Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-Isocenter Multiple-Target SRS Planning of Five to Ten Brain Metastases Using 5 mm Multileaf Collimator: Relationship between Prescription Dose, Number and Volume of Targets

Objective: To propose an expression relating the number and volume of targets with the prescription dose in determining normal brain volume receiving 12 Gy dose (V12) for five to ten brain metastases treated in linear accelerator-based stereotactic radiosurgery (SRS) planning. To determine the volume of tumor that can be treated within the brain tolerance dose, for different SRS prescription doses. Methods: Single-isocenter multiple-target (SIMT) SRS plans were devised for spherical targets that are modeled to simulate 47 tumor scenarios with varying tumor sizes and locations within the brain. Volumetric modulated arc therapy (VMAT) plans were devised using a 5-mm-leaf-width multi-leaf collimator (MLC) with high conformity and dose gradient in the Eclipse treatment planning system for the 21 Gy prescription dose with a 6FFF photon beam. The prescription dose was rescaled to 20 Gy, 18 Gy, 15 Gy and 12Gy to determine the brain V12 volume for a total of 235 SRS plans. Results: Linear correlation was observed between the number, volume and prescription dose of the tumor. The expression relating these parameters was constructed to predict the normal brain V12 volume. The maximum tumor volume that can be treated using SIMT SRS with a 5-mm MLC for 5 to 10 number of targets and for a prescription dose of 21 Gy, 20 Gy, 18 Gy and 15 Gy is determined. Conclusion: Using the expression obtained, V12 volume can be calculated using the number of tumors and the total volume of tumors from the pre-planning MRI data. The prescription dose and the SRS fractionation size can be determined before radiotherapy treatment planning.
Models of spatial representation in the medial entorhinal cortex

High-level cognitive abilities such as memory, navigation, and decision making rely on the communication between the hippocampal formation and the neocortex. At the interface between these two brain regions is the entorhinal cortex, a multimodal association area where neurons with remarkable representations of self-location have been discovered: the grid cells. Grid cells are neurons that fire according to the position of an animal in its environment. A single grid cell activates at multiple spatial locations with firing fields that are arranged in a strikingly-regular triangular pattern. Grid cells are thought to support animal’s navigation and spatial memory, but the cellular mechanisms that generate their patterns are still unknown. In this thesis, I study computational models of neural circuits to explain the emergence, inheritance, and amplification of grid-cell patterns. In the first part of the thesis, I focus on the initial formation of grid firing fields. I embrace the idea that periodic representations of space could emerge via a competition between persistently-active spatial inputs and the reluctance of a neuron to fire for long stretches of time. Building upon previous theoretical work, I propose a single-cell model that generates grid-like activity solely form spatially-irregular inputs, spike-rate adaptation, and Hebbian synaptic plasticity. Compared to previous proposals, my model achieves a higher level of biological realism, gives unprecedented analytical insights, and generates novel experimental predictions. In the second part of the thesis, I focus on the inheritance and amplification of grid-cell patterns. Motivated by the architecture of entorhinal microcircuits, I investigate how feed-forward and recurrent connections affect grid-cell tuning. I show that grids can be inherited across neuronal populations, and that both feed-forward and recurrent connections can improve the regularity of spatial firing. Finally, I show that a connectivity supporting these functions could self-organize in an unsupervised manner. Altogether, this thesis contributes to a better understanding of the principles governing the neuronal representation of space in the medial entorhinal cortex.
Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B‐lineage acute lymphoblastic leukemia: A report of 1021 patients from India

The published literature on hematological, clinical, flowcytometric‐immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low‐income countries. For newer classifications such as BCR::ABL1‐like ALLs, the scarcity of patient‐level data is even more pronounced.
Mechanisms underlying the prolonged activation of the genioglossus following arousal from sleep

Abstract Study Objectives Transient arousal from sleep has been shown to elicit a prolonged increase in genioglossus muscle activity that persists following the return to sleep and which may protect against subsequent airway collapse. We hypothesized that this increased genioglossal activity following return to sleep after an arousal is due to persistent firing of inspiratory-modulated motor units (MUs) that are recruited during the arousal. Methods Thirty-four healthy participants were studied overnight while wearing a nasal mask with pneumotachograph to measure ventilation and with 4 intramuscular genioglossus EMG electrodes. During stable N2 and N3 sleep, auditory tones were played to induce brief (3-15s) AASM arousals. Ventilation and genioglossus MUs were quantified before the tone, during the arousal and for 10 breaths after the return to sleep. Results A total of 1089 auditory tones were played and gave rise to 239 MUs recorded across arousal and the return to sleep in 20 participants (aged 23 ± 4.2 years and BMI 22.5 ± 2.2 kg/m2). Ventilation was elevated above baseline during arousal and the first post-arousal breath (p < .001). Genioglossal activity was elevated for five breaths following the return to sleep, due to increased firing rate and recruitment of inspiratory modulated MUs, as well as a small increase in tonic MU firing frequency. Conclusions The sustained increase in genioglossal activity that occurs on return to sleep after arousal is primarily a result of persistent activity of inspiratory-modulated MUs, with a slight contribution from tonic units. Harnessing genioglossal activation following arousal may potentially be useful for preventing obstructive respiratory events.
Development and Evaluation of p16 based Double Antibody Sandwich ELISA for Detection of Cervical Precancer and Cancer

Objective: Cervical cancer is the third most common cancer in women, worldwide. This study was designed to develop an affordable, accurate and simpler screening test like Enzyme-linked immunosorbent assay (ELISA) which is low cost and will help in bringing down the disease burden in resource poor countries. Methods: In this study, we have raised and evaluated monoclonal antibodies against recombinant p16 using immunohistochemistry (IHC), western blot, immunoprecipitation and ELISA. Double antibody sandwich ELISA (DAS-ELISA) and cytokeratin ELISA was designed for screening women with cervical dysplasia and cancer. Results: Cloned, expressed and purified recombinant p16 were used for generation of monoclonal antibodies. After initial screening, six clones were selected, and affinity purified. Except 155D11G10, which was isotype Immunoglobulin (Ig) G1 all the others were found to be IgG2b. 133A6G5 and 151A7B9 were found to be best for p16 IHC, both showed 70 – 80% and 80 – 90% of nuclear staining respectively. All the antibodies positively detected p16 from the HeLa lysates in western blot except 133A6G5. Studies using immunoprecipitation showed 133A6G5, specifically detected p16. DAS-ELISA developed using a combination of our p16 monoclonal antibodies showed sensitivity of up to 2pg. A pilot study using DAS-ELISA and cytokeratin ELISA in cervical samples revealed the assay sensitivity and specificity as 100% and 80%, respectively. Conclusion: Using combination of DAS-ELISA and cytokeratin ELISA we have developed an accurate and reliable method for the early detection of cervical cancer in a subject, with minimal false results. In the future after large scale validation, p16 ELISA could be used as a reliable tool for diagnostic purposes.
Strategies of diaspore dispersal investment in Compositae: the case of the Andean highlands

Abstract Background and Aims Understanding diaspore morphology and how much a species invests on dispersal appendages is key for improving our knowledge of dispersal in fragmented habitats. We investigate diaspore morphological traits in high-Andean Compositae and their main abiotic and biotic drivers and test whether they play a role in species distribution patterns across the naturally fragmented high-Andean grasslands. Methods We collected diaspore trait data for 125 Compositae species across 47 tropical high-Andean summits, focusing on achene length and pappus-to-achene length ratio, with the latter as a proxy of dispersal investment. We analysed the role of abiotic (temperature, elevation and latitude) and biotic factors (phylogenetic signal and differences between tribes) on diaspore traits and whether they are related to distribution patterns across the Andes, using phylogenomics, distribution modelling and community ecology analyses. Key Results Seventy-five percent of the studied species show small achenes (length <3.3 mm) and 67% have high dispersal investment (pappus length at least two times the achene length). Dispersal investment increases with elevation, possibly to compensate for lower air density, and achene length increases towards the equator, where non-seasonal climate prevails. Diaspore traits show significant phylogenetic signal, and higher dispersal investment is observed in Gnaphalieae, Astereae and Senecioneae, which together represent 72% of our species. High-Andean-restricted species found across the tropical Andes have, on average, the pappus four times longer than the achene, a significantly higher dispersal investment than species present only in the northern Andes or only in the central Andes. Conclusions Small achenes and high diaspore dispersal investment dominate among high-Andean Compositae, traits typical of mostly three tribes of African origin; but traits are also correlated with the environmental gradients within the high-Andean grasslands. Our results also suggest that diaspore dispersal investment is likely to shape species distribution patterns in naturally fragmented habitats.
Single Nucleotide Polymorphisms in Cytokine Genes are Associated with the Susceptibility to Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is the most common type of cancer among men in the Indian subcontinent. Cytokines regulate inflammation and angiogenesis in a variety of cancers. Genetic variability in the cytokine genes can potentially influence the predisposition to oral carcinogenesis. The aim of the current study was to investigate the associations of SNPs in cytokine genes with the susceptibility of oral squamous cell carcinoma. In the present study, we have analyzed the allelic frequency of 32 single nucleotide polymorphisms (SNPs) using MassArray-based iPLEX assay in 16 cytokine genes in 166 OSCC patients and 151 healthy subjects from central India. Out of 32 SNPs analyzed, five SNPs were significantly associated with the risk of OSCC. AA and GG genotypes of IL-1β +3953 were associated with an increased and decreased risk of OSCC, respectively. In several genetic models, GG genotype and G allele in IL-12A 3’UTR G>A were found to be associated with an increased risk of OSCC. Similarly, the GG genotype of IL-12B +1188 T>G was associated with increased susceptibility to OSCC. We conclude that SNPs in the genes coding for IL-1β, IL-12A and IL-12B are associated with increased genetic susceptibility to OSCC in the central Indian population.
Analysis and optimal control of some quasilinear parabolic equations

In this paper, we consider optimal control problems associated with a class of quasilinear parabolic equations, where the coefficients of the elliptic part of the operator depend on the state function. We prove existence, uniqueness and regularity for the solution of the state equation. Then, we analyze the control problem. The goal is to get first and second order optimality conditions. To this aim we prove the necessary differentiability properties of the relation control-to-state and of the cost functional.
Demographic Disparities in Mpox Vaccination Series Completion, by Route of Vaccine Administration — California, August 9, 2022–March 31, 2023

In August 2022, the Food and Drug Administration authorized JYNNEOS vaccine (modified vaccinia Ankara vaccine, Bavarian Nordic), a 2-dose series used for the prevention of Monkeypox virus infection, to be administered via a dose-sparing intradermal route, in addition to the previously authorized subcutaneous route. The California Department of Public Health investigated whether demographic disparities in vaccination series completion varied by route of administration of the recipient's first dose. Among California residents who received their first dose during August 9, 2022-March 31, 2023, a total of 59.8% received a second dose. Series completion was highest among non-Hispanic White persons (64.1%), persons aged ≥65 years (72.6%), and adults with male sex assignment at birth (62.1%); series completion was lowest among non-Hispanic Black or African American persons (51.3%), persons aged 18-24 years (42.9%), and adults assigned female sex at birth (42.8%). When the first dose was received by subcutaneous administration, overall series completion was 58.8% compared with 60.2% when the first dose was administered intradermally. Odds of series completion across all race and ethnicity groups, persons aged 18-64 years, community health conditions, and persons assigned male sex at birth were not greater when the first dose was administered subcutaneously compared with intradermally. Intradermal use of JYNNEOS vaccine did not lower overall 2-dose series completion rates. Continued efforts are needed to ensure persons at risk for Monkeypox virus infection receive both recommended doses.
Evaluation of Virtual Assessment for a High Stakes' Clinical Examination—Physician Assistant Students' and Their Examiners' Perspectives

Purpose This case study emerged from the necessity to reschedule an in-person long case examination to an online platform for physician assistant students' final clinical examination during COVID-19 restrictions. The aim of this study was to evaluate the experiences of students and examiners for a high stakes' clinical examination online. Methods This was an evaluation research study using the Context, Input, Process, Product model, which provided a framework to establish the effectiveness and/or success of an online format for a high stakes' clinical examination. All students and examiners were invited to take part in virtual interviews. Results The results suggest that both students (n = 5) and examiners (n = 7) agree that, although the stress of a face-to-face examination was lessened for the student, this was balanced by a new stressor of potential Internet problems. All agreed that a virtual setting for a high stakes' assessment is not transferable, with both groups citing the lack of opportunities to “read the patient” and “showcase their physical examination skills” as challenging. Conclusion Our study suggests that, in the context of balancing the risks of the pandemic with graduating health care professionals, the online clinical examination format met the required assessment criteria. Recommendations suggest that the long case could be planned so that students and patients are in the same setting to perform a physical examination, confirming the finding that questions on “how to” examine a patient are no substitute for “doing. ”
Effect of sex differences and time of oxytocin administration on treatment of rat model of autism spectrum disorder: Focused on necroptosis markers

Autism is a neurodevelopmental disorder. A variety of molecular and cellular abnormalities leads to behavioral deficits in autism. Nevertheless, its etiology and treatment strategy are not completely understood. Oxytocin has recently shown improvements in social functioning. This study aimed to evaluate the necroptosis pathway for the neuroprotective effects of oxytocin in the valproic acid‐induced autism spectrum disorder model. The autism spectrum disorder was induced by valproic acid on gestational day 12.5 (600 mg/kg, intraperitoneally). Offspring received intranasal oxytocin (1 μg/μL) on the 21st and 40th days after birth. The offspring behaviors were scrutinized by self‐grooming, marble‐burying, three‐chamber, and Morris water maze tests. Western blot was performed on the hippocampus and amygdala tissues to investigate the expression of RIP3 and MLKL markers. The valproic acid group demonstrated more anxiety, repetitive behaviors, and expression of RIP3 and MLKL markers, and less social interaction and spatial memory compared with the control group. Oxytocin considerably improved social interactions, preference for social novelty, and memory. The elevated expression of RIP3 and MLKL markers in valproic acid‐induced autistic rats were alleviated after treatment with oxytocin. We also highlighted the importance of age and gender in autism spectrum disorder interventions. Our findings suggested that oxytocin administration was as an effective treatment in two areas of repetitive/stereotyped behaviors, social interactions/cognitive function. Notably, early administration of oxytocin resulted in better therapeutic responses in autism‐like behaviors. The molecular tests introduce oxytocin as a potential candidate for reducing the expression of necroptosis mediators in the brain. This reinforced our hypothesis that the necroptosis pathway takes part in autism spectrum disorder.
A Unified Methodology to Evaluate the Radiated Noise Due to Turbulent Boundary Layer Flows

For vibro-acoustic applications, a turbulent wall pressure (TWP) fluctuations model was derived. The model is based on the resolution of Poisson's equation. The pressure is characterized in time and space through its spectrum in the frequency wave-number domain. The developed model follows trends commonly observed using Corcos model in a large frequency range but also shows new behaviors for low and high frequencies. The radiated noise due to TWP fluctuations is then computed in accordance with the form of the TWP spectrum. A specific computational methodology is proposed to perform the calculation without introducing limiting hypothesis on the radiated impedance.
Healthcare professionals’ perceptions of working on lifestyle management for patients with early rheumatoid arthritis — a qualitative study

ABSTRACT A healthy lifestyle should be recommended to all patients with inflammatory arthritis due to the increased risk for cardiovascular diseases. Healthcare professionals (HPs) are essential in supporting patients to achieve healthy lifestyle habits and are expected to follow international and national lifestyle management guidelines. Despite this, few studies have studied HPs’ perceptions of working on lifestyle management. Aim To explore HPs’ perceptions of working on lifestyle management for patients with early rheumatoid arthritis (RA). Methods In this qualitative study, individual interviews were conducted with 20 HPs. Qualitative content analysis was used, and three categories and six subcategories were identified. Results HPs’ perceptions of working on lifestyle management for patients with early RA revealed a need for commitment from different levels. This included commitment from healthcare managers and organizations prioritizing work on lifestyle management and providing competence development for HPs. Commitment within the team regarding coordination of interdisciplinary teamwork and development of a structured lifestyle management approach, and commitment to involving patients in lifestyle management, by facilitating patient engagement and a person-centred approach. Conclusions HPs’ perceptions of working on lifestyle management for patients with early RA revealed that commitment from healthcare managers, organizations, and the interdisciplinary team was essential to facilitate collaboration, patient involvement, and a person-centred approach.
Starvation-inactivated MTOR triggers cell migration via a ULK1-SH3PXD2A/TKS5-MMP14 pathway in ovarian carcinoma

ABSTRACT SH3PXD2A/TKS5 (SH3 and PX domains 2A) is a scaffold protein that promotes invadopodia formation and regulates cell migration; therefore, the overexpression of SH3PXD2A has been reported in various cancers. However, the molecular mechanisms of the SH3PXD2A-mediated cellular migration signaling pathway remain unknown. Here, we showed that the starvation-induced macroautophagy/autophagy or treatment with the MTOR inhibitor RAD001 elevated SH3PXD2A expression in ovarian cancer cell lines. SH3PXD2A formed a complex with ULK1 (unc-51 like autophagy activating kinase 1) and MTOR, as revealed by co-immunoprecipitation assay. Furthermore, ULK1 affected protein stability by phosphorylating SH3PXD2A at serine residues 112, 142, 146, 147, 175, and 348. Mutation of these six residues in SH3PXD2A reduced ULK1-mediated phosphorylation, blocked SH3PXD2A induction by treatment with RAD001, and reduced its binding to the cell membrane phospholipid phosphatidylinositol-3-phosphate (PtdIns3P) versus recruitment of MMP14 (matrix metallopeptidase 14) in ovarian cancer cells. Finally, the administration of RAD001 induced SH3PXD2A expression in tumor tissues, as revealed by the PDX mouse model. The clinical impact of SH3PXD2A was evaluated in ovarian and endometrial cancers using western blotting. The negative correlation between MTOR-mediated phospho-ULK1 and SH3PXD2A proteins was found in clinical specimen. Furthermore, the TCGA database revealed that the cumulative overall survival of ovarian cancer patients with higher SH3PXD2A RNA/protein expression in tumor lesions was reduced compared to those with lower SH3PXD2A expression. Our results suggest that the ULK1-SH3PXD2A-MMP14 axis might regulate the biological aggressiveness of ovarian cancer and serve as a therapeutic target in this malignancy. Abbreviations AMPK: AMP-activated protein kinase; CHX: cycloheximide; RAD001: everolimus; HBSS: Hanks’ balanced salt solution; LC-MS/MS: liquid chromatography-mass spectrometry/mass spectrometry; MMP14: matrix metallopeptidase 14; MTOR: mechanistic target of rapamycin kinase; MAPK: mitogen-activated protein kinase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; PtdIns3P: phosphatidylinositol-3-phosphate; PX: phox homology; SH3: Src homology 3; SH3PXD2A/TKS5: SH3 and PX domains 2A; SH3PXD2A-[6A]: S112A S142A S146A S147A S175A S348A mutant; ULK1: unc-51 like autophagy activating kinase 1