Miracle-dz/UniFAR-FTUs huggingface dataset:
The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory and spatial navigation deficits. The brain-derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment in APOE ɛ4 carriers but its role in APOE ɛ4-related spatial navigation deficits has not been established. Objective: We examined influence of APOE and BDNF Val66Met polymorphism combination on spatial navigation and volumes of selected navigation-related brain regions in cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (aMCI). Methods: 187 participants (aMCI [n = 116] and CU [n = 71]) from the Czech Brain Aging Study were stratified based on APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNFVal/Val, ɛ4–/BDNFMet, ɛ4+/BDNFVal/Val, and ɛ4+/BDNFMet. The participants underwent comprehensive neuropsychological examination, brain MRI, and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real-space human analogue of the Morris water maze. Results: Among the aMCI participants, the ɛ4+/BDNFMet group had the least accurate egocentric navigation performance (p < 0.05) and lower verbal memory performance than the ɛ4–/BDNFVal/Val group (p = 0.007). The ɛ4+/BDNFMet group had smaller hippocampal and entorhinal cortical volumes than the ɛ4–/BDNFVal/Val (p≤0.019) and ɛ4–/BDNFMet (p≤0.020) groups. Among the CU participants, the ɛ4+/BDNFMet group had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p < 0.05). Conclusion: The combination of APOE ɛ4 and BDNF Met polymorphisms is associated with more pronounced egocentric navigation impairment and atrophy of the medial temporal lobe regions in individuals with aMCI and less accurate allocentric navigation in CU older adults.
Limited plasticity of Drosophila suzukii wing spot size in 3 response to developmental temperature 4

: 24 Phenotypic plasticity is an important mechanism allowing adaptation to new environments and as such 25 it has been suggested to facilitate biological invasions. Under this assumption, invasive populations 26 are predicted to exhibit stronger plastic responses than native populations. Drosophila suzukii is an 27 invasive species whose males harbor a spot on the wing tip. In this study, by manipulating 28 developmental temperature, we compare the phenotypic plasticity of wing spot size of two invasive 29 populations with that of a native population. We then compare the results with data obtained from wild- 30 caught flies from different natural populations. While both wing size and spot size are plastic to 31 temperature, no difference in plasticity was detected between native and invasive populations, 32 rejecting the hypothesis of a special role of thermal plasticity in the invasion success. In contrast we 33 observed a remarkable stability in the spot-to-wing ratio across temperatures, as well as among 34 geographic populations. This stability suggests either that the spot relative size is under stabilizing 35 selection, or that its variation might be constrained by a tight developmental correlation between spot 36 size and wing size. Our data show that this correlation was lost at high temperature, leading to an 37 increased variation in the relative spot size, particularly marked in the two invasive populations. This 38 suggests (I) that D. suzukii ’s development is impaired by hot temperatures, in agreement with the cold- 39 adapted status of this species; (ii) that the spot size can be decoupled from wing size, rejecting the 40 hypothesis of an absolute constraint and suggesting that the wing color pattern might be under 41 stabilizing (sexual) selection; (iii) that such sexual selection might be relaxed in the invasive 42 populations. Finally, a subtle but consistent directional asymmetry in spot size was detected in favor of 43 the right side in all populations and temperatures, possibly indicative of a lateralized sexual behavior. 44 45 46
Carotenoids in Cancer Metastasis—Status Quo and Outlook

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.
H1 Hemagglutinin Priming Provides Long-Lasting Heterosubtypic Immunity against H5N1 Challenge in the Mouse Model

Current studies point out that an HA-mediated immunological imprint is established early in life during the first exposure to influenza viruses, which critically shapes and biases future immune responses. However, these findings have not been confirmed in animal models, and the precise mechanisms of this phenomenon are not clearly understood. ABSTRACT Influenza virus infections leave a signature of immune memory that influences future responses to infections with antigenically related strains. It has been hypothesized that the first exposure in life to H1N1 influenza virus imprints the host immune system, potentially resulting in protection from severe infection with H5N1 later in life through hemagglutinin (HA) stalk-specific antibodies. To study the specific role of the HA on protection against infection without interference of cellular immunity or humoral antineuraminidase immunity, we primed mice with influenza B viruses that express an H1 HA (group 1; B-H1), H3 HA (group 2; B-H3), or wild-type influenza B virus and subsequently challenged them at different time points with an H5N1 virus. Weight loss and survival monitoring showed that the B-H1-primed mice exhibited better protection against H5N1 compared to the control mice. Analysis of H5-specific serum IgG, before and 21 days after H5N1 challenge, evidenced the presence of anti-stalk H5 cross-reactive antibodies in the BH-1 group that were boosted by H5N1 infection. The increased immune responses and protection induced by priming with the B-H1 viruses lasted at least up to 1 year. Hence, a single HA priming based on natural infection induces long-lasting protective immunity against heterosubtypic strains from the same phylogenetic HA group in mice. This study gives mechanistic support to the earlier finding in humans that imprinting by H1 HA protects against H5N1 infections and that highly conserved regions on the HA, like the stalk, are involved in this phenomenon. IMPORTANCE Current studies point out that an HA-mediated immunological imprint is established early in life during the first exposure to influenza viruses, which critically shapes and biases future immune responses. However, studies in animal models are limited and the precise mechanisms of this phenomenon are under investigation. Studies that explore the effect of HA-specific immunity induced during natural infection on future exposures to heterosubtypic influenza strains are needed.
High-Throughput Optimization of Recombinant Protein Production in Microfluidic Gel Beads.

Efficient production hosts are a key requirement for bringing biopharmaceutical and biotechnological innovations to the market. In this work, a truly universal high-throughput platform for optimization of microbial protein production is described. Using droplet microfluidics, large genetic libraries of strains are encapsulated into biocompatible gel beads that are engineered to selectively retain any protein of interest. Bead-retained products are then fluorescently labeled and strains with superior production titers are isolated using flow cytometry. The broad applicability of the platform is demonstrated by successfully culturing several industrially relevant bacterial and yeast strains and detecting peptides or proteins of interest that are secreted or released from the cell via autolysis. Lastly, the platform is applied to optimize cutinase secretion in Komagatella phaffii (Pichia pastoris) and a strain with 5.7-fold improvement is isolated. The platform permits the analysis of >106 genotypes per day and is readily applicable to any protein that can be equipped with a His6 -tag. It is envisioned that the platform will be useful for large screening campaigns that aim to identify improved hosts for large-scale production of biotechnologically relevant proteins, thereby accelerating the costly and time-consuming process of strain engineering.
Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.
Anomalous surface diffusion: A numerical study

We present a numerical study of bulk‐mediated effective surface diffusion at liquid surfaces where surface‐active molecules adsorb and desorb on experimental time scales. Adsorbed molecules execute Levy walks on the interface, each step entailing desorption followed by bulk diffusion and readsorption elsewhere. Our results confirm the predicted anomalous scaling of surface displacement r at times before particles are finally lost to the bulk. Moments grow as 〈rq〉∼tζ(q), where ζ(q)=q for q<1, ζ(q)=(q+1)/2 for q≳1. We have also confirmed that the ‘‘speed’’ c which characterizes the q<1 behavior, r≊ct, is universally related to other observables: c=D/h where D and h are, respectively, the bulk diffusivity and the slope of the equilibrium adsorption isotherm.
mVis in the Wild: Pre-Study of an Interactive Visual Machine Learning System for Labelling

Many machine learning algorithms require a labelled training dataset. The task of labelling a multivariate dataset can be tedious, but can be supported by systems combining interactive visualisation and machine learning techniques into a single interface. mVis is such a system, providing a uniﬁed ecosystem to explore multivariate datasets and execute machine learning algorithms to build labelled datasets. This paper describes a pre-study evaluation of the mVis system, comprising case studies in two different domains: collaborative intelligence and daily activities. In each case study, a volunteer researcher was asked to use mVis to explore, analyse, and label their own dataset in their own environment, while thinking out loud. The case studies provided valuable leanings in terms of the usability of the system, understanding how different analysts work, and identifying important missing features.
Interaction of pH stress and demography leads to convergent evolution in the protist Tetrahymena thermophila

Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated the interaction between adaptation to pH-stress, and ecological conditions, specifically demography. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r0). Overall, evolution at low pH led to the convergence of r0 and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r0 and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r0, or decrease of α, depending on the genetic background. In conclusion, we show that demography can interact with abiotic stress, to impact the direction of evolution under abiotic stress.
Use of 3D printing in the planning of a patient with unerupted maxillary central incisors

Impacted central incisors are a clinical dilemma faced by orthodontists, oral and maxillofacial surgeons, paediatric and restorative dentists. Successful management requires a robust diagnosis and treatment planning process. This case report highlights the use of 3D printing to aid the treatment planning of a patient with bilateral unerupted maxillary central incisors due to two supernumerary teeth acting as a physical obstruction. The preoperative cone beam computed tomography scan allowed for production of the printed model to the exact size and dimensions of the unerupted teeth and supernumeraries to facilitate the planning of the case and to aid in consenting the patient for treatment.
Sistema basado en internet de las cosas (IoT) para la monitorización en tiempo real de variables de temperatura y humedad en un equipo de refrigeración de área de farmacia de un hospital de cuarto nivel

The lack of control of the variables, such as temperature and humidity in the storage of medicines, is linked to the alteration of the chemical properties of pharmaceutical products. The increase in temperature is directly related to the increase in the speed of medicines deterioration, while low temperatures can facilitate the formation of granules in certain vaccines. For this reason, the lack of control of these variables can become the main cause of an adverse event compromising the health status of the patient and putting their lives at risk. In the context of the new emerging technologies, the Internet of Things (IoT) has allowed the interlocking of communication systems with different industrial sectors. A sector that is no stranger to this technological change is the health sector, both in the care of people and in the monitoring of medical devices and equipment, and the construction of smart hospitals. The purpose of this work is to implement a system based on IoT which allows to prevent possible errors or failures in the traceability of the medicines conservation in the pharmacy area in a fourth level hospital. This is achieved through the supervision and control of the medical device that preserves the temperature and humidity of the medications allowing them to maintain their physical, chemical, microbiological, therapeutic and toxicological properties recommended by the manufacturer and current regulations. The implemented system was based on a centralized IoT architecture, which refers to a network that follows MQTT (Message Queue Telemetry Transport) and HTTPs (Hypertext Transfer Protocol Secure) protocols. These protocols allowed connecting objects via the internet to transmit information for the purpose of intelligent communication between objects and the central information system. SISTEMA BASADO EN INTERNET DE LAS COSAS (IoT) PARA LA MONITORIZACIÓN EN TIEMPO REAL DE VARIABLES DE TEMPERATURA Y HUMEDAD EN UN EQUIPO DE REFRIGERACIÓN DEL ÁREA DE FARMACIA DE UN HOSPITAL DE CUARTO NIVEL 3 The final implementation of the monitoring system allowed continuous recording of the temperature and humidity variables by establishing dynamic alarms in order to help identify and warn the responsible personnel about the unwanted behavior of the refrigeration equipment. It was possible to optimize the daily record of temperature and humidity.
Diagnostic Performance of Different Simulated Low-Dose Levels in Patients with Suspected Cervical Abscess Using a Third-Generation Dual-Source CT Scanner

The aim of this study was to investigate the effects of dose reduction on diagnostic accuracy and image quality of cervical computed tomography (CT) in patients with suspected cervical abscess. Forty-eight patients (mean age 45.5 years) received a CT for suspected cervical abscess. Low-dose CT (LDCT) datasets with 25%, 50%, and 75% of the original dose were generated with a realistic simulation. The image data were reconstructed with filtered back projection (FBP) and with advanced modeled iterative reconstruction (ADMIRE) (strengths 3 and 5). A five-point Likert scale was used to assess subjective image quality and diagnostic confidence. The signal-to-noise ratio (SNR) of the sternocleidomastoid muscle and submandibular gland and the contrast-to-noise ratio (CNR) of the sternocleidomastoid muscle and submandibular glandular fat were calculated to assess the objective image quality. Diagnostic accuracy was calculated for LDCT using the original dose as the reference standard. The prevalence of cervical abscesses was high (72.9%) in the cohort; the mean effective dose for all 48 scans was 1.8 ± 0.8 mSv. Sternocleidomastoid and submandibular SNR and sternocleidomastoid muscle fat and submandibular gland fat CNR increased with higher doses and were significantly higher for ADMIRE compared to FBP, with the best results in ADMIRE 5 (all p < 0.001). Subjective image quality was highest for ADMIRE 5 at 75% and lowest for FBP at 25% of the original dose (p < 0.001). Diagnostic confidence was highest for ADMIRE 5 at 75% and lowest for FBP at 25% (p < 0.001). Patient-based diagnostic accuracy was high for all LDCT datasets, down to 25% for ADMIRE 3 and 5 (sensitivity: 100%; specificity: 100%) and lower for FBP at 25% dose reduction (sensitivity: 88.6–94.3%; specificity: 92.3–100%). The use of a modern dual-source CT of the third generation and iterative reconstruction allows a reduction in the radiation dose to 25% (0.5 mSv) of the original dose with the same diagnostic accuracy for the assessment of neck abscesses.
ACDF With Total En Bloc Resection of Uncinate in Foraminal Stenosis of the Cervical Spine

Supplemental Digital Content is available in the text. Study Design: This was a prospective cohort study. Objectives: To find out any differences in clinical outcomes when adding an en bloc total uncinate process resection (TUPR) to conventional anterior cervical discectomy and fusion (ACDF) to relieve an impinged nerve root. Summary of Background Data: There has been a long debate on the extent of cervical decompression needed when ACDF is done for patients with foraminal stenosis. Materials and Methods: We included 606 patients who underwent ACDF due to foraminal stenosis. Minimum follow-up was 2 years. Patients with a soft disk herniation, myelopathy, anterior-posterior combined surgery or revision surgery were excluded. There were 275 patients (group U) who underwent ACDF with TUPR and 331 patients (group N) who underwent ACDF without TUPR. Clinical outcome measures were neck pain and arm pain, both assessed using Visual Analog Scale (VAS). We also measured Neck Disability Index (NDI) and patient-reported subjective improvement rate (PRSIR) in percentage. These parameters were measured preoperatively, immediately postoperatively, at 6 weeks as well as 3, 6, 9, 12 and 24 months. Statistical analysis was performed using independent sample t test and paired sample t test. Results: Preoperative neck and arm pain, and NDI were similar between the 2 groups. All 4 parameters in both groups improved significantly at 6 weeks follow-up and the improved outcomes were maintained up to the 24 month follow-up. There were no significant differences between the 2 groups in overall neck pain VAS, NDI, and PRSIR. There was a significant difference in arm pain VAS statistically all throughout the follow-up period, with group U having lesser arm pain. Conclusions: Overall clinical outcomes were significantly improved after the ACDF whether an en bloc uncinate process resection was added or not. However, arm pain VAS was significantly less statistically in the uncinate resection group at all times.