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Presented in this paper is an evaluation of human tissue penetration by millimeter wave (mmW) energy, particularly at 30, 35, 40 and 45 GHz. Numerical simulations show that the penetration depths in the tissue are (0.1000, 0.0937, 0.08869 and 0.08882) mm at the aforementioned frequency, respectively. It is also demonstrated that all mmW at those frequencies attenuate to zero at the epidermis which is the layer adjacent to the skin surface, without getting into the dermis which is the next layer. Crucially, these discoveries present fresh, previously unmentioned data within the current research literature. Furthermore, at the lower frequency of 24 GHz, computer simulations presented show that the propagating wave penetrates deeper (depth of 0.12 mm) and attenuates to zero at the dermis. This shows that the depth of penetration increases further at lower frequencies which strongly conforms to the principles of physical reasoning, thereby bolstering the reliability of the findings presented in this paper. The results collectively indicate that the absorption of mmW into the human tissue have limited significance when assessing compliance with electromagnetic field standards at mmW frequencies. It is reinforced in this paper why the human skin reduces the harmful effects of ultra-violet radiation. To lend credence to our formulation, certain aspects of the results obtained in this investigation when compared with similar results in the literature, show good agreements. [ABSTRACT FROM AUTHOR]

Presented in this paper is an evaluation of human tissue penetration by millimeter wave (mmW) energy, particularly at 30, 35, 40 and 45 GHz. Numerical simulations show that the penetration depths in the tissue are (0.1000, 0.0937, 0.08869 and 0.08882) mm at the aforementioned frequency, respectively. It is also demonstrated that all mmW at those frequencies attenuate to zero at the epidermis which is the layer adjacent to the skin surface, without getting into the dermis which is the next layer. Crucially, these discoveries present fresh, previously unmentioned data within the current research literature. Furthermore, at the lower frequency of 24 GHz, computer simulations presented show that the propagating wave penetrates deeper (depth of 0.12 mm) and attenuates to zero at the dermis. This shows that the depth of penetration increases further at lower frequencies which strongly conforms to the principles of physical reasoning, thereby bolstering the reliability of the findings presented in this paper. The results collectively indicate that the absorption of mmW into the human tissue have limited significance when assessing compliance with electromagnetic field standards at mmW frequencies. It is reinforced in this paper why the human skin reduces the harmful effects of ultra-violet radiation. To lend credence to our formulation, certain aspects of the results obtained in this investigation when compared with similar results in the literature, show good agreements.

This paper investigates the dynamics of mmWave at the free space-human skin interface. The four Fresnel equations tailored for parallel and perpendicular polarizations, are employed in the analysis. The research reveals that for human tissue with relative permittivities (18.99, 15.51, 13.35, 11.69, 10.40) and conductivities (22.48, 27.09, 29.76, 31.79, 33.38) S/m, when exposed to 5G mmWave frequencies (24, 30, 35, 40, 45) GHz, respectively, exhibits Brewster angles of (79º, 78º, 77º, 76º, 75º), respectively. Additionally, it is shown that Brewster angles exist between 60º and 80º which aligns with existing literature using Gabriel’s skin model. To further validate obtained results, use is made of the results of the Gabriel’s skin model at (40, 60, 80, 100) GHz with the respective permittivities and conductivities, to generate new power reflection coefficients for the parallel and perpendicular polarizations for the sake of comparative analysis. First, comparisons of the curves for the Gabriel’s skin model reported in the literature with this work, show fairly good agreements. Second, the Brewster angles of (78º, 76º, 74º, 73º) obtained from this work, for the respective frequencies compare favorably with (75º, 74º, 70º, 69º) extracted from Gabriel’s skin model curves reported in the literature, with all values falling within the expected range of 60º to 80º.

Aims: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro‐oncology speciality. Methods: As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology‐related findings, we conducted a result‐evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro‐oncology specialists. Results: The MDT identified key determinants impacting decision‐making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high‐risk nature. From this experience, we developed a decision‐making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. Conclusions: Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy‐related pathology, genetic disorders and degenerative diseases. [ABSTRACT FROM AUTHOR]

Toxic metals such as mercury, lead, and cadmium have multiple carcinogenic capacities, including the ability to damage DNA and incite inflammation. Environmental toxic metals have long been suspected to play a role in the pathogenesis of cancer, but convincing evidence from epidemiological studies that toxic metals are risk factors for common neoplasms has been difficult to gain. Another approach is to map the location of potentially toxic elements in normal human cells where common cancers originate, as well as in the cancers themselves. In this Perspective, studies are summarized that have used elemental biomapping to detect toxic metals such as mercury in human cells. Two elemental biomapping techniques, autometallography and laser ablation-inductively coupled-mass spectrometry imaging, have shown that multiple toxic metals exist in normal human cells that are particularly prone to developing cancer, and are also seen in neoplastic cells of breast and pancreatic tumors. Biomapping studies of animals exposed to toxic metals show that these animals take up toxic metals in the same cells as humans. The finding of toxic metals such as mercury in human cells prone to cancer could explain the increasing global incidence of many cancers since toxic metals continue to accumulate in the environment. The role of toxic metals in cancer remains to be confirmed experimentally, but to decrease cancer risk a precautionary approach would be to reduce emissions of mercury and other toxic metals into the environment from industrial and mining activities and from the burning of fossil fuels. [ABSTRACT FROM AUTHOR]

Musculoskeletal allografts represent an important practice in orthopedic surgeries and the demand for them has been growing. For this reason, in order to reduce clinical risk and to more efficiently manage the increase of allograft usage and also to optimize timing of the surgeries, the thawing and washing processes with aseptic technique were centralized in the department of Hospital Pharmacy. This study describe the design and execution of an adapted Media Fill Test (MFT) to demonstrate aseptic thawing and washing of allografts. For this specific and innovative setting, to better simulate the actual processing steps, a surrogate system was developed to simulate the tendon allograft. The aseptic technique of four operators was assessed and an initial performance validation and the first revalidation were described. All MFT were completed successfully, with no observation of turbidity. The readapted MFT shown in this study can provide insight into this innovative and growing field to other health professionals who want to implement this service. [ABSTRACT FROM AUTHOR]

This paper investigates the dynamics of mmWave at the free space-human skin interface. The four Fresnel equations tailored for parallel and perpendicular polarizations, are employed in the analysis. The research reveals that for human tissue with relative permittivities (18.99, 15.51, 13.35, 11.69, 10.40) and conductivities (22.48, 27.09, 29.76, 31.79, 33.38) S/m, when exposed to 5G mmWave frequencies (24, 30, 35, 40, 45) GHz, respectively, exhibits Brewster angles of (79°, 78°, 77°, 76°, 75°), respectively. Additionally, it is shown that Brewster angles exist between 60° and 80°, which aligns with existing literature using Gabriel's skin model. To further validate obtained results, use is made of the results of the Gabriel's skin model at (40, 60, 80, 100) GHz with the respective permittivities and conductivities, to generate new power reflection coefficients for the parallel and perpendicular polarizations for the sake of comparative analysis. First, comparisons of the curves for the Gabriel's skin model reported in the literature with this work, show fairly good agreements. Second, the Brewster angles of (78°, 76°, 74°, 73°) obtained from this work, for the respective frequencies compare favorably with (75°, 74°, 70°, 69°) extracted from Gabriel's skin model curves reported in the literature, with all values falling within the expected range of 60° to 80°. [ABSTRACT FROM AUTHOR]

In this paper, a theoretical study was carried out to calculate the proton energy loss in human tissues (Adipose tissue, Blood, Bone (Compact), Bone (Cortical), Brain, Eye lens, Lung, Skin, and Testicles) within the energy range of 1 MeV to 1000 MeV. We calculated the total stopping power for each tissue element separately using the Bethe-Bloch equation, and then used Bragg's rule for compounds to determine the tissue's total stopping power. The total stopping power is directly proportional to the atomic number divided by the target material's atomic mass (Z/A) and target material density (ρ), and inversely proportional to the target material's mean excitation energy (I) and proton energy (E). The results indicate that the stopping power was highest in the adipose tissue, and the lowest value was in the bone (cortical) at the same proton energy. We performed all calculations using the MATLAB program. We found a good match between the obtained results and the value of the P-Star code.

Down syndrome (DS), caused by triplication of chromosome 21, is the most frequent aneuploidy observed in the human population and represents the most common genetic form of intellectual disability and early-onset Alzheimer's disease (AD). Individuals with DS exhibit a wide spectrum of clinical presentation, with a number of organs implicated including the neurological, immune, musculoskeletal, cardiac, and gastrointestinal systems. Decades of DS research have illuminated our understanding of the disorder, however many of the features that limit quality of life and independence of individuals with DS, including intellectual disability and early-onset dementia, remain poorly understood. This lack of knowledge of the cellular and molecular mechanisms leading to neurological features of DS has caused significant roadblocks in developing effective therapeutic strategies to improve quality of life for individuals with DS. Recent technological advances in human stem cell culture methods, genome editing approaches, and single-cell transcriptomics have provided paradigm-shifting insights into complex neurological diseases such as DS. Here, we review novel neurological disease modeling approaches, how they have been used to study DS, and what questions might be addressed in the future using these innovative tools.

In three‐dimensional (3D) space, an unbiased and systemic view of human specimens between structures and functions is required. However, conventional histological sections from specimens have made only limited progress in exploring intact information about 3D biological tissues. With significant advances in optical physics and chemical engineering, state‐of‐the‐art tissue‐clearing methods can revolutionize the intact subcellular level of human tissue histological analysis, from thick human tissues to intact human organs. The present review summarizes the principle of tissue clearing so that a trainee researcher can implement effective human tissue‐clearing protocols. Furthermore, this review highlights existing tissue‐clearing methods in specific human tissue applications, describes imaging strategies, and presents various efficient computational approaches for processing and visualizing large image data. Finally, potential future directions for developing tissue‐clearing methods for human tissues are also discussed. [ABSTRACT FROM AUTHOR]

The proliferation of the ambient environment with many wireless communication infrastructures has constituted a source of concern, at least from health point of view. Hence, there is a need for the investigation of electromagnetic wave interaction with human tissue. This paper models electromagnetic wave propagation at the free-space-human tissue interface, in an attempt to understand how electromagnetic waves interact with the human skin. Maxwell’s equations were used to derive the governing equations of propagating electromagnetic waves in free space while the solution of the boundary-value problem arising from the incident electromagnetic wave at the free space-human tissue interface was found through the use of appropriate boundary conditions. The solution led to the emergence of four Fresnel equations, a pair each for perpendicular and parallel polarizations of the incident wave, at the boundary. Through the use of the Fresnel equations obtained, components of the incident electromagnetic wave power at the boundary can be quantified. Typical profiles of the normalized reflected and absorbed powers at the free space-human skin interface at 28, 60, and 73 GHz were computed, using measured values of permittivity of human tissue. It is found that the total absorption of the power of the incident wave by the human skin occurs when the angle of incidence is between 690 and 770 for the three frequencies used. This is irrespective of the polarization of the incident wave. Information on such distinct angles of incidence for total absorption of power does not appear to exist in the literature as they represent new, previously unreported facts in the existing body of research. Furthermore, computed profiles of reflected power versus incidence angle displayed here, for perpendicular polarization, demonstrate strong alignments with established literature, thus reinforcing the credibility of the results presented in this paper. [ABSTRACT FROM AUTHOR]

Consumers are exposed to mineral oil hydrocarbons (MOH) e.g. through foodstuffs and cosmetics. Upon ingestion, MOH follow the absorption pathway of dietary lipids. Analytical chemistry has revealed the presence of the main fraction, designated as mineral oil saturated hydrocarbons (MOSH), in mesenteric lymph nodes (MLNs), liver, spleen, and adipose tissue. Recent results from animal studies raised concerns about a long-term, possibly irreversible accumulation of some MOSH in humans. To address this issue, we performed a statistical re-analysis of published biopsy and autopsy data regarding the age-dependence of MOSH levels in human tissue. MOSH concentrations in MLNs and adipose tissue showed a 1.2–1.4-fold increase per decade, pointing to very long-term accumulation in both tissues. There was no evidence for age-dependent MOSH concentrations in liver and spleen. There was no sex difference in the MOSH concentrations in MLNs, suggesting a similar oral exposure for men and women. On average, women had a 2.2–2.5-fold higher MOSH concentration in the liver, spleen and adipose tissue compared to men. This finding may point to a sex difference in metabolism, in line with animal data. The use of certain cosmetics was a relevant predictor in addition to age. Women that used cosmetics like lipstick, hand cream, and sun cream had an average 2.1-fold higher MOSH concentration in abdominal subcutaneous fat than non-users. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer is a common malignancy affecting the urinary tract and effective biomarkers and for which monitoring therapeutic interventions have yet to be identified. Objectives: Major aim of this work was to perform metabolomic profiling of human bladder cancer and adjacent normal tissue and to evaluate cancer biomarkers. Methods: This study utilized nuclear magnetic resonance (NMR) and high-resolution nanoparticle-based laser desorption/ionization mass spectrometry (LDI-MS) methods to investigate polar metabolite profiles in tissue samples from 99 bladder cancer patients. Results: Through NMR spectroscopy, six tissue metabolites were identified and quantified as potential indicators of bladder cancer, while LDI-MS allowed detection of 34 compounds which distinguished cancer tissue samples from adjacent normal tissue. Thirteen characteristic tissue metabolites were also found to differentiate bladder cancer tumor grades and thirteen metabolites were correlated with tumor stages. Receiver-operating characteristics analysis showed high predictive power for all three types of metabolomics data, with area under the curve (AUC) values greater than 0.853. Conclusion: To date, this is the first study in which bladder human normal tissues adjacent to cancerous tissues are analyzed using both NMR and MS method. These findings suggest that the metabolite markers identified in this study may be useful for the detection and monitoring of bladder cancer stages and grades. [ABSTRACT FROM AUTHOR]

Abstract In three‐dimensional (3D) space, an unbiased and systemic view of human specimens between structures and functions is required. However, conventional histological sections from specimens have made only limited progress in exploring intact information about 3D biological tissues. With significant advances in optical physics and chemical engineering, state‐of‐the‐art tissue‐clearing methods can revolutionize the intact subcellular level of human tissue histological analysis, from thick human tissues to intact human organs. The present review summarizes the principle of tissue clearing so that a trainee researcher can implement effective human tissue‐clearing protocols. Furthermore, this review highlights existing tissue‐clearing methods in specific human tissue applications, describes imaging strategies, and presents various efficient computational approaches for processing and visualizing large image data. Finally, potential future directions for developing tissue‐clearing methods for human tissues are also discussed.

It is well known that the rheological properties of magnetorheological (MR) material change under a magnetic field. So far, most works on MR materials have been oriented toward actuating characteristics instead of sensing functions. In this work, to realize dynamic tactile motion, a spherical MR structure was designed as a sensor, incorporating a magnetic circuit core to provide maximum dynamic motion. After manufacturing a prototype (sample), a sinusoidal magnetic field of varying exciting frequency and magnitude was applied to the sample, and the dynamic contraction and relaxation motion depending on the exciting magnetic field was observed. Among the test results, when 10% deformation occurred, the instantaneous force generated was from 2.8 N to 8.8 N, and the force when relaxed was from 1.2 N to 3.5 N. It is also shown that the repulsive force within this range can be implemented using an acceptable input current. The special tactile sensing structure proposed in this work can be used as a sensor to measure the field-dependent viscoelastic properties of human tissues such as stomach, liver, and overall body. In addition, it could be usefully applied to robot surgery, because it can mimic the dynamic motions of various human organs under various surgical conditions. [ABSTRACT FROM AUTHOR]

There is a great need to understand human immune cells within tissue, where disease manifests and infection occurs. Tissue‐resident memory T cells (TRMs) were discovered over a decade ago, there is a great need to understand their role in human disease. We developed a 24‐color flow cytometry panel to comprehensively interrogate CD4+ and CD8+ TRMs isolated from human tissues. When interrogating cells within human tissue, enzymatic methods used to liberate cells from within the tissue can cause cleavage of cell surface markers needed to phenotype these cells. Here we carefully select antibody clones and evaluate the effect of enzymatic digestion on the expression of markers relevant to the identification of T cell residency, as well as markers relevant to the activation and immunoregulation status of these cells. We have designed this panel to be applicable across a range of human tissues including skin, intestine, and type II mucosae such as the vagina. [ABSTRACT FROM AUTHOR]

Hands‐on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German‐speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German‐speaking Europe. Clusters were established for "ethanol"‐, formaldehyde‐based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three‐fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table‐borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling‐ and floor‐borne air ventilation, and explosion‐proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here‐established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best‐suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits. [ABSTRACT FROM AUTHOR]

The present study aims to examine Max Clara’s (1899–1966) life and his scientific activities in Istanbul between 1950-1966. Clara’s career before and during the National Socialist era has been extensively studied. However, information is lacking regarding his later years and his relationships with his old colleagues and the academic world after being dismissed from academic life in the postwar period. This article presents information about Max Clara’s life in Istanbul based on primary sources kept at the Istanbul University Archives. Archival documents were supplemented by analyses on literature about the history of Istanbul University, refugee scholars in Turkey, Max Clara’s life, and his publications. Furthermore, the study attempted to find the histological and anatomical material Dr. Clara had brought with him from Germany in order to identify the National Socialist era victims from whom the materials had been harvested. This article clearly and extensively brings Max Clara’s life, academic work, and relations with the outside world during his Istanbul years into light. However, his histological and anatomical collection, which was divided into three parts after his passing, could not be accessed due to the reluctance the relevant institutions, faculty members, and new owners of the materials had. This study also deals with Clara’s involvement in unethical practices during the National Socialist era, such as medical experiments on prisoners and the use of the unethically procured bodies of the executed. The analysis of his academic publications reveals that they involved great inconsistencies and distortions and that these publications were not as important as was thought. [ABSTRACT FROM AUTHOR]

Collagen, along with proteoglycans, glycosaminoglycans, glycoproteins, and various growth factors, forms the extracellular matrix (ECM) and contributes to the complexity and diversity of different tissues. Herein, we compared the physicochemical and biological properties of ECM hydrogels derived from four different human tissues: skin, bone, fat, and birth. Pure human collagen type I hydrogels were used as control. Physical characterization of ECM hydrogels and assessment of cell response of cord-tissue mesenchymal stem cells (CMSCs) were performed. Decellularization efficiency was found to be >90% for all ECM. Hydroxyproline quantification assay showed that collagen content in birth ECM was comparable to collagen control and significantly greater than other sources of ECM. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of γ, β, α1 and α2 collagen chains in all ECMs. Gelation kinetics of ECM hydrogels was significantly slower than collagen control. Compressive modulus of skin ECM was the highest and birth ECM was the lowest. Skin and birth ECM hydrogels were more stable than bone and fat ECM hydrogels. CMSCs encapsulated in birth ECM hydrogels exhibited the highest metabolic activity. Rheological characterization revealed that all ECM-derived inks exhibited shear thinning properties, and skin-derived ECM inks were most suitable for extrusion-based bioprinting for the concentration and printing conditions used in this study. Overall, results demonstrate that the physicochemical and biological properties of ECM hydrogels vary significantly depending on the tissue source. Therefore, careful selection of tissue source is important for development of ECM-based biomimetic tissue constructs for regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Down syndrome (DS), caused by triplication of chromosome 21, is the most frequent aneuploidy observed in the human population and represents the most common genetic form of intellectual disability and early-onset Alzheimer’s disease (AD). Individuals with DS exhibit a wide spectrum of clinical presentation, with a number of organs implicated including the neurological, immune, musculoskeletal, cardiac, and gastrointestinal systems. Decades of DS research have illuminated our understanding of the disorder, however many of the features that limit quality of life and independence of individuals with DS, including intellectual disability and early-onset dementia, remain poorly understood. This lack of knowledge of the cellular and molecular mechanisms leading to neurological features of DS has caused significant roadblocks in developing effective therapeutic strategies to improve quality of life for individuals with DS. Recent technological advances in human stem cell culture methods, genome editing approaches, and single-cell transcriptomics have provided paradigm)shifting insights into complex neurological diseases such as DS. Here, we review novel neurological disease modeling approaches, how they have been used to study DS, and what questions might be addressed in the future using these innovative tools. [ABSTRACT FROM AUTHOR]

Cyanobacteria produce a variety of secondary metabolites, including toxins that may contribute to the development of disease. Previous work was able to detect the presence of a cyanobacterial marker in human nasal and broncoalveolar lavage samples; however, it was not able to determine the quantification of the marker. To further research the relationship between cyanobacteria and human health, we validated a droplet digital polymerase chain reaction (ddPCR) assay to simultaneously detect the cyanobacterial 16S marker and a human housekeeping gene in human lung tissue samples. The ability to detect cyanobacteria in human samples will allow further research into the role cyanobacteria plays in human health and disease. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains. We analyzed 5 brain regions (middle frontal gyrus, occipital pole, rostral cingulate cortex, caudal cingulate cortex, and basal ganglia) of 76 brain bank subjects (mean age ± SE 90 ± 1.4 years). Prussian blue positivity, used as an index of CMH, was subjected to quantitative analysis for all 5 brain regions. Brains from the top and bottom quartiles (n = 19 each) were compared for quantitative immunohistological findings of smooth muscle actin, claudin-5, and fibrinogen, and for Sclerosis Index (SI) (a measure of arteriolar remodeling). Brains in the top quartile (i.e. with most extensive CMH) had significantly higher SI in the 5 brain regions combined (0.379 ± 0.007 vs 0.355 ± 0.008; p

Abstract Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non‐central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of pathology in archived non‐CNS tissues, taken as part of routine clinical practice during life from people with ALS. We examined tissue from 13 people who went on to develop ALS; including sporadic ALS (n = 12) and C9orf72 hexanucleotide repeat expansion (n = 1). The tissue cohort consisted of 68 formalin‐fixed paraffin embedded samples from 21 surgical cases (some patients having more than one case over their lifetimes), from 8 organ systems, which we examined for evidence of phosphorylated TDP‐43 (pTDP‐43) pathology. We identified pTDP‐43 aggregates in multiple cell types of the GI tract, including macrophages and dendritic cells within the lamina propria; as well as ganglion/neuronal and glial cells of the myenteric plexus. Aggregates were also noted within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non‐CNS pTDP‐43 pathology, aggregates were present prior to ALS diagnosis and in some instances preceded neurological symptom onset by more than 10 years. These data imply that patients with microscopically unexplained non‐CNS symptoms could have occult protein aggregation that could be detected many years prior to neurological involvement.

The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation (cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2 weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.

Animal models of human brain disorders permit researchers to explore disease mechanisms and to test potential therapies. However, therapeutic molecules derived from animal models often translate poorly to the clinic. Although human data may be more relevant, experiments on patients are constrained, and living tissue is unavailable for many disorders. Here, we compare work on animal models and on human tissue for three epileptic syndromes where human tissue is excised therapeutically: (1) acquired temporal lobe epilepsies, (2) inherited epilepsies associated with cortical malformations, and (3) peritumoral epilepsies. Animal models rest on assumed equivalencies between human brains and brains of mice, the most frequently used model animal. We ask how differences between mouse and human brains could influence models. General principles and compromises in model construction and validation are examined for a range of neurological diseases. Models may be judged on how well they predict novel therapeutic molecules or new mechanisms. The efficacy and safety of new molecules are evaluated in clinical trials. We judge new mechanisms by comparing data from work on animal models with data from work on patient tissue. In conclusion, we stress the need to cross‐verify findings from animal models and from living human tissue to avoid the assumption that mechanisms are identical. [ABSTRACT FROM AUTHOR]

Non-invasive thermal therapy for subcutaneous tumors with the assistance of gold nanoparticles and surface cooling measures was proposed in the present study. To achieve real-time monitoring of 3-D temperature distribution and accurate measurement of thermal response, we developed a theoretical approach in which the dual-phase-lag (DPL) biological heat transfer model and Henriques' burn estimation model were employed. A closed-form solution for temperature distribution in the skin tissue can be obtained from this new model by employing the Green's function method. In addition, the influences of the embedment of gold nanoparticles, surface cooling, and non-Fourier effects on the temperature, thermal damage, and size of the burnt region were discussed in detail. The present model performs well in addressing the difficult issue of temperature and burn prediction inside human tissue. It is found that the combination of gold nanoparticles and surface cooling can concentrate thermal empyrosis in the subcutaneous tumor to enhance tumor elimination and protect both skin and deeper healthy tissue. This study provides theoretical support for the improvement and development of laser thermotherapy for subcutaneous tumors.

Down syndrome (DS), caused by triplication of chromosome 21, is the most frequent aneuploidy observed in the human population and represents the most common genetic form of intellectual disability and early-onset Alzheimer’s disease (AD). Individuals with DS exhibit a wide spectrum of clinical presentation, with a number of organs implicated including the neurological, immune, musculoskeletal, cardiac, and gastrointestinal systems. Decades of DS research have illuminated our understanding of the disorder, however many of the features that limit quality of life and independence of individuals with DS, including intellectual disability and early-onset dementia, remain poorly understood. This lack of knowledge of the cellular and molecular mechanisms leading to neurological features of DS has caused significant roadblocks in developing effective therapeutic strategies to improve quality of life for individuals with DS. Recent technological advances in human stem cell culture methods, genome editing approaches, and single-cell transcriptomics have provided paradigm-shifting insights into complex neurological diseases such as DS. Here, we review novel neurological disease modeling approaches, how they have been used to study DS, and what questions might be addressed in the future using these innovative tools.

Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) are traditionally considered strictly neurological disorders. However, clinical presentation is not restricted to neurological systems, and non‐central nervous system (CNS) manifestations, particularly gastrointestinal (GI) symptoms, are common. Our objective was to understand the systemic distribution of pathology in archived non‐CNS tissues, taken as part of routine clinical practice during life from people with ALS. We examined tissue from 13 people who went on to develop ALS; including sporadic ALS (n = 12) and C9orf72 hexanucleotide repeat expansion (n = 1). The tissue cohort consisted of 68 formalin‐fixed paraffin embedded samples from 21 surgical cases (some patients having more than one case over their lifetimes), from 8 organ systems, which we examined for evidence of phosphorylated TDP‐43 (pTDP‐43) pathology. We identified pTDP‐43 aggregates in multiple cell types of the GI tract, including macrophages and dendritic cells within the lamina propria; as well as ganglion/neuronal and glial cells of the myenteric plexus. Aggregates were also noted within lymph node parenchyma, blood vessel endothelial cells, and chondrocytes. We note that in all cases with non‐CNS pTDP‐43 pathology, aggregates were present prior to ALS diagnosis and in some instances preceded neurological symptom onset by more than 10 years. These data imply that patients with microscopically unexplained non‐CNS symptoms could have occult protein aggregation that could be detected many years prior to neurological involvement. [ABSTRACT FROM AUTHOR]

Sodium–glucose cotransporter 2 (SGLT2) occurs in the proximal renal tubule cells. We investigate the hepatic expression of SGLT2 and its related factors in patients with chronic liver disease. This is a retrospective human study. The liver tissues were biopsied from patients with chronic liver disease (n = 30). The expression levels of SGLT2 were evaluated by immunostaining. Furthermore, the undirected graphical model was used to identify factors associated with hepatic expression levels of SGLT2. The SGLT2 expression was observed in not only the kidney, but also the liver in immunostaining (SGLT2 intensity: kidney 165.8 ± 15.6, liver 114.4 ± 49.0 arbitrary units, P < 0.01) and immunoblotting. There was no significant difference in hepatic expression of SGLT2 in the stratified analysis according to age, sex, BMI, and the severity of the liver disease. In the undirected graphical model, SGLT2 directly interacted with various factors such as sex, fatty change, neutrophil-to-lymphocyte ratio, triglyceride, hemoglobin A1c, creatinine, and albumin (partial correlation coefficient 0.4–0.6 for sex and 0.2–0.4 for others). The expression of SGLT2 was observed in the hepatocytes of patients with chronic liver disease. The undirected graphical model demonstrated the complex interaction of hepatic expression levels of SGLT2 with gender, inflammation, renal function, and lipid/glucose/protein metabolisms. [ABSTRACT FROM AUTHOR]

Thioredoxin-Interacting Protein (TXNIP) has been shown to have significant pathogenic roles in many human diseases, particularly those associated with diabetes and hyperglycemia. Its main mode of action is to sequester thioredoxins, resulting in enhanced oxidative stress. The aim of this study was to identify if cellular expression of TXNIP in human aged and Alzheimer’s disease (AD) brains correlated with pathological structures. This study employed fixed tissue sections and protein extracts of temporal cortex from AD and aged control brains. Studies employed light and fluorescent immunohistochemical techniques using the monoclonal antibody JY2 to TXNIP to identify cellular structures. Immunoblots were used to quantify relative amounts of TXNIP in brain protein extracts. The major finding was the identification of TXNIP immunoreactivity in selective neuronal populations and structures, particularly in non-AD brains. In AD brains, less neuronal TXNIP but increased numbers of TXNIP-positive plaque-associated microglia were observed. Immunoblot analyses showed no significant increase in levels of TXNIP protein in the AD samples tested. In conclusion, this study identified altered patterns of expression of TXNIP in human brains with progression of AD pathology.

Currently, the use of autografts is the gold standard for the replacement of many damaged biological tissues. However, this practice presents disadvantages that can be mitigated through tissue-engineered implants. The aim of this study is to explore how machine learning can mechanically evaluate 2D and 3D polyvinyl alcohol (PVA) electrospun scaffolds (one twisted filament, 3 twisted filament and 3 twisted/braided filament scaffolds) for their use in different tissue engineering applications. Crosslinked and non-crosslinked scaffolds were fabricated and mechanically characterised, in dry/wet conditions and under longitudinal/transverse loading, using tensile testing. 28 machine learning models (ML) were used to predict the mechanical properties of the scaffolds. 4 exogenous variables (structure, environmental condition, crosslinking and direction of the load) were used to predict 2 endogenous variables (Young's modulus and ultimate tensile strength). ML models were able to identify 6 structures and testing conditions with comparable Young's modulus and ultimate tensile strength to ligamentous tissue, skin tissue, oral and nasal tissue, and renal tissue. This novel study proved that Classification and Regression Trees (CART) models were an innovative and easy to interpret tool to identify biomimetic electrospun structures; however, Cubist and Support Vector Machine (SVM) models were the most accurate, with R2 of 0.93 and 0.8, to predict the ultimate tensile strength and Young's modulus, respectively. This approach can be implemented to optimise the manufacturing process in different applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus, a process named adult hippocampal neurogenesis, contribute to maintaining healthy cognitive functions throughout life. The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues. The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has, however, not been established. This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans. While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease, consensual results have yet to be reached to fully explore this hypothesis. In this review, we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases, especially in Alzheimer’s disease. We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease. In particular, we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems, as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues, could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.

Traumatic heterotopic ossification (HO) refers to the abnormal ectopic osteogenesis following trauma, causing limb dysfunction and seriously lowering the life quality of patients. Aberrant osteogenic behavior of progenitor cells that ectopically accumulated within the soft tissues are believed to be responsible for HO formation. However, the detailed mechanism still remained to be clarified. Here in this study, we successfully isolated osteoprogenitors from human heterotopic ossification tissues (HO‐ops) and identified their stemness and multi‐directional differentiation potential. Using alkaline phosphatase staining together with alizarin red staining, we confirmed that the HO‐ops in the heterotopic ossified tissues gained greater osteogenic potential than the normal human bone marrow mesenchymal stem cells (HBMSCs). RT‐qPCR also indicated that HO‐ops obtained more gene transcriptions of critical osteogenic determinators than HBMSCs. In addition, through Western blot, we proved that ERK signaling pathway and hedgehog signaling pathway were significantly activated in the HO‐ops. When U0126 and cyclopamine were used to inhibit ERK signaling and hedgehog signaling respectively, the osteogenic potential of HO‐ops decreased significantly. The hedgehog signaling and ERK signaling also showed cross‐talk in HO‐ops during osteogenic differentiation in HO‐ops during osteogenic differentiation. The elevated ERK signaling and hedgehog signaling were further confirmed in the human traumatic HO sample sections by immunohistochemical staining. In sum, our results showed that the activation of ERK and hedgehog signaling pathway jointly enhanced the osteogenic potential of HO‐ops to induce the formation of traumatic HO, which provides novel insights into the molecular basis of HO formation and offers promising targets for future therapeutic strategy. [ABSTRACT FROM AUTHOR]

Keywords: animal models; epilepsy; epileptogenesis; human tissue; Seizure EN animal models epilepsy epileptogenesis human tissue Seizure 4575 4578 4 11/03/22 20221101 NES 221101 Epilepsy and models Epilepsy is one of the most common severe neurological diseases, affecting up to 70 million people worldwide (Ngugi et al., 2010). Cross Talk opposing view: Animal models of epilepsy are more useful than human tissue-based approaches Here, we argue that, despite advances in human tissue models, animal models of epilepsy remain more useful for interrogating basic mechanisms and novel therapeutics in epilepsy. Co-morbidities and non-seizure aspects of epilepsy Whilst epilepsy has classically been most closely associated with seizures, it is increasingly recognised that co-morbidities can include challenges with memory, sleep, and mental health (Mula et al., 2021). [Extracted from the article]

Collagen, along with proteoglycans, glycosaminoglycans, glycoproteins, and various growth factors, forms the extracellular matrix (ECM) and contributes to the complexity and diversity of different tissues. Herein, we compared the physicochemical and biological properties of ECM hydrogels derived from four different human tissues: skin, bone, fat, and birth. Pure human collagen type I hydrogels were used as control. Physical characterization of ECM hydrogels and assessment of cell response of cord-tissue mesenchymal stem cells (CMSCs) were performed. Decellularization efficiency was found to be >90% for all ECM. Hydroxyproline quantification assay showed that collagen content in birth ECM was comparable to collagen control and significantly greater than other sources of ECM. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed the presence of γ, β, α1 and α2 collagen chains in all ECMs. Gelation kinetics of ECM hydrogels was significantly slower than collagen control. Compressive modulus of skin ECM was the highest and birth ECM was the lowest. Skin and birth ECM hydrogels were more stable than bone and fat ECM hydrogels. CMSCs encapsulated in birth ECM hydrogels exhibited the highest metabolic activity. Rheological characterization revealed that all ECM-derived inks exhibited shear thinning properties, and skin-derived ECM inks were most suitable for extrusion-based bioprinting for the concentration and printing conditions used in this study. Overall, results demonstrate that the physicochemical and biological properties of ECM hydrogels vary significantly depending on the tissue source. Therefore, careful selection of tissue source is important for development of ECM-based biomimetic tissue constructs for regenerative medicine applications.

Cyanobacteria produce a variety of secondary metabolites, including toxins that may contribute to the development of disease. Previous work was able to detect the presence of a cyanobacterial marker in human nasal and broncoalveolar lavage samples; however, it was not able to determine the quantification of the marker. To further research the relationship between cyanobacteria and human health, we validated a droplet digital polymerase chain reaction (ddPCR) assay to simultaneously detect the cyanobacterial 16S marker and a human housekeeping gene in human lung tissue samples. The ability to detect cyanobacteria in human samples will allow further research into the role cyanobacteria plays in human health and disease.

Introduction: Anatomical sciences involve handling of human tissues and, therefore, application of principles of bioethics is central to anatomical practice. For a considerable period of time, anatomy was practiced without ethical norms as concept of ethics developed during second half of twentieth century. Hence, possible glimpse into contrast in ethical standards between anatomy in the past and present was deemed as an intriguing research theme. Methods: A literature search was undertaken from indexed databases (Medline and Pubmed, Scopus, Embase, CINAHL Plus, Web of Science and Google Scholar). Relevant data were extracted from 37 articles that were selected from an initial pool of 752 articles based on search criteria set for the study. Results: Prevalent anatomical practices in the past such as dissection of executed criminals, acts of vivisection, illegal procurement of human remains, use of human tissues obtained as part of war crimes and dissection of human fetuses as well as their archival were analyzed through prism of established ethical norms in present day. The observations from past were presented vis-à-vis ethical practices undertaken in present times such as use of donated bodies and/or body parts procured through legal means for dissection, adherence to ethical norms during dissection, archival of human tissues mandating stringent regulation and dignified disposal of human remains. Existing loop holes were identified and future prospects regarding ethical standards in anatomy were highlighted based on rational judgment of existing trends. Conclusion: The article concludes with defense on future prospects of ethics in anatomy based on documented arguments. [ABSTRACT FROM AUTHOR]

Antisense inhibition of microRNAs is an emerging preclinical approach to pharmacoresistant epilepsy. A leading candidate is an "antimiR" targeting microRNA‐134 (ant‐134), but testing to date has used rodent models. Here, we develop an antimiR testing platform in human brain tissue sections. Brain specimens were obtained from patients undergoing resective surgery to treat pharmacoresistant epilepsy. Neocortical specimens were submerged in modified artificial cerebrospinal fluid (ACSF) and dissected for clinical neuropathological examination, and unused material was transferred for sectioning. Individual sections were incubated in oxygenated ACSF, containing either ant‐134 or a nontargeting control antimiR, for 24 h at room temperature. RNA integrity was assessed using BioAnalyzer processing, and individual miRNA levels were measured using quantitative reverse transcriptase polymerase chain reaction. Specimens transported in ACSF could be used for neuropathological diagnosis and had good RNA integrity. Ant‐134 mediated a dose‐dependent knockdown of miR‐134, with approximately 75% reduction of miR‐134 at 1 μmol L−1 and 90% reduction at 3 μmol L−1. These doses did not have off‐target effects on expression of a selection of three other miRNAs. This is the first demonstration of ant‐134 effects in live human brain tissues. The findings lend further support to the preclinical development of a therapy that targets miR‐134 and offer a flexible platform for the preclinical testing of antimiRs, and other antisense oligonucleotide therapeutics, in human brain. [ABSTRACT FROM AUTHOR]

Great strides have been made over the past 30 years in understanding the neurodevelopmental changes underlying the intellectual disability (ID) in Down syndrome (DS). Detailed studies of human tissue coupled with findings from rodent and induced pluripotent stem cells (iPSCs) model systems have uncovered the changes in neurogenesis, synaptic connectivity, and myelination that drive the anatomical and physiological changes resulting in the disability. However, there remain significant conflicting data between human studies and the models. To fully understand the development of ID in DS, these inconsistencies need to be reconciled. Here, we review the well documented neurodevelopmental phenotypes found in individuals with DS and examine the degree to which widely used models recapitulate these phenotypes. Resolving these areas of discord will further research on the molecular underpinnings and identify potential treatments to improve the independence and quality of life of people with DS. [ABSTRACT FROM AUTHOR]

Simple Summary: Tackling and curing cancer is still one of the most important challenges of biomedical research. Lung cancer is among the most diverse and lethal types, therefore identifying alterations in proteins participating in events leading to this disease is crucial. By analyzing and comparing the tissue proteomics profile of small cell lung cancer, as well as non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) subtypes, following on-surface tryptic digestion, we aimed to identify the key dysregulated pathways. Proteins altered between cancerous and respective adjacent normal tissue were determined to reveal common and lung cancer type-specific changes. These proteins can contribute to a more precise classification of lung cancer and, following validation, can further improve the currently available diagnostic panels. Lung cancer is the leading cause of tumor-related mortality, therefore significant effort is directed towards understanding molecular alterations occurring at the origin of the disease to improve current treatment options. The aim of our pilot-scale study was to carry out a detailed proteomic analysis of formalin-fixed paraffin-embedded tissue sections from patients with small cell or non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma). Tissue surface digestion was performed on relatively small cancerous and tumor-adjacent normal regions and differentially expressed proteins were identified using label-free quantitative mass spectrometry and subsequent statistical analysis. Principal component analysis clearly distinguished cancerous and cancer adjacent normal samples, while the four lung cancer types investigated had distinct molecular profiles and gene set enrichment analysis revealed specific dysregulated biological processes as well. Furthermore, proteins with altered expression unique to a specific lung cancer type were identified and could be the targets of future studies. [ABSTRACT FROM AUTHOR]

This article explores how communication and interaction design were used in the augmented reality experience, Donate Yourself. It aims to demystify some of the ethical and personal concerns around the donation of organs, tissue and body data for scientific and medical research. The research finds different modes of provoking thought around a central question: can augmented reality be used to open debates on who has access to our biological and digital traces beyond death? Taking into account how COVID-19 has made the public deeply reconsider their biological and data bodies, the paper documents and contextualizes the making of Donate Yourself, which was created in collaboration with interactive design collective body>data>space and scientists from the Human Cell Atlas project (HCA). In doing so, it explores the contested histories of human tissue in research and contemporizes these relations by looking at the way HCA members use and care for human tissue and data in their work. A range of methods that were used to capture diverse public attitudes and ethical concerns about donation using participatory approaches included: the co-creation of design probes with HCA scientists, online workshops, qualitative interviews, a documentation zine and public maker jam. These methodological lenses, and the data they produce, were used to construct a non-linear narrative and digital bricolage that is experienced as a hybrid public walking tour. Five themes were generated for the augmented reality experiences: care, trust, immortal, consent, future. This triangulation of science, technology and the arts was materialized in a webAR walking trail that ran during November 2021, which was accessed by the public via QR codes as part of the larger One Cell At A Time online exhibition, funded by the Wellcome Trust. [ABSTRACT FROM AUTHOR]

BackgroundAnterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature.MethodsIntracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs) (both left and right), vertebral arteries (VAs) (side more affected), and basilar arteries (BAs).ResultsProgressive atherosclerotic lesions were present in 91(71%) of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p