Modern Medical Laboratory Journal

Lung cancer has one of the highest incidence rates and mortality rates among all common cancers worldwide. Early detection of suspicious lung nodules is crucial in fighting lung cancer. In recent years, with the proliferation of clinical data like low-dose computed tomography (LDCT), histology whole slide images, electronic health records, and sensor readings from medical IoT devices etc., many artificial intelligence tools have taken more important roles in lung cancer management. Artificial intelligence (AI) is good at handling a large volume of computational and repeated labor work and is suitable for assisting doctors in analyzing image-dominant diseases like lung cancer. Scientists have shown long-standing efforts to apply AI in lung cancer screening via CXR and chest CT since the 1960s. Several grand challenges were held to find the best AI model. Currently, the FDA have approved several AI programs in CXR and chest CT reading, which enables AI systems to take part in lung cancer detection. Following the success of AI application in the radiology field, AI was applied to digitalized whole slide imaging (WSI) annotation. Integrating with more information, like demographics and clinical data, the AI systems could play a role in decision-making by classifying EGFR mutations and PD-L1 expression. AI systems also help clinicians to estimate the patient’s prognosis by predicting drug response, the tumor recurrence rate after surgery, radiotherapy response, and side effects.
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In a study published Aug. 31 in The BMJ, researchers found that men who consumed high rates of ultra-processed foods were at 29% higher risk for developing colorectal cancer. Colorectal cancer is the third most commonly diagnosed malignancy among both men and women in the United States and the second leading cause of death from cancer worldwide. Diet has been recognized as an important modifiable risk factor for colorectal cancer. Meanwhile, ultra-processed foods (that is, industrial ready-to-eat or ready-to-heat formulations made of little or no whole foods) now contribute 57% of total daily calories consumed by American adults, which has been continuously increasing in the past two decades. This study links men who consumed high rates of ultra-processed foods to a 29% higher risk for developing colorectal cancer than men who consumed much smaller amounts. The researchers did not find the same association in women.
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Axolotls have the ability to regenerate brain areas following an injury. Researchers have mapped cell types and genes associated with neurodegeneration in the axolotl brain, discovering some similarities in the human brain. The findings could pave the way for new neurodegenerative therapies. They etermined the cellular diversity of the axolotl telencephalon using single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing (snATAC-seq), as well as spatial transcriptomics. They identified regionally distributed neuron, ependymoglia, and neuroblast populations and determined their conservation with amniotes by using comparative analyses. They found that the axolotl telencephalon contains glutamatergic neurons with transcriptional similarities to neurons of the turtle and mouse hippocampus, dorsal cortex, and olfactory cortex. Olfactory cortex–like neurons also show conserved neuronal input projections from the olfactory bulb. Axolotl γ-aminobutyric acid–releasing (GABAergic) inhibitory neurons show signatures of different subregions of the ganglionic eminence and resemble turtle and mouse GABAergic inhibitory neurons. They conclude that in the postembryonic axolotl, telencephalon neurogenesis progresses through diverse neuroblast progenitors, which are associated with specific neuron types and dependent on shared as well as specific regulatory programs. They found implementation of these same programs in regenerative neurogenesis, which indicates that brain injury activates neurogenesis through existing pathways after inducing an injury-specific ependymoglia state. Regenerated neurons reestablish their previous connections to distant brain regions, suggesting potential functional recovery. Their insight into how the axolotl brain regenerates may inform studies of brain regeneration in other organisms.
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Scientists from the University of Cambridge have created model embryos without eggs or sperm from mouse stem cells that form a brain, a beating heart, and the foundations of all the other organs of the body. It represents a new avenue for recreating the first stages of life. The recipe for mammalian life is simple: take an egg, add sperm and wait. But a new paper demonstrates that there’s another way. Under the right conditions, stem cells can divide and self-organize into an embryo on their own. Embryonic stem cells (ESC) can undergo many aspects of mammalian embryogenesis in vitro, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem cells (TSCs), extraembryonic endoderm stem cells (XEN), and inducible-XEN cells (iXEN). In this study, they assembled stem-cell-derived embryos in vitro from mouse ESCs, TSCs and iXEN cells and showed that they recapitulate whole natural mouse embryo development in utero to day 8.5. Their embryo model displays head-folds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extra-embryonic yolk sac that initiates blood island development. Importantly, they demonstrate that the neurulating embryo model assembled from Pax6 knockout-ESCs aggregated with wild-type TSCs and iXENs recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous Pax6 knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse lineages and genes in development. Their results demonstrate the self-organization ability of embryonic and two types of extra-embryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.
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Scientists from the Terasaki Institute for Biomedical Innovation (TIBI) have developed a contact lens that can capture and detect exosomes, nanometer-sized vesicles found in bodily secretions which have the potential for being diagnostic cancer biomarkers. Exosomes, a form of small extracellular vesicles, play a crucial role in the metastasis of cancers and thus are investigated as potential biomarkers for cancer diagnosis. However, conventional detection methods like immune-based assay and microRNA analyses are expensive and require tedious pretreatments and lengthy analysis time. Since exosomes related to cancers are reported to exist in tears, a poly(2-hydroxyethyl methacrylate) contact lens embedded with antibody-conjugated signaling microchambers (ACSM-PCL) capable of detecting tear exosomes is reported. The ACSM-PCL exhibits high optical transparency and mechanical properties, along with extraordinary biocompatibility and good sensitivity to exosomes. A gold nanoparticle colorimetric assay is employed to visualize captured exosomes. The ACSM-PCL can detect exosomes in the pH range of 6.5–7.4 (similar to the human tear pH) and have a strong recovery yield in bovine serum albumin solutions. In particular, the ACSM-PCL can detect exosomes in various solutions, including regular buffer, cell culture media from various cell lines, and human tears. Finally, the ACSM-PCL can differentiate expression of exosome surface proteins hypothesized as cancer biomarkers. With these encouraging results, this ACSM-PCL is promised to be the next generation smart contact lens as an easy-to-use, rapid, noninvasive monitoring platform of cancer pre-screening and supportive diagnosis.
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A team of Yale scientists developed a new technology, OrganEx, which restored cell, organ function in pigs one hour after death. this technology consists of a perfusion device similar to heart-lung machines -- which do the work of the heart and lungs during surgery -- and an experimental fluid containing compounds that can promote cellular health and suppress inflammation throughout the pig's body. 
After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. In this study which is published by Nature, they describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Their analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.

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Brazilian twins (Three-year-olds Bernardo and Arthur Lima) who were joined at the head have been successfully separated with the help of virtual reality, last week. For the first time, surgeons in separate countries wore headsets and operated in the same "virtual reality room" together. The teams spent months trialling techniques using virtual reality projections of the twins, based on CT and MRI scans. The twins had seven surgeries, involving more than 27 hours of operating time in the final operation alone, and almost 100 medical staff.
Virtual reality is the name given to the technology that allows a user to simulate a situation or experience of interest, using a VR headset, within an interactive but computer-generated environment. The simulation is immersive and may require the use of special 3-D goggles with a screen, or gloves that provide sensory feedback, to help the user learn from experience in this virtual world. Virtual reality can be used to help medical professionals visualize the interior of the human body, thus unveiling otherwise inaccessible areas. For one, the dissection of cadavers, which was a norm for every new medical student, has given way to the study of human anatomy via virtual reality.
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Ultrasound is widely used for the noninvasive imaging of tissues and organs, but this method requires close contact between the transducer and the target area. This can make it difficult to acquire images over a long period of time, especially if the patient needs to be mobile. Continuous imaging of internal organs over days could provide crucial information about health and diseases and enable insights into developmental biology. Engineers at Massachusetts Institute of Technology report a bioadhesive ultrasound (BAUS) device that consists of a thin and rigid ultrasound probe robustly adhered to the skin via a couplant made of a soft, tough, antidehydrating, and bioadhesive hydrogel-elastomer hybrid. The BAUS device provides 48 hours of continuous imaging of diverse internal organs, including blood vessels, muscle, heart, gastrointestinal tract, diaphragm, and lung. The BAUS device could enable diagnostic and monitoring tools for various diseases.
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Heart disease — the leading cause of death in the U.S. — is so deadly in part because the heart, unlike other organs, cannot repair itself after injury. That is why tissue engineering, ultimately including the wholesale fabrication of an entire human heart for transplant, is so important for the future of cardiac medicine.

To build a human heart from the ground up, researchers need to replicate the unique structures that make up the heart. This includes recreating helical geometries, which create a twisting motion as the heart beats. It’s been long theorized that this twisting motion is critical for pumping blood at high volumes, but proving that has been difficult, in part because creating hearts with different geometries and alignments has been challenging.
Helical alignments within the heart’s musculature have been speculated to be important in achieving physiological pumping efficiencies. Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the heart’s musculature using current techniques.
For the first time, bioengineers have developed the first biohybrid model of human ventricles with helically aligned beating cardiac cells, and have shown that muscle alignment does, in fact, dramatically increase how much blood the ventricle can pump with each contraction. In this study, they report focused rotary jet spinning (FRJS), an additive manufacturing approach that enables rapid fabrication of micro/nanofiber scaffolds with programmable alignments in three-dimensional geometries. Seeding these scaffolds with cardiomyocytes enabled the biofabrication of tissue-engineered ventricles, with helically aligned models displaying more uniform deformations, greater apical shortening, and increased ejection fractions compared with circumferential alignments. The ability of FRJS to control fiber arrangements in three dimensions offers a streamlined approach to fabricating tissues and organs, with this work demonstrating how helical architectures contribute to cardiac performance.
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Sound—including music and noise—can relieve pain in humans, but the underlying neural mechanisms remain unknown. Scientists have identified the neural mechanisms through which sound blunts pain in mice. The findings could inform development of safer methods to treat pain. They discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACx^Glu) to the thalamic posterior (PO) and ventral posterior (VP) nuclei. Optogenetic or chemogenetic inhibition of the ACx^Glu→PO and ACx^Glu→VP circuits mimicked the low-SNR sound–induced analgesia in inflamed hindpaws and forepaws, respectively. Artificial activation of these two circuits abolished the sound-induced analgesia. a new study revealed the corticothalamic circuits underlying sound-promoted analgesia by deciphering the role of the auditory system in pain processing.

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A team of scientists from the University of Tokyo has developed a skin-equivalent coating for robotic limbs, with the resulting tissue-engineered material boasting water-repellant and self-healing properties. The covering materials of humanoid robots have gone through transformations from stiff and heavy materials to soft and compliant materials to better mimic the appearance and function of human beings. In this study, they reported a biohybrid approach to generate robots covered with tissue-engineered skin. The skin coverage not only results in a human-like appearance but also enables self-healing functions. They demonstrated the seamless coverage of a three-joint robotic finger by culturing a single piece of skin tissue surrounding the robotic finger. Furthermore, inspired by the medical treatment of deeply burned skin using grafted hydrogels, they demonstrated wound repair of a dermis equivalent covering a robotic finger by culturing the wounded tissue grafted with a collagen sheet. Taken together, these findings showed the potential of a paradigm shift from traditional robotics to the new scheme of biohybrid robotics that leverage the advantages of both living materials and artificial materials.
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A 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator has been presented which can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality.
Microfluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. The system can be multiplexed and scaled up to process large volumes of the industry. 
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Transmission electron microscopy (TEM) with its various imaging modes and analytical abilities, is now an indispensable tool for chemical and structural characterization at the nanoscale of all types of materials. It is a microscopy technique in which a beam of energetic electrons is transmitted through a sample and the interaction of electrons with the sample forms an image. The image is then magnified and focused onto an imaging device, such as a fluorescent screen, a layer of photographic film, or a sensor like a charge-coupled device. At lower magnifications TEM image contrast is due to differential absorption of electrons by the material due to differences in its composition or thickness. 
X-ray emission consequent to the interaction of the primary electron beam with the sample, can also be detected by an energy-dispersive spectrometer (EDS) within the TEM. As the resulting X-ray energies are characteristic of the atomic structure of the element they originated from, the spectra generated can be used to identify the constituent elements.
It is also possible to measure the loss of energy from the inelastic scattering of electrons in specimen transmission (EELS). This information can be used to infer elemental composition, chemical bonding, valence and conduction band electronic properties.
A scanning transmission electron microscope (STEM) is a type of TEM. While in TEM parallel electron beams are focused perpendicular to the sample plane, in STEM the beam is focused at a large angle and is converged into a focal point. The transmitted signal is collected as a function of the beam location as it is rastered across the sample.
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Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. In a recent study which has been done by the multidisciplinary Zurich research team,  transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion has been reported. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.
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High Performance Liquid Chromatography (HPLC) is a form of column chromatography that pumps a sample mixture or analyte in a solvent (known as the mobile phase) at high pressure through a column with chromatographic packing material (stationary phase). The sample is carried by a moving carrier gas stream of helium or nitrogen. HPLC has been used for the direct quantification of individual ecdysteroids in biological samples. This requires of course high sensitivity because of the low concentrations encountered and adequate sample clean up. 
Reversed-phase HPLC (RP-HPLC) is the most commonly used mode of HPLC and, as the name implies, this mode is just the reverse of normal phase HPLC (NP-HPLC), whereby the stationary phase is more nonpolar than the eluting solvent. Generally, RP-HPLC has a nonpolar stationary phase, e.g., C₁₈ silica, and a moderately polar aqueous mobile phase. 
In RP-HPLC there is strong attraction between the polar solvent and polar molecules in the mixture being passed through the column, but there is not much attraction between the hydrocarbon chains attached to the silica (the stationary phase) and the polar molecules in the solution. Therefore, polar molecules in the mixture spend most of their time moving with the solvent. Nonpolar compounds in the mixture tend to form attractions with the hydrocarbon groups because of van der Waals dispersion forces. They are less soluble in the solvent because of the need to break hydrogen bonds as they squeeze in between the water or methanol molecules. They spend less time in solution in the solvent, and this slows them down on their way through the column, which means longer retention time. In RP-HPLC the polar molecules travel through the column more quickly.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes and are ubiquitously used for their anti-inflammatory properties. However, COX inhibition alone fails to explain numerous clinical outcomes of NSAID usage. Screening commonly used NSAIDs in primary human and murine myeloid cells demonstrated that NSAIDs could be differentiated by their ability to induce growth/differentiation factor 15 (GDF15), independent of COX specificity. Using genetic and pharmacologic approaches, NSAID-mediated GDF15 induction was dependent on the activation of nuclear factor erythroid 2-related factor 2 (NRF2) in myeloid cells. Sensing by Cysteine 151 of the NRF2 chaperone, Kelch-like ECH-associated protein 1 (KEAP1) was required for NSAID activation of NRF2 and subsequent anti-inflammatory effects both in vitro and in vivo. Myeloid-specific deletion of NRF2 abolished NSAID-mediated tissue protection in murine models of gout and endotoxemia. This highlights a noncanonical NRF2-dependent mechanism of action for the anti-inflammatory activity of a subset of commonly used NSAIDs.
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Kienbock's Disease, also known as avascular necrosis (AVN), is the avascular necrosis of the lunate which can lead to progressive wrist pain and abnormal carpal motion. Diagnosis can be made with wrist radiographs in advanced cases but may require MRI for detection of early disease.
There is no single cause of Kienbock’s disease. It can be caused by multiple factors such as:
Skeletal variations, Trauma, and other medical conditions: Kienbock’s disease can be found more commonly in people who have medical conditions that affect blood supply. It is also associated with diseases like lupus, sickle cell anemia and cerebral palsy.
Although there's no single cure for Kienböck's disease, medications, immobilizing the wrist and surgery have been used for the management of the disease. 
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Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as “triple whammy”. Diuretics and RAS inhibitors, such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. Researchers at the University of Waterloo used computer-simulated drug trials to model the interactions of the three drugs and the impact on the kidney. They found that in people with certain medical profiles, the combination can cause acute kidney injury, which in some cases can be permanent. They utilized sex-specific computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that low water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI. Triple treatment involving an ACE inhibitor, furosemide, and NSAID results in blood pressure levels similar to double treatment with ACEI and furosemide. Additionally, the male and female hypertensive models act similarly in most situations, except for the ACE inhibitor and NSAID double treatment.
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