AI-based selection of individuals for supplemental MRI in population-based breast cancer screening: the randomized ScreenTrustMRI trial.

Screening mammography reduces breast cancer mortality, but studies analyzing interval cancers diagnosed after negative screens have shown that many cancers are missed. Supplemental screening using magnetic resonance imaging (MRI) can reduce the number of missed cancers. However, as qualified MRI staff are lacking, the equipment is expensive to purchase and cost-effectiveness for screening may not be convincing, the utilization of MRI is currently limited. An effective method for triaging individuals to supplemental MRI screening is therefore needed. We conducted a randomized clinical trial, ScreenTrustMRI, using a recently developed artificial intelligence (AI) tool to score each mammogram. We offered trial participation to individuals with a negative screening mammogram and a high AI score (top 6.9%). Upon agreeing to participate, individuals were assigned randomly to one of two groups: those receiving supplemental MRI and those not receiving MRI. The primary endpoint of ScreenTrustMRI is advanced breast cancer defined as either interval cancer, invasive component larger than 15 mm or lymph node positive cancer, based on a 27-month follow-up time from the initial screening. Secondary endpoints, prespecified in the study protocol to be reported before the primary outcome, include cancer detected by supplemental MRI, which is the focus of the current paper. Compared with traditional breast density measures used in a previous clinical trial, the current AI method was nearly four times more efficient in terms of cancers detected per 1,000 MRI examinations (64 versus 16.5). Most additional cancers detected were invasive and several were multifocal, suggesting that their detection was timely. Altogether, our results show that using an AI-based score to select a small proportion (6.9%) of individuals for supplemental MRI after negative mammography detects many missed cancers, making the cost per cancer detected comparable with screening mammography. ClinicalTrials.gov registration: NCT04832594 .

Harnessing Immunomodulatory Polymers for Treatment of Autoimmunity, Allergy, and Transplant Rejection.

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.

Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).

Use of an AI Score Combining Cancer Signs, Masking, and Risk to Select Patients for Supplemental Breast Cancer Screening.

Background Mammographic density measurements are used to identify patients who should undergo supplemental imaging for breast cancer detection, but artificial intelligence (AI) image analysis may be more effective. Purpose To assess whether AISmartDensity-an AI-based score integrating cancer signs, masking, and risk-surpasses measurements of mammographic density in identifying patients for supplemental breast imaging after a negative screening mammogram. Materials and Methods This retrospective study included randomly selected individuals who underwent screening mammography at Karolinska University Hospital between January 2008 and December 2015. The models in AISmartDensity were trained and validated using nonoverlapping data. The ability of AISmartDensity to identify future cancer in patients with a negative screening mammogram was evaluated and compared with that of mammographic density models. Sensitivity and positive predictive value (PPV) were calculated for the top 8% of scores, mimicking the proportion of patients in the Breast Imaging Reporting and Data System "extremely dense" category. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and was compared using the DeLong test. Results The study population included 65 325 examinations (median patient age, 53 years [IQR, 47-62 years])-64 870 examinations in healthy patients and 455 examinations in patients with breast cancer diagnosed within 3 years of a negative screening mammogram. The AUC for detecting subsequent cancers was 0.72 and 0.61 (P < .001) for AISmartDensity and the best-performing density model (age-adjusted dense area), respectively. For examinations with scores in the top 8%, AISmartDensity identified 152 of 455 (33%) future cancers with a PPV of 2.91%, whereas the best-performing density model (age-adjusted dense area) identified 57 of 455 (13%) future cancers with a PPV of 1.09% (P < .001). AISmartDensity identified 32% (41 of 130) and 34% (111 of 325) of interval and next-round screen-detected cancers, whereas the best-performing density model (dense area) identified 16% (21 of 130) and 9% (30 of 325), respectively. Conclusion AISmartDensity, integrating cancer signs, masking, and risk, outperformed traditional density models in identifying patients for supplemental imaging after a negative screening mammogram. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kim and Chang in this issue.

Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia.

Acute myeloid leukemia is a poor-prognosis cancer commonly stratified by genetic aberrations, but these mutations are often heterogeneous and fail to consistently predict therapeutic response. Here, we combine transcriptomic, proteomic, and phosphoproteomic datasets with ex vivo drug sensitivity data to help understand the underlying pathophysiology of AML beyond mutations. We measure the proteome and phosphoproteome of 210 patients and combine them with genomic and transcriptomic measurements to identify four proteogenomic subtypes that complement existing genetic subtypes. We build a predictor to classify samples into subtypes and map them to a "landscape" that identifies specific drug response patterns. We then build a drug response prediction model to identify drugs that target distinct subtypes and validate our findings on cell lines representing various stages of quizartinib resistance. Our results show how multiomics data together with drug sensitivity data can inform therapy stratification and drug combinations in AML.

Differences and similarities in false interpretations by AI CAD and radiologists in screening mammography.

OBJECTIVE: We aimed to evaluate the false interpretations between artificial intelligence (AI) and radiologists in screening mammography to get a better understanding of how the distribution of diagnostic mistakes might change when moving from entirely radiologist-driven to AI-integrated breast cancer screening. METHODS AND MATERIALS: This retrospective case-control study was based on a mammography screening cohort from 2008 to 2015. The final study population included screening examinations for 714 women diagnosed with breast cancer and 8029 randomly selected healthy controls. Oversampling of controls was applied to attain a similar cancer proportion as in the source screening cohort. We examined how false-positive (FP) and false-negative (FN) assessments by AI, the first reader (RAD 1) and the second reader (RAD 2), were associated with age, density, tumor histology and cancer invasiveness in a single- and double-reader setting. RESULTS: For each reader, the FN assessments were distributed between low- and high-density females with 53 (42%) and 72 (58%) for AI; 59 (36%) and 104 (64%) for RAD 1 and 47 (36%) and 84 (64%) for RAD 2. The corresponding numbers for FP assessments were 1820 (47%) and 2016 (53%) for AI; 1568 (46%) and 1834 (54%) for RAD 1 and 1190 (43%) and 1610 (58%) for RAD 2. For ductal cancer, the FN assessments were 79 (77%) for AI CAD; with 120 (83%) for RAD 1 and with 96 (16%) for RAD 2. For the double-reading simulation, the FP assessments were distributed between younger and older females with 2828 (2.5%) and 1554 (1.4%) for RAD 1 + RAD 2; 3850 (3.4%) and 2940 (2.6%) for AI+RAD 1 and 3430 (3%) and 2772 (2.5%) for AI+RAD 2. CONCLUSION: The most pronounced decrease in FN assessments was noted for females over the age of 55 and for high density-women. In conclusion, AI could have an important complementary role when combined with radiologists to increase sensitivity for high-density and older females. ADVANCES IN KNOWLEDGE: Our results highlight the potential impact of integrating AI in breast cancer screening, particularly to improve interpretation accuracy. The use of AI could enhance screening outcomes for high-density and older females.

"The Terrors of Kingly Power": The Unusual Dental Pathology of King Pyrrhus of Epirus.

Pyrrhus of Epirus, widely respected and feared by his contemporaries, was a legendary figure in the ancient world. In this paper, we investigate Plutarch's description of the king's unique dental pathology. There are several possibilities to explain the ancient king's presentation, including several different types of developmental dysplasia. However, our conclusion is that it was likely due to a significant dental calculus overgrowth, often seen in the ancient Greek diet of the time. Whatever the underlying cause, Pyrrhus' intimidating visage helped secure the king a legacy that lasts to this day.

Piriform Rim Asymmetry in Unilateral Cleft Lip and Palate Patients Before Orthognathic Surgery.

BACKGROUND: Complete unilateral cleft lip and palate (UCLP) creates a continuity defect on the nasal floor, which contributes to nasal asymmetry. Traditionally, piriform rim symmetry has been evaluated by comparing cleft and noncleft sides. No study has compared the magnitude of perinasal asymmetry in UCLP patients with a control group of patients without clefts. PURPOSE: To address the following question: In UCLP patients, whose alveolar clefts are reconstructed with alveolar bone grafts (ABGs), is the magnitude of remaining piriform rim asymmetry similar to that of patients without UCLP? STUDY DESIGN SETTING, SAMPLE: This is a retrospective cohort study that used the cone beam computed tomography of UCLP and non-UCLP patients to evaluate the piriform rim symmetry. The sample was derived from patients who presented for orthognathic surgery between January 2015 and December 2022. To be included, patients had to have a maxillary deficiency. The cleft group had ABG performed with symphyseal bone harvest and bone morphogenetic protein application. Patients were excluded from the control group if they had clinical asymmetry and nasal septum deviation. Patients from the UCLP group were excluded if they failed the first attempt of ABG or had a syndrome. Preorthognathic cone beam computed tomography was used to measure the distance from the inferior and lateral aspects of the piriform rim to reference lines. PREDICTOR VARIABLE: UCLP status grouped as present or absent (control). OUTCOME VARIABLES: The magnitude of piriform rim asymmetry defined as the millimetric distance from the inferior and lateral aspects of the piriform rim to reference lines. COVARIATES: The covariates were age, sex, tissue thickness at the level of the alar base, and turbinate size. ANALYSIS: Welch's two-sample t-test was utilized to compare means. A level of significance of 5% (P < .05) was used for all analyses. To analyze the reliability of the measurements intraexaminer and interexaminer errors were tested using the Weir method. RESULTS: A total of 60 patients were included, 30 in each group. The mean age of UCLP patients was 16.76 (range 13 to 25), and the control group was 17 (range 13 to 25), P = .71. The UCLP group had 12 girls, and the control had 18 girls (P = .12). In the UCLP group, the mean discrepancy between affected and unaffected sides at the inferior aspect of the piriform rim was 3.9 mm (range 0.9 to 7 mm, P < .01), and in the control group the discrepancy between right and left sides was 0.1 mm (0-2.1 mm, P = .87). The mean discrepancy between affected and unaffected sides at the lateral aspect of the piriform rim was 3.6 mm (range 0.7 to 7.6 mm, P < .01) in the UCLP group, and in the control group the discrepancy between right and left sides was 0.1 mm (range 0.1 to 5.8 mm, P = .78) in the control group. The mean alar base soft tissue thickness discrepancy was 3.1 mm (range 0.9 to 7.9 mm, P < .01) in the UCLP group and 0 mm (range -1.8 to 1.9 mm, P = .97) in the control group. The mean difference in the turbinate area in the UCLP group was 314 mm2 (range 797 to 2,898) and in the control group 35 mm2 (range 702 to 2,302) (P = .19). CONCLUSION: ABG with symphyseal bone and bone morphogenetic protein was not able to provide the same level of piriform symmetry observed in patients without a cleft. Alar base tissue was thicker on the cleft side, and the turbinate size demonstrated greater variability in the UCLP patients.

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers.

Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials.

Enduring sex-dependent effects of lipopolysaccharide treatment on the hypothalamic-pituitary-gonadal axis in mice.

Pubertal stress causes enduring sexual behavior dysfunction in males and females, but the underlying mechanism remains unknown. These changes may arise from pubertal programming of the hypothalamic-pituitary-gonadal axis. Previous findings show that stress exposure downregulates the hypothalamic-pituitary-gonadal axis, particularly through the reduction of the neuropeptide kisspeptin (Kiss1) and its receptor (Kiss1R). Although acute changes in kiss1 and Kiss1r genes have been observed following pubertal immune stress, it is unclear whether immune stress-induced downregulation of kiss1 and kiss1r persists beyond puberty. The current study investigated the enduring sex-specific consequences of lipopolysaccharide on the expression of Kiss1 and Kiss1r in 160 pubertal or adult mice at multiple time points. Six-week and 10-week-old male and female mice were treated with either saline or with lipopolysaccharide. Mice were euthanized either 8 h or 4 weeks following treatment. Although we did not identify any sex differences, our results revealed that lipopolysaccharide treatment decreases hypothalamic Kiss1 and Kiss1r in both pubertal and adult mice within 8 h of treatment. The decreased hypothalamic Kiss1 expression persists 4 weeks later only in mice treated with lipopolysaccharide during puberty. Our findings highlight the age-dependent vulnerability of the hypothalamic-pituitary-gonadal axis to immune stress, providing a better understanding of the mechanisms implicated in allostatic shift during immune stress. Finally, our findings also show the effects of immune stress on various components of the hypothalamic-pituitary-gonadal axis, which could have implications for sexual and fertility-related dysfunctions.

Amino Acid Derivatives of Chlorin-e6-A Review.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation.

VAI-B: a multicenter platform for the external validation of artificial intelligence algorithms in breast imaging.

Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data. Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data on-premises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes. Results: To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database. Conclusions: We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wish to obtain an evaluation of different AI systems on their images.

The significance of the extent of tissue embedding for the detection of incidental prostate carcinoma on transurethral prostate resection material: the more, the better?

The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium-aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1-38) vs. a median of 15 (range 2-74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.

Loss of mouse Stmn2 function causes motor neuropathy.

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration accompanied by aberrant accumulation and loss of function of the RNA-binding protein TDP43. Thus far, it remains unresolved to what extent TDP43 loss of function directly contributes to motor system dysfunction. Here, we employed gene editing to find whether the mouse ortholog of the TDP43-regulated gene STMN2 has an important function in maintaining the motor system. Both mosaic founders and homozygous loss-of-function Stmn2 mice exhibited neuromuscular junction denervation and fragmentation, resulting in muscle atrophy and impaired motor behavior, accompanied by an imbalance in neuronal microtubule dynamics in the spinal cord. The introduction of human STMN2 through BAC transgenesis was sufficient to rescue the motor phenotypes observed in Stmn2 mutant mice. Collectively, our results demonstrate that disrupting the ortholog of a single TDP43-regulated RNA is sufficient to cause substantial motor dysfunction, indicating that disruption of TDP43 function is likely a contributor to ALS.

Implementation of quality improvement coaching versus physician communication training for improving human papillomavirus vaccination in primary care: a randomized implementation trial.

Many US health departments (HDs) conduct in-person quality improvement (QI) coaching to help primary care clinics improve their HPV vaccine delivery systems and communication. Some HDs additionally conduct remote communication training to help vaccine prescribers recommend HPV vaccination more effectively. Our aim was to compare QI coaching and communication training on key implementation outcomes. In a cluster randomized trial, we offered 855 primary care clinics: 1) QI coaching; 2) communication training; or 3) both interventions combined. In each trial arm, we assessed adoption (proportion of clinics receiving the intervention), contacts per clinic (mean number of contacts needed for one clinic to adopt intervention), reach (median number of participants per clinic), and delivery cost (mean cost per clinic) from the HD perspective. More clinics adopted QI coaching than communication training or the combined intervention (63% vs 16% and 12%, both p < .05). QI coaching required fewer contacts per clinic than communication training or the combined intervention (mean = 4.7 vs 29.0 and 40.4, both p < .05). Communication training and the combined intervention reached more total staff per clinic than QI coaching (median= 5 and 5 vs 2, both p < .05), including more prescribers (2 and 2 vs 0, both p < .05). QI coaching cost $439 per adopting clinic on average, including follow up ($129/clinic), preparation ($73/clinic), and travel ($69/clinic). Communication training cost $1,287 per adopting clinic, with most cost incurred from recruitment ($653/clinic). QI coaching was lower cost and had higher adoption, but communication training achieved higher reach, including to influential vaccine prescribers.

Our cluster randomized trial compared two interventions that health departments commonly use to increase HPV vaccination coverage: quality improvement (QI) coaching and physician communication training. We found that QI coaching cost less and was more often adopted by primary care clinics, but communication training reached more staff members per clinic, including vaccine prescribers. Findings provide health departments with data needed to weigh the implementation strengths and challenges of QI coaching and physician communication training for increasing HPV vaccination coverage.

Skin cancer and sun protective behaviours in water-based sports: A scoping review.

BACKGROUND: Individuals who participate in outdoor sports are subject to an increased risk of developing skin cancer. To date, there has been no review examining skin cancer and sun protective behaviours specific to outdoor, water-based sports. Therefore, this scoping reviews objectives were to (a) summarize volume and type of the scientific literature available relating to skin cancer, (b) examine current sun protective behaviours and (c) identify knowledge gaps to inform future research. METHOD: A scoping review was conducted to address the objectives following the PRISMA guidelines. Seven databases were searched; identified studies were screened based on title, abstract and full text for outdoor water-based sports, which examined skin cancer and/or sun protective behaviours. Data were extracted, synthesized and critically appraised using a modified AXIS tool. Percentage frequencies were calculated, and key results were placed in tabular or graphical presentation. RESULTS: Nine cross-sectional studies were identified, all defined as low-level evidence. A combined sample of 4377 participants across six countries and five water-based sports showed BCC (71%) was the most common skin cancer, followed by melanoma (18%) and SCC (10%). The head (41%) and upper limbs (27%) were the most common location. CONCLUSION: This review highlights the minimal research available and demonstrates those in water-based sports are at high risk of developing skin cancer. Due to difficulty adhering to sun protective behaviours, the most prevalent location is the upper body. Included studies were of low-level evidence, providing opportunity for future research to expand upon the gaps in the current literature.

Comparison of MET gene amplification analysis by next-generation sequencing and fluorescence in situ hybridization.

MET gene alterations are known to be involved in acquired resistance to epidermal growth factor receptor inhibition. MET amplifications present a potential therapeutic target in non-small cell lung cancer. Although next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are conventionally used to assess MET amplifications, there are currently no clinically defined cut-off values for NGS, with FISH still being the gold standard. A collective of 20 formalin-fixed paraffin-embedded lung cancer tissue samples (mean age 64 years) were selected based on increased MET gene copy number (CNV) status or the presence of mutations detected by NGS (GeneReader, QIAGEN) and were further assessed by FISH (MET/CEN7, Zytomed). Of these, 17 tumor samples were MET-amplified and one patient was found to have a MET rearrangement by NGS, while two samples had no MET gene alteration. In contrast to the NGS result, FISH analysis showed only one highly amplified sample and 19 negative samples. The single highly amplified case detected by FISH was also positive by NGS with a fold change (FC) of 3.18 and a mean copy number (CNMV 10-100%) of 20.5. Therefore, for the assessment of MET amplifications using the QIAGEN NGS workflow, we suggest detecting amplified cases with an FC value of ≥ 3.0 and a CNMV 10-100% value of ≥ 20.0 by FISH. In summary, NGS allows for DNA- and RNA-based analysis of specific MET gene amplifications, point mutations or rearrangements.

Stem-cell clinics in the UK: a web-based study.

Aim: Explore the nature and extent of web-based promotion of stem cell treatments marketed by clinics in the UK. Materials & methods: Web-based analysis of clinics in the UK using predefined variables, with analysis of eligible clinics according to preset criteria of ethical relevance. Results: A majority (79%) of UK clinics were judged to be problematic. Information was found to be lacking, misleading or otherwise problematic in several respects, including a lack of information on risks of adverse effects, unjustifiably optimistic depictions of therapeutic effectiveness, and questionable presentational approaches such as the use of celebrity patient testimonials. Conclusion: In a majority of cases, commercial clinics in the UK portray stem-cell therapies on their websites in ethically questionable ways.

Rationale and Preclinical Evaluation of a Multimodal Topical Body Skincare Product for Toning and Tightening.

A novel tightening and toning cream (TTC) was designed to improve body skin quality at multiple levels by engaging several key pathways that contribute to skin function, strength, and integrity. Evaluation of gene expression in both human in vitro 3D skin and ex vivo skin treated with TTC demonstrated changes reflecting improved extracellular matrix and dermal integrity, lymphatic drainage, mitigation of inflammation, cellular clearance and recycling, and adipocyte metabolism. This study provides the rationale and preclinical support for the use of TTC as a standalone agent to improve body skin quality or in combination with body contouring procedures. J Drugs Dermatol. 2021;20(10):1041-1044. doi:10.36849/JDD.6401.