Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebrovascular Reactivity Mapping Without Gas Challenges: A Methodological Guide

Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms. Assessment of CVR is usually based on the use of a vasoactive stimulus combined with a CBF measurement technique. Although transcranial Doppler ultrasound has been frequently used to obtain global flow velocity measurements, MRI techniques are being increasingly employed for obtaining CBF maps. For the vasoactive stimulus, vasodilatory hypercapnia is usually induced through the manipulation of respiratory gases, including the inhalation of increased concentrations of carbon dioxide. However, most of these methods require an additional apparatus and complex setups, which not only may not be well-tolerated by some populations but are also not widely available. For these reasons, strategies based on voluntary breathing fluctuations without the need for external gas challenges have been proposed. These include the task-based methodologies of breath holding and paced deep breathing, as well as a new generation of methods based on spontaneous breathing fluctuations during resting-state. Despite the multitude of alternatives to gas challenges, existing literature lacks definitive conclusions regarding the best practices for the vasoactive modulation and associated analysis protocols. In this work, we perform an extensive review of CVR mapping techniques based on MRI and CO2 variations without gas challenges, focusing on the methodological aspects of the breathing protocols and corresponding data analysis. Finally, we outline a set of practical guidelines based on generally accepted practices and available data, extending previous reports and encouraging the wider application of CVR mapping methodologies in both clinical and academic MRI settings.
Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy

Lymph node recurrent prostate cancer is a common clinical scenario that is likely to increase significantly with the widespread adoption of novel positron emission tomography (PET) agents. Despite increasing evidence that localized therapy is disease modifying, most men with lymph node recurrent prostate cancer receive only systemic therapy with androgen deprivation therapy (ADT). For men who receive localized therapy the intent is often to delay receipt of systemic therapy. Little evidence exists on the optimal combination of local and systemic therapy in this patient population. In this hypothesis generating review, we will outline the rationale and propose a framework for combining involved field SBRT with risk adapted intermittent ADT for hormone sensitive nodal recurrent prostate cancer. In patients with a limited number of nodal metastases, involved field stereotactic body radiation therapy (SBRT) may have a role in eliminating castrate-resistant clones and possibly prolonging the response to intermittent ADT. We hypothesize that in a small percentage of patients, such a treatment approach may lead to long term remission or cure.
Effects of Simulated Microgravity on Ultrastructure and Apoptosis of Choroidal Vascular Endothelial Cells

Background It was confirmed that simulated microgravity (SMG) led to ultrastructural alterations and apoptosis in many types of microvascular endothelial cells. However, whether SMG would also affect choroidal vascular endothelial cells (CVECs) remains unknown. This study was designed to investigate the effects of SMG on ultrastructure and apoptosis of CVECs. Methods The rotary cell culture system (RCCS) was utilized to simulate microgravity condition. Human CVECs were cultured under normal gravity (NG) or SMG condition for 3 days. The ultrastructure was viewed under transmission electron microscopy, and the organization of F-actin was observed by immunofluorescence staining. Additionally, the apoptosis percentage was calculated using flow cytometry. Moreover, the mRNA and protein expression of BAX, Bcl-2, Caspase3, Cytochrome C, p-AKT, and p-PI3K were detected with quantitative PCR and Western blot at different exposure time. Results In the SMG group, CVECs presented with a shrunk cell body, chromatin condensation and margination, mitochondria vacuolization, and apoptotic bodies. The amount of F-actin decreased, and the filaments of F-actin were sparse or even partly discontinuous after cultivation under SMG for 72 h. The proportions of apoptotic CVECs in SMG groups at 24 and 72 h were significantly higher than those in the NG group (P < 0.001). The mRNA and protein expression of Bax, Caspase3, and Cytochrome C of CVECs in SMG groups at 24 and 72 h significantly increased than those of the NG group, respectively (P < 0.001). The alterations of p-AKT and p-PI3K protein expression possessed similar trends. On the contrary, the mRNA and protein expression of Bcl-2 in CVECs under SMG at 24 and 72 h were significantly less than that of the NG group, respectively (P < 0.001). Conclusion Simulated microgravity conditions can lead the alterations of the F-actin structure and apoptosis of CVECs. The Bcl-2 apoptosis pathway and PI3K/AKT pathway may participate in the damage of CVECs caused by SMG.
Discrete Spawning Aggregations of the Loliginid Squid Doryteuthis gahi Reveal Life-History Interactions of a Dwarf Morphotype at the Center of Its Distribution Range

Heterogeneous environmental conditions along the Humboldt Current System (HCS) influence the life-history strategy of a variety of species in different ways. There is limited information on latitudinal traits of coastal cephalopods as part of the interacting species in pelagic and benthic environments. The present study used the loliginid squid Doryteuthis gahi as a model organism to: (1) evaluate latitudinal traits on egg laying patterns, (2) characterize a particular spawning ground, (3) quantify the isotopic variation from different tissues, (4) evaluate potential trophic ontogenetic changes, (5) determinate trophic position, and (6) isotopically estimate the relative importance of putative preys in the squid’s assimilated diet. Results evidenced that egg-masses collected between 2014 and 2020 presented similar patterns along northern-central Chile (27–36°S), with females attaching small egg-capsules (10–50 mm length) through the year and over a variety of anthropogenic and natural substrates. At a small scale (Coquimbo; 29°S), early life history traits showed distinct patterns depending on SST, with warmer collection periods (∼18°C) evidencing larger capsules and smaller embryos, although small paralarvae were obtained over the 4-year sampling period. In this site, sampling of older ontogenetic stages supported the constant presence of small-sized squids (19–77 mm ML). Males had larger mean sizes compared to females and undetermined specimens, with a high proportion of mature stages. Observations in captivity were extended for up to 110 d, validating that small females (45–64 mm ML) spawn the small egg-capsules typically observed in the field. Differences in stable isotope composition between beaks and soft tissues of adult squids were lower for δ13C values (1.1 vs. 1.4‰, respectively) and higher for δ15N values (5.3 vs. 4.7‰, respectively). Isotopic composition through ontogeny found similar δ13C and δ15N values, suggesting that carbon sources (pelagic origin) and trophic position did not change significantly, with copepods, euphausiids and nereid polychaetes being the most important preys. This study unveils the permanent occurrence of a small reproductive morphotype of D. gahi in shallow coastal habitats of northern-central Chile (i.e., center of the distribution range), providing the first insights for understanding the species’ potential adaptations to heterogeneous conditions in the HCS and the unexplored distribution gap between the two centers of abundance (Peru and the Falkland/Malvinas islands).
RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I

The macrophage stimulating protein (MSP)–Recepteur d’origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic dendritic cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.
Staying Alive: Long-Term Success of Bottlenose Dolphin Interventions in Southwest Florida

Small cetaceans face persistent threats from fisheries interactions, making effective mitigation a priority for conservation. In southwest Florida, interactions come primarily from small-scale recreational hook and line and trap/pot fisheries, with regional stranding network partners working with federal agency managers to assess and intervene as possible in cases of live animal entanglement. Evaluating success of intervention cases is difficult due to financial and logistical constraints which may preclude detailed follow-up monitoring. Survival over the initial 6 weeks post-release has been used as a marker of short-term success for small-cetacean rescue and/or rehabilitation cases. Early intervention prior to stranding, especially via remote disentanglement or rescue and immediate re-release onsite, can save entangled free-ranging dolphins facing life-threatening anthropogenic injuries. However, given the costs associated with interventions, it is important to understand the benefits of these endeavors not only to save individuals, but also to establish if and how saved individuals contribute to social functioning, survival and reproduction within small, resident populations facing multiple concurrent threats. Here we provide evidence from 27 well-documented common bottlenose dolphin (Tursiops truncatus) intervention cases during 1985–2019 where follow-up monitoring over multiple years sheds light on the longer-term success of these efforts and potential benefits to local populations. Nearly all rescued individuals (92%) survived longer than 6 weeks post-release (mean minimum survival period = 5 years, range 0–35 years), with 13 still observed frequently within their prior resident communities, in good physical health, and engaging in normal behavior. Survivorship rates did not decline substantially between 1 and 5 years post-rescue, meaning survival beyond 1 year may be a useful benchmark of long-term success. Rescued females that reached reproductive maturity (n = 4) have produced 12 post-intervention offspring to date. Social network analysis and demographic modeling applied to cases from the long-term resident community in Sarasota Bay confirmed that animals maintain social connections post-intervention and that interventions result in higher population growth rates. While not every intervention succeeds, this study demonstrates the conservation value of pre-stranding interventions which allow individuals that otherwise would be lost to remain viable and productive members of local populations when prevention of anthropogenic injury is not possible.
Whole-Genome Phylogenetic Analysis Reveals a Wide Diversity of Non-O157 STEC Isolated From Ground Beef and Cattle Feces

Shiga toxin-producing Escherichia coli (STEC) causes foodborne outbreaks that can lead to complications such as hemolytic uremic syndrome. Their main reservoir is cattle, and ground beef has been frequently associated with disease and outbreaks. In this study, we attempted to understand the genetic relationship among STEC isolated in Chile from different sources, their relationship to STEC from the rest of the world, and to identify molecular markers of Chilean STEC. We sequenced 62 STEC isolated in Chile using MiSeq Illumina. In silico typing was determined using tools of the Center Genomic Epidemiology, Denmark University (CGE/DTU). Genomes of our local STEC collection were compared with 113 STEC isolated worldwide through a core genome MLST (cgMLST) approach, and we also searched for distinct genes to be used as molecular markers of Chilean isolates. Genomes in our local collection were grouped based on serogroup and sequence type, and clusters were formed within local STEC. In the worldwide STEC analysis, Chilean STEC did not cluster with genomes of the rest of the world suggesting that they are not phylogenetically related to previously described STEC. The pangenome of our STEC collection was 11,650 genes, but we did not identify distinct molecular markers of local STEC. Our results showed that there may be local emerging STEC with unique features, nevertheless, no molecular markers were detected. Therefore, there might be elements such as a syntenic organization that might explain differential clustering detected between local and worldwide STEC.
What Are the Costs of Diagnostics and Treatment of Lyme Borreliosis in Poland?

Lyme borreliosis (LB) is a growing epidemiological threat in many areas of the world, including North America and Europe. Due to the lack of effective protection against this disease, it seems important to ensure a timely diagnosis for effective treatment and the prevention of serious health consequences. The aim of this study was to assess the costs of diagnosis and treatment of Lyme disease in Poland. The costs incurred for the medical payer were analyzed. The cost of hospitalization due to LB for one patient in 2018 was estimated to be ~582.39 EUR, which constituted 53.10% of the average monthly salary of that year. In the analyzed period (2008–2018), the number of people treated by medical services due to Lyme disease increased, both in hospitalization and ambulatory specialist care. Although, the costs of hospitalization were the highest of the two, we noticed a change ratio between hospitalization and ambulatory specialist care in favor of the latter.
Circadian Rhythm of Blood Pressure of Dipper and Non-dipper Patients With Essential Hypertension: A Mathematical Modeling Approach

Blood pressure in humans presents a circadian variation profile with a morning increase, a small postprandial valley, and a deeper descent during night-time rest. Under certain conditions, the nocturnal decline in blood pressure can be reduced or even reversed (non-dipper), which is related to a significantly worse prognosis than a normal fall pattern (dipper). Despite several advances in recent years, our understanding of blood pressure's temporal structure, its sources and mechanisms is far from complete. In this work, we developed an ordinary differential equation-based mathematical model capable of capturing the circadian rhythm of blood pressure in dipper and non-dipper patients with arterial hypertension. The model was calibrated by means of global optimization, using 24-h data of systolic and diastolic blood pressure, physical activity, heart rate, blood glucose and norepinephrine, obtained from the literature. After fitting the model, the mean of the normalized error for each data point was <0.2%, and confidence intervals indicate that all parameters were identifiable. Sensitivity analysis allowed identifying the most relevant parameters and therefore inferring the most important blood pressure regulatory mechanisms involved in the non-dipper status, namely, increase in sympathetic over parasympathetic nervous tone, lower influence of physical activity on heart rate and greater influence of physical activity and glucose on the systemic vascular resistance. In summary, this model allows explaining the circadian rhythm of blood pressure and deepening the understanding of the underlying mechanisms and interactions integrating the results of previous works.
Supercritical Fluid Extraction Combined with Ultrahigh Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry for Determination of Extractables to Evaluate Compatibility of Drugs with Rubber Closures

Biological activity and pharmacological efficacy of protein drugs may be affected by the compatibility between drug and packaging materials. The compatibility of rubber closures seal cap has become the focus of many studies due to its complicated formulation. Despite of the significance of the issue, currently, there is little available data about organic leachables in drugs which is also not comprehensive. Since the concentration of migrants in drug is usually low and the matrix is complicated, the establishment of overall profile of extractables is crucial for the characterization of leachables. Herein, the supercritical fluid extraction (SFE) method was used because of its great extraction capacity and efficiency for low to medium polar extractables in rubber stoppers. The SFE conditions were optimized by response surface methodology (RSM). Experimental results of the extract yield were close to the predicted values (R2 = 0.95). Then the extractables were qualitatively and quantitatively analyzed with ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Finally, risk assessment was made by comparing predicted exposure with injection permitted daily exposure (pPDE) limit or threshold recommended by threshold of toxicological concern (TTC). The results showed that there are many extractables such as glyceride, fatty acids and derivatives, antioxidants, and degradation products. Among them degradation products were in the majority and content of 17 substances exceeded corresponding limits. Considering their unknown toxicology, more experiments are therefore needed to provide information on their toxicology and risk assessment. The study provides a reference for the compatibility of drugs, and quality supervision of pharmaceuticals packaging.
DEVELOPMENT OF A SIMULATOR FOR X-RAY FLUORESCENCE SPECTROMETRY USING DISTRIBUTED PROCESSING

On the study of energy transport by ionizing electromagnetic radiation, the computer simulation is naturally justiﬁed. First, because the simulation is free of risk to the analyst, second because the simulation is cheaper than the real investment. However, the simulation techniques based on Monte Carlo methods present a well known problem: the time wasted to yield the result. As the complexity of the modelling increases, the time increases. The X-ray ﬂuorescence spectrometry is a very ﬂexible technique that permits someone studies the chemical composition of the sample. Before someone builds an X-ray ﬂuorescence system, it is recommended to study the feasibility of the setup over a speciﬁc spectrometric modality. And this step can be easily performed through simulation. The probability of X-ray ﬂuorescence production is very low compared to other interaction mechanisms. So, the time spent to reach a speciﬁc statistic is large. To overcome the problem, the simulation could be implemented in a way to explore the modern computer and graphic processor units (GPUs) and to use parallel programming languages. The goal of the paper is to show the development of a simulator based on parallel programming language to explore the computer resource to solve the problem of eﬃciency of simulation using Monte Carlo method in an ED-XRF simulation. The ED-XRF setup was simulated to analyse two samples built with iron and covered one with nickel and other with copper. To validate the simulator, the results were compared with other simulator. The spectra of each sample generated by the developed simulator and other are shown.
Wireless Electronic Skin with Integrated Pressure and Optical Proximity Sensing

Electronic skins and tactile sensors can provide the sense of touch to robotic manipulators. These sensing modalities complement existing long range optical sensors and can provide detailed information before and after contact. However, integration with existing systems can be challenging due to size constraints, the interface geometry, and restrictions of external wiring used to interface with the sensor. Here, we introduce a low-profile, wireless electronic skin for direct integration with existing robotic manipulators. The flexible electronic skin combines pressure, optical proximity sensing, and a micro-LIDAR device in a small, low profile package. Each of the sensors are characterized individually and the system is demonstrated on Robonaut 2, an anthropomorphic robot designed to work in environments designed for humans. We demonstrate the sensor can be used for contact sensing, mapping of local unknown environments, and to provide medical monitoring during an emergency in a remote area.
Exploiting DNA repair pathways for tumor sensitization, mitigation of resistance, and normal tissue protection in radiotherapy

More than half of cancer patients are treated with radiotherapy, which kills tumor cells by directly and indirectly inducing DNA damage, including cytotoxic DNA double-strand breaks (DSBs). Tumor cells respond to these threats by activating a complex signaling network termed the DNA damage response (DDR). The DDR arrests the cell cycle, upregulates DNA repair, and triggers apoptosis when damage is excessive. The DDR signaling and DNA repair pathways are fertile terrain for therapeutic intervention. This review highlights strategies to improve therapeutic gain by targeting DDR and DNA repair pathways to radiosensitize tumor cells, overcome intrinsic and acquired tumor radioresistance, and protect normal tissue. Many biological and environmental factors determine tumor and normal cell responses to ionizing radiation and genotoxic chemotherapeutics. These include cell type and cell cycle phase distribution; tissue/tumor microenvironment and oxygen levels; DNA damage load and quality; DNA repair capacity; and susceptibility to apoptosis or other active or passive cell death pathways. We provide an overview of radiobiological parameters associated with X-ray, proton, and carbon ion radiotherapy; DNA repair and DNA damage signaling pathways; and other factors that regulate tumor and normal cell responses to radiation. We then focus on recent studies exploiting DSB repair pathways to enhance radiotherapy therapeutic gain.