Breast cancer is a global health concern, necessitating continuous advancements in diagnostic medical imaging technologies for early detection and improvement of treatment. This paper presents an overview of the past, present and future of breast cancer imaging using light and some results from the current studies. The paper specifically presents the role of Diffuse Optical Tomography (DOT) in breast cancer imaging. Conventional methods, such as X-ray mammography, face limitations. Diffuse Optical Tomography, a non-invasive light-based imaging modality can provide quantitative descriptive and architectural information about breast tissue. The paper discusses the key challenges and recent developments in breast cancer imaging using DOT to overcome some key challenges. This paper aims to contribute to the understanding of the evolving technological landscape in breast cancer imaging using light for improving early detection and patient outcomes.

We used an ultrasensitive, broadband optomechanical ultrasound sensor to study the acoustic signals produced by pressurized nitrogen escaping from a variety of small syringes. Harmonically related jet tones extending into the MHz region were observed for a certain range of flow (i.e., Reynolds number), in qualitative agreement with historical studies on gas jets emitted from pipes/orifices of much larger dimensions. For higher turbulent flow rates, we observed broadband ultrasonic emission in the ~ 0 – 5 MHz range, likely limited on the upper end by attenuation in air. These observations are made possible by the broadband, ultrasensitive response (for air-coupled ultrasound) of our optomechanical devices. Aside from their theoretical interest, our results could have practical implications for the non-contact monitoring and detection of early-stage leaks in pressured fluid systems.

There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.

In contrast to lytic phages, filamentous phages are assembled in the inner membrane and secreted across the bacterial envelope without killing the host. For assembly and extrusion of the phage across the host cell wall, filamentous phages code for membrane-embedded morphogenesis proteins. In the outer membrane of E. coli, the protein gp4 forms a pore-like complex, while gp1 and gp11 form a complex in the inner membrane of the host. By comparing sequences with other filamentous phages, we identified putative Walker A and B motifs in gp1 with a conserved lysine in the Walker A motif (K14), and a glutamic and aspartic acid in the Walker B motif (D88, E89). In this work we demonstrate that both, Walker A and Walker B, are essential for phage production. The crucial role of these key residues suggest that gp1 is likely to be a molecular motor driving phage assembly. We further identified essential residues for the function of the assembly complex. Mutations in three out of six cysteine residues abolish phage production. Similarly, two out of six conserved glycine residues are crucial for gp1 function. We hypothesise that the residues represent molecular hinges allowing domain movement for nucleotide binding and phage assembly.

Threats emerging from microplastics pollution in the marine environment have received much global attention. This review assessed sources, fate, and impacts of microplastics in marine ecosystems and identified gaps. Most studies document ubiquity of microplastics and associated environmental effects. Effects include impacts to marine ecosystems, risks to biodiversity, and threats to human health. Microplastic leakage into marine ecosystems arises from plastic waste mismanagement and a lack of effective mitigative strategies. This review identified a scarcity of microplastics mitigation strategies across different stakeholders. Lack of community involvement in microplastic monitoring or ecosystem conservation exists due to limited existence of stakeholder co-management initiatives. Although some management strategies exist for controlling the effects of microplastics (often implemented by local and global environmental groups); a standardized management strategy to mitigate microplastics in coastal areas is urgently required. There is a need to identify focal causes of microplastic pollution in the marine environment through further environmental research. This would extend to creating more effective policies as well as harmonized and extended efforts of educational campaigns and incentives for counteraction and plastic waste reduction, while mandating stringent penalties for polluting the marine environment. This will help reduce microplastic leakage into the environment.

Conditional heteroskedastic financial time series are commonly modelled by (G)ARCH processes. ARCH(1) and GARCH were recently established in C[0,1] and L^2[0,1]. This article provides sufficient conditions for the existence of strictly stationary solutions, weak dependence and finite moments of (G)ARCH processes for any order in C[0,1] and L^p[0,1]. It deduces explicit asymptotic upper bounds of estimation errors for the shift term, the complete (G)ARCH operators and the projections of ARCH operators on finite-dimensional subspaces. The operator estimaton is based on Yule-Walker equations, and estimating the GARCH operators also involves a result estimating operators in invertible linear processes being valid beyond the scope of (G)ARCH. Moreover, our results regarding (G)ARCH can be transferred to functional AR(MA).

Tsunami modeling and simulation has changed in the past few years more than it had in decades, especially so with respect to coastal inundation. Among other things, this change is supported by the approaching era of exa-scale computing, whether via GPU or more likely forms of hybrid computing whose presence is growing across the geosciences. For reasons identified across this review, exa-scale computing efforts will impact the on-shore, highly turbulent r\'egime to higher degree than the 2D shallow water equations used to model tsunami propagation in the open ocean. This short review describes the different approaches to tsunami modeling from generation to impact and underlines the limits of each model based on the flow r\'egime. Moreover, from the perspective of a future comprehensive multi-scale modeling infrastructure to simulate a full tsunami, we underline the current challenges associated with this approach and review the few efforts that are currently underway to achieve this goal. A table of existing tsunami software packages is provided along with an open Github repository to allow developers and model users to update the table with additional models as they are published and help with model discoverability.

Formulating a novel concept about the origin of human aging has been constrained by the dominance of a “classic theory” that was proposed nearly 70 years ago. Despite concern over the validity of some of its assumptions, the theory remained basic to our understanding of aging’s relationship with natural selection (NS). However, the logic upon which it rests was tested and subsequently challenged. The present theory describes the single cause of human aging consistent with Darwin’s evolutionary requirement for selection of adaptive traits. It describes an emergent property of the developmental program (DP), that is expressed upon completion of ontogenesis. It involves redundant expression of regulatory processes from the last stage of the DP. That mechanism subsequently preserves a non-aging, stable interval of unchanging NS during which reproductive fitness is achieved. Thereafter, loss of DP regulatory redundancy due to reliability limits, stochastic mutation accumulation, reproductive and a specific type of DNA damage, initiates aging which causes an inexorable decline in strength of NS to begin. It starts approximately a decade later than proposed in the classic theory. Since reproduction and aging are inextricably linked by the same emergent property, selection of that regulatory mechanism makes both traits products of NS.

We describe results from a Monte-Carlo simulation of Bell-CHSH type correlations in hydrodynamic walkers. We study feasibility of a real life walker test with relevant hydrodynamic parametric ranges. We observe the generic formation of pairs of walkers strongly anti-correlated both in position and momentum. With this source of entangled walkers, we model the insertion of 2 pins in the bath as a notion of measure, akin to the polarizers of photonic Bell tests. This insertion of pins, either static or dynamic, introduces 2 weak field signals. Each field has the physical form of a standing wave Bessel hat, representing the non-local (field mediated) influences of the measure on the walkers. With this representation of the measure, we develop protocol for a Bell game with actual hydrodynamic walkers. We model both static and dynamic insertion of pins in the walker bath. Static pins give us numerical S > 2, as a permissible Bell violation for a non-local (field based) effect. Dynamic insertion of the pins, however, leads to causal space separation of the two arms. We observe the again expected S ≤ 2. We argue for the hydrodynamic implementation and observation of these effects as a walker visualization of Bell inequalities.

Two pilot scale desalination system employing carbon modified nano-sized, zero valent metals (n-ZVM) were maufactured and tested to determine (1) the degree to which high salt water (20 to 130 mS) could be desalinated and (2) if this degree of desalination could be maintained throughout an extended treatment period. Two pilot systems were tested (referred to as Generation 1 and Generation 2) consisting of parallel lines of 4 individual reactors in series, a settling tank and an activated carbon cell at the end of each reactor line. The system capacity was 300 gal in Generation 1 and 600 gal in Generation 2 total with a total hydraulic residence time of 6 hours per reactor line (one hour per cell/tank). A slurry of n-ZVM was introduced in the first reactor on each line to yield approximately 5 to 45 grams of nano-metal per 100 L of influent salt water. The n-ZVM slurry was made from mixing tea extract with metal salts (eg ferrous sulfate, ferric chloride) to produce the carbon modified metal slurry. Initial runs focused on dosing required to achieve maximum salt removal at each of three influent salt contents, 28 mS, 44 mS and 123 mS. Once dosing was set, continuous runs (14 days, 23 days and 9 days) were carried out to (1) examine the ability of the pilot to maintain the removal efficiency over an extended period, (2) to determine the weaknesses inherent in the pilot systems, and (3) to begin to develop CAPEX and OPEX estimates for the pilot and pre-design full scale mobile desalination unit (MDU) system. Results demonstrated that maximum removal occurred with 10 g/100L of salt for the 30 mS salt solution,16 g/100 L of salt for the 40 mS influent water and 40 g/100 L for the 130 mS influent. Salt removal (expressed as Na and Cl removed) approached 78% for the 30 mS influent and 41 mS influent respectively while removal for the highest salt influent (130 mS) approached 81 %. Addition of greater amounts of carbon modified slurry than those described resulted in a pH less than 6 which inhibits continued salt removal and would require addition of calcium or magnesium oxides/hydroxides or bicarbonate solutions at the influent side to achieve greater salt removal and of course greater cost per gallon. Continuous operation over the extended time-period showed no significant decrease in salt removal with typical day to day variation of no more than 10% suggesting that this approach to desalination could rapidly provide usable water from saline aquifers, seawater or even produced water. Treatment of saline waters at 30 mS or less yields effluent water in the range necessary for irrigation use of many crops while treatment of seawater or produced water levels of salt (40 mS or higher) yields effluent in the range of 8 to 10 mS a range ideal for RO influent that would prevent the production of large volumes of brine. Pilot testing continues with seawater extracted from Puget Sound, Seattle WA and higher levels of salt to better represent produced water.

(RADA)4 nanoscaffolds are excellent candidates for use as peptide delivery vehicles: they are relatively easy to synthesize with custom bio-functionality, and assemble in situ to allow a focal point of release. This enables (RADA)4 to be utilized in multiple release strategies by embedding a variety of bioactive molecules in an all-in-one ‘construct’. One novel strategy focuses on the local, on-demand release of peptides triggered via proteolysis of tethered peptide sequences. However, the spatial-temporal morphology of self-assembling nanoscaffolds may greatly influence the ability for enzymes to both diffuse into as well as actively cleave substrates. Fine structure and its impact on overall affect on peptide release is poorly understood. In addition, fractal networks observed in nanoscaffolds are linked to the fractal nature of diffusion in these systems. Therefore, matrix morphology and fractal dimension of virgin (RADA)4 and mixtures of (RADA)4 and matrix metalloproteinase 2 (MMP-2) cleavable substrate modified (RADA)4 were characterized over time. Sites of high (GPQG+IASQ, CP1) and low (GPQG+PAGQ, CP2) cleavage activity were chosen. Fine structure was visualized using established according to established methods. After 2 hrs of incubation, nanofiber networks showed an established fractal nature, however nanofibers continued to bundle in all cases as incubation times increased. It was observed that despite extensive nanofiber bundling after 24 hrs of incubation time, the CP1 and CP2 nanoscaffolds were susceptible to MMP-2 cleavage. The properties of these engineered nanoscaffolds characterized herein illustrate that they are an excellent candidate as an enzymatically initiated peptide delivery platform.

This data descriptor summarizes the process applied and data gathered from 50 publications/papers reporting on the use of photography generated by tourists, tour operators and members of the public, with a particular focus on the crowdsourcing of photographs through online platforms and social networking sites (SNSs) as a method of research for wildlife conservation and ecotourism. The papers were collected in a systematic literature review to inform a pilot study of the feasibility of using SNSs to crowdsource georeferenced photographs of endangered Bornean Pygmy Elephants (Elephas maximus borneensis) taken by ecotourists along the Lower Kinabatangan River region of Sabah, Malaysia. Papers were sourced using the Murdoch University Findit online-search tool to search over 100 databases, including Proquest, Scopus and Web of Science. The criteria for a paper to be included in the review (and shared via the dataset attached to this this data descriptor) were that it was peer-reviewed, published in English, between 1997 and the 31 December 2017, had the full text accessible online and reported on a study or studies that utilized photographs that tourists, tour operators and/or members of the public generated and shared via SNSs or online platforms.

Asaia bacteria commonly comprise part of the microbiome of many mosquito species in the genera Anopheles and Aedes, including important vectors of infectious agents. Their close association with multiple organs and tissues of their mosquito hosts enhances the potential for paratransgenesis for delivery of anti-malaria or anti-virus effectors. The molecular mechanisms involved in the interactions between Asaia and mosquito hosts, as well as Asaia and other bacterial members of the mosquito microbiome, remained unexplored. Here, we determined the genome sequence of the strain W12 isolated from Anopheles stephensi mosquitoes, compared them to other Asaia species associated with plants or insects, and investigated some properties of the bacteria relevant to their symbiosis with host mosquitoes. The assembled genome of strain W12 has a size of 3.94 MB, which is the largest among Asaia spp studied so far. At least 3,585 coding sequences were predicted. The insect-associated Asaia including strain W12 carried more glycoside hydrolase (GH) encoding genes (31 per genome) than those isolated from plants (22 per genome). W12 had the most predicted regulatory protein components (213) among the selected Asaia (ranging from 131 to 211), indicating its great capability to adapt to frequent environmental changes in the mosquito gut. Two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases (cyoABCD-1 and cyoABCD-2) were found in most of Asaia genomes, which possibly offer alternative terminal oxidases and allow the flexible transition of respiratory pathways. Genes involved in the production of acetoin and 2,3-butandiol have been identified in Asaia sp. W12.

Purpose: Social responsibility has been accepted as a core value of nursing profession, particularly in the area of health disparity, but it seems to be difficult to understand for what is meant by social responsibility. The purpose of this study was to explore ways to define the concept of social responsibility of nursing in order to understand the meaning of social responsibility in the field of nursing profession. Methods: The concept analysis process by Walker and Avant was used to clarify the meaning of social responsibility of nursing. Results: Defining attributes of social responsibility of nursing included praxis, as approach to strategizing for social and structural change of inequity, care for an oppressed group which is under social suffering caused by the privilege and power, and action for health policy change in social and political unequal contexts. The antecedents of social responsibility of nursing included reflectivities in identifying personal characteristics, taking seriously the perspective of other vulnerable population, recognizing social environmental status quo (‘fair or unfair’), developing competences in ethical and moral reasoning with social issues. Consequences of social responsibility of nursing were achieving social justice, as equal access to basic human health need in societal level, equal access to effective nursing practice delivery system and development of health promotion policy for world health administrative practices (“health for all”) in nursing. Conclusion: This study provides a guidance to direct future studies through the procedure of identifying conceptual attributes in the context of social responsibility of nursing. Future studies are suggested to develop instruments for social responsibility as well as development of educational programs to promote social responsibility competences in nursing students and nurses.

To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in the phosphate and composition of the renal filtrate, and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully this will raise questions and stimulate new ideas for further research.

Dietary restrictions or reductions such as fasting for weight loss, are often difficult to adhere to in the long term due to increased appetite and food cravings. Recently, gastrointestinal delivery of bitter hops extract has been shown to be effective at reducing appetite in men. Our aim was to determine the effect of bitter hops on appetite and cravings in women, using a day-long, water-only fast. Thirty adult women were recruited and required to fast for 24 h from 1800 h to 1800 h on three occasions and given an ad libitum meal to break each fast. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 125 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. Treatment with both the HD and LD treatment groups exhibited a significant (p < 0.05) reduction in appetite and cravings for food. Two participants reported loose stools and one reported heart-burn while on the HD treatment, and one participant reported loose stools while on the LD treatment. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and shows that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food.

Snow crab replaced groundfish fisheries as the primary focus of the Newfoundland and Labrador (NL) fishing industry in the mid-1990s. Over the past three decades, management philosophies in this male-only fishery have shifted from promoting industry expansion to promoting industry rationalization to implementing Precautionary Approach (PA) management. Until the mid-2010s, there were regionalized management strategies characterized by higher exploitation rates in northern than southern sub-stock units along the NL marine shelves. However, in the late 2010s, exploitation rates were permitted to elevate to high levels across the entire stock range in association with a large resource decline and evidence of biological harm through fishing emerged in chronically depleted areas. In 2019, when stock and fishery productivity were near historic lows, a multi-indicator PA system was informally introduced into management of the resource. This event coincided with anticipated improvements in stock and fishery performance. This paper examines the extent to which the multi-indicator PA management system, focused on promotion of both biological protection and maximization of fishing efficiency, may have contributed to recent improvements in stock and fishery status. A suite of indicators from areas implementing PA guidance into management in 2019 prior to formal adoption of the PA system in 2023 suggest the system has been highly beneficial in promoting rapid recovery, improving stock and fishery performance metrics to levels matching or exceeding historic levels under similar conditions. We discuss capacity of the system to better safeguard biological aspects of resource and fisheries productivity moving forward under a scenario of an expectant resource decline.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Lineage plasticity, the switching of cells from one lineage to another has been recognized to be a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of Epithelial-Mesenchymal Transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Recent studies have elucidated the diversity of genes encoding venom in sea anemones. However, most of those genes are yet to be explored in an evolutionary context. Insulin is a common peptide across metazoans and has been coopted into a predatory venom in many venomous lineages. In this study, we focus on the diversity of insulin-derived venoms in sea anemones and on elucidating their evolutionary history. We sourced data for 34 species of sea anemones and found sequences belonging to two venom families that have Insulin PFAM annotations (Cono-Insulin, VP302). Our findings show that both families have undergone duplication events. Members of each of the independently evolving clades have consistent predicted protein structures and distinct dN/dS values. Our work also shows that VP302 is part of a multidomain venom contig and has experienced a secondary gain into the venom system of cuticulate sea anemones.

An accurate, economical, and reliable device for detecting falls in persons ambulating with the assistance of an orthopedic walker is crucially important for the elderly and patients with limited mobility. Existing wearable devices such as wristbands are not designed for walker users, and patients may not wear them at all times. This research proposes a novel idea of attaching an internet-of-things (IoT) device with an inertial measurement unit (IMU) sensor directly to an orthopedic walker to perform real-time fall detection as well as activity logging. A dataset is collected and labeled for walker users in four activities, including idle, motion, step, and fall. Classic machine learning algorithms are evaluated using the dataset by comparing their classification performance. Deep learning with convolutional neural network (CNN) is also explored. Furthermore, the hardware prototype is designed by integrating a low-power microcontroller for onboard machine learning, an IMU sensor, a rechargeable battery, and Bluetooth wireless connectivity. The research results show the promise of improved safety and well-being of walker users.

Background: As a result of the pandemic, families and children have faced physical, emotional, and mental challenges. However, there has been little attention given to the relationship between the COVID-19 pandemic and child development. This systematic review aims to identify the impact of the pandemic on child development, globally. Methods: This study follows the PRISMA guidelines for the systematic review of 16 quantitative and qualitative studies conducted between 2020-2023. Results: This systematic review suggest that the COVID-19 pandemic played a crucial role in hindering child development in early childhood. Conclusion: Therefore, it is important to promote and implement the use of policies and strategies to overcome these obstacles.

Primates are traditionally considered to have a poor sense of smell. However, olfaction is important for non-human primates as demonstrated by conspicuous scent-marking behaviours in lemurs. We studied two family groups (N=4) of crowned lemurs (Eulemur coronatus) housed at Colchester and Twycross zoos (UK) by combining behavioural observations and chemical analyses of scent-marks. We recorded observations of olfactory behaviours for 201 h using instantaneous scan sampling. We investigated the volatile compounds of ano-genital odour secretions using solid-phase microextraction and gas chromatography-mass spectrometry. Males scent-marked most frequently, displaying ano-genital marking for allomarking, head marking for countermarking and wrist marking in specific areas of the enclosure. Females displayed ano-genital marking predominantly on feeding devices. We detected a total of 38 volatile components in all male ano-genital scent-marks and 26 in all female samples of ano-genital odour secretions, including a series of esters, aldehydes, ketones, alcohols, terpenes, volatile fatty acids and hydrocarbons that have been identified in odour profiles of other primates. In conclusion, we found sexual dimorphism in crowned lemurs. Male head and wrist marking behaviours might play defensive territorial functions, while ano-genital marking would be related to socio-sexual communication as chemical mate-guarding. Female ano-genital marking might be involved in resource defense.

ARBTools is a Python library containing a Lekien-Marsden type tricubic spline method for interpolating three-dimensional scalar or vector fields presented as a set of discrete data points on a regular cuboid grid. ARBTools was developed for simulations of magnetic molecular traps, in which the magnitude, gradient and vector components of a magnetic field are required. Numerical integrators for solving particle trajectories are included, but the core interpolator can be used for any scalar or vector field. The only additional system requirements are NumPy.

Scutellaria multicaulis, a member of the Lamiaceae, is a medicinal plant indigenous to Iran, Afghanistan, and Pakistan. It has been widely used as a prominent herb in traditional medicine for thousands of years. This plant is reported with baicalein, wogonin, and chrysin flavonoids as a significant group of chemical ingredients, which can cure different diseases such as breast cancer. S. multicaulis leave extract was used for the bioreduction of silver nanoparticles (SmL-Ag-NPs), and their phytochemical contents and antioxidant, antibacterial, anti-proliferative, and apoptotic activity were evaluated. Optimal physicochemical properties of SmL-Ag-NPs were obtained by mixing 5% of leave extract and 2 mM of aqueous AgNO3 solution and confirmed by characterization studies including UV–visible spectrophotometry, FE-SEM, EDX, DLS, zeta potential, TGA, SERS, XRD and FTIR Spectroscopy. SmL-Ag-NPs exhibited higher content of TPC (Total Phenolic Content) and TFC (Total Flavonoid Content) and potential antioxidant activity. SmL-Ag-NPs also demonstrated dose-dependent cytotoxicity against MDA-MB231 cells multiplication with an IC50 value of 37.62 μg/mL at 48h through inducing cell apoptosis. This is the first report on the biosynthesis of silver nanoparticles using S. multicaulis leave extract, which can provide treatment for cancer diseases and reduce some negative effects of chemotherapy.

The surge in popularity of Delta-8 Tetrahydrocannabinol (D8-THC) products, coupled with a lack of stringent regulation and oversight, has given rise to concerns regarding consumer safety and compliance with existing laws. This article delves into the challenges posed by the unregulated sale of D8-THC products, emphasizing the potential for contamination with prohibited constituents, including Delta-9 Tetrahydrocannabinol (D9-THC). The 2018 Farm Bill dictates that D9-THC concentrations must not exceed 0.3%, necessitating precise testing methods for accurate validation. Existing testing procedures, particularly involving High-Performance Liquid Chromatography (HPLC), face difficulties in distinguishing between D8 and D9 peaks, necessitating adjustments in parameters to enhance accuracy. The development of more refined testing methodologies is crucial for companies to ensure compliance, prevent adverse health effects, and provide consumers with accurately characterized cannabinoid profiles in the products they purchase.

Our objective was to evaluate whether pregnancy is prolonged by use of a proteomics-based maternal serum screening test followed by treatment interventions. This is a secondary analysis of the PREVENT-PTB randomized trial comparing screening with the PreTRM test versus no screening. The primary trial analysis found no significant between-group difference in preterm birth rate. Rather than considering a dichotomous outcome (preterm vs term), we treated gestational age at birth as a continuous variable using survival analysis. We also evaluated between-group difference in NICU length of stay and duration of respiratory support. Results indicated that pregnancy was significantly prolonged in subjects screened with PreTRM test compared to controls (adjusted hazard ratio 0.53, 95% confidence interval 0.36-0.78, P &lt;0.01). Newborns of screened subjects had significantly shorter NICU stay but no significant decrease in duration of respiratory support. In the PreTRM screen-positive group, interventions that were associated with pregnancy prolongation included care management and low-dose aspirin but not 17-hydroxyprogesterone caproate. We concluded that screening with the PreTRM test followed by interventions for screen-positive pregnancies can prolong pregnancy and reduce NICU-LOS.

Patients often need the use of their arms to assist with functional activities, but after bone disruption, pushing is frequently limited to less than 4.5 kg. No method exists to measure arm weight bearing objectively in clinical settings. This project aimed to design, construct, and test a walker for patients who need to limit arm force to prevent excessive bone stress during post-fracture (iatrogenic or traumatic) ossification. First, a qualitative study was conducted to obtain critiques of a Clinical Force Measuring (CFM) walker prototype from rehabilitation professionals. Key statements and phrases were coded that allowed “themes” to emerge from transcribed interviews, which guided device revisions. Next, a second CFM Walker prototype was designed based on the qualitative data and device criteria/constraints and finally tested. The result was fabrication of a new lightweight, streamlined, and cost-effective prototype walker with a simple visual display and auditory cue with upper limit alarms. Key features included attachments for medical equipment and thin film force-sensing resistors integrated into the walker handles that progressively activated 3 LEDs and a buzzer when arm force exceeded programmed thresholds. The innovative CFM Walker will help patients with restricted arm weight bearing, especially elderly adults, recover safer and faster in the future.

Most quantum gravity theories endow space-time with a discreet nature by space quantization on the order of Planck length (lp ). This discreetness could be demonstrated by confirmation of Lorentz invariance violations (LIV) manifested at length scales proportional to lp. In this paper, space-time line elements compatible with the uncertainty principle are calculated for a homogeneous, isotropic expanding Universe represented by the Friedmann-Lemaitre-Robertson-Walker solution to General Relativity (FLRW or FRW metric). To achieve this, the covariant geometric uncertainty principle (GeUP) is applied as a constraint over geodesics in FRW geometries. A generic expression for the quadratic proper space-time line element is derived, proportional to Planck length-squared and dependent on two contributions. The first is associated to the energy-time uncertainty, and the second depends on the Hubble function. The results are in agreement with space-time quantization on the expected length orders, according to quantum gravity theories and experimental constraints on LIV.

The first two decades of the 21st-century have seen the emergence of the modern citizen science movement, increased demand for niche eco and wildlife tourism experiences, and the willingness of people to voluntarily share information and photographs online. To varying extents, the rapid growth of these three phenomena has been driven by the availability of portable smart devices, access to the Web 2.0 internet from almost anywhere on the planet, and the development of applications and services, including social media/networking sites (SNSs). In addition, the number of peer-reviewed publications that explore how text and images shared on SNSs can be data-mined for academic research has surged in recent years. This systematic quantitative review has two goals. The first goal is to provide an oversight of how the photographs that ecotourists share online are contributing to wildlife tourism research. The second goal is to promote the emerging photovoice technique as a theoretical context for social research based on the photographs and comments that ecotourists share on SNSs. From the perspectives of community benefits, conservation behaviours, and environmental education, there are many similarities between authentic ecotourism experiences and quality ecological citizen science programs. Much of the literature regarding the theory and practice of citizen science reports on the difficulties of attracting, training, motivating and retaining community members. The synthesis of this review is that crowdsourcing wildlife and tourism data from comments and photographs that ecotourists share on SNSs is a credible method of research that provides a self-replenishing pool of citizen scientists.

Tissue programmed death ligand-1 (PD-L1) protein is the recognized predictive immune biomarker of immune checkpoint inhibitor (ICI) treatment benefit in metastatic non-small cell lung cancer (NSCLC). However, tissue PD-L1 protein testing can be limited by tumor heterogeneity and fraught with tissue acquisition difficulties. A plasma PD-L1 assay potentially overcomes these tissue limitations. Patients with metastatic NSCLC treated with first-line ICI-based treatment and available results of plasma cfRNA PD-L1 by real-time polymerase chain reaction (RT-PCR) and tissue PD-L1 protein PD-L1 with the Dako 22C3 monoclonal antibody were retrospectively assessed for median and landmark 3-year overall survival (OS). OS was identical whether positive plasma cfRNA PD-L1 expression or positive tissue PD-L1 protein expression (median OS 15 months; 3-year landmark OS 30%; hazard ratio (HR) 0.97; 95% CI, 0.44-2.10). Positive plasma cfRNA PD-L1 patients also demonstrated a numerically longer median and higher 3-year OS compared to patients lacking PD-L1 expression (median 15 months versus 8 months; 3-year landmark OS 30% versus 15%; HR 0.56; 95% CI, 0.27-1.17). Plasma cfRNA PD-L1 expression by RT-PCR was similarly predictive of ICI-based treatment benefit as tissue PD-L1 protein expression.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By miRNA-Sequencing analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression in the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis that miRNAs are important regulators of retinoic acid-induced neuronal outgrowth and regeneration in regeneration-competent species.

Gait abnormalities are one of the distinguishing symptoms of patients with Parkinson's disease (PD) that contribute to fall risk. Our study compares the gait parameters of people with PD when they walk through a predefined course without assistance, with a conventional walker, and with a motorized walker under different speed cues. Six PD subjects were recruited at the New York Institute of Technology College of Osteopathic Medicine to participate in this study. Spatial posture and gait data of the test subjects were collected via a VICON motion capture system. We developed a framework to process and extract gait features and applied statistical analysis on these features to examine the significance of the findings. The results showed that motorized walkers with haptic cues significantly improved gait symmetry of PD subjects. Specifically, the asymmetry index of the gait cycle time was reduced from 6.7% when walking without assistance to 0.56% and below when using a walker. Furthermore, the double support time of a gait cycle was reduced by 4.88% compared to walking without assistance.

Lineage diversity can refer to the number of genetic lineages within species or to the number of deeper evolutionary lineages, such as genera or families, within a community. Community lineage diversity (CLD) is of interest to ecologists, evolutionary biologists, biogeographers, and those setting conservation priorities. Despite its relevance, it is not clear how to best quantify CLD. With North American tree communities as an example, we test which taxonomic and phylogenetic metrics best measure CLD. We find that phylogenetic metrics outperform taxonomic metrics. Faith’s phylogenetic diversity performs well, but is skewed towards the number of lineages in recent time. The best metric is newly derived here, and termed time integrated lineage diversity (TILD). Mapping the lineage diversity of tree communities across the contiguous United States, we find a spatial pattern differing from that of species richness in key areas. The Pacific Northwest, Great Lakes Region, state of Maine, and south-eastern piedmont and coastal plain forests all emerge as areas high in lineage diversity, but relatively lower in species richness. We urge the consideration of lineage diversity, as well as species richness, when setting conservation priorities.

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field.

Background: Portable oxygen concentrators (POCs) have shown efficacy in delivering adequate oxygen for various patient scenarios; however, there is a lack of research on POCs’ efficacy across different respiratory rates specifically among COPD patients. Methods: This bench study was conducted using the IngMar Medical Active Servo Lung 5000 attached to flexible tubing, which simulated an adult patient’s nares. An oxygen analyzer (Maxtec Handi+) was connected to the tubing 6 inches below the nares to estimate the inspired oxygen concentration at the adult trachea. A standard nasal cannula was placed in the simulated patient nares, which was also attached to each POC. The IngMar Lung was programmed to simulate a COPD patient at the following respiratory rates: 15, 20, 30, and 40 breaths/min. POC devices were then compared to an oxygen wall outlet and a standard oxygen concentrator (non-portable CAIRE device). The POCs included the CAIRE FreeStyle Comfort (with Autosat), CAIRE FreeStyle Comfort (without Autosat), Inogen G4, Inogen G5, Phillips SimplyGo Mini, GCE Zen-O lite, Drive Medical iGo2, and Kingon POCs. Descriptive statistics and ANOVAs were computed to determine statistically significant differences between POCS and control devices (wall oxygen and standalone oxygen concentrator). Results: Across most respiratory rate scenarios, the wall oxygen and standalone oxygen concentrator (control group) resulted higher oxygen measurements compared to the POCs. Among the POCs on setting 2, the highest oxygen measurement for 15, 30, and 40 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity 5 (24.43%, 24.81%, and 25.0%, respectively). On setting 2, the 20 breaths/min highest oxygen measurement was the Inogen G4 (24.43%). For setting 5, the highest oxygen measurement for 15 breaths/min and 40 breaths/min was the CAIRE FreeStyle Comfort without AutoSat (31.56% and 26.13%, respectively), while the highest oxygen measurement for 20 breaths/min was the Inogen G5 (30.26%), and the highest oxygen measurement for 30 breaths/min was the CAIRE FreeStyle Comfort with AutoSat on sensitivity level 5 (27.89%). Conclusions: The oxygen administered through the wall and the standalone CAIRE oxygen concentrator all delivered higher oxygen levels compared to the POCs (with the exception of the 40 breaths/min scenario on setting 2). However, among the POCs, the CAIRE Freestyle Comfort with AutoSat, CAIRE Freestyle Comfort without AutoSat, and the Inogen G4 all performed the best among the various breathing rate scenarios.

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries [1]. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease [1], all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under transcriptional regulation of both the nuclear and the mitochondrial genome, to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, to dynamics which regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function to cause disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs including the ovary (oocyte and granulosa cell), uterus, placenta, and circulation to cause reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in transgenerational transmission of PCOS and metabolic disorders.

This article discusses a focused study on visualizing the flow patterns in a two-phase pulsating heat pipe (PHP) using Fe₃O₄/water as the working fluid at 3 V/V% concentration. The research also aims to meticulously examine phase change phenomena in the heating section, particularly focusing on bubble formation and expansion processes. A high-speed video camera was utilized to capture dynamic insights into the behavior of the Fe₃O₄/water mixture. Based on the findings, a straightforward model was developed to explain bubble generation and growth in the mixture, serving as a useful reference for future PHP designs and optimizations. Visual observations also noted the stable nature of the Fe₃O₄/water nanofluid over a four-day period, confirming its consistency throughout the experiments. Moreover, the impact of heat load variation on the evaporator section was assessed using controlled heat inputs ranging from 10 to 80 Watts. Observations on the arrangement of slugs and plugs at a 50% filling ratio revealed interesting self-adjusting flow patterns in response to increasing heat inputs, providing valuable insights into PHP operational dynamics. Notably, the oscillatory flow behavior of Fe₃O₄/water, the chosen working fluid, exhibited greater activity in comparison to water. This distinctive flow behavior contributed to achieving heightened thermal performance efficiency for the Fe₃O₄/water system, attributed to its faster attainment of the annular flow condition.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

Government-led legislation is a key strategy to reduce plastic pollution; however, societal perception can heavily influence government intervention for environmental issues. To understand the public acceptability of government action to reduce plastic pollution, we examine the perception of existing and upcoming legislative action on single-use plastics by means of a structured survey with additional semi-structured interviews. Our focus is on the four Atlantic provinces of Canada, which was the first region in Canada to implement provincial-wide legislation for plastic reduction at the consumer level in 2019. Results show strong public support (77 %, n = 838) for bans on single-use plastic bags at the consumer level, and for further plastic pollution reduction legislation. However, the level of support differed between regions and by demographics. Semi-structured interviews show that decision-makers should increase efforts in raising consumer awareness and standardizing regulations across jurisdictions for smoother transitions prior to legislative action.

Objective: To determine if higher weight-to-length z-scores after 32 weeks of gestation are associated with higher Pulmonary Scores (PS) in preterm infants requiring respiratory support using a prospective observational study. Methods: Infants born <30 weeks, with a post-menstrual age (PMA) of 30-33 weeks were enrolled. Weight, infant’s length, and head circumference were measured weekly. Data on calories/kg/d, protein g/kg/d, weight for length percentiles, z-scores, and BMI at 33 through 40 weeks PMA were collected. PS was calculated. Results: We analyzed 91 infants. The mean gestational age was 26.9 ± 1.7 weeks. There was a significant association between PS and W/L z scores(p<0.0001). For every one-unit increase in W/L z-scores, PS increased by 0.063. There was a significant association between PS and W/L percentiles (p = 0.0017) as well as BMI (p = <0.0001). For every unit increase in W/L percentiles, PS increased by 0.002, and for a unit increase in BMI, PS increased by 0.04. The association remained significant after postnatal steroids, sex, corrected, and birth gestational ages were included in the regression analysis. Nutrition did not affect anthropometric measurements. Conclusion: Our study is the first to demonstrate that higher BMI and W/L may adversely affect respiratory severity in infants.

Adiponectin (APN) has been thoroughly investigated for its role in various human disorders. It is fascinating to note that this peptide plays an essential role as a therapeutic agent to cure a plethora of disorders. Our aim is to elucidate the applications and therapeutic potential of this peptide, demonstrating its involvement in age-related macular degeneration (AMD) and other metabolic disorders. APN has been correlated with many ocular disorders and metabolic disorders. The localization and expression of APN in various tissues were the first markers of its local actions. Screening this peptide on a wider platform helps to confirm its application as a novel peptide in various diseases. Altered levels of APN have been well elucidated in the progression of metabolic disorders, and its targeted administration has resulted in combating dysregulation of biochemical and molecular pathways involved in disease pathology. A close association of oxidative stress is also known to contribute to the onset of retinal disorders. Among so many APN has been shown to have a promising response in the context of wet AMD, but further studies are needed to elucidate its full potential in humans.

The combination of e-commerce and the green economy allows enterprises to distribute their green products directly to consumers through Internet channels. This paper investigates the impact of service spillovers on emission reduction and channel decisions in a two-echelon supply chain,in which the supplier is a Stackelberg leader and the retailer is a follower.By comparing the equilibrium outcomes of the single-channel and dual-channel supply chain in a setting with and without retail services, we observe that the supplier prefers to encroach on the market when services that retail locations provide largely spillover to and benefit the direct sales channel. Contrary to popular belief, a higher degree of service spillovers is beneficial for the retailer to get more returns under the dual-channel structure, whereas supplier encroachment will lead to a decline in the service level if the spillover degree is relatively low. In addition, the emission reduction level of products under supplier encroachment is always higher than that employed in the single-channel structure if consumers have both low-carbon preference and high degree of service sensitivity. Furthermore, we extend the equilibrium decisions under a carbon cap-and-trade (CCT) mechanism; the results fully verify the above conclusions. Interestingly, the implementation of a carbon price not only motivates carbon emission abatement and supplier encroachment, but also helps achieve a win-win outcome for supply chain members when service spillovers happen.

Rapid technological advancements in information communication technologies have enabled water resource data collection at greater spatial and temporal scale. However, this water data is often limited to the purposes of its primary collection, and limits decisions made by stakeholders towards sustainable urban water management. This empirically focused research paper examines how water practitioners involved in strategic planning can capture additional values from integrating different water data. Furthermore, the perception of 22 urban water practitioners across Australia are presented, regarding the importance of and difficulty in using water data for strategic planning, and the necessary steps for achieving integrated water management practices. Interviewees perception revealed gaps in available water resource data (i.e. water quality, ground water, stormwater, and urban water use), and limitations of industry guidelines for operating within existing governance frameworks. Overall, the research highlights the Australian urban water sector’s perception of water data’s crucial role in representing stakeholders interest; however, changes made in water data’s collection are required for an integrated water management approach. Implications for future open water data standard are discussed.

Adult stem cells (ASCs) can be cultured with difficulty from most tissues, often requiring chemical or transgenic modification to achieve adequate quantities. We show here that mouse primary fibroblasts grown in suspension change from the elongated and flattened morphology observed under standard adherent culture conditions generating rounded cells with large nuclei and scant cytoplasm expressing the mesenchymal stem cell (MSC) marker (Sca1; Ly6A) within 24hrs. Based on this initial observation, we describe here a suspension culture method that, irrespective of the lineage used, mouse fibroblast, primary human somatic cells (fibroblasts, hepatocytes and keratinocytes), is capable of generating a high yield of cells in spheroid form which display expression of ASCs surface markers, circumventing the anoikis which often occurs at this stage. Moreover, mouse fibroblasts-derived spheroids can be differentiated into adipogenic and osteogenic lineages. Analysis of single cell RNA sequence data identified 8 distinct cell clusters with one in particular comprising approximately 10% of the cells showing high levels of proliferative capacity expressing high levels of genes related to MSCs and self-renewal as well as extracellular matrix (ECM). We believe the rapid, high-yield generation of proliferative, multi-potent ASC-like cells by the process we term suspension-induced stem cell transition (SIST) could have significant implications for regenerative medicine.

Atherosclerosis is a leading cause of cardiovascular disease and mortality worldwide. Alterations in the gut microbiota composition, known as gut dysbiosis, have been shown to contribute to atherosclerotic cardiovascular disease (ACVD) development through several pathways. Disruptions in gut homeostasis are associated with activation of immune processes and systemic inflammation. The gut microbiota produces several metabolic products, namely trimethylamine (TMA), which is used to produce the proatherogenic metabolite trimethylamine-N-oxide (TMAO). Short chain fatty acids (SCFAs), including acetate, butyrate, and propionate, and certain bile acids (BAs) produced by the gut microbiota lead to inflammation resolution and decrease atherogenesis. Chronic low-grade inflammation is associated to common risk factors for atherosclerosis, including metabolic syndrome, type 2 diabetes mellitus (T2DM), and obesity. Novel strategies for reducing ACVD include the use of nutraceuticals such as resveratrol, modification of glucagon-like peptide 1 (GLP-1) levels, supplementation with probiotics, and administration of prebiotic SCFAs and BAs. Investigation into the relationship between the gut microbiota and its metabolites, and the host immune system could reveal promising insight into ACVD development, prognostic factors, and treatments.

Retinoic acid (RA) is the biologically active metabolite of vitamin A,and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting. However, few studies have demonstrated the role of miRNAs in RA-induced neurite sprouting. By R-Seq analysis, we identify 482 miRNAs in the regenerating CNS of the mollusc Lymnaea stagnalis, 219 of which represent potentially novel miRNAs. Of the remaining conserved miRNAs, 38 show a statistically significant up or downregulation in regenerating CNS as a result of RA treatment. We further characterized the expression of one neuronally-enriched miRNA upregulated by RA, miR-124. We demonstrate for the first time that miR-124 is expressed within the cell bodies and neurites of regenerating motorneurons. Moreover, we identify miR-124 expression within the growth cones of cultured ciliary motorneurons (Pedal A), whereas expression from the growth cones of another class of respiratory motorneurons (RPA) was absent in vitro. These findings support our hypothesis miRNAs are important regulators of retinoic acid induced neuronal outgrowth and regeneration in regeneration-competent species.

Tidal stream energy is a low carbon energy source. Tidal stream turbines operate in a turbulent environment, and the effect of the structure between the turbine and seabed on this environment is not fully understood. An experimental study using 1:72 scale models based on a commercial turbine design was carried out to study the support structure influence on turbulence intensity around turbine blades. The study was conducted using the wave-current tank at LABIMA, University of Florence. A realistic flow environment (ambient turbulent intensity = 11%) was established. Turbulence intensity was measured upstream and downstream of a turbine mounted on two different support structures (one resembling a commercial design, the other the same with an additional vertical element), in order to quantify any variation in turbulence and performance between the support structures. Turbine drive power was used to calculate power generation. Acoustic Doppler Velocimetry was used to record and calculate upstream and downstream turbulence intensity. In otherwise identical conditions, performance variation of only 4% was observed between two support structures. Turbulent intensity at 1, 3 and 5 blade diameters, both upstream and downstream, showed variation up to 21% between the two cases. The additional turbulent structures generated by the additional element of the second support structure appears to cause this effect, and the upstream propagation of turbulent intensity is believed to be permitted by surface waves. This result is significant for the prediction of turbine array performance.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

We develop an optimized force-field for poly(3-hexylthiophene) (P3HT) and demonstrate its utility for predicting thermodynamic self-assembly. In particular, we consider short oligomer chains, model electrostatics and solvent implicitly, and coarsely model solvent evaporation. We quantify the performance of our model to determine what the optimal system sizes are for exploring self-assembly at combinations of state variables. We perform molecular dynamics simulations to predict the self-assembly of P3HT at ~350 combinations of temperature and solvent quality. Our structural calculations predict that the highest degrees of order are obtained with good solvents just below the melting temperature. We find our model produces the most accurate structural predictions to date, as measured by agreement with grazing incident X-ray scattering experiments.

Phosphorus is required by laying hens for a variety of biological functions. It is usually provided in excess, in a readily digestible inorganic form in diet formulations. However, this does not represent an efficient use of a finite resource and can result in water pollution. Plant bound phosphorus in phytate, is common in commercial poultry diets, and represents an alternate source of phosphorus, however poultry lacks the enzyme to digest it. By adding enzymes to their diets, the availability of this phytate-bound phosphorus can be increased allowing for the reduced inclusion of inorganic P in the diet formulation. Therefore, this study was conducted to examine the effect of a natural enzyme complex that contains phytase and xylanase in layer diets. Novogen Brown Classic layers (n=314) were fed one of two diets: (T1) control diet or (T2) control diet plus a natural mixed-enzyme product with both, phytase and xylanase. Experimental diets were provided for 12 days after which the excreta from each pen were collected for an additional three days to determine total retention and ileal digestibility of phosphorus and gross energy. At the end of the trial the birds were euthanized, and their ileal contents were collected. Productivity parameters were also recorded over the course of the study. The amount of phosphorus detected in the excreta of the control group was significantly higher than the amount detected in the enzyme-supplemented group (P<0.05). Both phosphorus retention and phosphorus ileal digestibility were significantly higher in the enzyme-supplemented birds (P<0.001). Gross energy digestibility was significantly higher in the enzyme-supplemented birds for both the total tract and ileal samples (P<0.001). There were only numerical improvements, not significant, in the layer productivity parameters. This study showed that the enzyme supplement can improve total retention and ileal digestibility of phosphorus and gross energy in older layers.

In a bandsaw machine the blade guides provide additional stiffness and help to align the blade near the cutting region. Typically these are either in form of blocks made of carbide or ceramics or as sealed bearings. Abrasive particles, generated while cutting hard and brittle materials like natural stones, settle between the contact surfaces of the guides and the blade causing wear and premature failure. The hydrostatic guide system as presented in this work, is a contactless blade guiding method that uses force of several pressurized water jets to align the blade to the direction of the cut. For this investigation, cutting tests were performed on a marble block using a galvanic diamond coated bandsaw blade with the upper roller guides replaced by hydrostatic guides. The results show that the hydrostatic guides help to reduce the passive force while cutting to a constant near zero in contrast to the traditional guides. This also resulted in reduced surface roughness of the stone plates that were cut indicating a reduction in lateral vibration of the band. Additionally, it has also been shown that using hydrostatic guides the bandsaw blade can be tilted to counter the bandsaw drift opening opportunities for further research in active alignment control. This original research work has shown that the hydrostatic guide systems are capable of replacing and in fact perform better than state of the art bearing or block guides particularly for stone cutting applications.

This work communicates a review on Balmer series hydrogen beta line measurements and applications for analysis of white dwarf stars. Laser-induced plasma investigations explore electron density and temperature ranges comparable to white dwarf star signatures such as Sirius B, the companion to the brightest star observable from the earth. Spectral line shape characteristics of the hydrogen beta line include width, peak separation, and central dip-shift, thereby providing three indicators for electron density measurements. The hydrogen alpha line shows two primary line-profile parameters for electron density determination, namely, width and shift. Both Boltzmann plot and line-to-continuum ratios yield temperature. The line-shifts recorded with temporally- and spatially- resolved optical emission spectroscopy of hydrogen plasma in laboratory settings can be larger than gravitational redshifts that occur in absorption spectra from radiating white dwarfs. Published astrophysical spectra display significantly diminished Stark or pressure broadening contributions to red-shifted atomic lines. Gravitational redshifts allow one to assess the ratio of mass and radius of these stars, and subsequently, the mass from cooling models.

We prove that the probability of “A OR B”, where A and B are events or hypotheses that are recursively dependent (OR is the logico-probabilistic operator) is given by a "Hyperbolic Sum Rule” (HSR) relation isomorphic to the hyperbolic-tangent double-angle formula, and that this HSR is Maximum Entropy (MaxEnt). The possibility of recursive probabilities is excluded by the “Conventional Sum Rule” (CSR) which we also prove MaxEnt (within its narrower domain of applicability). The concatenation property of the HSR is exploited to enable analytical, consistent and scalable calculations for multiple recursive hypotheses: such calculations are not conveniently available for the CSR, and are also intrinsic to current artificial intelligence and machine learning architectures presently considered intractable to analytical study and methodological validation. We also show that it is as reasonable to state that “probability is physical” (it is not merely a mathematical construct) as it is to state that “information is physical” (now recognised as a truism of communications network engineering). We relate this treatment to the physics of Quantitative Geometrical Thermodynamics which is defined in complex hyperbolic (Minkowski) spacetime, and show how the HSR is isomorphic to other physical quantities including certain components important for digital signal processing.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

We describe a vision for a national-scale heavy mineral (HM) map generated through automated mineralogical identification and quantification of HMs contained in floodplain sediments from large catchments covering most of Australia. The composition of the sediments reflects the dominant rock types in each catchment, with the generally resistant HMs largely preserving the mineralogical fingerprint of their host protoliths through the weathering-transport-deposition cycle. Heavy mineral presence/absence, absolute and relative abundance, and co-occurrence are metrics useful to map, discover and interpret catchment lithotype(s), geodynamic setting, magmatism, metamorphic grade, alteration or mineralization. Underpinning this vision is a pilot project, focusing on a subset of the national sediment sample archive, which is used to demonstrate the feasibility of the larger, national-scale project. We preview a bespoke, cloud-based mineral network analysis (MNA) tool to visualize, explore and discover relationships between HMs as well as between them and geological setting or mineral deposits. We envisage that the Heavy Mineral Map of Australia and MNA tool will contribute significantly to mineral prospectivity analysis and modeling here, particularly for technology critical elements and their host minerals, which are central to the global economy transitioning to a more sustainable, decarbonized paradigm.

The importance of enzymes in the poultry industry is ever increasing because they help to extract as many nutrients as possible from the raw material available and reduce environmental impacts. Therefore, an experiment was conducted to examine the effect of a natural enzyme complex (ASC) on diets low in AME, Ca and P. Ross 308 broilers (n = 900) were fed one of four diets: (1) positive control (PC) with no enzyme added (AME 12.55 MJ/kg, AVPhos 4.8 g/kg and AVCal 9.6 g/kg); (2) negative control (NC) with no enzyme added and down-specified for AME, Ca and P (AME 12.18 MJ/kg, AVPhos 3.3 g/kg, AVCal 8.1 g/kg); (3) negative control plus ASC at 200 g/t; and (4) negative control plus ASC at 400 g/t. Broiler performance, digesta viscosity, tibia mineralization and mineral content were analyzed at d 21. Between d 18 and 20, excreted DM, GE, total nitrogen, Ca, and P were analyzed. ASC at 200 g/t and 400 g/t improved the FCR (p = 0.0014) significantly when compared with that of the NC. There were no significant differences in BW or FI between the treatments. Birds fed ASC at 200 g/t and 400 g/t had significantly improved digesta viscosity (p &lt; 0.0001) compared with that of the PC and NC and had significantly higher excreted DM digestibility (p &lt; 0.01) than the NC and the PC with 400 g/t ASC. ASC inclusion significantly improved P retention (p &lt; 0.0001) compared with that in the PC. Ca retention was significantly increased by 400 g/t ASC compared with that in the PC and NC (p &lt; 0.001). AME was significantly higher (p &lt; 0.0001) for all treatments compared with that in the NC. There were no significant differences between treatments for any of the bone measurements. This study showed that feeding ASC can support the performance of broilers when fed a specification reduced in Ca, P and AME, with the greatest results being seen with the higher inclusion level of ASC.

Material efficiency is a key element of new thinking to address the challenges of reducing impacts on the environment and of resource scarcity, whilst at the same time meeting service and functionality demands on materials. Directly related to material efficiency is the concept of the Circular Economy, which is based on the principle of optimising the utility embodied in materials and products through the life cycle. Whilst steel, as a result of high recycling rates, is one of the most ‘circular’ of all manufactured materials, significant opportunities for greater material efficiency exist, which are yet to be widely implemented. In the field of Life Cycle Management, Life Cycle Assessment (LCA) is commonly used to assess the environmental benefits of recovering and recycling materials through the manufacturing supply chain and at end-of-life. As well as containing information to calculate environmental impacts, LCA models also provide the flows of materials through the product life cycle and can also be used to quantify material efficiency and the circularity of a product system. Using an example taken from renewable energy generation, this paper explores the correlation between product circularity and the environmental case for strategies designed to improve material efficiency. An LCA-based methodology for accounting for the recovery and re-use of materials from the supply chain, and at end-of-life, is used as the basis for calculating the carbon footprint benefits of five material efficiency scenarios. Resulting carbon footprints were then compared with a number of proposed material circularity indicators. Two conclusions from this exercise were that i) LCA methodologies based around end-of-life approaches are well placed for quantifying the environmental benefits of material efficiency and circular economy strategies and ii) when applying indicators relating to the circularity of materials these should also be supported by LCA studies.

Developing a biomolecular detection method that minimizes photodamage while maintaining an environment suitable for biological constituents to maintain their physiological state is expected to drive new diagnostic and mechanistic breakthroughs. In addition, ultra-sensitive diagnostic platforms are needed for rapid and point-of-care technologies for various diseases. Considering this, surface-enhanced Raman scattering (SERS) is proposed as a non-destructive and sensitive approach to address the limitations of fluorescence, electrochemical, and other optical detection techniques. However, to advance the applications of SERS, novel approaches to enhance the signal of substrate materials are needed to improve reproducibility and costs associated with manu-facture and scale-up. Due to their physical properties and synthesis, semiconductor-based nanostructures have gained increasing recognition as SERS substrates; however, low signal en-hancements have offset their widespread adoption. To address this limitation and assess the po-tential for use in biological applications, zinc oxide (ZnO) was coated with different concentra-tions (0.01-0.1 M) of gold (Au) precursor. When crystal violet (CV) was used as a model target with the synthesized substrates, the highest enhancement was obtained with ZnO coated with 0.05 M Au precursor. This substrate was subsequently applied to differentiate exosomes derived from three cell types to provide insight into their molecular diversity. We anticipate this work will serve as a platform for colloidal hybrid SERS substrates in future bio-sensing applications.

Patients recovering from bone disruption due to trauma or surgery need to limit movement to minimize shear force, thereby protecting callus formation and osteogenesis. Patients often use their arms to assist with functional activities, but pushing is frequently limited to <10 lb (4.5 kg). With only verbal instructions, patients’ ability to accurately limit weight-bearing (WB) force is poor. A therapeutic intervention to improve patient adherence with upper extremity (UE) WB guidelines during functional mobility using an instrumented walker could be beneficial. Therefore, the purpose of this article is to describe a feedback training protocol to improve the ability to modulate weight-bearing force in older adults and then provide an overview of the efficacy of this protocol and subsequent development of a Clinical Force Measuring Walker. An instrumented walker was used to measure UE WB during functional mobility in older healthy subjects (n = 30) before, during, and after (immediately and 2 hours) a visual and auditory concurrent feedback training session. During feedback training, force was significantly reduced with all 3 sessions as compared to baseline. When using the front wheeled walker, UE WB force during the second and third feedback training trials went down compared to the first trial. During the third feedback training trial, force was greater than the two previous trials while transferring sit-to-stand and stand-to-sit. After completion of practice with feedback, UE WB force was significantly reduced and remained so 2 hours later. These findings suggest that feedback training is effective for helping patients to modulate UE WB. Use of an instrumented walker and feedback training would be beneficial in clinical practice, especially with older patients. A more intensive feedback training with additional trials and or simultaneous visual and auditory cues during whole-practice may be needed to get UE WB below a 10 lb threshold.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

Health care in Canada is managed by provinces/territories. We investigated regional differences in survival among Canadians diagnosed with central nervous system (CNS) tumours. We identified 50,670 patients diagnosed with a first-ever primary CNS tumour between 2008 and 2017 with follow-up until December 31, 2017. We selected the four highest incidence histologies and used proportional hazards regression to estimate hazard ratios (HRs) for five regions (British Columbia, Prairie provinces, Ontario, Atlantic provinces and the Territories), adjusting for sex, tumour behaviour and patient age. Ontario had the best survival profile for all histologies investigated. The Atlantic provinces had the highest HR for glioblastoma (HR=1.26, 95% CI:1.18-1.35) and malignant glioma not otherwise specified (NOS) (Overall: HR=1.87, 95% CI:1.43-2.43; Pediatric population: HR=2.86, 95% CI:1.28-6.39). For meningioma, the Territories had the highest HR (HR=2.44, 95% CI:1.09-5.45) followed by the Prairie provinces (HR=1.52, 95% CI:1.38-1.67). For malignant unclassified tumours, the highest HRs were in British Columbia (HR=1.45, 95% CI:1.22-1.71) and the Atlantic provinces (HR=1.40, 95% CI:1.13-1.74). There are regional differences in the survival of CNS patients at the population level for all four specific histological types of CNS tumours investigated. Factors contributing to these observed regional survival differences are unknown and warrant further investigation.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

Desktop fused filament fabrication (FFF) 3D printers have been growing in popularity among hobbyist and professional users as a prototyping and low-volume manufacturing tool. One issue these printers face is the inability to determine when a defect has occurred rendering the print unusable. Several techniques have been proposed to detect such defects but many of these approaches are tailored to one specific fault (e.g., filament runout/jam), use expensive hardware such as laser distance sensors, and/or use machine vision algorithms which are sensitive to ambient conditions, and hence can be unreliable. This paper proposes a versatile, reliable, and low-cost system, named MTouch, to detect millimeter-scale defects that tend to make prints unusable. At the core of MTouch is an actuated contact probe designed using a low-power solenoid, magnet, and hall effect sensor. This sensor is used to check for the presence, or absence, of the printed object at specific locations. The MTouch probe demonstrated 100% reliability, which was significantly higher than the 74% reliability achieved using a commercially available contact probe (the BLTouch). Additionally, an algorithm was developed to automatically detect common print failures such as layer shifting, bed separation, and filament runout using the MTouch probe. The algorithm was implemented on a Raspberry Pi mini-computer via an Octoprint plug-in. In head-to-head testing against a commercially available print defect detection system (The Spaghetti Detective), the MTouch was able to detect faults 44% faster on average while only increasing the print time by 8.49%. In addition, MTouch was able to detect faults The Spaghetti Detective was unable to identify such as layer shifting and filament runout/jam.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

The design is described of a readily useable technology for routine paddock-scale soil porosity estimation. The method is non-contact (proximal) and typically from sensors mounted on a small farm vehicle around 1 m above the soil surface. Challenges arise from the need to have a compact low-power rigid structure and to allow for pasture cover and surface roughness. The high-frequency regime for acoustic reflections from a porous material is a function of the porosity , the tortuosity , and the angle of incidence . There is no dependence on frequency, so measurements must be conducted at two or more angles of incidence in order to obtain two or more equations in the unknown soil properties and . A system requiring a single transmitter/receiver pair to be moved from one angle to another is not viable for rapid sampling. Therefore, the design includes at least two transmitter/reflector pairs placed at identical distances from the ground so that they would respond identically to power reflected from a perfectly reflecting surface. A single 25 kHz frequency is a compromise which allows for the frequency-dependent signal loss from a natural rough agricultural soil surface. Multiple-transmitter and multiple-microphone arrays are described which give a good signal to noise ratio while maintaining a compact system design. The resulting arrays have a diameter of 100 mm. Pulsed ultrasound is used so that the reflected sound can be separated from sound travelling directly through the air horizontally from transmitter to receiver. The average porosity estimated for soil samples in the laboratory and in the field is found to be within around 0.04 of the porosity measured independently. This level of variation is consistent with uncertainties in setting the angle of incidence, although assumptions made in modelling the interaction of ultrasound with the rough surface no doubt also contribute.

This Article demonstrates how an eigendecomposition problem is inputted into a quantum circuit, how gates are applied in the quantum circuit, and how the output measurements are the correct eigenvalues. This process is known as quantum phase estimation (QPE). A quantum harmonic oscillator example, a foundational quantum physical chemistry problem, is demonstrated within the context of QPE. A particle in a box example, another quantum physical chemistry problem, may be solved by QPE with a caveat. These examples are of the limiting cases of diagonal matrices. Future advances in taking matrix inverses for solving linear sets of equations or finding ground state energies in the Schrödinger equation will use the principles implemented in this Article.

Despite great strides in diagnosis and treatment, cardiac diseases remain the number one cause of mortality in the developed world, with rates catching up at an alarming rate in the developing world. Targeted delivery of therapeutics, specifically to cardiomyocytes, would open up new frontiers. Our prior work using a combinatorial in vitro and in vivo phage display methodology identified a 12-amino acid long peptide that targets cardiomyocytes selectively after an intravenous injection in as little as 5 mins, and hence was termed cardiac targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension for development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed on the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10µM of Cyanine-5.5 labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by more extensive studies performed by Eurofins in stably transfected cell lines for an extensive list of GPCR-coupled receptors. Positive data for GPCR-coupled receptors was interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting 60, 6-week-old, wild-type CD1, male/female mice (1:1) injected with CTP (150 µg/Kg) intravenously. Mice were weighed immediately before injections and daily thereafter. Cohorts of mice were euthanized on day 0, 1, 2, 7 and 14 with inhalational CO2, followed by opening of the chest cavity, collection of blood via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after injections of CTP (150 µg/Kg) to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. In the Eurofins Cardiac Profiler Qube, no significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed by RT-qPCR. There was no change in blood pressures before and after injections with CTP at 10 mg/Kg. Blood counts and chemistries showed no evidence of significant hematological, hepatic or renal toxicities. Lastly, there was no significant difference in cardiac function, size or mass before and after CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies, in good laboratory practices fashion, are needed with more prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC aetiology contributes to development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8 % of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells. Here, we discuss current literature about GSLs and their abundance in normal liver cells, Gaucher disease and HCC. Furthermore, we review the involvement of UGCG/GlcCer in multidrug resistance development, globosides as a potential prognostic marker for HCC, gangliosides as a potential liver cancer stem cell marker, and the role of sulfatides in tumor metastasis. Only a limited number of molecular mechanisms executed by GSLs in HCC are known, which we summarize here briefly.

Community-level wastewater monitoring for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has demonstrated useful correlation with both coronavirus disease 2019 (COVID-19) case numbers and clinical testing positivity. Wastewater monitoring on college campuses has demonstrated promising predictive capacity for the presence and absence of COVID-19 cases. However, to date, such monitoring has largely relied upon composite or grab samples and reverse transcription quantitative PCR (RT-qPCR) techniques, which limits the accessibility and scalability of wastewater monitoring. In this study, we piloted a workflow that uses tampons as passive swabs for collection and reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect SARS-CoV-2 RNA in wastewater. Results for the developed workflow were available same day, with a time to result following tampon swab collection of approximately three hours. The RT-LAMP 95% limit of detection (76 gene copies reaction-1) was greater than RT-droplet digital PCR (ddPCR; 3.3 gene copies reaction-1). Nonetheless, during a building-level wastewater monitoring campaign conducted in the midst of weekly clinical testing of all students, the workflow demonstrated a same-day positive predictive value (PPV) of 33% and negative predictive value (NPV) of 80% for incident COVID-19 cases. The NPV is comparable to that reported by wastewater monitoring using RT-qPCR. These observations suggest that even with lower analytical sensitivity the tampon swab and RT-LAMP workflow offers a cost-effective and rapid approach that could be leveraged for scalable same-day building-level wastewater monitoring for COVID-19.

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.

In tropical Africa, forests and savannas are the two most widespread biomes and potentially represent alternative stable states with divergent species composition. A classic, but untested, hypothesis posited by White (1983) suggests that the transition zones between forests and savannas contain a floristically impoverished assemblage with few representatives from each biome. Further, the evolutionary dimension of diversity has received limited attention, despite its importance for understanding the biogeographic history of biomes. Here, we quantify species richness and several measures of evolutionary diversity in 1° grid cells, using c. 300K occurrence records of trees and shrubs combined with biome affiliation data for 3,125 species. We find that assemblages in transition zones hold fewer woody species than assemblages in forest and savanna zones, as posited by White. However, transition zones hold more phylogenetic diversity than expected given their species richness, whether one considers forest and savanna assemblages separately or together. We also show that the Congo basin forest has low levels of phylogenetic diversity given the number of species and highlight south-eastern African savannas as a centre of savanna woody species richness and phylogenetic diversity. Regions with high phylogenetic diversity given the number of both forest and savanna species were centred around the Dahomey Gap and Cameroon, mainly in transition zones. Overall, our study shows that even if floristically impoverished, transition zones lead to unexpectedly high evolutionary diversity, suggesting they are important centres of evolutionary innovation and diversification.

The COVID-19 crisis has resulted in a shortage of personal protective equipment (PPE) [1]. COVID-19 is currently the leading cause of death in the United States[2]. Health care providers caring for COVID-19 patients or at high risk of being exposed to the SARS-CoV-2 virus benefit from a face shield to protect against aerosol droplets that could hit the face and minimize the chance of inadvertently touching the face with contaminated hands, and air filtration to filter out aerosolized SARS-CoV-2. Adapting commercially available full-faced snorkel masks has been proposed as an alternative to narrow the gap in PPE [3]. Here we explore a full-faced snorkel mask with commercially available particulate filters.

The seismic events of 2015 in Nepal exposed the challenges associated with constructing earthquake-resistant 2-story self-built stone masonry structures in high-elevation rural regions, especially post-disaster. The Department of Urban Development and Building Construction (DUDBC) provided designs that failed to preserve the local architectural landscape and craftsmanship while adding unfamiliar knowledge and technology. To address the challenges related to architecture, structure, and socio-economic concerns in designing and implementing post-earthquake houses, a need-based building development framework is required for standardized practice. This study presents a novel framework to assess, design, and implement a self-built house after a disaster, consisting of five stages: 1) post-disaster problem assessment, 2) need identification, 3) material selection, 4) design development, and 5) validation and implementation. Based on this framework, we proposed a novel gabions building construction technology for two-story stone masonry structures that effectively mitigate post-disaster challenges such as logistic, resilience, and socioeconomic aspects while improving disaster resiliency specifically in the high-elevation rural areas of Nepal. The proposed two-story gabion building preserves architectural values, enhances structural integrity, and provides cost-effectiveness when compared with its DUDBC peer models while providing much-needed relief to the vulnerable community. The proposed resilient house, G- 2.1, utilizes locally sourced materials and craftsmanship, and innovative gabion technology that ensures affordability and facilitates knowledge transfer. The contribution of this study includes a development framework and a two-story gabions house that is most suitable for self-built post-disaster reconstruction and resilient to local architecture and socio-economic conditions while providing structural integrity and safety.

Increased salinity caused by saltwater intrusion or runoff from de-icing salts can severely affect freshwater vegetation and deteriorate aquatic ecosystems. These habitats can be restored with freshwater ecotypes (locally adapted populations) that tolerate above-normal salinity. Vallisneria americana is a prominent species in many freshwater ecosystems that responds differently to abiotic conditions such as substrate composition and fertility, so in this study we evaluated the effects of salt stress on 24 ecotypes of V. americana. Instant Ocean aquarium salt was used to create saline solutions [0.2 to 20.0 parts per thousand (ppt)], then plants were abruptly exposed to these solutions and maintained in these concentrations for 5 weeks before being visually assessed for quality and destructively harvested. Analysis of variance and non-linear regression were used to calculate LC₅₀ values – the lethal concentration of salt that reduced plant biomass and quality by 50% compared to control treatment. Growth rate and visual quality varied significantly among ecotypes, and ecotypes that were most and least sensitive to salt had 50% biomass reductions at 0.47 and 9.10 ppt, respectively. All ecotypes survived 10.0 ppt salinity concentration but none survived at 20.0 ppt, which suggests the maximum salinity concentration tolerated by these ecotypes is between 15.0 and 20.0 ppt.

The influence of lignin modification on drug release and pH-dependent releasing behaviour of oral solid dosage form was investigated using three different formulations. The first formulation contains microcrystalline cellulose (MCC101) as excipient and paracetamol as active pharmaceutical ingredient (API). The second formulation includes Alcell lignin and MCC 101 as excipient and paracetamol, and the third formulation consists of carboxylated Alcell lignin, MCC 101 and paracetamol. Direct compaction was carried out in order to prepare the tablets. Lignin can be readily chemically modified due to the existence of different functional groups in its structure. The focus of this investigation is on lignin carboxylation and its influence on paracetamol control release behaviour at varying pH. Results suggest that carboxylated lignin tablets had the highest drug release, which is linked to their faster disintegration and lower tablet hardness.

The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action – to uncover and develop anti-viral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analog prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of its mechanism of action, discovery, and the current studies exploring its clinical effectiveness.

This pilot study explores the potential of using a citizen science approach for sourcing volunteered geographic information via social media to research wildlife tourism interactions with endangered Borneo Pygmy Elephants on the lower Kinabatangan River in Sabah, Malaysia. Such information is critical if the lower Kinabatangan region is to achieve the United Nations Sustainable Development Goals through a sustainable tourism industry based around viewing the pygmy elephants. Guests and guides from the Sukau Rainforest Lodge were encouraged to become close-range remote sensors by sharing geotagged photographs of pygmy elephant sightings on Flickr. A ten week on-ground trail generated 247 photographs shared by 17 individual contributors with approximately two-thirds (65%) of photographs being georeferenced for the time and location of the elephant sighting. Plotting those sighting to explore the vegetation matrix (i.e. remnant forest or oil palm plantation) showed almost three-quarter (73%) of the sightings occurred within 1 km of an oil palm plantation. Of greater concern is that one in two sightings (50%) along the river occurred within the 500 m of an oil palm planation, which is inside the riparian buffer that the Sabah Government recommended for conservation of the elephants in their Lower Kinabatangan range. This study therefore demonstrates proof of concept for this research method and its further application at the nexus of wildlife conservation and sustainable ecotourism research.

Membranes are a selective barrier that allows certain species (molecules and ions) to pass through while blocking others. Some rely on size exclusion, where larger molecules get stuck while smaller ones permeate through. Others use differences in charge or polarity to attract and repel specific species. Membranes can be used to purify air and water by allowing only air and water molecules to pass through but preventing contaminants such as microorganisms and particles or to separate target gas or vapor, such as H2, CO₂, from other gases. The higher the flux and selectivity, the better a material is for membranes. The desirable performance can be tuned through material type (polymers, ceramics, and biobased materials), microstructure (porosity and tortuosity), and surface chemistry. Most membranes are made from plastic from petroleum-based resources, which contribute to global climate change and plastic pollution. Cellulose can be an alternative sustainable resource to make renewable membranes. Cellulose exists in plant cell walls as natural fibers, which can be broken down into smaller components such as cellulose fibrils, nanofibrils, nanocrystals, and cellulose macromolecules through mechanical and chemical processing. Membranes made from reassembling these particles and molecules have variable pore architecture, porosity, and separation properties and therefore have a wide range of applications in nano-, micro-, and ultrafiltration or forward osmosis. Despite their advantages, cellulose membranes face some challenges. Improving the selectivity of membranes for specific molecules often comes at the expense of permeability. The stability of cellulose membranes in harsh environments or under continuous operation needs further improvement. Research is ongoing to address these challenges and develop advanced cellulose membranes with enhanced performance. This article reviews the microstructure, fabrication methods, and potential applications of cellulose membranes, providing some critical insights into processing-structure-property relationships for current state-of-the-art cellulosic membranes that could be used to rationally improve their performance.

Limiting harm to organisms via genetic sampling is an important consideration for rare species. Nondestructive sampling techniques have been developed to address this issue in freshwater mussels. Two methods, visceral swabbing and tissue biopsies, have proven to be effective for DNA sampling, though it is unclear as to which method is preferable for genotyping-by-sequencing (GBS). Tissue biopsies may cause undue stress and damage to organisms, while visceral swabbing potentially reduces the chance of such harm. Our study compared the efficacy of these two DNA sampling methods for generating GBS data for the Unionid freshwater mussel, Texas Pigtoe (Fusconaia askewi). Our results find both methods generate quality sequence data, though some considerations are in order. Tissue biopsies produced significantly higher DNA concentrations and larger numbers of reads when compared to swabs, though there was no significant association between starting DNA concentration and number of reads generated. Swabbing produced greater sequence depth (more reads per sequence) while tissue biopsies revealed greater coverage across the genome (at lower sequence depth). Patterns of genomic variation as characterized in principal component analyses were similar regardless of the sampling method, suggesting that the less invasive swabbing is a viable option for producing quality GBS data in these organisms.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Neurodegenerative protein conformational diseases are characterized by misfolding and aggregation of metastable proteins encoded within the host genome. The host is also home to thousands of proteins encoded within exogenous genomes harbored by bacteria, fungi, and viruses. Yet, their contributions to host protein-folding homeostasis, or proteostasis, remain elusive. Recent studies, including our previous work, suggest that bacterial products contribute to toxic aggregation of endogenous host proteins. We refer to these products as bacteria-derived protein aggregates (BDPAs). Furthermore, antibiotics were recently associated with increased risk for neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis  possibly by virtue of altering the composition of the human gut microbiota. Other studies have shown a negative correlation between disease progression and antibiotic administration, supporting their protective effect against neurodegenerative diseases. These contradicting studies emphasize the complexity of the human gut microbiota, the gut-brain axis, and the effect of antibiotics. Here, we further our understanding of bacteria’s effect on host protein folding using the model Caenorhabditis elegans. We employed genetic and chemical methods to demonstrate that the proteotoxic effect of bacteria on host protein folding correlates with the presence of BDPAs. Furthermore, the abundance and proteotoxicity of BDPAs are influenced by gentamicin, an aminoglycoside antibiotic that induces protein misfolding, and by butyrate, a short-chain fatty acid that we previously found to affect host protein aggregation and the associated toxicity. Collectively, these results increase our understanding of host-bacteria interactions in the context of protein conformational diseases.

Small modular reactors (SMR) (&lt;300 MW) offer a potentially attractive nuclear energy option for the middle-east region (MER). Currently, the MER uses a significant amount of fossil fuel to process heat applications such as water desalination and in petroleum refineries and chemical plants, besides generating electricity. SMR technologies represent an opportunity to meet future energy demand in the MER. This paper discusses issues related to the future development and use of SMR technology in nuclear-renewable hybrid energy systems for application in the middle east. SMRs have also been examined as part of a resilient hybrid energy system that combines nuclear energy with renewable energy and traditional fossil energy to produce chemicals, fuels, and electricity. This paper presents the results of a techno-economic analysis of a Nuclear-Renewable-Conventional Hybrid Energy System. The paper concludes that SMR technology will be an essential feature of future hybrid energy systems for the MER.

Box tree moth, Cydalima perspectalis is native to East Asia where it occurs on Buxus trees. Its natu-ral distribution includes China, Japan, Korea and India, and it was accidentally introduced into Europe, Middle East, North America and north Africa through the trade in Buxus spp., where it can cause considerable damage. In the native range of C. perspectalis, three tachinids (Diptera, Tachinidae) are known to parasitize larvae of C. perspectalis, including Exorista sp., Pseudoperichaeta nigrolineata (Walker 1853) and Compsilura concinnata (Meigen 1824). Data on tachinid parasitoids parasitizing C. perspectalis on the European continent include only P. nigrolineata. Field collection of mature larvae and pupae of C. perspectalis during July 2020 in four locations in Split – Dalmatia County in Croatia resulted in collection of live tachinid larvae that were reared to adults. The tachinid specimens were identified at the Natural History Museum, London, UK, as Nemorilla flo-ralis (Fallén, 1810) (Diptera, Tachinidae). Conservatively, 1.2 – 2.4 % parasitism rate was achieved. This is the first world record of N. floralis parasitism on C. perspectalis larvae, which can be added as a potential tool for C. perspectalis biological control.

Tissue programmed death ligand-1 (PD-L1) protein expression is predictive of immune checkpoint inhibitor (ICI) benefit. However, tissue PD-L1 can be fraught with tissue acquisition and heterogeneity limitations. Plasma testing can overcome these limitations. However, the overall survival (OS) predictive benefit of plasma PD-L1 assays have not been well characterized. Patients with stage IV non-small cell lung cancer (NSCLC) and plasma cfRNA PD-L1 by PCR expression were identified and assessed for OS. 16 patients treated with front-line ICI-based regimens were assessed and represented a real-world patient population with over half with a performance status of 2 or greater. 10 contemporaneous patients at the same institution treated with chemotherapy alone were also identified and assessed. With a median follow-up of 33 months, median OS was 13 months with a 30% 3-year OS for the ICI treated patients compared to a median OS of 3 months and a 10% 3-year OS for those treated with chemotherapy alone. Comparative log-rank test p-value = 0.014 and a hazard ratio 0.376 (95%-CI 0.134-1.057). Plasma cfRNA PD-L1 was associated with a statistically significant survival benefit from ICI-based treatment compared to chemotherapy in the first line treatment of a real-world patient population of advanced NSCLC.

3D printing technology has brought about a paradigm shift in the delivery of clinical care in medicine and dentistry. There are several different 3D printing technologies, which, along with different printable materials with unique biomechanical properties, allows for a wide range of applications for 3D printing in dentistry. The clinical use of 3D printing has created versatile applications which streamline our digital workflow. Technological advancements have also paved the way for the integration of new dental materials in dentistry. This paper provides an overview of the mechanisms of 3D printing, the dental materials relevant to each mechanism and the possible applications of these materials within different areas of dentistry. Understanding the existing spectrum of 3D printing applications in dentistry will serve to further expand its use in the dental field.

Development of the continental shelf has accelerated significantly as nations around the world seek to harness offshore renewable energy. Many areas marked for development align with submerged palaeolandscapes. Poorly understood and difficult to protect, these vulnerable, prehistoric landscapes provide specific challenges for heritage management. Indeed, there now appears to be a schism between what underwater cultural heritage policy intends and what it is achieving in practice. Shortcomings in international and national legislature ensures that large parts of the continental shelf, including areas under development, may have little or no legal protection.

This review focuses on developments that quantify grain quality with a range of spectral sensors in an on-farm setting. If the application of sensor technologies were expanded and adopted on-farm, growers could identify the impact and manage the harvesting operation to meet a range of quality targets and provide an economic advantage to the farming enterprise.

Background: In the span of just two years, tracking the COVID-19 pandemic through wastewater surveillance has advanced from early reports of successful SARS-CoV-2 RNA detection in untreated wastewater to implementation of programs in at least 60 countries. Early wastewater monitoring efforts primarily originated in research laboratories and are now transitioning into more formal surveillance programs run in commercial and public health laboratories. A major challenge in this progression has been to simultaneously optimize methods and build scientific consensus while implementing surveillance programs, particularly during the rapidly changing landscape of the pandemic. Translating wastewater surveillance results for effective use by public health agencies also remains a key objective for the field. Objectives: We examine the evolution of wastewater surveillance to identify model collaborations and effective partnerships that have created rapid and sustained success. We propose needed areas of research and key roles academic researchers can play in the framework of wastewater surveillance to aid in the transition of early monitoring efforts to more formalized programs within the public health system. Discussion: Wastewater surveillance has rapidly developed as a public health tool Clinical testing programs are ramping down and home testing is on the rise, making wastewater monitoring important for future surveillance of COVID-19. Our experience in initiating and implementing wastewater surveillance programs in the United States has allowed us to reflect on key barriers and organizational challenges and draw useful lessons. As wastewater surveillance programs are formalized, the working relationships developed between academic researchers, commercial and public health laboratories, and data users should continue and should promote knowledge co-development. While wastewater surveillance has demonstrated utility for tracking COVID-19, there remain technical challenges and open scientific questions that researchers are equipped to address, which will contribute to building robust surveillance programs that provide public health practitioners with new insights into population health.

The coronavirus disease 2019 (COVID-19) pandemic has led to wastewater surveillance becoming an important tool for monitoring the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within communities. As a result, molecular methods, in particular reverse transcription-quantitative PCR (RT-qPCR), have been employed to generate large data sets aimed at the detection and quantification of SARS-CoV-2 in wastewater. Although RT-qPCR is rapid and sensitive, there is no standard method that fits all use cases, there are no certified quantification standards and experiments are carried out using numerous different assays, reagents, instruments, and data analysis protocols. These variations can lead to the reporting of erroneous quantitative data resulting in potentially misleading interpretations and conclusions. We have reviewed the SARS-CoV-2 wastewater surveillance literature focusing on the variability of RT-qPCR data as revealed by inconsistent standard curves and associated parameters. We find that variation in these parameters and deviations from best practices as described in The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines suggest a lack of reproducibility and reliability in quantitative measurements of SARS-CoV-2 RNA in wastewater.

Rheumatoid arthritis (RA); is a chronic systemic autoimmune disease which causes loss of joint function and significantly reduces quality of life. Plasma metabolite concentrations of disease-modifying anti-rheumatic drugs (DMARDs) can influence treatment efficacy and toxicity. This study explored the relationship between DMARD metabolising gene variants and plasma metabolite levels in RA patients. DMARD metabolite concentrations were determined by tandem mass-spectrometry in plasma samples from 100 RA patients with actively flaring disease, collected at two intervals. Taqman-probes were used to discriminate single nucleotide polymorphism (SNP) genotypes in cohort genomic DNA: rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Mean plasma concentrations of methotrexate (MTX) and MTX-7-OH metabolites were higher (p<0.05, C.I. 95%) at baseline in rs4149081 GA genotype patients. Patients with rs1476413 SNP TT or CT alleles in the have significantly higher (p<0.001, 95% C.I) plasma poly-glutamate metabolites at both study time points and correspondingly elevated disease activity scores. Patients with the rs17421511 SNP AA allele reported significantly lower pain scores (p<0.05, 95% C.I.) at both study intervals. Genotyping strategies could help prioritise treatments to RA patients most likely to gain clinical benefit, whilst minimizing toxicity.

Plankton monitoring by microscopy offers long-term ecological perspective of plankton com-munities but different detection approaches are biased uniquely. Genetic identification of marine plankton has become standard but is still not used in routine monitoring. This study assessed the diversity of plankton taxa using 18S high throughput sequencing from 2011-2012 from small-volume (~200ml) samples from the Water and Microplankton Sampler (WaMS) deployed on the Continuous Plankton Recorder platform (CPR). The 18S-HTS survey revealed a bias towards heterotrophic taxa, and phototrophs under 10µm within the photosynthetic community. In comparison with phytoplankton microscopic counts from the CPR survey and Western Channel Observatory station L4, only 8-12 taxonomic families were common to all three surveys, with a bias towards larger diatoms and dinoflagellate taxa in microscopy surveys. The WaMS survey detected a contrasting but complementary taxa set to that of microscopic surveys. Additional Quantitative PCR was carried out on the picoeukaryotic pelagophyte, Aureococcus anophagefferens, and the nanoeukaryotic potential harmful algae, Pseudo-nitzschia delicatissima, from 2011-2013. This confirmed the persistence presence of A. anophagefferens in the Western Channel and an elevated abundance of both species in 2011. Species specific seasonality were distinct from those of aggregrate phytoplankton groups.

The application of adaptive antennas in wireless communication systems is examined in this review of the literature, with particular attention to how well they can transmit and receive signals by dynamically adjusting radiation patterns. The review covers a range of artificial intelligence (AI) approaches that have been used to enhance adaptive antenna performance in beamforming, channel estimation, interference mitigation, and spectrum utilization. Although adaptive antennas have the potential to improve wireless communication systems, the paper also discusses their limitations, including computational complexity, interference sensitivity, and the significance of precise channel state information (CSI) estimates.

Nutrient regulation in aquaponic environments has been the topic of research for many years. Most have focused on appropriate control of nutrients in an aquaponic set-up, but very little research has been done on commercial scale applications. In our model, the input data was sourced on a weekly basis from three commercial aquaponic farms in South-East Texas over the course of a year. Due to limited number of data points, dimensionality reduction techniques like pair-wise correlation matrix was used to remove the highly correlated predictors. Feature selection techniques like the XGBoost classifier and Recursive Feature Elimination with ExtraTreesClassifier were used to rank the features in order of their relative importance. Ammonium and calcium were found to be the top two nutrient predictors and based on the months in which lettuce was cultivated, the median of these nutrient values from the historical dataset served as the optimal concentrations to be maintained in the aquaponic solution. To accomplish this, Vernier sensors were used to measure the nutrient values and actuator systems were built to dispense the appropriate nutrient into the ecosystem via a closed loop.

Abstract: In order to accelerate deployment of distributed recycling by providing low-cost feed stocks of granulated post-consumer waste plastic, this study analyzes an open source waste plastic granulator system. It is designed, built and tested for its ability to convert post-consumer waste, 3-D printed products and waste into polymer feedstock for recyclebots of fused particle/granule printers. The technical specifications of the device are quantified in terms of power consumption (380 to 404W for PET and PLA, respectively) and particle size distribution. The open source device can be fabricated for less than USD$2000 in materials. The experimentally-measured power use is only a minor contribution to the overall embodied energy of distributed recycling of waste plastic. The resultant plastic particle size distributions were found to be appropriate for use in both recyclebots and direct material extrusion 3-D printers. Simple retrofits are shown to reduce sound levels during operation by 4dB-5dB for the vacuum. These results indicate that the open source waste plastic granulator is an appropriate technology for community, library, makespace, fab lab or small business-based distributed recycling.

The illegal wildlife trade is a significant threat to global biodiversity, often targeting already threatened species. In combating the trade, it is critical to know the provenance of the traded animal or part, to facilitate targeted conservation actions, such as education and enforcement. Here we present and compare two methods, portable X-ray fluorescence (pXRF) and stable isotope analysis (SIA), to determine both the geographic and source provenance (captive or wild) of traded animals and their parts. Using three critically endangered, frequently illegally traded Philippine species, the Palawan forest turtle (Siebenrockiella leytensis), the Philippine cockatoo (Cacatua haematuropygia), and the Philippine pangolin (Manis culionensisis) we demonstrate that using these methods we can more accurately assign provenance using pXRF data (x ̅ = 83%), than SIA data (x ̅ = 47%). Our results indicate that these methods provide a valuable forensic tool that can be used in combating the illegal wildlife trade.

Buerger's disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.