An orthotopic prostate cancer model for new treatment development using syngeneic or patient-derived tumors.

BACKGROUND: There are limited preclinical orthotopic prostate cancer models due to the technical complexity of surgical engraftment and tracking the tumor growth in the mouse prostate gland. Orthotopic xenografts recapitulate the tumor microenvironment, tumor stromal interactions, and clinical behavior to a greater extent than xenografts grown at subcutaneous or intramuscular sites. METHODS: This study describes a novel micro-surgical technique for orthotopically implanting intact tumors pieces from cell line derived (transgenic adenocarcinoma mouse prostate [TRAMP]-C2) or patient derived (neuroendocrine prostate cancer [NEPC]) tumors in the mouse prostate gland and monitoring tumor growth using magnetic resonance (MR) imaging. RESULTS: The TRAMP-C2 tumors grew rapidly to a predetermined endpoint size of 10 mm within 3 weeks, whereas the NEPC tumors grew at a slower rate over 7 weeks. The tumors were readily detected by MR and confidently identified when they were approximately 2-3 mm in size. The tumors were less well-defined on CT. The TRAMP-C2 tumors were characterized by amorphous sheets of poorly differentiated cells similar to a high-grade prostatic adenocarcinoma and frequent macroscopic peritoneal and lymph node metastases. In contrast, the NEPC's displayed a neuroendocrine morphology with polygonal cells arranged in nests and solid sheets and high count. There was a local invasion of the bladder and other adjacent tissues but no identifiable metastases. The TRAMP-C2 tumors were more hypoxic than the NEPC tumors. CONCLUSIONS: This novel preclinical orthotopic prostate cancer mouse model is suitable for either syngeneic or patient derived tumors and will be effective in developing and advancing the current selection of treatments for patients with prostate cancer.

Targeting the CXCL12/CXCR4 pathway to reduce radiation treatment side effects.

High precision, image-guided radiotherapy (RT) has increased the therapeutic ratio, enabling higher tumor and lower normal tissue doses, leading to improved patient outcomes. Nevertheless, some patients remain at risk of developing serious side effects.In many clinical situations, the radiation tolerance of normal tissues close to the target volume limits the dose that can safely be delivered and thus the potential for tumor control and cure. This is particularly so in patients being re-treated for tumor progression or a second primary tumor within a previous irradiated volume, scenarios that are becoming more frequent in clinical practice.Various normal tissue 'radioprotective' drugs with the potential to reduce side effects have been studied previously. Unfortunately, most have failed to impact clinical practice because of lack of therapeutic efficacy, concern about concurrent tumor protection or excessive drug-related toxicity. This review highlights the evidence indicating that targeting the CXCL12/CXCR4 pathway can mitigate acute and late RT-induced injury and reduce treatment side effects in a manner that overcomes these previous translational challenges. Pre-clinical studies involving a broad range of normal tissues commonly affected in clinical practice, including skin, lung, the gastrointestinal tract and brain, have shown that CXCL12 signalling is upregulated by RT and attracts CXCR4-expressing inflammatory cells that exacerbate acute tissue injury and late fibrosis. These studies also provide convincing evidence that inhibition of CXCL12/CXCR4 signalling during or after RT can reduce or prevent RT side effects, warranting further evaluation in clinical studies. Greater dialogue with the pharmaceutical industry is needed to prioritize the development and availability of CXCL12/CXCR4 inhibitors for future RT studies.

Living Naked in the Cold: New Insights into Metabolic Feasibility in Primeval Cultures.

The people of three primeval cultures lived naked or nearly naked in regions where they experienced air temperatures of ± 5 degrees Celsius during cold seasons. These were the Australian Aboriginal peoples, the Bushmen of southern Africa, and the Yamana and the Alakaluf of Tierra del Fuego. Recent meta-analyses of data on human metabolic rate and metabolic endurance enable a quantitative demonstration of feasibility: Thermoregulation at winter air temperatures while naked was feasible in the three cultures for significantly longer than 50-180 days per year (sufficient for the duration of winter). Considering the life histories of the people, their estimated, time-averaged daily (24 hours) metabolic rates in winter were 2.6 times basal-similar to the highest daily rates empirically measured in extant peoples. Although the primeval peoples' way of life was metabolically expensive, it was as feasible as the lifestyles of peoples in today's world who live at the upper bound of the metabolically possible.

Nutritional Management of Cats and Dogs with Diabetes Mellitus.

This article reviews the nutritional assessment and management of diabetic dogs and cats. It discusses how to determine appropriate nutritional goals for individual patients, including comorbid patients with diabetes. Considerations for macronutrient and micronutrient modifications will be reviewed.

Feature Mapping for Rice Leaf Defect Detection Based on a Custom Convolutional Architecture.

Rice is a widely consumed food across the world. Whilst the world recovers from COVID-19, food manufacturers are looking to enhance their quality inspection processes for satisfying exportation requirements and providing safety assurance to their clients. Rice cultivation is a significant process, the yield of which can be significantly impacted in an adverse manner due to plant disease. Yet, a large portion of rice cultivation takes place in developing countries with less stringent quality inspection protocols due to various reasons including cost of labor. To address this, we propose the development of lightweight convolutional neural network architecture for the automated detection of rice leaf smut and rice leaf blight. In doing so, this research addresses the issue of data scarcity via a practical variance modeling mechanism (Domain Feature Mapping) and a custom filter development mechanism assisted through a reference protocol for filter suppression.

A Dynamic Multi-Mobile Agent Itinerary Planning Approach in Wireless Sensor Networks via Intuitionistic Fuzzy Set.

In recent research developments, the application of mobile agents (MAs) has attracted extensive research in wireless sensor networks (WSNs) due to the unique benefits it offers, such as energy conservation, network bandwidth saving, and flexibility of open usage for various WSN applications. The majority of the proposed research ideas on dynamic itinerary planning agent-based algorithms are efficient when dealing with node failure as a result of energy depletion. However, they generate inefficient groups for MAs itineraries, which introduces a delay in broadcasting data return back to the sink node, and they do not consider the expanding size of the MAs during moving towards a sequence of related nodes. In order to rectify these research issues, we propose a new Graph-based Dynamic Multi-Mobile Agent Itinerary Planning approach (GDMIP). GDMIP works with "Directed Acyclic Graph" (DAG) techniques and distributes sensor nodes into various and efficient group-based shortest-identified routes, which cover all nodes in the network using intuitionistic fuzzy sets. MAs are restricted from moving in the predefined path and routes and are responsible for collecting data from the assigned groups. The experimental results of our proposed work show the effectiveness and expediency compared to the published approaches. Therefore, our proposed algorithm is more energy efficient and effective for task delay (time).

QED radiative corrections for accelerator neutrinos.

Neutrino oscillation experiments at accelerator energies aim to establish charge-parity violation in the neutrino sector by measuring the energy-dependent rate of νe appearance and νµ disappearance in a νµ beam. These experiments can precisely measure νµ cross sections at near detectors, but νe cross sections are poorly constrained and require theoretical inputs. In particular, quantum electrodynamics radiative corrections are different for electrons and muons. These corrections are proportional to the small quantum electrodynamics coupling α ≈ 1/137; however, the large separation of scales between the neutrino energy and the proton mass (~GeV), and the electron mass and soft-photon detection thresholds (~MeV) introduces large logarithms in the perturbative expansion. The resulting flavor differences exceed the percent-level experimental precision and depend on nonperturbative hadronic structure. We establish a factorization theorem for exclusive charged-current (anti)neutrino scattering cross sections representing them as a product of two factors. The first factor is flavor universal; it depends on hadronic and nuclear structure and can be constrained by high-statistics νµ data. The second factor is non-universal and contains logarithmic enhancements, but can be calculated exactly in perturbation theory. For charged-current elastic scattering, we demonstrate the cancellation of uncertainties in the predicted ratio of νe and νµ cross sections. We point out the potential impact of non-collinear energetic photons and the distortion of the visible lepton spectra, and provide precise predictions for inclusive observables.

Nestling Altricial Rodents and Lagomorphs Are Not Ectotherms.

AbstractBased on the synthesis of data on metabolic rates of 15 species investigated at moderate ambient temperatures, nestlings of most studied species of altricial rodents and lagomorphs exhibit thermoregulatory control of thermogenesis within 3 d after birth, signifying that they express physiological thermoregulation for 86%-100% of their time as nestlings. Classifying nestlings as ectotherms (or poikilotherms) is thus inappropriate and fosters misconceptions regarding their body temperatures (Tb's), control of Tb-sensitive functions (e.g., cardiac output), and energetics of development. The fact that nestlings live as litters in nests means that their thermoregulatory capacities in their actual, natural lives often far exceed the capacities they exhibit as isolated individuals-pointing to a pressing need for improved understanding of the physiology of litters. Litters in nests are already known in two cases to exhibit true homeothermy at ages when individuals studied in isolation express only modest thermoregulatory abilities. Golden (Syrian) hamster nestlings are exceptional, requiring 2 wk to develop thermoregulatory thermogenesis. They are properly considered ectotherms at up to 2 wk of age, helping to clarify that most species-being dramatically different-are not.

Domain Feature Mapping with YOLOv7 for Automated Edge-Based Pallet Racking Inspections.

Pallet racking is an essential element within warehouses, distribution centers, and manufacturing facilities. To guarantee its safe operation as well as stock protection and personnel safety, pallet racking requires continuous inspections and timely maintenance in the case of damage being discovered. Conventionally, a rack inspection is a manual quality inspection process completed by certified inspectors. The manual process results in operational down-time as well as inspection and certification costs and undiscovered damage due to human error. Inspired by the trend toward smart industrial operations, we present a computer vision-based autonomous rack inspection framework centered around YOLOv7 architecture. Additionally, we propose a domain variance modeling mechanism for addressing the issue of data scarcity through the generation of representative data samples. Our proposed framework achieved a mean average precision of 91.1%.

Digital quantitative tissue image analysis of hypoxia in resected pancreatic ductal adenocarcinomas.

Background: Tumor hypoxia is theorized to contribute to the aggressive biology of pancreatic ductal adenocarcinoma (PDAC). We previously reported that hypoxia correlated with rapid tumor growth and metastasis in patient-derived xenografts. Anticipating a prognostic relevance of hypoxia in patient tumors, we developed protocols for automated semi-quantitative image analysis to provide an objective, observer-independent measure of hypoxia. We further validated this method which can reproducibly estimate pimonidazole-detectable hypoxia in a high-through put manner. Methods: We studied the performance of three automated image analysis platforms in scoring pimonidazole-detectable hypoxia in resected PDAC (n = 10) in a cohort of patients enrolled in PIMO-PANC. Multiple stained tumor sections were analyzed on three independent image-analysis platforms, Aperio Genie (AG), Definiens Tissue Studio (TS), and Definiens Developer (DD), which comprised of a customized rule set. Results: The output from Aperio Genie (AG) had good concordance with manual scoring, but the workflow was resource-intensive and not suited for high-throughput analysis. TS analysis had high levels of variability related to misclassification of cells class, while the customized rule set of DD had a high level of reliability with an intraclass coefficient of more than 85%. Discussion: This work demonstrates the feasibility of developing a robust, high-performance pipeline for an automated, quantitative scoring of pimonidazole-detectable hypoxia in patient tumors.

Correction: Turner et al. Steatitis in Cold-Stunned Kemp's Ridley Sea Turtles (Lepidochelys kempii). Animals 2021, 11, 898.

In the original publication [...].

Modeling the impact of spatial oxygen heterogeneity on radiolytic oxygen depletion during FLASH radiotherapy.

Purpose.It has been postulated that the delivery of radiotherapy at ultra-high dose rates ('FLASH') reduces normal tissue toxicities by depleting them of oxygen. The fraction of normal tissue and cancer cells surviving radiotherapy depends on dose and oxygen levels in an exponential manner and even a very small fraction of tissue at low oxygen levels can determine radiotherapy response. To quantify the differential impact of FLASH radiotherapy on normal and tumour tissues, the spatial heterogeneity of oxygenation in tissue should thus be accounted for.Methods.The effect of FLASH on radiation-induced normal and tumour tissue cell killing was studied by simulating oxygen diffusion, metabolism, and radiolytic oxygen depletion (ROD) over domains with simulated capillary architectures. To study the impact of heterogeneity, two architectural models were used: (1) randomly distributed capillaries and (2) capillaries forming a regular square lattice array. The resulting oxygen partial pressure distribution histograms were used to simulate normal and tumour tissue cell survival using the linear quadratic model of cell survival, modified to incorporate oxygen-enhancement ratio effects. The ratio ('dose modifying factors') of conventional low-dose-rate dose and FLASH dose at iso-cell survival was computed and compared with empirical iso-toxicity dose ratios.Results.Tumour cell survival was found to be increased by FLASH as compared to conventional radiotherapy, with a 0-1 order of magnitude increase for expected levels of tumour hypoxia, depending on the relative magnitudes of ROD and tissue oxygen metabolism. Interestingly, for the random capillary model, the impact of FLASH on well-oxygenated (normal) tissues was found to be much greater, with an estimated increase in cell survival by up to 10 orders of magnitude, even though reductions in mean tissue partial pressure were modest, less than ∼7 mmHg for the parameter values studied. The dose modifying factor for normal tissues was found to lie in the range 1.2-1.7 for a representative value of normal tissue oxygen metabolic rate, consistent with preclinical iso-toxicity results.Conclusions.The presence of very small nearly hypoxic regions in otherwise well-perfused normal tissues with high mean oxygen levels resulted in a greater proportional sparing of normal tissue than tumour cells during FLASH irradiation, possibly explaining empirical normal tissue sparing and iso-tumour control results.

Using augmented reality to improve patient outcomes with negative pressure wound therapy.

INTRODUCTION: Augmented reality (AR) is a burgeoning digital technology that is finding more frequent use in health care. The benefits of AR, such as hands-free imaging and remote viewing, make this a tool particularly suited to wound care. To the author's knowledge, no attempts have been made to leverage this technology in a way that might improve patient outcomes. Similarly, few studies on remote wound consultation focus on the inpatient setting. OBJECTIVE: This study demonstrated the use of AR to improve the outcome of patients undergoing negative pressure wound therapy. MATERIALS AND METHODS: A case-control study of 27 patients treated in a rural Louisiana hospital was performed. A retrospective control group (n = 15) was identified and compared with similar cases (n = 12) that used AR by the bedside nursing staff and an offsite certified wound care clinician. RESULTS: At univariate analysis, the treatment group was found to have fewer unintended surgical revisions (P =.002), fewer interruptions in therapy time (P =.01), and fewer readmissions related to wound infection (P =.004) compared with the control group. Correlational testing was performed and showed a significant correlation between the number of dressings performed and the number of complications that arose (0.71) as well as between premature dressing removals and number of readmissions related to infection (0.74). CONCLUSIONS: The results of this study, although preliminary, show how AR can be used in the acute care setting to positively influence outcomes of patients undergoing wound care. Further testing is necessary to replicate these findings and assess the use of AR with other advanced modalities or for other indications in the acute care setting.

City-scale energetics: window on adaptive thermal insulation in North American cities.

Previous research demonstrated that cities are similar to individual mammals in their relationship between the rate of energy use for heating and outdoor air temperature (Ta). At Tas requiring heating of indoor living spaces, the energy-Ta plot of a city contains information on city-wide thermal insulation (I), making it possible to quantify city-wide I by use of the city as the unit of measure. We develop methods for extracting this insulation information, deriving the methods from prior research on mammals. Using these methods, we address the question: in North America, are cities built in particularly cold locations constructed in ways that provide greater thermal insulation than ones built in thermally more moderate locations? Using data for 42 small and medium-size cities and two information-extraction methods, we find that there is a statistically significant inverse relationship between city-wide I and T10-year, the average city Ta over a recent 10-year period (range of T10-year: - 11 to 26 °C). This relationship represents an energy-conserving trend, indicating that cities in cold climates have greater built-in thermal insulation than cities in warm climates. However, the augmentation of insulation in cold climates is only about half as great as would be required to offset fully the increased energy cost of low Tas in a cold climate, and T10-year explains just 5-11% of the variance in measured insulation, suggesting that cities in North America vary greatly in the extent to which thermal insulation has been a priority in city development.

Neodymium-Doped Yttrium Aluminum Garnet Laser Photobiomodulation May Improve Neurosensory Function after Surgical Injury to Cranial Nerve V: A Report of Three Consecutive Cases.

OBJECTIVE: The purpose of this report was to document clinical responses to Nd:YAG laser energy in patients with surgical injury to terminal branches of the trigeminal nerve. BACKGROUND: Limited evidence from in vitro, animal, and human studies suggests infrared laser energy may positively influence recovery after peripheral or cranial nerve injury, although clinical effects of neodymiumdoped yttrium aluminum garnet (Nd:YAG) lasers remain unstudied in this context. METHODS: We applied Nd:YAG laser energy in the treatment of three consecutive patients presenting with altered neurosensory function following various oral and maxillofacial procedures. The time interval between surgical injury and laser photobiomodulation ranged from one week to two years. RESULTS: All patients exhibited reduction in the area of diminished sensation and partial recovery of normal neurosensory function. The two patients with long-standing neurosensory deficiency experienced near complete recovery of intraoral sensation, with residual zones of diminished sensation from the perioral skin. CONCLUSIONS: Although all patients in this case series demonstrated clinical improvements compared with baseline, controlled studies are needed to determine whether Nd:YAG laser energy accelerates or enhances recovery of neurosensory function after surgical nerve injury. Studies establishing the relative efficacies of Nd:YAG and diode lasers appear warranted.

Abscisic acid supports colonization of Eucalyptus grandis roots by the mutualistic ectomycorrhizal fungus Pisolithus microcarpus.

The pathways regulated in ectomycorrhizal (EcM) plant hosts during the establishment of symbiosis are not as well understood when compared to the functional stages of this mutualistic interaction. Our study used the EcM host Eucalyptus grandis to elucidate symbiosis-regulated pathways across the three phases of this interaction. Using a combination of RNA sequencing and metabolomics we studied both stage-specific and core responses of E. grandis during colonization by Pisolithus microcarpus. Using exogenous manipulation of the abscisic acid (ABA), we studied the role of this pathway during symbiosis establishment. Despite the mutualistic nature of this symbiosis, a large number of disease signalling TIR-NBS-LRR genes were induced. The transcriptional regulation in E. grandis was found to be dynamic across colonization with a small core of genes consistently regulated at all stages. Genes associated to the carotenoid/ABA pathway were found within this core and ABA concentrations increased during fungal integration into the root. Supplementation of ABA led to improved accommodation of P. microcarpus into E. grandis roots. The carotenoid pathway is a core response of an EcM host to its symbiont and highlights the need to understand the role of the stress hormone ABA in controlling host-EcM fungal interactions.

Effects of a flotation vest and water flow rate on limb kinematics of Siberian Huskies swimming against a current.

OBJECTIVE: To evaluate the effects of a flotation vest (FV) and water flow rate (WFR) on limb kinematics of dogs swimming against a current. ANIMALS: 7 (1 male and 6 female) healthy adult Siberian Huskies. PROCEDURES: Dogs were habituated to swim with and without an FV beside an investigator in a continuous-flow pool against WFRs up to 2.9 km/h. During each of 4 experimental sessions in a repeated-measures study, markers were wrapped around the right carpus and tarsus, and a video was recorded while each dog swam with or without an FV for about 2 minutes at each of 7 WFRs between 0 and 2.9 km/h when the WFR was incrementally decreased or increased. Motion tracking software was used to measure stroke excursion and frequency. RESULTS: Stroke excursion varied more than frequency among all dogs and in response to changes in experimental conditions. The male dog and 1 female dog were unable to complete the study. For the remaining 5 dogs across all experimental conditions, mean tarsus excursion was 30% that of the carpus. Mean total excursion (sum of the excursion-frequency products for the carpus and tarsus) decreased when an FV was worn and increased with WFR by 69% and 19% when WFR was incrementally increased and decreased, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, range of motion during swimming was greater for the carpus than tarsus, when an FV was not worn, and increased more with WFR when WFR was incrementally increased. Those factors should be considered during swimming-based rehabilitation.