Application Of Therapy Research Articles

Ginsenoside Rd reduces cell proliferation of non-small cell lung cancer cells by p53-mitochondrial apoptotic pathway

Ginsenoside Rd is a tetracyclic triterpenoid derivative, widely existing in Panax ginseng, Panax notoginseng and other traditional Chinese medicines. Many studies have proved that ginsenoside Rd have a variety of significant biological activities on certain types of cancer. However, the mechanism of ginsenoside Rd remains unclear in lung cancer. The findings of this study reveal that GS-Rd inhibits the proliferation of NSCLC cells, induces apoptosis, and suppresses migration and invasion. The results showed Ginsenoside Rd inhibited the cell proliferation (∼99.52 %) by S phase arrest in cell cycle and promoted the apoptosis (∼54.85 %) of NSCLC cells. It also inhibited the migration and invasion of cells (p < 0.001). The expression levels of related mitochondrial apoptosis proteins (Bax/Bcl-2/Cytochrome C) and matrix metalloproteinases (MMP-2/-9) were significantly changed. The results showed that ginsenoside Rd inhibited the proliferation of tumor cells by activating p53/bax-mediated mitochondrial apoptosis and the expression of key enzymes for cell apoptosis caspase-3/cleaved-caspase-3 were significantly increased. This research contributes to a better understanding of the anti-tumor effects and molecular mechanisms of GS-Rd, paving the way for its potential development and clinical application in NSCLC therapy.

Prediction of Parkinson’s Disease using Handwriting Analysis and Voice Dataset- A Review

Parkinson's disease is a common neurological movement illness that impairs motor coordination. Parkinson’s disease (PD) symptoms and severity, however, differ from person to person. By extracting insights, trends, and possibilities from the data, data research can be utilized to uncover solutions to problems in medical research by utilizing data, machine learning algorithms, and cutting-edge technology. Among the less evident early signs of Parkinson's disease are tremors, muscle stiffness, imbalance problems, and difficulty walking. There is currently no test to detect the illness early on, when symptoms might not be evident. However, handwriting and hand- drawn subjects in humans have been linked to PD. In addition to being a useful tool for PD prediction, speech smearing functions as an early warning system. In order to control symptoms and maybe halt the disease's progression, early detection makes it possible to organize treatments and intervene promptly. For those with Parkinson's disease, early application of certain therapies and medications can extend survival and enhance quality of life.

Clinical applicability of guideline-recommended molecular targets and genome-targeted cancer therapies.

11049 Background: Genomic testing has expanded the possibilities of precision medicine, particularly for advanced, treatment-resistant cancer cases. However, the clinical relevance of most genetic alterations remains uncertain, which can lead physicians to overestimate the benefits of tailored therapies. The National Comprehensive Cancer Network (NCCN) guidelines are cancer-specific treatment recommendations that often determine insurance coverage. We assessed the evidence for clinical benefit and actionability of molecular targets for genome-targeted cancer drugs recommended by NCCN. Methods: We identified genome-targeted therapies for solid cancers from the most recent NCCN guidelines. Trial design characteristics were obtained from publications supporting the NCCN recommendations. Genome target actionability was assessed with the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). This ranges from genome alternation-therapy combinations that lead to improved outcomes (Tier I) to treatments with potential clinical relevance (Tiers II or III) to those with undetermined relevance (Tiers IV to X). Clinical benefit was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT Tier I in combination with a given treatment associated with studies demonstrating substantial clinical benefit by ESMO-MCBS (Grades 4-5) were designated as high-benefit, while those linked to studies achieving an ESMO-MCBS Grade of 3 were categorized as promising but unproven. Results: We extracted411 recommendations from NCCN supporting 74 genome-targeted drugs targeting 50 driver alterations. Most recommendations (346/411, 84%) referred to clinical trial data, while one-sixth (65/411, 16%) relied on case reports or preclinical studies. Clinical trials were mostly Phase I or Phase II (271/346, 78%), single arm (262/346, 76%), and evaluated overall response rate as the primary endpoint (271/346, 78%). Over half of target recommendations had Tier I target actionability (246/411, 60%), over one-third were Tier II or III (142/411, 35%), and the rest were undetermined (23/411, 6%). Among 267 scorable trials,12% (32/267) demonstrated substantial clinical benefit (ESMO-MCBS Grades 4-5) and 45% (121/267) were Grade 3. When combining both frameworks,12% (32/267) genomic-based cancer treatments were high-benefit and 33% (88/267) were promising-but-unproven. Conclusions: About one-eighth of genome-targeted cancer therapies recommended in NCCN guidelines received a high benefit rating, while one-third were identified as having a promising but unproven substantial benefit according to the ESCAT and ESMO-MCBS frameworks. Ensuring NCCN recommendations are aligned with well-documented clinical benefits is crucial for promoting informed, evidence-based genomic-guided treatment decisions.

Outcomes of ide-cel in patients with relapsed/refractory multiple myeloma: A single-institution experience.

e19500 Background: Idecabtagene vicleucel (ide-cel) is a novel CAR T-cell therapy that targets B-cell maturation antigen (BCMA). This single-center retrospective study reports the real-world clinical outcomes of ide-cel therapy in patients with relapsed/refractory multiple myeloma (RRMM) with the additional goal of investigating host predictive factors for therapy performance. Methods: We conducted a retrospective review of adult patients with RRMM who received ide-cel between 2021 and 2023 at University of California San Diego Health and had at least six months of follow-up data available. Data on baseline characteristics, efficacy responses, and adverse reactions (including CRS and ICANS grading per ASTCT) were obtained. Treatment responses were recorded according to the International Myeloma Working Group criteria. Survival analyses were based on Kaplan-Meier and Cox proportional hazards methods. Results: A total of 25 patients with RRMM were included. The median age was 65 (range, 50-79). 48% of patients were male. Patients received a median of six lines of prior therapy with 12% of patients receiving prior BCMA-targeted therapy. Six patients (24%) had confirmed high-risk cytogenetics while twelve patients (48%) had extramedullary disease. The median follow-up was 11.4 months. The objective response rate was 84%; sCR was seen in 56% of patients, VGPR in 16%, PR in 12%, and PD in 16%. Four patients in sCR have since relapsed. Five deaths were observed (20%), all due to progressive disease. Median PFS for the cohort was 13.9 months (95% CI, 9.21 – NR); among responders, PFS was 20.6 months (95% CI, 11.9 – NR). Median OS was NR (95% CI, 19.3 month – NR). The respective PFS and OS at 12 months was 57% (95% CI, 37% – 86%) and 83% (95% CI, 69% – 100%). Of 11 patients who had relapsed/refractory disease to ide-cel, six were alive at time of last follow-up; three are responding to teclistamab, two to talquetamab, and one to radiation. The incidence of CRS and ICANS was 92% (grade 3-4: 4%) and 12% (grade 3-4: 8%), respectively. Univariate and multivariate analysis did not reveal any significant predictive markers of superior PFS or OS, including age, ECOG, mSMART classification, high-risk cytogenetics, extramedullary disease, median number of lines of prior therapy, prior BCMA-targeted therapy, and triple/penta-class refractory disease. Conclusions: Despite our patients having a high median number of prior lines of therapy, our response and toxicity rates were similar to the findings in the current literature, including those observed in the landmark KarMMa-1 trial. We did not find any significant predictive factors of PFS or OS with the caveat of a small sample size. Further research remains necessary to identify potential predictors that may discriminate responders from non-responders, which will improve the application of CAR T-cell therapy in patients with RRMM.

Digital cognitive–behavioural therapy application compared with zolpidem for the treatment of insomnia: protocol for an exploratory randomised controlled trial

IntroductionInsomnia is a common health problem and cognitive–behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application...

Orthotic Thermoplastic Demonstrates a Similar Contamination Potential with Bacillus Bacteria Recovered from Thermoplastic Radiation Therapy Patient Masks

Thermoplastics used to construct a variety of patient medical devices can become contaminated by harmful bacteria. We investigated whether two different Bacillus species recovered from patient radiation therapy thermoplastic masks could similarly contaminate thermoplastic material used to construct patient orthoses (splints). Bacillus bacteria form dormant spores, which have been shown to enhance its attachment to thermoplastics. Bacterial attachment and recovery were examined using an orthotic thermoplastic with an anti-stick coating being compared to uncoated material used in radiation therapy applications. Triplicate sample squares were seeded with a saline suspension of either B. cereus (MAB03F) or B. megaterium (DAB01F) containing a similar number of spores. Squares were subsequently sampled at 1 h, 1 week, 2 weeks, 4 weeks, and 8 weeks. The number of recovered bacteria was counted. Differences in material hydrophobicity were determined by water contact angle analysis. Both Bacillus species attached to each material within 1 h, and their spores were recovered at 8 weeks. However, a decreasing trend in adhesion, over time, was noted to the coated material with an opposite increasing trend in the uncoated material. Decreased Bacillus species spore adhesion to coated material with a lower hydrophobicity suggests a greater potential for spore transfer to patients wearing contaminated orthoses.

Exploring the Impact of Adequate Energy Supply on Nutrition, Immunity, and Inflammation in Elderly Patients with Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) progression in the elderly is notably influenced by nutritional, immune, and inflammatory status. This study aimed to investigate the impact of adequate energy supply on these indicators in COPD patients. COPD patients meeting specific criteria were recruited and categorized into energy-adequate and energy-deficient groups based on their energy supply. Comparable demographic factors such as age, gender, smoking and drinking history, COPD duration, inhaled drug classification, and home oxygen therapy application were observed. Notable differences were found in BMI and inhaled drug use between the two groups. The energy-adequate group exhibited significant improvements in various health indicators, including lymphocyte count, hemoglobin, CRP, total cholesterol, prealbumin, albumin, PNI, SII, SIRI, CAR, and CONUT scores in the secondary auxiliary examination. These positive changes suggest a notable enhancement in nutritional, immune, and inflammatory status. This research highlights the substantial benefits of adequate energy supply in elderly COPD patients. The observed improvements in nutritional, immune, and inflammatory markers underscore the importance of addressing energy needs to positively influence disease-related outcomes in this population. These findings have implications for developing targeted interventions to optimize the well-being of elderly individuals with COPD.

Ferroptosis-related genes DUOX1 and HSD17B11 affect tumor microenvironment and predict overall survival of lung adenocarcinoma patients

Background: Recent studies have found that ferroptosis-related genes (FRGs) have broad applications in tumor therapy. However, the predictive potential of these genes in lung adenocarcinoma (LUAD) remains to be fully characterized. We aimed to investigate the FRGs that might be potential targets for LUAD. Methods: We screened the RNA sequencing samples from LUAD patients from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of DEGs was performed. The risk model was constructed to evaluation and validation FRGs. We explored the immune landscape of LUAD and controls. The value of FRGs in diagnosing LUAD was tested in the GSE30219, GSE37745, GSE0081 datasets, and qPCR was used to verify their diagnostic value in LUAD patients in our hospital. Results: A total of 1327 DEGs in quantitative proteomics were obtained, of which ferroptosis-related DEGs were 259. Enrichment analysis showed significant enrichment in the absorption and metabolism of fatty acids and arachidonic acid. The upregulated genes (GCLC, RRM2, AURKA, SLC7A5, and SLC2A1) and downregulated genes (ANGPTL7, ALOX15, ALOX15B, HSD17B11, IL33, TSC22D3, and DUOX1) were selected as core genes in tissue samples from 62 patients by qPCR. DUOX1 and HSD17B11 were obtained by bioinformatics analysis, both of which showed similar expression trends at the RNA and protein levels. The Kaplan–Meier method showed that DUOX1 and HSD17B11 were closely related to the overall survival (OS) of LUAD patients. Conclusion subsections: Ferroptosis-related genes DUOX1 and HSD17B11 are of considerable value in the diagnosis of LUAD patients. Their low expression suggests an increased recurrence rate and leads to a decrease in the patient quality of life.

Human post-mortem organotypic brain slice cultures: a tool to study pathomechanisms and test therapies

Human brain experimental models recapitulating age- and disease-related characteristics are lacking. There is urgent need for human-specific tools that model the complex molecular and cellular interplay between different cell types to assess underlying disease mechanisms and test therapies. Here we present an adapted ex vivo organotypic slice culture method using human post-mortem brain tissue cultured at an air-liquid interface to also study brain white matter. We assessed whether these human post-mortem brain slices recapitulate the in vivo neuropathology and if they are suitable for pathophysiological, experimental and pre-clinical treatment development purposes, specifically regarding leukodystrophies. Human post-mortem brain tissue and cerebrospinal fluid were obtained from control, psychiatric and leukodystrophy donors. Slices were cultured up to six weeks, in culture medium with or without human cerebrospinal fluid. Human post-mortem organotypic brain slice cultures remained viable for at least six weeks ex vivo and maintained tissue structure and diversity of (neural) cell types. Supplementation with cerebrospinal fluid could improve slice recovery. Patient-derived organotypic slice cultures recapitulated and maintained known in vivo neuropathology. The cultures also showed physiologic multicellular responses to lysolecithin-induced demyelination ex vivo, indicating their suitability to study intrinsic repair mechanisms upon injury. The slice cultures were applicable for various experimental studies, as multi-electrode neuronal recordings. Finally, the cultures showed successful cell-type dependent transduction with gene therapy vectors. These human post-mortem organotypic brain slice cultures represent an adapted ex vivo model suitable for multifaceted studies of brain disease mechanisms, boosting translation from human ex vivo to in vivo. This model also allows for assessing potential treatment options, including gene therapy applications. Human post-mortem brain slice cultures are thus a valuable tool in preclinical research to study the pathomechanisms of a wide variety of brain diseases in living human tissue.

Vitamin A - potential anticancer weapon

Introduction: Vitamin A, one of the most popular vitamins that people usually associate with eye health or beautiful skin, also has many other functions and uses. Recently many scientists conducted studies to determine if vitamin A could be a new weapon against cancers. Aim of the study: The aim of the study was to discuss recent findings regarding the impact of Vitamin A and other retinoids on potential applications in anticancer therapy. Materials and methods: This review of studies is based on scientific articles available in PubMed and Google Scholar databases. The names of the cancers were juxtaposed with term "Vitamin A" and with term "Retinoids" to gather data regarding the effect of retinoids on cancer treatment and prevention. Results: After analyzing the gathered publications, it is possible to conclude that retinoids can have a positive impact on cancer treatment. Some of them can induce apoptosis of cancer cells and others can reduce their proliferation. Moreover, retinoids can also play an important role in preventing cancers, such as ovarian, breast, cervical, or skin cancer. The role of retinoids in the prevention of prostate cancer remains unclear due to conflicting research results. Conclusion: The studies have shown promising results which indicate a need for further research into anticancer mechanisms of retinoids. Specifically, more research is needed to explore the positive impact of retinoid use in treating cancer diseases. The significant potential of retinoids may make it possible to include them in clinical practice and develop an effective therapeutic strategy for cancer treatment based on them.

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study.

Purpose: Acute heart failure (AHF) is associated with high morbidity and mortality, and the prognosis is particularly poor in older patients. Although the application of guideline-directed medical therapy (GDMT) has shown a positive impact on prognosis, the effects are less clear in older age groups. The aim of this study was to analyze real-world data regarding GDMT and outcomes in older HF patients. Methods: This is a prospective cohort study from a secondary care hospital in central Switzerland. A total of 97 consecutive patients aged ≥60 years were enrolled between January 2019 and 2022. The main outcome parameters were prescribed GDMT at discharge, and in case of rehospitalization, GDMT at readmission, and survival in terms of all-cause mortality and HF-related hospitalizations during a 3-year follow-up period. Results: Follow-up data were available for 93/97 patients. The mean age was 77.8 ± 9.8 years, 46% being female. The mean left ventricular ejection fraction (LVEF) was 35.3 ± 13.9%, with a mean BNP level of 2204.3 ± 239 ng/L. Upon discharge, 86% received beta-blockers and 76.3% received renin-angiotensin system (RAS) inhibitors. At rehospitalization for AHF, beta-blockers use was significantly lower and decreased to 52.8% (p = 0.003), whereas RAS inhibitor use increased slightly to 88.9% (p = 0.07), and SGLT-2 inhibitors showed a significant increase from 5.4% vs. 47.2% (p = 0.04). GDMT prescription was not dependent on LVEF. Overall, 73.1% of patients received two-stage or three-stage GDMT at discharge, whereas this percentage decreased to 61% at rehospitalization (p = 0.01). Kaplan-Meier analysis for the combined outcome rehospitalization and death stratified by LV function showed significant differences between LVEF groups (aHR: 0.6 [95% CI: 0.44 to 0.8]; p = 0.0023). Conclusions: Our results indicate that first, the majority of older AHF patients from a secondary care hospital in Switzerland were not on optimal GDMT at discharge and even fewer at readmission, and second, that prognosis of the population is still poor, with almost half of the patients having been rehospitalized or died during a 3-year follow-up period under real-world conditions, without significant difference between women and men. Our findings underline the need for further improvements in the medical treatment of AHF, in particular in older patients, to improve prognosis and to reduce the burden of disease.

Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading.

A major component of the extracellular matrix (ECM), laminins, modulates cells via diverse receptors. Their fragments have emerging utility as components of "ECM-mimetics" optimized to promote cell-based therapies. Recently, we reported that a bioactive laminin peptide known as A99 enhanced cell binding and spreading via fusion to an elastin-like polypeptide (ELP). The ELP "handle" serves as a rapid, noncovalent strategy to concentrate bioactive peptide mixtures onto a surface. We now report that this strategy can be further generalized across an expanded panel of additional laminin-derived elastin-like polypeptides (LELPs). A99 (AGTFALRGDNPQG), A2G80 (VQLRNGFPYFSY), AG73 (RKRLQVQLSIRT), and EF1m (LQLQEGRLHFMFD) all promote cell spreading while showing morphologically distinct F-actin formation. Equimolar mixtures of A99:A2G80-LELPs have synergistic effects on adhesion and spreading. Finally, three of these ECM-mimetics promote the neurite outgrowth of PC-12 cells. The evidence presented here demonstrates the potential of ELPs to deposit ECM-mimetics with applications in regenerative medicine, cell therapy, and tissue engineering.

Visible and Red Light-Triggered Anticancer Profile of a Ferrocene-Re(I)-Tricarbonyl Conjugate: Experimental and Theoretical Studies.

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 μM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.

Characterization of selected additive manufacturing materials for synchrotron monochromatic imaging and broad-beam radiotherapy at the Australian synchrotron-imaging and medical beamline

Objective. This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline. Approach. Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities. Main results. Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments. Significance and conclusion. These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study.

Targeted Therapy of Tumors and Cancer Stem Cells based on Oxidant-Regulated Redox Pathway and its Mechanism.

A malignant tumor is a frequent and common disease that severely threatens human health. Many mechanisms, such as cell signaling pathway, anti-apoptosis mechanism, cell stemness, metabolism, and cell phenotype, have been studied to explain the reasons for chemotherapy, radioresistance, and tumor recurrences in antitumor treatment. Cancer stem cells (CSCs) are important tumor cell subclasses that can potentially organize and regulate stem cell properties. Growing evidence suggests that CSCs can initiate tumors and constitute a significant factor in metastasis, recurrence, and treatment resistance. The inability to completely target and remove CSCs is a considerable obstacle in tumor treatment. Therefore, drugs and therapeutic strategies that can effectively intervene with CSCs are essential for the treatment of different tumor types. However, the current strategies and efficacy of targeted elimination of CSCs are very limited. Oxidative stress has been recognized to play a crucial role in cancer pathophysiology. Moreover, reactive oxygen species (ROS) production and imbalance of the built-in cellular antioxidant defense system are hallmarks of tumor and cancer etiology. The current paper will focus on the regulation and mechanism behind oxidative stress in tumors and cancer stem cells and its tumor therapy applications. Additionally, the article discusses the role of CSCs in causing tumor treatment resistance and recurrence based on a redox perspective. The study also emphasizes that targeted modulation of oxidative stress in CSCs has great potential in tumor therapy, providing novel prospects for tumor therapy.

Magnetic field generator for the calibration of magnetometers and electromagnetic compatibility (EMC) and electromagnetic interference (EMI) compliance

A standard magnetic field generation system from 1 to 30 μT between DC and 20 kHz has been demonstrated for the calibration of DC/AC magnetometers. The system includes a laboratory-designed Helmholtz coil, shunt resistor, digital multimeter, and dedicated power source. The DC coil constant of the Helmholtz coil was determined to be 10.586 μT/A using a single-axis fluxgate magnetometer. The homogeneity analysis was carried out for the Helmholtz coil to identify the uniformity along the x, y, and z axes. The system for DC generation was standardized and compared by measuring the field values using a single-axis fluxgate magnetometer. Further, the system was validated for AC generation by a search coil with a known turn area (1.3767 ± 0.0027 m2). Moreover, the measured magnetic field values using a search coil were compared with a commercial magnetometer to identify the variation in generated and measured magnetic fields. The described system can have significant utilities in calibration, electromagnetic interference electromagnetic interference/electromagnetic compatibility (EMI/EMC) testing, magnetic susceptibility testing, and magnetic field therapy applications. The expanded uncertainty of the Helmholtz coil in generating a magnetic field was 0.2–1.6% (at k = 2) from DC to 20 kHz.

High-resolution genome-wide mapping of chromosome-arm-scale truncations induced by CRISPR–Cas9 editing

Clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) is a powerful tool for introducing targeted mutations in DNA, but recent studies have shown that it can have unintended effects such as structural changes. However, these studies have not yet looked genome wide or across data types. Here we performed a phenotypic CRISPR–Cas9 scan targeting 17,065 genes in primary human cells, revealing a ‘proximity bias’ in which CRISPR knockouts show unexpected similarities to unrelated genes on the same chromosome arm. This bias was found to be consistent across cell types, laboratories, Cas9 delivery methods and assay modalities, and the data suggest that it is caused by telomeric truncations of chromosome arms, with cell cycle and apoptotic pathways playing a mediating role. Additionally, a simple correction is demonstrated to mitigate this pervasive bias while preserving biological relationships. This previously uncharacterized effect has implications for functional genomic studies using CRISPR–Cas9, with applications in discovery biology, drug-target identification, cell therapies and genetic therapeutics.

Research advances on TIL therapy for colorectal cancer.

Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy. Tumor-infiltrating lymphocyte (TIL) therapy, a form of adoptive cellular therapy (ACT), involves isolating T lymphocytes from tumor tissues, in vitro expansion, and reintroduction into the body to target and eliminate tumor cells. This article presents an overview of the development and application of TIL therapy in CRC, as well as the associated challenges.

New G-Triplex DNA Dramatically Activates the Fluorescence of Thioflavin T and Acts as a Turn-On Fluorescent Sensor for Uracil-DNA Glycosylase Activity Detection.

G-triplexes are G-rich oligonucleotides composed of three G-tracts and have absorbed much attention due to their potential biological functions and attractive performance in biosensing. Through the optimization of loop compositions, DNA lengths, and 5'-flanking bases of G-rich sequences, a new stable G-triplex sequence with 14 bases (G3-F15) was discovered to dramatically activate the fluorescence of Thioflavin T (ThT), a water-soluble fluorogenic dye. The fluorescence enhancement of ThT after binding with G3-F15 reached 3200 times, which was the strongest one by far among all of the G-rich sequences. The conformations of G3-F15 and G3-F15/ThT were studied by circular dichroism. The thermal stability measurements indicated that G3-F15 was a highly stable G-triplex structure. The conformations of G3-F15 and G3-F15/ThT in the presence of different metal cations were studied thoroughly by fluorescent spectroscopy, circular dichroism, and nuclear magnetic resonance. Furthermore, using the G3-F15/ThT complex as a fluorescent probe, a robust and simple turn-on fluorescent sensor for uracil-DNA glycosylase activity was developed. This study proposes a new systematic strategy to explore new functional G-rich sequences and their ligands, which will promote their applications in diagnosis, therapy, and biosensing.

Penerapan Terapi Hiperbarik Oksigen Terhadap Penyembuhan Luka Pada Pasien Ulkus Kaki Diabetik: Studi Literatur

Background: Diabetic foot ulcers are advanced complications experienced by people with diabetes mellitus that have a negative impact and must be treated immediately. One method that can be done to overcome the incidence of diabetic foot ulcers is hyperbaric oxygen therapy. This therapy is known to facilitate wound healing by improving wound tissue perfusion, increasing fibroblast replication and collagen production and increasing phagocytic ability. Purpose: The purpose of this study was to determine the application of hyperbaric oxygen therapy to wound healing in diabetic foot ulcer patients. Methods: The method used in this writing is literature review, with secondary data obtained from previous research with empirical studies of the last 10 years, data sources are accessed through the google scholar database, by taking journals that are relevant to the research topic. Results: This study shows that the results that have been carried out on the administration of hyperbaric oxygen therapy to diabetic foot ulcers, show the ability to heal wounds in a fast time and more effective results. Conclusion: Based on the results of literature review research by collecting several journals, it is concluded that the management of hyperbaric oxygen therapy in diabetic foot ulcer patients is more effective, cost-effective, and increases the prevalence of wound healing.