Miracle-dz/UniFAR-FTUs huggingface dataset:
Silencing lncRNA LINC01410 suppresses cell viability yet promotes apoptosis and sensitivity to temozolomide in glioblastoma cells by inactivating PTEN/AKT pathway via targeting miR-370-3p

Abstract Background Long non-coding RNAs (LncRNAs) are involved in glioblastoma (GBM), but the role of long intergenic non-protein coding RNA 01410 (lncRNA LINC01410) is poorly understood. Methods The expression of LINC01410 in GBM tissues and cells was analyzed. After transfection or temozolomide (TMZ) treatment, the cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry. The targeting relationship between LINC01410 and microRNA (miR)-370-3p was confirmed by dual-luciferase reporter assay. Expressions of LINC01410, miR-370-3p and drug resistance- and Phosphatase and Tensin Homolog (PTEN)/AKT pathway-related factors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results LINC01410 expression was upregulated in GBM, and silencing of LINC01410 decreased cell viability. A slowed decreased trend in cell viability yet an increased half maximal inhibitory concentration (IC50 for TMZ) value and increased expressions of drug resistance-related factors as well as LINC01410 were found in TMZ-resistant GBM cells. Silencing of LINC01410 also decreased the IC50 value yet promoted the sensitivity and apoptosis in TMZ-resistant cells, while upregulating the expression of PTEN and downregulating the phosphorylation of AKT. MiR-370-3p could competitively bind to LINC01410 and its expression was decreased in both parental and TMZ-resistant GBM cells. Downregulation of miR-370-3p reversed the effects of LINC01410 silencing on cell viability, apoptosis and the expressions of miR-370-3p and PTEN/AKT pathway-related factors. Conclusion Silencing of LINC01410 inhibits cell viability yet enhances apoptosis and sensitivity to TMZ in GBM cells by inactivating PTEN/AKT pathway via targeting miR-370-3p.
Determination of the composition and thickness of chromel and alumel thin films on different substrates by quantitative energy dispersive spectroscopy analysis

Thin films of two alloys (chromel and alumel), with thickness less than 100 nm, were obtained by plasma deposition technique, namely filtered cathodic vacuum arc (FCVA). The elemental analyses were performed by quantitative energy dispersive spectroscopy (EDS) microanalysis and Rutherford backscattering spectrometry (RBS). The applicability of EDS to such thin films as these was established by analysis of films deposited on substrates of different atomic numbers, specifically vitreous carbon, silicon, copper, and tin. We found that a substrate with atomic number similar to the mean atomic number of the film constituents is best for reliable EDS results, when compared to RBS. The compatibility between quantitative EDS measurements and RBS measurements, as well as comparison between the thin film elemental composition and the bulk material composition, was assessed by statistical analysis. Good consistency between EDS and RBS measurements was found for both chromel and alumel thin films when copper was used as substrate material. We observed severely overlapping peaks in the RBS output for the case of alumel films so that EDS analysis was crucial. We also compared thickness measurements determined by EDS and RBS, and we found good agreement for the case of alumel film on copper substrate, and 15% agreement for chromel film on copper substrate.
Hemolytic Anemia after Acute Hepatitis B Virus Infection: A Case Report and Systematic Review

Hemolytic anemia and pure red cell aplasia are rare hematological complications of hepatitis B virus infection. We herein report a 24-year-old man who was diagnosed with hemolytic anemia and possible transient pure red cell anemia eight weeks after a severe episode of acute hepatitis B virus infection. Rapid recovery was observed with conservative management. Hemoglobin returned to baseline within three months. As the clinical features of hemolytic anemia associated with hepatitis B virus have not yet been elucidated, we conducted a systematic review and present an analysis of the 20 reported cases, including our present case.
Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors

Liver cells cultured in 3D bioreactors is an interesting option for temporary extracorporeal liver support in the treatment of acute liver failure and for animal models for preclinical drug screening. Bioreactor capacity to eliminate drugs is generally used for assessing cell metabolic competence in different bioreactors or to scale-up bioreactor design and performance for clinical or preclinical applications. However, drug adsorption and physical transport often disguise the intrinsic drug biotransformation kinetics and cell metabolic state. In this study, we characterized the intrinsic kinetics of lidocaine elimination and adsorption by porcine liver cells cultured in 3D four-compartment hollow fiber membrane network perfusion bioreactors. Models of lidocaine transport and biotransformation were used to extract intrinsic kinetic information from response to lidocaine bolus of bioreactor versus adhesion cultures. Different from 2D adhesion cultures, cells in the bioreactors are organized in liver-like aggregates. Adsorption on bioreactor constituents significantly affected lidocaine elimination and was effectively accounted for in kinetic analysis. Lidocaine elimination and cellular monoethylglicinexylidide biotransformation featured first-order kinetics with near-to-in vivo cell-specific capacity that was retained for times suitable for clinical assist and drug screening. Different from 2D cultures, cells in the 3D bioreactors challenged with lidocaine were exposed to close-to-physiological lidocaine and monoethylglicinexylidide concentration profiles. Kinetic analysis suggests bioreactor technology feasibility for preclinical drug screening and patient assist and that drug adsorption should be accounted for to assess cell state in different cultures and when laboratory bioreactor design and performance is scaled-up to clinical use or toxicological drug screening.
Metal-organic frameworks for diagnosis and therapy of infectious diseases

Abstract Infectious diseases are one of the leading cause of mortality and morbidity worldwide. Metal-Organic Frameworks (MOFs), which are porous coordination materials composed of bridging organic ligands and metallic ions or clusters, exhibits great potential to be used against several pathogens, such as bacteria, viruses, fungi and protozoa. MOFs can show sustained release capability, high surface area, adjustable pore size and structural flexibility, which makes them good candidates for new therapeutic systems. This review provides a detailed summary of the biological application of MOFs, focussing on diagnosis and treatment of infectious diseases. MOFs have been reported for usage as antimicrobial agents, drug delivery systems, therapeutic composites, nanozymes and phototherapies. Furthermore, different MOF-based biosensors have also been developed to detect specific pathogens by electrochemical, fluorometric and colorimetric assays. Finally, we present limitations and perspectives in this field.
Validation of digital microscopy: Review of validation methods and sources of bias

Digital microscopy (DM) is increasingly replacing traditional light microscopy (LM) for performing routine diagnostic and research work in human and veterinary pathology. The DM workflow encompasses specimen preparation, whole-slide image acquisition, slide retrieval, and the workstation, each of which has the potential (depending on the technical parameters) to introduce limitations and artifacts into microscopic examination by pathologists. Performing validation studies according to guidelines established in human pathology ensures that the best-practice approaches for patient care are not deteriorated by implementing DM. Whereas current publications on validation studies suggest an overall high reliability of DM, each laboratory is encouraged to perform an individual validation study to ensure that the DM workflow performs as expected in the respective clinical or research environment. With the exception of validation guidelines developed by the College of American Pathologists in 2013 and its update in 2021, there is no current review of the application of methods fundamental to validation. We highlight that there is high methodological variation between published validation studies, each having advantages and limitations. The diagnostic concordance rate between DM and LM is the most relevant outcome measure, which is influenced (regardless of the viewing modality used) by different sources of bias including complexity of the cases examined, diagnostic experience of the study pathologists, and case recall. Here, we review 3 general study designs used for previous publications on DM validation as well as different approaches for avoiding bias.
Human Mesenchymal Stem Cells Seeded on the Natural Membrane to Neurospheres for Cholinergic-like Neurons

This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton’s jelly (WJ) was carried out using “explant” and mononuclear cells by the density gradient from umbilical blood and characterized by flow cytometry. hMSCs were seeded in a natural functional biopolymer membrane to produce neurospheres. RT-PCR was performed on hMSCs and neurospheres derived from the umbilical cord. Neural precursor cells were subjected to a standard cholinergic-like neuron differentiation protocol. Dissociated neurospheres, neural precursor cells, and cholinergic-like neurons were characterized by immunocytochemistry. hMSCs were CD73+, CD90+, CD105+, CD34- and CD45- and demonstrated the trilineage differentiation. Neurospheres and their isolated cells were nestin-positive and expressed NESTIN, MAP2, ßIII-TUBULIN, GFAP genes. Neural precursor cells that were differentiated in cholinergic-like neurons expressed ßIII-TUBULIN protein and choline acetyltransferase enzyme. hMSCs seeded on the natural membrane can differentiate into neurospheres, obtaining neural precursor cells without growth factors or gene transfection before cholinergic phenotype differentiation.
Post-Treatment Adverse Health Correlates among Prostate Cancer Survivors in a Sample of Men Residing in Atlantic Canada

Background: Recent large population-based studies have shed light on an association between prostate cancer (PCa) survivorship and mental health, which emerged when the comparison group was either men without a history of cancer or those with any other type of cancer except prostate. Here we examine the role of surgery alone, compared to other types of treatment modalities in this association in a population-based sample of men with prostate or other types of cancer. Methods: A cross-sectional analysis was conducted on a subsample of 632 male participants aged 36–69 from the 2009–2015 survey cycle of the Atlantic PATH cohort study. The primary outcomes were the presence of mild, moderate or severe depression or anxiety indicators and were assessed using the seven-item generalized anxiety disorder (GAD-7) scale and the nine-item Patient Health Questionnaire (PHQ-9), respectively. The presence of a lifetime history of PCa or other form of cancer (except PCa) was the main predictor variable and was assessed in cancer treatment modality (surgery or other types of treatment modalities) stratified analyses. Covariates included age, marital status, household income, comorbidity, and survivorship time. Results: The presence of depression in this sample was prevalent among 17.7% of men, and of anxiety among 9.3% of men. Survivors who were treated with surgery for their PCa diagnosis had 7.55 statistically significantly higher odds of screening positive for current depression symptoms compared with those of other forms of cancer in controlled analyses. These differences were not observed for anxiety. Conclusions: These findings emphasize the need for multidisciplinary survivorship care plans among PCa patients, especially those who undergo surgery. Targeted programming aimed at prioritizing and delivering comprehensive mental health support to PCa survivors early in the survivorship journey is justified.
Management of Mycosis Fungoides with Topical Chlormethine/Mechlorethamine Gel: A Columbia University Cutaneous Lymphoma Center Experience

Mycosis fungoides is a type of cutaneous T-cell lymphoma, which accounts for the majority of cases of cutaneous T-cell lymphoma. Mycosis fungoides can be classified as early-stage (IA–IIA) or late-stage (IIB or greater) disease. In early-stage mycosis fungoides, skin-directed therapies are commonly used to manage the disease. Chlormethine, or mechlorethamine, is a topical chemotherapeutic, which has been in use for over 60 years. In 2013, the US Food and Drug Administration approved chlormethine/mechlorethamine gel (Valchlor®) for treatment of stage IA and IB mycosis fungoides. Chlormethine/mechlorethamine gel is an effective therapy; however, its use may be limited by the development of adverse cutaneous reactions. Off-label dosing modifications, as well as co-administration of topical steroids and an aggressive moisturization regimen, can be used to reduce these side-effects. We report here 4 cases of mycosis fungoides treated with chlormethine/mechlorethamine gel at the Comprehensive Skin Cancer Center at Columbia University Irving Medical Center, which provide insights into the use of this therapy in clinical practice.
Azole-Resistance Development; How the Aspergillus fumigatus Lifecycle Defines the Potential for Adaptation

In order to successfully infect or colonize human hosts or survive changing environments, Aspergillus fumigatus needs to adapt through genetic changes or phenotypic plasticity. The genomic changes are based on the capacity of the fungus to produce genetic variation, followed by selection of the genotypes that are most fit to the new environment. Much scientific work has focused on the metabolic plasticity, biofilm formation or the particular genetic changes themselves leading to adaptation, such as antifungal resistance in the host. Recent scientific work has shown advances made in understanding the natural relevance of parasex and how both the asexual and sexual reproduction can lead to tandem repeat elongation in the target gene of the azoles: the cyp51A gene. In this review, we will explain how the fungus can generate genetic variation that can lead to adaptation. We will discuss recent advances that have been made in the understanding of the lifecycle of A. fumigatus to explain the differences observed in speed and type of mutations that are generated under different environments and how this can facilitate adaptation, such as azole-resistance selection.
Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin’s inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin’s anticancer effect.
Tuning the structural and catalytic properties of copper(II)-based complexes containing pyridine-2,6-diimines

Abstract Four mononuclear penta coordinated copper(II) chelates, [CuLnBr2] nH2O, containing the tridentate neutral ligands, pyridine-2,6-diimine (Ln), were prepared via the template technique. Analytical and several physicochemical methods have been used to characterize the prepared metal chelates. Square-pyramidal stereochemistry was described to the current copper(II) complexes. DFT technique has been applied to optimize the structure of the running diimines and their corresponding copper-based compounds. Ligand substitution study performed to link the catalytic potency of the candidate oxidase mimics and their lability characters. Spectral investigations reveal that nature of substituents of the chelated ligands effectively tuning the Lewis acidity of copper(II) centers. Biomimetics of redox proteins specifically containing copper were examined towards the aerobic oxidation of polyphenol. Kinetic studies with the stopped-follow technique showed a close association between the Lewis acidity of the copper(II) nuclei of the prepared chelates and their oxidase-like activity. The catalytic activity of the natural enzyme (catechol oxidase from sweet potatoes) measured and compared with that for the present CuII chelates. The thermodynamic parameter drive force (ΔG° or λ) of the performed oxidation processes was determined from the values of redox potential of the chemical species involved in these catalytic reactions. The proposed catalytic reactions pathways have been discussed based on the outcomes of the kinetic investigations. Communicated by Ramaswamy H. Sarma
Sinus Mucosa Thickness Changes and Ostium Involvement after Maxillary Sinus Floor Elevation in Sinus with Septa. A Cone Beam Computed Tomography Study

Background: A thickening of the sinus mucosa is observed after sinus floor augmentation. The objective of this retrospective study was to evaluate the influence of the presence of septa in the dimensional variation and ostium involvement over time of the Schneiderian mucosa after sinus floor augmentation. Materials and Methods: Fifteen sinuses with septa (septa group) and 15 without (control group) were selected. CBCTs taken before surgery, and were analyzed after 1 week and after 9 months. Schneiderian membrane thickness changes over time and involvement of the ostium were evaluated. Results: Four perforations occurred in the septa group and none in the control group. After 1 week of healing, the sinus mucosa thickness increased in height by 5.7 mm and 7.1 mm in the septa and control groups, respectively. In this period, the patency of the ostium decreased in both groups, and three infundibula were obstructed in the septa group, and five in the control group. The mucosa was thicker and the edema was closer to the ostium in the control compared to in the septa group. After 9 months of healing, the dimensions regressed to normal pattern and no obstruction of the infundibula were observed. No statistically significant differences were found between septa and control groups. Conclusions: after one week of healing, the sinus mucosa increased in dimensions in both septa and control groups. However, the sinus mucosa presented a tendency of being thicker and closer to the ostium, resulting in a higher number of infundibula obstructions, in the control group compared to in the septa group. After 9 months, the sinus mucosa regressed to normal dimensions and no obstructions of the infundibula were observed in any group.
Cochlear fibrocyte and osteoblast lineages expressing type 2 deiodinase identified with a Dio2  CreERt2 allele.

Type 2 deiodinase (Dio2) amplifies levels of 3,5,3'-L-triiodothyronine (T3), the active form of thyroid hormone, and is essential for cochlear maturation and auditory development. However, cellular routes for endocrine signaling in the compartmentalized, anatomically complex cochlea are little understood. Dio2 generates T3 from thyroxine (T4), a more abundant thyroid hormone precursor in the circulation, and is dramatically induced in the cochlea before the onset of hearing. The evidence implies that specific Dio2-expressing cell types critically mediate T3 signaling but these cell types are poorly defined because Dio2 is expressed transiently at low levels. Here, using a Dio2 CreERt2 knockin that activates a fluorescent reporter, we define Dio2-expressing cochlear cell types at high resolution in male or female mice. Dio2-positive cells were detected in vascularized supporting tissues but not in avascular internal epithelia, indicating segregation of T3-generating and T3-responding tissues. In the spiral ligament and spiral limbus, Dio2-positive fibrocytes clustered around vascular networks that convey T4 into cochlear tissues. In the otic capsule, Dio2-positive osteoblasts localized at cartilage surfaces as the bony labyrinth matures. We corroborated the identities of Dio2-positive lineages by RNA-sequencing of individual cells. The results suggest a previously unrecognized role for fibrocytes in mediating hormonal signaling. We discuss a model whereby fibrocytes mediate paracrine-like control of T3 signaling to the organ of Corti and epithelial target tissues.
Acceptability, technological feasibility and educational value of remotely facilitated simulation based training: A scoping review

ABSTRACT Although remote teaching and learning is not new to medical education, the Covid-19 pandemic has heightened its importance as a mode of education delivery. This scoping review aims to provide a narrative/iterative summary of the current literature in assessing the acceptability, educational value and technological feasibility of remotely facilitated (RF) simulation-based training (SBT) – ‘telesimulation’, for medical students and facilitators. The review was conducted using the method described by Arksey and O’Malley. A systematic process was followed to search multiple electronic databases supplemented with a general internet search to identify any relevant grey literature. The search strategy was developed in collaboration with medical students and educators familiar with SBT. Nine articles were identified as fitting the review inclusion criteria. The results indicated that RF SBT was positively viewed by participants but may not be viewed as equivalent to locally facilitated SBT. Participants of RF SBT felt confident to deal with common acute scenarios, believed it could expand their knowledge and skills and in turn would improve patient care in the clinical setting. Facilitators found RF SBT to be technologically feasible, promoting the acquisition of desired learning outcomes. Future research should assess the reaction to, and learning acquired during RF SBT, particularly, the perception and attitudes of facilitators. A clear research gap was identified in literature assessing the role of RF SBT in behavioural change and improved clinical care outcomes. Addresing these gaps will clarify the role of RF SBT in medical education.