Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetics and the evolution of form: Experimental manipulation of a chromatin modification causes species‐specific changes to the craniofacial skeleton

A central question in biology is the molecular origins of phenotypic diversity. While genetic changes are key to the genotype–phenotype relationship, alterations to chromatin structure and the physical packaging of histone proteins may also be important drivers of vertebrate divergence. We investigate the impact of such an epigenetic mechanism, histone acetylation, within a textbook example of an adaptive radiation. Cichlids of Lake Malawi have adapted diverse craniofacial structures, and here we investigate how histone acetylation influences morphological variation in these fishes. Specifically, we assessed the effect of inhibiting histone deacetylation using the drug trichostatin A (TSA) on developing facial structures. We examined this during three critical developmental windows in two cichlid species with alternate adult morphologies. Exposure to TSA during neural crest cell (NCC) migration and as postmigratory NCCs proliferate in the pharyngeal arches resulted in significant changes in lateral and ventral shape in Maylandia, but not in Tropheops. This included an overall shortening of the head, widening of the lower jaw, and steeper craniofacial profile, all of which are paedomorphic morphologies. In contrast, treatment with TSA during early chondrogenesis did not result in significant morphological changes in either species. Together, these data suggest a sensitivity to epigenetic alterations that are both time‐ and species‐dependent. We find that morphologies are due to nonautonomous or potentially indirect effects on NCC development, including in part a global developmental delay. Our research bolsters the understanding that proper histone acetylation is essential for early craniofacial development and identifies a species‐specific robustness to developmental change. Overall, this study demonstrates how epigenetic regulation may play an important role in both generating and buffering morphological variation.
Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists

Abstract Background Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. Materials and Methods Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan–Meier plots and Cox proportional hazard models adjusted for putative confounders. Results Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50–1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65–2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37–1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42–3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26–1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88–8.77) vs the reference. Conclusion In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.
A Systematic Review of Gait Analysis in the Context of Multimodal Sensing Fusion and AI

Background: Neurological diseases are a leading cause of disability and mortality. Gait, or human walking, is a significant predictor of quality of life, morbidity, and mortality. Gait patterns and other kinematic, kinetic, and balance gait features are accurate and powerful diagnostic and prognostic tools. Objective: This review article focuses on the applicability of gait analysis using fusion techniques and artificial intelligence (AI) models. The aim is to examine the significance of mixing several types of wearable and non-wearable sensor data and the impact of this combination on the performance of AI models. Method: In this systematic review, 66 studies using more than two modalities to record and analyze gait were identified. 40 studies incorporated multiple gait analysis modalities without the use of artificial intelligence to extract gait features such as kinematic, kinetic, margin of stability, temporal, and spatial gait parameters, as well as cerebral activity. Similarly, 26 studies analyzed gait data using multimodal fusion sensors and AI algorithms. Results: The research summarized here demonstrates that the quality of gait analysis and the effectiveness of AI models can both benefit from the integration of data from many sensors. Meanwhile, the utilization of EMG signals in fusion data is especially advantageous. Conclusion: The findings of this review suggest that a smart, portable, wearable-based gait and balance assessment system can be developed using multimodal sensing of the most cutting-edge, clinically relevant tools and technology available. The information presented in this article may serve as a vital springboard for such development.
Flow impacts on estuarine finfish fisheries of the Gulf of Carpentaria

The estuaries of Australia s tropical rivers support commercial fisheries for finfish and shellfish valued at over $220 million per annum. There are also significant tourism-related and local recreational and indigenous fisheries for icon species such as barramundi. Development of water resources in Australia's Tropical Rivers region is being considered for the Flinders, Mitchell, McArthur, Roper, Daly and Victoria catchments. Greater knowledge of the freshwater requirements of tropical aquatic ecosystems, including estuaries is crucial, so that the communities of catchments where water resource development occurs can be assured that the downstream effects of such development are considered and managed based on the best available knowledge.
PENGARUH PRODUK WISATA, DESTINATION IMAGE, DAN WORD OF MOUTH TERHADAP KEPUTUSAN BERKUNJUNG (Studi Kasus pada Pengunjung Objek Wisata Goa Kreo Semarang)

Increased tourism industry make tourist visits in some areas is increasing, its specialty in Central of Java. One of them Attractions is Goa Kreo in Semarang that have unique tourism potential which is inhabited by macaque monkeys. However, the number of tourists from Q1 2014 to Q1 2015 occurred volatile and tend to decline. While the results of pre-research, in getting the dissatisfaction of visitors to the tourism product, in addition to the ideals / image imagined visitors, slightly different from those in Goa Keo. It is fear of the existence of negative information spread among tourists. This study aims to determine the influence of Tourism Products, Destination Image and Word of Mouth to the Decision to Visit Attractions Goa Kreo. This type of research is explanatory research, in which the data collection techniques used is by means of questionnaire, the selected sample of 100 people with accidental sampling and purposive sampling. Respondents are visitor attractions Goa Kreo who've been to Goa Kreo and Goa Kreo find out information from others. The results showed that the Tourism Product and significant effect on Decision to Visit viewed by contributing 18.1% and the rest is explained by other factors. Destination Image influential and significant to the Decision to Visit viewed by contributing 39.1% and the rest is explained by other factors. Word of Mouth influential and significant to the Decision to Visit viewed by contributing 42.6% and the rest is explained by other factors. While, simultaneously Travel Products, Destination Image and Word of Mouth influential and significant to the Decision to Visit. That is, the better the product Tourism, Destination Image and Word of Mouth, make higher the Decision to Visit on Goa Kreo. Additionally Word of Mouth has the most dominant influence to Decision to Visit with regression coefficient of 0.438. The results obtained by analyzing primary data using validity, reliability test, correlation coefficient, determination coefficient, simple linear regression, multiple linear regression, and a significance test (t test and F) with SPSS 20.0. Based on this, the researchers suggested that managers Attractions Goa Kreo further enhance the tourism product, which adds to signpost the way to Goa Kreo, improving tourist attractions, improved facilities and more active in offering a guide to visitors, as well as clarify the job description of employees, thus increasing tourists visit Goa Kreo.
Evaluating the pharmacokinetic and pharmacodynamic impact of different modes of ticagrelor administration

ABSTRACT Introduction Alternative administration modes for oral P2Y12 inhibitors, particularly ticagrelor, have emerged as a potential alternative to overcome the limitations associated with the delayed onset of action of these drugs in patients who are unable to swallow or with impaired absorption. Areas covered This comprehensive literature review aims to provide an overview of the current state of knowledge on the pharmacokinetics and administration modes of ticagrelor, including factors that may affect its action. It also compares the pharmacokinetics of ticagrelor with that of other drugs with similar uses to provide a comprehensive understanding of the potential advantages and limitations of different modalities of P2Y12 administration. For this purpose, Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov were searched from database inception to July 2023. Expert opinion Among the different alternatives, crushed formulations, especially for ticagrelor, have emerged as the most promising option, showing early and robust platelet inhibition. However, important questions remain unanswered, such as the comparative clinical benefits of crushed ticagrelor versus standard administration, the cost-effectiveness of alternative modes compared to intravenous P2Y12 inhibitors such as cangrelor, and the important limitations associated with the concomitant use of opioids, who have been proven to impair even the action of crushed ticagrelor.
Pattern and Process in the Earliest Colonization of the Mediterranean Islands

When and how were the Mediterranean islands first settled? Has insularity itself—the special characteristics of islands everywhere—acted as a constraint on the manner and rate of their colonization by man? If so, is it possible for archaeologists to make use of ecological and biogeographical models which have been developed to account for the abundance and diversity of animals and plants on islands of varying size and remoteness? This paper offers a brief review of the available data on the first of these important questions, seen in the light of the second and third, and it proposes some modifications to the scenarios of colonization to be found in most current accounts of early island prehistory in the Mediterranean. As a reflection of personal research interests, I emphasize the east Mediterranean evidence, but there are useful insights to be gleaned, I believe, by comparing what we find there with the pattern for the islands of the west.
Out-of-hours admissions in patients treated with immune checkpoint inhibitors and their primary management with steroids.

INTRODUCTION The incidence of immune-related adverse events (irAEs) from immune checkpoint inhibitors (ICI) is well described. However, the impact on emergency care services is not. This study investigated the incidence of irAEs out-of-hours, and the management used to mitigate symptoms and side effects. METHODS This retrospective cohort study reviewed all emergency presentations triaged by the acute oncology team between December 2021 and June 2022, between 5 pm and 9 am. Patients were identified from triage audit sheets and remaining data points were retrieved from electronic health records. Inclusion criteria included all adult patients admitted on an ICI at one tertiary centre. RESULTS In 7 months, 970 patients called the acute oncology helpline 11% (n = 109) of patients were on an ICI treatment. After clinical review, 78% (n = 70) resulted in hospital admissions, with length of stay cumulating to 496 bed days. 56% (n = 39) of patients delayed reporting symptoms, ranging between 12 hours and 10 days from symptom onset to seeking support. 49% (n = 34) patients received steroids to manage suspected irAEs. Dexamethasone was the most common steroid used in 71% (n = 24) of patients, and variation was found in prescribed doses. CONCLUSIONS These results underline the urgent need to address patient and staff education on adverse effects related to ICI. Patients require a comprehensive understanding of the symptoms and importance of prompt reporting. Staff education on recognition and treatment management is needed to reduce variation in practice. Further research is needed to identify barriers in symptom reporting and focus on realtime reporting to reduce the out-of-hours burden on services.
Subcutaneous deuterated substrate administration in mice: An alternative to tail vein infusion

Tail‐vein catheterization and subsequent in‐magnet infusion is a common route of administration of deuterium (2H)‐labeled substrates in small‐animal deuterium (D) MR studies. With mice, because of the tail vein's small diameter, this procedure is challenging. It requires considerable personnel training and practice, is prone to failure, and may preclude serial studies. Motivated by the need for an alternative, the time courses for common small‐molecule deuterated substrates and downstream metabolites in brain following subcutaneous infusion were determined in mice and are presented herein.
Evaluation of Soil Hydraulic Limitations in Determining Plant-Available-Water in Light Textured Soils

Chapters 1 and 2 identify the aims and objectives of the study, as well as the hypotheses and assumptions required. The relevant literature on soil water availability and plant response to water stress is explored. In particular these two chapters explain that plants extract water from soils by regulating a host of physiological mechanisms at their disposal – some plants are more efficient than others at doing this. As soil dries out, plants must ‘sense’ and gradually integrate the net effect of many soil conditions including: increasing soil aeration, as well as matric and osmotic suctions and soil strength, but also diminishing soil hydraulic conductivity. Plants, therefore, gradually take up water more slowly as the soil dries, depending on environmental conditions and other factors, all of which vary enormously on an hourly basis and which are difficult to predict let alone measure. Groenevelt et al. (2001; 2004) proposed a model, the Integral Water Capacity (IWC) to predict the effects of soil physical and chemical restrictions on water availability, but this model has not yet been tested against the performance of realplants. Evaluation of this model forms the primary focus of this study. The IWC uses the soil water retention curve, θ(h), to produce a differential water capacity, C(h)= dθ/dh, which is then reduced using various weighting functions, ω(h),to account for the above limiting physical and chemical properties, then integrated to produce a total amount of water that can be extracted from the soil by plants. The key, of course, is to identify robust weighting functions for each of the limiting soilconditions, yet this is no easy task because the limiting soil conditions often interact.For example, as the soil dries out, the hydraulic conductivity drops while aeration,strength and salinity all increase to varying extents – this makes it difficult to quantify the effect of any one limitation. In the present study it was therefore decided to focus solely on the unsaturated soil hydraulic conductivity as the major limiting soil condition. A significant drop in the soil hydraulic conductivity during a dry period after rainfall or irrigation can make the difference between crop success and failure, particularly in Mediterranean and arid environments. The aims of the study were to: 1) Evaluate the effect of declining soil hydraulic conductivity on soil water availability in the absence of all other known soil physical limitations. 2) Evaluate the link between real plant response to water stress and that predicted using the IWC model of Groenevelt et al. (2001) for a range of different plant species, planting densities, soil types and environmental conditions. 3) Evaluate the utility of the hydraulic conductivity function of Grant et al. (2010) in weighting the water capacity. Chapter 3 identifies the main methods used in the study. It explains that two different, light-textured soils were selected (Very fine sand and Loamy sand), for some pot experiments designed to compare the predicted and measured…
Rivaroxaban Plus Aspirin Versus Aspirin Alone After Endovascular Revascularization for Symptomatic PAD: Insights From VOYAGER PAD

BACKGROUND: Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER. METHODS: The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included. RESULTS: Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76–0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76–1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67–0.98]; P interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54–0.90]; P=0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30–58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06–2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40–1.87]; P=0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02–1.52]), although this finding was isolated to specific regions. CONCLUSIONS: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease.
Infectious etiologies among post‐donation deferrals in a military blood donation center

The burden of transfusion‐transmitted infections among blood recipients remains low due to extensive pre‐ and post‐donation screening. However, the military has the unique challenge of providing blood in austere environments with limited testing capabilities. This study evaluates the infectious etiologies of deferred blood donors at a large military blood donation center.
Targeting aberrant sialylation and fucosylation in prostate cancer cells using potent metabolic inhibitors

Abstract Aberrant glycosylation is a hallmark of cancer and is not just a consequence, but also a driver of a malignant phenotype. In prostate cancer, changes in fucosylated and sialylated glycans are common and this has important implications for tumor progression, metastasis, and immune evasion. Glycans hold huge translational potential and new therapies targeting tumor-associated glycans are currently being tested in clinical trials for several tumor types. Inhibitors targeting fucosylation and sialylation have been developed and show promise for cancer treatment, but translational development is hampered by safety issues related to systemic adverse effects. Recently, potent metabolic inhibitors of sialylation and fucosylation were designed that reach higher effective concentrations within the cell, thereby rendering them useful tools to study sialylation and fucosylation as potential candidates for therapeutic testing. Here, we investigated the effects of global metabolic inhibitors of fucosylation and sialylation in the context of prostate cancer progression. We find that these inhibitors effectively shut down the synthesis of sialylated and fucosylated glycans to remodel the prostate cancer glycome with only minor apparent side effects on other glycan types. Our results demonstrate that treatment with inhibitors targeting fucosylation or sialylation decreases prostate cancer cell growth and downregulates the expression of genes and proteins important in the trajectory of disease progression. We anticipate our findings will lead to the broader use of metabolic inhibitors to explore the role of fucosylated and sialylated glycans in prostate tumor pathology and may pave the way for the development of new therapies for prostate cancer.