsbelastning som manga ganger inverkar pa privatlivet. Uppgifterna kan vara obestamda, osynliga och ovantade och samtliga talar om vikten av granssattning, prioritering och delegering. For det fjarde utgor det mellanmanskliga samspelet en vasentlig grund som nya chefer maste forhalla sig till i sin roll, vilket innebar konflikter, konflikthantering, kanslor pa arbetet och att reglera dessa genom reflektion och inre dialog. Vad galler processen av chefsblivande verkar lar- och insiktsprocesser ske genom erfarenhet i form av reflektion, traning, misstag och feedback fran andra. Vidare verkar det for lar- och insiktsprocesser vara betydelsefullt att fa stod pa informella och formella plan i chefsrollen och i utvecklingsprocessen, men samtidigt ha en viss frihet och ett handlingsutrymme att agera inom.
Boosting the mechanical strength and solubility-enhancement properties of hydroxypropyl-β-cyclodextrin nanofibrous films

Abstract 2-hydroxypropyl-β-cyclodextrin (HPβCD) nanofiber films have high surface-to-volume ratio and show high dissolution rate of hydrophobic drugs. However, the solubility-enhancement effect of HPβCD films may not be enough to include an effective dose in a sublingually administrable film. Moreover, unmodified HPβCD films are very brittle and difficultly transported and/or handled. So, the addition of polyethylene glycol (PEG) as a plasticizer was suggested to improve their ultimate tensile strength (UTS) and solubilization of hydrophobic drugs. Accordingly, six nanofiber films were developed and characterized, using three molecular weights of PEG (400, 1500 and 6000 Da) with two concentrations each (1:100 and 2:100 PEG:HPβCD), in addition to the unmodified HPβCD nanofibrous film. The results revealed that adding 1:100 of PEG 400 increases the UTS (∼2-fold) and the average fiber diameter (AFD) (∼3-fold). Moreover, the addition of PEG 400 significantly increased the solubility of two hydrophobic model drugs; coumarin (up to 7.7-fold of the original solubility) and 2-nitroimidazole (up to 1.6-fold of the original solubility). However, with higher PEG concentration/molecular weight, both AFD and UTS of the films decreased. On the other hand, it was noted that the solubility of the two model drugs decreased upon using 1500-Da PEG, and then increased with 6000-Da PEG.
Peripherally Inserted Central Venous Catheters (PICC) versus totally implantable venous access device (PORT) for chemotherapy administration: a meta-analysis on gynecological cancer patients

Background and aim: Ninety-four thousand gynecological cancer diagnoses are performed each year in the United States. The majority of these tumors require systemic adjuvant therapy. Sustained venous access was overcome by indwelling long-term central venous catheter (CVC). The best choice of which CVC to use is often arbitrary or dependent on physician confidence. This meta-analysis aims to compare PORT and peripherally inserted central catheter (PICC) outcomes during adjuvant treatment for gynecological cancer. Methods: Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses statement (PRISMA)were used to conduct the meta-analysis. Results: 1320 patients were included, 794 belonging to the PORT group and 526 to the PICC group. Total complication rates were fewer in the PORT group, p = 0.05. CVC malfunction was less frequent in the PORT group than in the PICC group, p <0.01. Finally, thrombotic events were less expressed in the PORT group than in the PICC group, p = 0.02. No difference was found in operative complication, migration, malposition, extravasation, infection, and complication requiring catheter removal. Conclusions: PORT had fewer thrombotic complications and fewer malfunction problems than PICC devices. Unless specific contraindications, PORTs can be preferred for systemic treatment in gynecological cancer patients. (www.actabiomedica.it)
Design and testing of a deformable wind turbine blade control surface

Wind tunnel tests were conducted on a 1.3 m chord NACA 63–418 blade section fitted with an adaptive trailing edge flap. The 20% chord flap had an aramid honeycomb core covered with a silicone skin and was actuated using servo motors. The honeycomb core had a high stiffness in the thickness direction but was compliant in chordwise bending. These anisotropic properties offer a potential solution for the conflicting design requirements found in morphing trailing edge structures. Static and dynamic tests were performed up to a Reynolds number of 5.4 × 106. The tests showed that deflecting the flap from − 10° to + 10° changes the blade section lift coefficient by 1.0 in non-stalled conditions. Dynamic tests showed the flap to be capable of operating up to 9° s−1 using a 15 V power supply. A two-dimensional static aeroelastic model of the morphing flap was developed to analyse strains, predict actuator requirements and study fluid–structure interaction effects. The model was used to conduct parametric studies to further improve the flap design. Potential applications include wind turbine blade load alleviation and increased wind energy capture.
Scalar PWM algorithms for four-switch three-phase inverters

Four-switch three-phase inverters (FSTPIs) have been proposed to be used in low-cost applications because of the reduced number of semiconductor devices, and space vector pulse width modulation (SVPWM) techniques have also been introduced to control FSTPIs. However, high-performance controllers are needed to implement complicated SVPWM algorithms, which limits their low-cost applications. To simplify algorithms and reduce the cost of implementation, an equivalent scalar method for SVPWM of FSTPIs is proposed. SVPWM for FSTPIs is actually a sine PWM by modulating two sine waves of 60° phase difference with a triangle wave, so such a special sine PWM can be used to control FSTPIs. The simulation and experimental results demonstrate the validity of the proposed method.
Tunneling nanotube formation promotes survival against 5‐fluorouracil in MCF‐7 breast cancer cells

Tunneling nanotubes (TNTs) are F‐actin‐based open‐ended tubular extensions that form following stresses, such as nutritional deprivation and oxidative stress. The chemotherapy agent 5‐fluorouracil (5‐FU) represents a significant stressor to cancer cells and induces thymidine deficiency, a state similar to nutritional deprivation. However, the ability of 5‐FU to induce TNT formation in cancer cells and potentially enhance survival has not been explored. In this study, we examined whether 5‐FU can induce TNT formation in MCF‐7 breast cancer cells. Cytotoxic doses of 5‐FU (150–350 μm) were observed to significantly induce TNT formation beginning at 24 h after exposure. TNTs formed following 5‐FU treatment probably originated as extensions of gap junctions as MCF‐7 cells detach from cell clusters. TNTs act as conduits for exchange of cellular components and we observed mitochondrial exchange through TNTs following 5‐FU treatment. 5‐FU‐induced TNT formation was inhibited by over 80% following treatment with the F‐actin‐depolymerizing agent, cytochalasin B (cytoB). The inhibition of TNTs by cytoB corresponded with increased 5‐FU‐induced cytotoxicity by 30–62% starting at 48 h, suggesting TNT formation aides in MCF‐7 cell survival against 5‐FU. Two other widely used chemotherapy agents, docetaxel and doxorubicin induced TNT formation at much lower levels than 5‐FU. Our work suggests that the therapeutic targeting of TNTs may increase 5‐FU chemotherapy efficacy and decrease drug resistance in cancer cells, and these findings merits further investigation.
Progress in Water, Sanitation and Hygiene (WASH) coverage and potential contribution to the decline in diarrhea and stunting in Ethiopia.

Inadequate safe water supply and poor sanitation and hygiene continue to be important risk factors for diarrhoea and stunting globally. We used data from the four rounds of the Ethiopian Demographic and Health Survey and applied the new World Health Organization (WHO)/UNICEF Joint Monitoring Program (JMP) service standards to assess progress in water, sanitation and hygiene (WASH) coverage between 2000 and 2016. We also performed an age-disaggregated pooled linear probability regression analysis followed by a decomposition analysis to determine whether changes in WASH practices have contributed to the changing prevalence of diarrhoea and stunting in children under 5 years of age. We observed a significant increase in the coverage of safe drinking water and adequate sanitation facilities over the period. At the national level, the use of a basic water source increased from 18% in 2000 to 50% in 2016. Open defecation declined from 82% to 32% over the same period. However, in 2016, only 6% of households had access to a basic sanitation facility, and 40% of households had no handwashing facilities. The reduction in surface water use between 2000 and 2016 explained 6% of the decline in diarrhoea observed among children aged 0-5 months. In children aged 6-59 months, between 7% and 9% of the reduction in stunting were attributable to the reduction in open defecation over this period. Despite progress, improvements are still needed to increase basic WASH coverage in Ethiopia. Our findings showed that improvements in water and sanitation only modestly explained reductions in diarrhoea and stunting.