Miracle-dz/UniFAR-FTUs huggingface dataset:
Insertion Depth for Optimized Positioning of Precurved Cochlear Implant Electrodes

Supplemental Digital Content is available in the text Hypothesis: Generic guidelines for insertion depth of precurved electrodes are suboptimal for many individuals. Background: Insertion depths that are too shallow result in decreased cochlear coverage, and ones that are too deep lift electrodes away from the modiolus and degrade the electro-neural interface. Guidelines for insertion depth are generically applied to all individuals using insertion depth markers on the array that can be referenced against anatomical landmarks. Methods: To normalize our measurements, we determined the optimal position and insertion vector where a precurved array best fits the cochlea for each patient in an IRB-approved, N = 131 subject CT database. The distances from the most basal electrode on an optimally placed array to anatomical landmarks, including the round window (RW) and facial recess (FR), was measured for all patients. Results: The standard deviations of the distance from the most basal electrode to the FR and RW are 0.65 mm and 0.26 mm, respectively. Owing to the high variability in FR distance, using the FR as a landmark to determine insertion depth results in >0.5 mm difference with ideal depth in 44% of cases. Alignment of either of the two most proximal RW markers with the RW would result in over-insertion failures for >80% of cases, whereas the use of the third, most medial marker would result in under-insertion in only 19% of cases. Conclusions: Normalized measurements using the optimized insertion vector show low variance in distance from the basal electrode position to the RW, thereby suggesting it as a better landmark for determining insertion depth than the FR.
The associations of the BDNF and APOE polymorphisms, hippocampal subfield volumes, and episodic memory performance across the lifespan

In this study, we explored the associations between the brain derived neurotrophic factor (BDNF) and the apolipoprotein E (APOE) polymorphisms and hippocampal subfields in 127 healthy participants (18–85 years). MRI datasets were collected on a 4.7 T system. Participants were administered the Wechsler Memory Scale to evaluate episodic memory function. Significant associations of both polymorphisms were present only in older adults (≥50 years). BDNF polymorphism was associated with larger dentate gyrus volumes within the anterior hippocampus (head) in Met‐carriers compared to Val/Val homozygotes. We found that in Met‐carriers total hippocampal volume predicted performance on visuospatial memory tasks. APOE polymorphism was associated with larger total hippocampal volume, especially in cornu ammonis 1–3 and subiculum in APOE ɛ2 carriers compared to both ɛ4 and ɛ3 carriers, while APOE ɛ3 and ɛ4 carriers did not differ from each other. APOE polymorphism was associated with better performance on visuospatial memory tasks in APOE ε2 carriers in comparison to ε4 carriers.
Limb salvage procedure in immunocompromised patients with therapy‐resistant leg ulcers—The value of ultra‐radical debridement and instillation negative‐pressure wound therapy

The purpose of this study was to analyse the outcome of our established triple treatment strategy in therapy‐resistant deep‐thickness chronic lower leg ulcers. This limb salvage approach consists of ultra‐radical surgical debridement, negative‐pressure wound therapy (NPWT) with or without instillation, and split‐thickness skin grafting. Between March 2003 and December 2019, a total of 16 patients and 24 severe cases of lower leg ulcers were eligible for inclusion in this highly selective population. A total of seven patients received immunosuppressive medication. Complete wound closure was achieved in 25% and almost 90% of included lower leg ulcer cases after 3 and 24 months of our triple treatment strategy, respectively. The overall limb salvage rate was 100%. Bacterial colonisation of these wounds was significantly reduced after multiple surgical debridements and NPWT. Fasciotomy and radical removal of devitalised tissue such as deep fascia, tendons, and muscles combined with NPWT showed promising results in terms of the overall graft take rate. This treatment strategy was considered as last resort for limb salvage in such a critically ill and immunocompromised patient population. Surgeons should be aware of its efficacy and consider the triple treatment strategy especially if no other limb salvage option remains.
The role of stretch, tachycardia and sodium‐calcium exchanger in induction of early cardiac remodelling

Stretch and tachycardia are common triggers for cardiac remodelling in various conditions, but a comparative characterization of their role in the excitation‐transcription coupling (ETC) and early regulation of gene expression and structural changes is lacking. Here, we show that stretch and tachycardia directly induced hypertrophy of neonatal rat cardiac myocytes and also of non‐myocytes. Both triggers induced similar patterns of hypertrophy but had largely distinct gene expression profiles. ACTA1 served as good hypertrophy marker upon stretch, while RCAN1 was found increased in response to tachycardia in a rate‐dependent fashion. Mechanistically, several calcium‐handling proteins, including the sodium‐calcium exchanger (NCX), contributed to ETC. Phosphorylation of the calcium/calmodulin‐dependent protein kinase II (CaMKII) was elevated and occurred downstream of NCX activation upon tachycardia, but not stretch. Microarray profiling revealed that stretch and tachycardia regulated around 33% and 20% genes in a NCX‐dependent manner, respectively. In conclusion, our data show that hypertrophy induction by stretch and tachycardia is associated with different gene expression profiles with a significant contribution of the NCX.
Morphological diversities and eco-geographical structuring of Ethiopian camel (Camelus dromedarius) populations

The objectives of this study were to identify and characterize indigenous camel ecotypes and to assess phenotypic diversity and relationship of camel populations in Ethiopia. A total of 494 heads of camels were investigated for phenotypic characterization. The study involved Jijiga, Liben, Gelleb, Hoor and Shinille from Somali as well as Amibara and Mille camel populations from Afar national regional states, which are the major camel rearing areas. The results showed that average barrel and heart girths of Liben camel population were significantly (p
Mating in the absence of fertilization promotes a growth-reproduction versus lifespan trade-off in female mice

Significance Pregnancy and lactation are energetically costly and can have negative effects for later-life reproduction and lifespan. To become pregnant females must mate, and these mating interactions with males could also have long-term effects on female life history. Evidence supporting this prediction has been lacking until now. Here we show that allowing female mice to mate early in life, with only sterilized males, permanently affects female life history and aging. Mated females gain and maintain body weight across life, have a greater late-life reproductive output, but suffer a shorter lifespan. These responses explain some trade-offs previously attributed to pregnancy and lactation and highlight that exposure to sexual stimuli alone can have a major effect on female life history in mammals. Trade-offs between growth, reproduction, and lifespan constrain animal life histories, leading to evolutionary diversification of life history cycles in different environments. In female mammals, gestation and lactation are expected to impose the major costs of reproduction, driving reproductive trade-offs, although mating also requires interactions with males that could themselves influence life history. Here we show that a male’s presence by itself leads to lifelong alterations in life history in female mice. Housing C57BL/6J female mice with sterilized males early in life led to an increase in body weight, an effect that persisted across life even when females were later allowed to produce pups. We found that those females previously housed with sterile males also showed enhanced late-life offspring production when allowed to reproduce, indicating that earlier mating can influence subsequent fecundity. This effect was the opposite to that seen in females previously housed with intact males, which showed the expected trade-off between early-life and late-life reproduction. However, housing with a sterile male early in life came at a cost to lifespan, which was observed in the absence of females ever undergoing fertilization. Endocrinologically, mating also permanently reduced the concentration of circulating prolactin, a pituitary hormone influencing maternal care. Changes in hormone axes that influence reproduction could therefore help alter life history allocation in response to opposite-sex stimuli. Our results demonstrate that mating itself can increase growth and subsequent fecundity in mammals, and that responses to sexual stimuli could account for some lifespan trade-offs normally attributed to pregnancy and lactation.
Identification of bilobetin metabolites, in vivo and in vitro, based on an efficient ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry strategy.

Bilobetin, a natural compound extracted from Ginkgo biloba, has various pharmacological activities such as anti-oxidation, anti-cancer, anti-bacterial, anti-fungal, anti-inflammatory, anti-viral, and promoting osteoblast differentiation. However, few studies have been conducted and there are no reports on its metabolites owing to its low content in nature. In addition, it has been reported to have potential liver and kidney toxicity. Therefore, this study aimed to identify the metabolites of bilobetin in vitro and in vivo. Bilobetin was incubated with liver microsomes to determine metabolites in vitro, and faeces and urine were collected after oral administration to rats to determine metabolites in vivo. After the samples were processed, they were measured using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. As a result, a total of 21 and 9 metabolites were detected in vivo and in vitro, respectively. Demethylation, demethylation and loss of water, demethylation and hydrogenation, demethylation and glycine conjugation, oxidation, methylation, oxidation and methylation, and hydrogenation were the main metabolic pathways. This study is the first to identify the metabolites of bilobetin and provides a theoretical foundation for the safe use of bilobetin in clinical application and the development of new drugs. This article is protected by copyright. All rights reserved.
Epidemiology and clinical course of COVID-19 in Shanghai, China

ABSTRACT Background: Novel coronavirus pneumonia (COVID-19) is prevalent around the world. We aimed to describe epidemiological features and clinical course in Shanghai. Methods: We retrospectively analysed 325 cases admitted at Shanghai Public Health Clinical Center, between January 20 and February 29, 2020. Results: 47.4% (154/325) had visited Wuhan within 2 weeks of illness onset. 57.2% occurred in 67 clusters; 40% were situated within 53 family clusters. 83.7% developed fever during the disease course. Median times from onset to first medical care, hospitalization and negative detection of nucleic acid by nasopharyngeal swab were 1, 4 and 8 days. Patients with mild disease using glucocorticoid tended to have longer viral shedding in blood and feces. At admission, 69.8% presented with lymphopenia and 38.8% had elevated D-dimers. Pneumonia was identified in 97.5% (314/322) of cases by chest CT scan. Severe-critical patients were 8% with a median time from onset to critical disease of 10.5 days. Half required oxygen therapy and 7.1% high-flow nasal oxygen. The case fatality rate was 0.92% with median time from onset to death of 16 days. Conclusion: COVID-19 cases in Shanghai were imported. Rapid identification, and effective control measures helped to contain the outbreak and prevent community transmission.
Activation of the NLRP3 Inflammasome by Particles from the Echinococcus granulosus Laminated Layer

The interaction of dendritic cells and macrophages with a variety of rigid noncellular particles triggers activation of the NLRP3 inflammasome and consequent secretion of interleukin 1β (IL-1β). Noncellular particles can also be generated in the context of helminth infection, since these large pathogens often shed their outermost structures during growth and/or molting. One such structure is the massive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stages of cestodes of the genus Echinococcus. ABSTRACT The interaction of dendritic cells and macrophages with a variety of rigid noncellular particles triggers activation of the NLRP3 inflammasome and consequent secretion of interleukin 1β (IL-1β). Noncellular particles can also be generated in the context of helminth infection, since these large pathogens often shed their outermost structures during growth and/or molting. One such structure is the massive, mucin-based, soft, flexible laminated layer (LL), which protects the larval stages of cestodes of the genus Echinococcus. We show that particles from the Echinococcus granulosus LL (pLL) trigger NLRP3- and caspase-1-dependent IL-1β in lipopolysaccharide (LPS)-primed mouse bone marrow-derived dendritic cells (BMDC). This response can be elicited by pLL too large for phagocytosis and nonetheless requires actin dynamics, Syk, and phosphatidylinositol 3-kinase (PI3K). These three requirements had already been observed in our previous study on the alteration by pLL of CD86, CD40, IL-10, and IL-12 responses to LPS in BMDC; however, we now show that these alterations are independent of NLRP3 and caspase-1. In other words, an initial interaction with particles requiring actin dynamics, Syk, and PI3K, but not phagocytosis, elicits both NLRP3-dependent and NLRP3-independent responses. Intraperitoneal injection of pLL induced IL-1β, suggesting that contact with LL materials induces IL-1β in the E. granulosus infection setting. Our results extend our understanding of NLRP3 inflammasome activation by noncellular particulate materials both to helminth-derived materials and to flexible/soft materials.
Consumption Rates of Six Species of Marine Benthic Naked Amoebae (Gymnamoebia) From Sediments in The Clyde Sea Area

Six species of naked amoebae, ranging in size from 45 to 3258 μm3, were isolated from benthic sediments of the Clyde Sea area. The number of fluorescently labelled bacteria (FLB) consumed by these amoebae was determined at 5, 10, 15 and 20°C. Consumption rates varied markedly, ranging from 0·2 to 194·7 bacteria h−1 (equivalent to 0·16–155·8 μim3 bacterial biomass). However, only some of these values were considered to be optimal; several of the uptake values were too low to account for the measured growth rates of amoebae. Using the optimal consumption rate data, the mean specific rates increased from 0·042 bacteria h−1 μm3 at 5°C to 0·131 bacteria h−1 μm−3 at 20°C. This is the first study to detail the ingestion rates of a range of bacterivorous marine gymnamoebae.
Child Sexual Abuse and Risk of Revictimization: Impact of Child Demographics, Sexual Abuse Characteristics, and Psychiatric Disorders

Approximately half of child sexual abuse (CSA) victims report sexual revictimization later in life; however, there is limited rigorous evidence concerning factors contributing to sexual and nonsexual forms of revictimization. This article investigates the relationships between CSA and a range of revictimization experiences. It also examines the role of other individual-level factors (demographics, CSA characteristics, psychiatric disorders) in the risk of revictimization. The study compares data from a prospective-longitudinal study of 2,759 Australian children (<17 years old) alleged to have experienced contact–CSA between 1964 and 1995, and a comparison group matched on sex and age. In each case, CSA was deemed likely to have occurred according to expert forensic medical opinion. Abused children and comparisons were followed to age 35 years on average, and their lifetime official crime victimization histories and public mental health service records were extracted from statewide population-level administrative databases. Relative to comparisons, CSA victims experienced significantly higher rates of revictimization, with marked elevations in odds for interpersonal revictimization (i.e., sexual assault, physical assault, threats of violence, and stalking). The CSA–physical assault relationship was moderated by sex, with a stronger association for female victims. Among CSA victims, victim sex, age at index abuse, and several psychiatric diagnostic categories were independently associated with revictimization risk, with different patterns of vulnerability emerging depending on the nature of revictimization. Overall, CSA victims are vulnerable to a range of revictimization experiences later in life. Findings have implications for the identification of particular groups of sexually abused children at heightened risk for revictimization and the role mental health services may play in mitigating risk.
DETECTION OF GLYPHOSATE-RESISTANT PALMER AMARANTH (Amaranthus palmeri) IN AGRICULTURAL AREAS OF MATO GROSSO, BRAZIL

The recent introduction of Palmer amaranth (Amaranthus palmeri) in Brazilian agricultural areas may promote several changes on weed management, especially in no-till systems and in glyphosate-resistant crops, since glyphosate-resistant biotypes of A. palmerihave been frequently selected in other countries. Therefore, this research was developed in order to evaluate the glyphosate susceptibility of a Palmer amaranth biotype recently identified in the State of Mato Grosso, Brazil. For this purpose, glyphosate susceptibility of three Amaranthusbiotypes was compared: A.hybridus var. patulus, collected in the State of Rio Grande do Sul - Brazil; A.hybridus var. patulus, collected in the State of Sao Paulo - Brazil; and A.palmeri, collected in the State of Mato Grosso - Brazil. Dose-response curves were generated for all biotypes, considering eight rates of glyphosate and six replicates. All the experiments were repeated twice. Both A.hybridus biotypes were satisfactorily controlled by glyphosate, demanding rates equal to or lower than 541.15 g a.e. ha-1 for 80% control (LD80). The A.palmeri biotype was not controlled by glyphosate in any of the assessments and required rates greater than 4,500 g a.e. ha-1 to reach LD80, which are economically and environmentally unacceptable. Comparison of the Brazilian A.palmeri biotype to the A. hybridus biotypes, as well as, to the results available in scientific international literature, led to the conclusion that the Brazilian Palmer amaranth biotype is resistant to glyphosate.
The Political De-determination of Legal Rules and the Contested Meaning of the ‘No Bailout’ Clause

Traditional debates on legal theory have devoted a great deal of attention to the question of the determinacy of legal rules. With the aid of social sciences and linguistics, this article suggests a way out of the ‘determinate–indeterminate’ dichotomy that has dominated the academic debate on the topic so far. Instead, a dynamic approach is proposed, in which rules are deemed to undergo processes of political ‘de-determination’ and ‘redetermination’. To illustrate this, the article uses the example of Article 125 of the Treaty on the Functioning of the European Union, the ‘no bailout’ provision, which played a major role in the management of the Euro-crisis. As will be shown, with the start of the crisis, this provision, whose meaning was once scarcely controversial, became the object of intense interpretative disagreement. As it became politically relevant, the rule also became the site of interpretative competitions, until the intervention of the European Court of Justice disambiguated and redefined its meaning.
Supersaturated Lipid-Based Formulations to Enhance the Oral Bioavailability of Venetoclax

Increasing numbers of beyond Rule-of-Five drugs are emerging from discovery pipelines, generating a need for bio-enabling formulation approaches, such as lipid-based formulations (LBF), to ensure maximal in vivo exposure. However, many drug candidates display insufficient lipid solubility, leading to dose-loading limitations in LBFs. The aim of this study was to explore the potential of supersaturated LBFs (sLBF) for the beyond Rule-of-Five drug venetoclax. Temperature-induced sLBFs of venetoclax were obtained in olive oil, Captex® 1000, Peceol® and Capmul MCM®, respectively. A Peceol®-based sLBF displayed the highest drug loading and was therefore evaluated further. In vitro lipolysis demonstrated that the Peceol®-based sLBF was able to generate higher venetoclax concentrations in the aqueous phase compared to a Peceol®-based suspension and an aqueous suspension. A subsequent bioavailability study in pigs demonstrated for sLBF a 3.8-fold and 2.1-fold higher bioavailability compared to the drug powder and Peceol®-based suspension, respectively. In conclusion, sLBF is a promising bio-enabling formulation approach to enhance in vivo exposure of beyond Rule-of-Five drugs, such as venetoclax. The in vitro lipolysis results correctly predicted a higher exposure of the sLBF in vivo. The findings of this study are of particular relevance to pre-clinical drug development, where maximum exposure is required.
A Cellular Automaton Model as a First Model-Based Assessment of Interacting Mechanisms for Insulin Granule Transport in Beta Cells

In this paper a first model is derived and applied which describes the transport of insulin granules through the cell interior and at the membrane of a beta cell. A special role is assigned to the actin network, which significantly influences the transport. For this purpose, microscopically measured actin networks are characterized and then further ones are artificially generated. In a Cellular Automaton model, phenomenological laws for granule movement are formulated and implemented. Simulation results are compared with experiments, primarily using TIRF images and secretion rates. In this respect, good similarities are already apparent. The model is a first useful approach to describe complex granule transport processes in beta cells, and offers great potential for future extensions. Furthermore, the model can be used as a tool to validate hypotheses and associated mechanisms regarding their effect on exocytosis or other processes. For this purpose, the source code for the model is provided online.
Gastrotricha and metazoan phylogeny

The phylogenetic position of the Gastrotricha within Bilateria and relationships among gastrotrich subgroups are reanalysed using morphological, developmental, nonsequence molecular, and ecological characters, together with the conserved regions of small‐subunit ribosomal RNA genes (SSU rDNA). The analysis shows that traditional ‘Macrodasyida’ is a paraphyletic stemline of Chaetonotida, with Dactylopodolida, Redudasys, and Turbanellida as the basalmost gastrotrich groups. The ‘Cycloneuralia hypothesis’, which assumes sister group relationships between Gastrotricha and Ecdysozoa is supported. The sensitivity analysis of the combined dataset yields the following scheme of relationships of the main bilaterian clades: (1) Acoelomorpha is a basalmost bilaterian clade; (2) both Deuterostomia and Protostomia (less Acoelomorpha) are monophyletic; (3) the phylogenetic position of Ectoprocta, Brachiopoda + Phoronida, and Cycloneuralia within Protostomia is unstable; (4) Trochozoa (incl. Entoprocta, Nemertea, Lobatocerebrum, and possibly Jennaria), Platyhelminthes s.s. , and Gnathifera‐Myzostomida form a clade (‘Spiralia’); (5) Cycliophora and possibly also Chaetognatha may be close to the gnathiferans. Evolution of metazoan ciliation and cycloneuralian cuticle is discussed. It is concluded that cycloneuralian and gastrotrich ancestors were multiciliate and had epidermal cilia covered by cuticular sheaths.