Miracle-dz/UniFAR-FTUs huggingface dataset:
Iterative time-reversal for multi-frequency hyperthermia

Time-reversal (TR) is a known wideband array beam-forming technique that has been suggested as a treatment planning alternative in deep microwave hyperthermia for cancer treatment. While the aim in classic TR is to focus the energy at a specific point within the target, no assumptions are made on secondary lobes that might arise in the healthy tissues. These secondary lobes, together with tissue heterogeneity, may result in hot-spots (HSs), which are known to limit the efficiency of the thermal dose delivery to the tumor. This paper proposes a novel wideband TR focusing method that iteratively shifts the focus away from HSs and towards cold-spots from an initial TR solution, a procedure that improves tumor coverage and reduces HSs. We verify this method on two different applicator topologies and several target volume configurations. The algorithm is deterministic and runs within seconds, enabling its use for real-time applications. At the same time, it yields results comparable to those obtained with global stochastic optimizers such as Particle Swarm.
Surface Nanostructuring of a CuAlBe Shape Memory Alloy Produces a 10.3 ± 0.6 GPa Nanohardness Martensite Microstructure

Severe plastic deformation (SPD) has led to the discovery of ever stronger materials, either by bulk modification or by surface deformation under sliding contact. These processes increase the strength of an alloy through the transformation of the deformation substructure into submicrometric grains or twins. Here, surface SPD was induced by plastic deformation under frictional contact with a spherical tool in a hot rolled CuAlBe-shape memory alloy. This created a microstructure consisting of a few course martensite variants and ultrafine intersecting bands of secondary martensite and/or austenite, increasing the nanohardness of hot-rolled material from 2.6 to 10.3 GPa. In as-cast material the increase was from 2.4 to 5 GPa. The friction coefficient and surface damage were significantly higher in the hot rolled condition. Metallographic evidence showed that hot rolling was not followed by recrystallisation. This means that a remaining dislocation substructure can lock the martensite and impedes back-transformation to austenite. In the as-cast material, a very fine but softer austenite microstructure was found. The observed difference in properties provides an opportunity to fine-tune the process either for optimal wear resistance or for maximum surface hardness. The modified hot-rolled material possesses the highest hardness obtained to date in nanostructured non-ferrous alloys.
Hypoxia-Mediated Decrease of Ovarian Cancer Cells Reaction to Treatment: Significance for Chemo- and Immunotherapies

Hypoxia, a common factor ruling the microenvironment composition, leads to tumor progression. In this hypoxic context, cytokines and cells cooperate to favor cancer development and metastasis. Tumor hypoxia is heterogeneously distributed. Oxygen gradients depend on the vicinity, functionality of blood vessels, and oxygen ability to diffuse into surrounding tissues. Thus, the vasculature state modulates the microenvironment of the tumor cells. Cells sense and react to small variations in oxygen tension, which explains the lack of tumor cells’ unicity in their reaction to drugs. Ovarian cancers are highly hypoxia-dependent, ascites worsening the access to oxygen, in their reactions to both chemotherapy and new immunotherapy. Consequently, hypoxia affects the results of immunotherapy, and is thus, crucial for the design of treatments. Controlling key immunosuppressive factors and receptors, as well as immune checkpoint molecule expression on tumor, immune and stromal cells, hypoxia induces immunosuppression. Consequently, new approaches to alleviate hypoxia in the tumor microenvironment bring promises for ovarian cancer immunotherapeutic strategies. This review focuses on the effects of hypoxia in the microenvironment and its consequences on tumor treatments. This opens the way to innovative combined treatments to the advantage of immunotherapy outcome in ovarian cancers.
Mid-infrared absorption spectroscopy of methane across a 14.4THz spectral range using a broadband femtosecond optical parametric oscillator based on aperiodically poled lithium niobate

Conventionally optical parametric oscillators (OPOs) have been used in high-resolution absorption-spectroscopy as narrow-band tuneable sources where the measurement resolution is determined by the OPO output linewidth, rather than the wavelength resolution of the detector. In contrast, the absorption spectroscopy of gases and other media has for many years been carried out using instruments such as Fourier-transform infrared (FTIR) spectrometers or high-resolution diffraction-grating-based tuneable monochromators. These techniques commonly utilise broadband thermal sources with highly-divergent illumination beams limiting their use in remote sensing or fibre delivery applications. The work presented here reports a new approach to FTIR spectroscopy based around a novel Ti:sapphire pumped, signal-resonant OPO that uses a 10mm crystal of aperiodically-poled lithium niobate (APPLN) as the gain medium producing an idler output covering a 3.2-3. 85μm tuning range with a typical full-width-half-maximum bandwidth of 85nm. Methane was used to demonstrate the technique since the OPO tuning range almost completely covers the strongest mid-infrared absorption lines of methane from 3.0-3. 7μm (limited only by the available resonator optics). A double-beam Michelson interferometer was built around the OPO idler beam using a helium-neon laser as the second beam to self-calibrate each trace. Course tuning of the OPO resulted in the measurement of absorption data across the 3.2-3. 85μm tuning range using methane held at pressures ranging from 2000mbar down to 25mbar. A maximum resolution of around 1cm-1 was achieved using a simple rapidly scanning mirror assembly indicating that with further development this approach could yield very high-resolution measurements.
Powerful Plant Antioxidants: A New Biosustainable Approach to the Production of Rosmarinic Acid

Modern lifestyle factors, such as physical inactivity, obesity, smoking, and exposure to environmental pollution, induce excessive generation of free radicals and reactive oxygen species (ROS) in the body. These by-products of oxygen metabolism play a key role in the development of various human diseases such as cancer, diabetes, heart failure, brain damage, muscle problems, premature aging, eye injuries, and a weakened immune system. Synthetic and natural antioxidants, which act as free radical scavengers, are widely used in the food and beverage industries. The toxicity and carcinogenic effects of some synthetic antioxidants have generated interest in natural alternatives, especially plant-derived polyphenols (e.g., phenolic acids, flavonoids, stilbenes, tannins, coumarins, lignins, lignans, quinines, curcuminoids, chalcones, and essential oil terpenoids). This review focuses on the well-known phenolic antioxidant rosmarinic acid (RA), an ester of caffeic acid and (R)-(+)-3-(3,4-dihydroxyphenyl) lactic acid, describing its wide distribution in thirty-nine plant families and the potential productivity of plant sources. A botanical and phytochemical description is provided of a new rich source of RA, Satureja khuzistanica Jamzad (Lamiaceae). Recently reported approaches to the biotechnological production of RA are summarized, highlighting the establishment of cell suspension cultures of S. khuzistanica as an RA chemical biofactory.
Managing occluded stents in biliary obstruction using radiofrequency ablation combined with 125I-strand brachytherapy.

PURPOSE We aimed to assess the effectiveness of percutaneous radiofrequency ablation (PRFA) combined with iodine-125 (125I) seed strand brachytherapy (125I-BT) for treatment of occluded biliary stents. METHODS From November 2015 to September 2017, 13 consecutive patients with occluded biliary metal stents, implanted for malignant obstruction, underwent PRFA combined with 125I-BT to reopen the bile duct. Data included clinical and technical success, stent patency, complications, and overall survival. RESULTS The clinical and technical success rates were both 100%. One month after treatment, the total serum bilirubin level had decreased significantly (P < 0.001). Early complications of cholangitis or hemobilia were experienced by one patient each. Three patients (23.1%) had late complications, including two cases of cholangitis and one case of cholecystitis. During the mean follow-up of 233±82.9 days (range, 88-365 days), the stent patency time was 239±26.5 days (95% CI, 187-291 days), and the 6-month stent patency rate was 68.4%. Five patents died; the mean survival time was 298±30.1 days (95% CI, 239-358 days). The 6-month survival rate was 83%. CONCLUSION PRFA therapy combined with 125I-BT is feasible and safe for patients with occluded metal stents placed for malignant biliary obstruction. Nevertheless, randomized controlled trails are needed to confirm the effectiveness of this new approach.
Analytical methods for assessing changes induced by gamma exposure in an animal model.

OBJECTIVE Ionizing radiation can cause radio-induced changes in the cellular metabolome due to the breakdown of DNA bonds. Our goal was to find the early tissue response to radiation exposure supported by distinct analytical methods. METHODS Histological analyses were performed on the organs extracted from rats to search for microscopic changes. The histological slides stained with hematoxyline-eosin (HE) were analyzed in magnification (40x). Subsequently, the tissues were subjected to mass spectrometry that allowed molecular analysis and DESI-MSI that generated the molecular image of lipids, assessing changes in intensities, especially in the brain. RESULTS The histological analysis found nonspecific inflammatory changes; no areas of fibrosis, necrosis, or apoptosis were identified, suggesting non-morphological tissue alterations. However, the DESI-MSI images of brain lipids allowed the observation of many radio-induced changes in the lipid's intensities. CONCLUSIONS No early radio induced histological or mass weight changes in the radiation exposed rats could be observed at 5 Gy. However, early changes in the molecular level were observed in the DESI-MSI images of the brain lipids. The DESI-MSI method proved to be efficient and relevant, allowing a regional molecular analysis of the tissues, expanding a new field of study that is still in its infancy: radiometabolomics.
Characteristics associated with feeding organic foods during complementary feeding: the nationwide Étude Longitudinale Française depuis l’Enfance (ELFE) birth cohort

Abstract Organic food consumption and its effects on health remain understudied in adults and in children. The aim of this study was to describe family characteristics associated with feeding infants organic foods during the complementary feeding period. The analysis included 9764 children from the French Étude Longitudinale Française depuis l’Enfance (ELFE) birth cohort. In addition to telephone interviews conducted at 2, 12 and 24 months, a monthly questionnaire about milk feeding and complementary foods (including organic foods) was completed by parents between 3 and 10 months. Associations between family characteristics and feeding with organic foods during complementary feeding were analysed by multivariable multinomial logistic regression. Overall, 51 % of infants never consumed organic food during the complementary feeding period (up to 10 months), 24 % sometimes, 15 % often and 9 % always or almost always. As compared with infants never fed organic foods, those ‘often’ or ‘always’ fed organic foods were born to older mothers, with higher education level or family income, and lower pre-pregnancy BMI. As compared with never-smoking women, women who had stopped smoking before pregnancy were more likely to feed their infant organic foods. Feeding with organic foods was also related to long breast-feeding duration and later introduction to complementary foods. To conclude, associations between feeding with organic foods and family socio-economic position as well as infant feeding practices need to be considered when studying the impact of organic foods on children’s health and development.
Prioritisation of areas for early detection of southward movement of arctic fox rabies based on historical surveillance data in Quebec, Canada

Abstract Arctic rabies virus variant (ARVV) is enzootic in Quebec (Canada) north of the 55th parallel. With climate change, increased risk of re-incursion of ARVV in more densely populated southern regions raises public and animal health concerns. The objective of this study was to prioritise geographical areas to target for an early detection of ARVV incursion south of the 55th parallel based on the historical spatio-temporal trends of reported rabies in foxes in Quebec. Descriptive analyses of fox rabies cases from 1953 to 2017 were conducted. Three periods show increases in the number of fox rabies cases in southern regions and indicate incursion from northern areas or neighbouring provinces. The available data, particularly in central and northern regions of the province, were scarce and of low spatial resolution, making it impossible to identify the path of spread with precision. Hence, we investigated the use of multiple criteria, such as historical rabies cases, human population density and red fox (Vulpes vulpes) relative abundance, to prioritise areas for enhanced surveillance. This study underscores the need to define and maintain new criteria for selecting samples to be analysed in order to detect rapidly ARVV cases outside the current enzootic area and any potential re-incursion of the virus into central and southern regions of the province.
Vitamin C Recycling Regulates Neurite Growth in Neurospheres Differentiated In Vitro

The reduced form of vitamin C, ascorbic acid (AA), has been related with gene expression and cell differentiation in the cerebral cortex. In neurons, AA is mainly oxidized to dehydroascorbic acid (DHA); however, DHA cannot accumulate intracellularly because it induces metabolic changes and cell death. In this context, it has been proposed that vitamin C recycling via neuron–astrocyte coupling maintains AA levels and prevents DHA parenchymal accumulation. To date, the role of this mechanism during the outgrowth of neurites is unknown. To stimulate neuronal differentiation, adhered neurospheres treated with AA and retinoic acid (RA) were used. Neuritic growth was analyzed by confocal microscopy, and the effect of vitamin C recycling (bystander effect) in vitro was studied using different cells. AA stimulates neuritic growth more efficiently than RA. However, AA is oxidized to DHA in long incubation periods, generating a loss in the formation of neurites. Surprisingly, neurite growth is maintained over time following co-incubation of neurospheres with cells that efficiently capture DHA. In this sense, astrocytes have high capacity to recycle DHA and stimulate the maintenance of neurites. We demonstrated that vitamin C recycling in vitro regulates the morphology of immature neurons during the differentiation and maturation processes.
Use of oral progestogen in women with threatened miscarriage in the first trimester: a randomized double-blind controlled trial.

STUDY QUESTION Will use of oral progestogen in women with threatened miscarriage in the first trimester reduce the miscarriage rate when compared with placebo? SUMMARY ANSWER Use of oral progestogen in women with threatened miscarriage in the first trimester did not reduce miscarriage before 20 weeks when compared with placebo. WHAT IS KNOWN ALREADY Miscarriage is a common complication of pregnancy and occurs in 15-20% of clinically recognized pregnancies. Use of vaginal progestogens is not effective in reducing miscarriage but there is still no good evidence to support use of oral progestogen for the treatment of threatened miscarriage. STUDY DESIGN, SIZE, DURATION This was a randomized double-blind controlled trial. A total of 406 women presenting with threatened miscarriage in the first trimester were recruited from 30 March 2016 to May 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Women attending Early Pregnancy Assessment Clinics because of vaginal bleeding during the first trimester were recruited and randomly assigned to use dydrogesterone 40 mg orally, followed by 10 mg orally three times a day or placebo until 12 completed weeks of gestation or 1 week after the bleeding stopped, whichever was later. The primary outcome was the miscarriage rate before 20 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE The two groups of women had comparable age, BMI, number of previous miscarriages, gestation and ultrasound findings at presentation. The miscarriage rate before 20 weeks of gestation was similar in both groups, being 12.8% (26/203) in the progestogen group and 14.3% (29/203) in the placebo group (relative risk 0.897, 95% CI 0.548-1.467; P = 0.772). The live birth rate was 81.3% in the progestogen group versus 83.3% in the placebo group (P = 0.697). No significant differences were found between the two groups in terms of obstetric outcomes and side effects. LIMITATIONS, REASONS FOR CAUTION The primary outcome was the miscarriage rate, rather than the live birth rate. Women were recruited from Early Pregnancy Assessment Clinics and those with heavy vaginal bleeding might be admitted into wards directly instead of attending Early Pregnancy Assessment Clinic. The severity of vaginal bleeding was subjectively graded by women themselves. The sample size was not adequate to demonstrate a smaller difference in the miscarriage rate between the progestogen and placebo groups. We did not exclude women with multiple pregnancy, which increased the risk of miscarriage although there was only one set of twin pregnancy in the placebo group. WIDER IMPLICATIONS OF THE FINDINGS Use of oral progestogen is not recommended in women with threatened miscarriage in the first trimester. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Health and Medical Research Fund, HKSAR (reference number 12132341). All authors declared no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov with an identifier NCT02128685. TRIAL REGISTRATION DATE 1 May 2014. DATE OF FIRST PATIENT'S ENROLMENT 30 March 2016.
Role of alpha-lipoic acid in vascular function: A systematic review of human intervention studies

Abstract Alpha-lipoic acid (ALA) has long been the focus of interest due to its promising effects on cardiometabolic risk factors. The aim of this systematic review was to summarize findings from existing human intervention studies evaluating the effect of ALA on vascular function. We performed a systematic search in the PubMed, SCOPUS, and Web of science electronic databases from inception until 1 July 2020. A total of 1106 records were identified from the database search, of which 12 were eligible: nine addressed chronic effects and three measured acute effects of ALA on vascular function. Of 11 trials that evaluated endothelial function by methods such as flow-mediated dilation (n = 7), reactive hyperemia (n = 2) and ACh-induced endothelium-dependent vasodilation (n = 2), 10 reported a significant improvement in endothelial function. In contrast, none of six trials examining the response of endothelium-independent vasodilation reported the favorable impact. The effect of ALA on arterial stiffness measures has been poorly studied. ALA appears to improve endothelial function through increasing the bioavailability of endothelium-derived nitric oxide as well as decreasing oxidative stress and inflammation. In conclusion, these results suggest improvement of endothelial function, but not endothelium-independent vasodilation as a potential mechanism by which ALA attenuates cardiovascular diseases.
An Angiotensin-Responsive Connection from the Lamina Terminalis to the Paraventricular Nucleus of the Hypothalamus Evokes Vasopressin Secretion to Increase Blood Pressure in Mice

Blood pressure is controlled by endocrine, autonomic, and behavioral responses that maintain blood volume and perfusion pressure at levels optimal for survival. Although it is clear that central angiotensin type 1a receptors (AT1aR; encoded by the Agtr1a gene) influence these processes, the neuronal circuits mediating these effects are incompletely understood. The present studies characterize the structure and function of AT1aR neurons in the lamina terminalis (containing the median preoptic nucleus and organum vasculosum of the lamina terminalis), thereby evaluating their roles in blood pressure control. Using male Agtr1a-Cre mice, neuroanatomical studies reveal that AT1aR neurons in the area are largely glutamatergic and send projections to the paraventricular nucleus of the hypothalamus (PVN) that appear to synapse onto vasopressin-synthesizing neurons. To evaluate the functionality of these lamina terminalis AT1aR neurons, we virally delivered light-sensitive opsins and then optogenetically excited or inhibited the neurons while evaluating cardiovascular parameters or fluid intake. Optogenetic excitation robustly elevated blood pressure, water intake, and sodium intake, while optogenetic inhibition produced the opposite effects. Intriguingly, optogenetic excitation of these AT1aR neurons of the lamina terminalis also resulted in Fos induction in vasopressin neurons within the PVN and supraoptic nucleus. Further, within the PVN, selective optogenetic stimulation of afferents that arise from these lamina terminalis AT1aR neurons induced glutamate release onto magnocellular neurons and was sufficient to increase blood pressure. These cardiovascular effects were attenuated by systemic pretreatment with a vasopressin-1a-receptor antagonist. Collectively, these data indicate that excitation of lamina terminalis AT1aR neurons induces neuroendocrine and behavioral responses that increase blood pressure. SIGNIFICANCE STATEMENT Hypertension is a widespread health problem and risk factor for cardiovascular disease. Although treatments exist, a substantial percentage of patients suffer from “drug-resistant” hypertension, a condition associated with increased activation of brain angiotensin receptors, enhanced sympathetic nervous system activity, and elevated vasopressin levels. The present study highlights a role for angiotensin Type 1a receptor expressing neurons located within the lamina terminalis in regulating endocrine and behavioral responses that are involved in maintaining cardiovascular homeostasis. More specifically, data presented here reveal functional excitatory connections between angiotensin-sensitive neurons in the lamina terminals and vasopressin neurons in the paraventricular nucleus of the hypothalamus, and further indicate that activation of this circuit raises blood pressure. These neurons may be a promising target for antihypertensive therapeutics.