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* Context.-Machine learning applications in the pathology clinical domain are emerging rapidly. As decision support systems continue to mature, laboratories will increasingly need guidance to evaluate their performance in clinical practice. Currently there are no formal guidelines to assist pathology laboratories in verification and/or validation of such systems. These recommendations are being proposed for the evaluation of machine learning systems in the clinical practice of pathology. Objective.-To propose recommendations for performance evaluation of in vitro diagnostic tests on patient samples that incorporate machine learning as part of the pre-analytical, analytical, or post-analytical phases of the laboratory workflow. Topics described include considerations for machine learning model evaluation including risk assessment, predeployment requirements, data sourcing and curation, verification and validation, change control management, human-computer interaction, practitioner training, and competency evaluation. Data Sources.-An expert panel performed a review of the literature, Clinical and Laboratory Standards Institute guidance, and laboratory and government regulatory frameworks. Conclusions.-Review of the literature and existing documents enabled the development of proposed recommendations. This white paper pertains to performance evaluation of machine learning systems intended to be implemented for clinical patient testing. Further studies with real-world clinical data are encouraged to support these proposed recommendations. Performance evaluation of machine learning models is critical to verification and/or validation of in vitro diagnostic tests using machine learning intended for clinical practice. (Arch Pathol Lab Med. 2024;148:e335-e361; doi: 10.5858/arpa.2023-0042-CP), Institution of machine learning (ML) in the pathology clinical domain has gained momentum and is rapidly advancing. As ML-based clinical decision support (CDS) systems continue to mature, laboratories will increasingly [...]

Abstract Hepatocellular carcinoma (HCC) remains a significant global health challenge with few effective treatment options. The dysregulation of endoplasmic reticulum (ER) stress responses has emerged as a pivotal factor in HCC progression and therapy resistance. Long non-coding RNAs (lncRNAs) play a crucial role as key epigenetic modifiers in this process. Recent research has explored how lncRNAs influence ER stress which in turn affects lncRNAs activity in HCC. We systematically analyze the current literature to highlight the regulatory roles of lncRNAs in modulating ER stress and vice versa in HCC. Our scrutinization highlights how dysregulated lncRNAs contribute to various facets of HCC, including apoptosis resistance, enhanced proliferation, invasion, and metastasis, all driven by ER stress. Moreover, we delve into the emerging paradigm of the lncRNA-miRNA-mRNA axis, elucidating it as the promising avenue for developing novel biomarkers and paving the way for more personalized treatment options in HCC. Nevertheless, we acknowledge the challenges and future directions in translating these insights into clinical practice. In conclusion, our review provides insights into the complex regulatory mechanisms governing ER stress modulation by lncRNAs in HCC.

PURPOSE: To characterize the recovery of diagnostic cardiovascular procedure volumes in U.S. and non-U.S. facilities in the year following the initial COVID-19 outbreak. MATERIALS AND METHODS: The International Atomic Energy Agency (IAEA) coordinated a worldwide study called the IAEA Noninvasive Cardiology Protocols Study of COVID-19 2 (INCAPS COVID 2), collecting data from 669 facilities in 107 countries, including 93 facilities in 34 U.S. states, to determine the impact of the pandemic on diagnostic cardiovascular procedure volumes. Participants reported volumes for each diagnostic imaging modality used at their facility for March 2019 (baseline), April 2020, and April 2021. This secondary analysis of INCAPS COVID 2 evaluated differences in changes in procedure volume between U.S. and non-U.S. facilities and among U.S. regions. Factors associated with return to prepandemic volumes in the United States were also analyzed in a multivariable regression analysis. RESULTS: Reduction in procedure volumes in April 2020 compared with baseline was similar for U.S. and non-U.S. facilities (-66% vs -71%, P = .27). U.S. facilities reported greater return to baseline in April 2021 than did all non-U.S. facilities (4% vs -6%, P = .008), but there was no evidence of a difference when comparing U.S. facilities with non-U.S. high-income country (NUHIC) facilities (4% vs 0%, P = .18). U.S. regional differences in return to baseline were observed between the Midwest (11%), Northeast (9%), South (1%), and West (-7%, P = .03), but no studied factors were significant predictors of 2021 change from prepandemic baseline. CONCLUSION: The reductions in cardiac testing during the early pandemic have recovered within a year to prepandemic baselines in the United States and NUHICs, while procedure volumes remain depressed in lower-income countries.Keywords: SPECT, Cardiac, Epidemiology, Angiography, CT Angiography, CT, Echocardiography, SPECT/CT, MR Imaging, Radionuclide Studies, COVID-19, Cardiovascular Imaging, Diagnostic Cardiovascular Procedure, Cardiovascular Disease, Cardiac Testing Supplemental material is available for this article. © RSNA, 2023.

BackgroundIntra-atrial shunts are associated with an elevated risk of embolic stroke of undetermined source (ESUS). Percutaneous occluder implantation is recommended as secondary prevention in younger patients. This study aims to compare the outcome after shunt occlusion between younger and older patients with a history of presumed paradox embolism and to evaluate the impact of high-volume shunting in an elderly population.MethodsWe conducted a single-center, retrospective, observational study, involving 187 patients who underwent interventional percutaneous PFO or ASD occlusion at our center between 2013 and 2023.ResultsThe mean age of participants was 51.8 ± 11.8 years, with 76 patients aged ≤50 years and 111 patients aged >50 years. Older patients presented more cardiovascular risk factors. The presence of atrial septum aneurysm or large shunting was evenly distributed (ASA 26.3% vs. 28.8%, p = 0.833, mean shunt defect size 6.67 vs. 7.23 mm, p = 0.151). There were no significant differences in procedural or intrahospital complications. The event rate during the 6-month follow-up was low. Recurrence of arterial embolism occurred in 1.6% of the younger and 3.8% of the older patients (p = 0.817). Comparison of high-volume shunts (defect size ≥10 mm or passage ≥20 bubbles during bubble study) with low-volume shunts in this elderly cohort with a mean age ≥50 years showed no significant difference in outcomes. There was a statistically non-significant trend toward a higher rate of residual shunt at the end of the procedure in the high-volume shunt group (2.9% vs. 9.8%, p = 0.0894). This difference was not observed at the 6-month follow-up anymore (14.5 vs. 12.1%, p = 0.628). Two unsuccessful implantation attempts were reported in the high-volume shunt group, while none were observed in the low-volume shunt group (p = 0.372). No intervention-related deaths occurred in this patient cohort during follow-up.ConclusionOcclusion of relevant, intra-atrial shunting is a safe and effective option for secondary prevention of cryptogenic embolism in patients over 50 years of age. The beneficial outcome was irrespective of a high-volume shunting before implantation.

This study aimed to systematically evaluate and quantify the risk of adverse maternal and neonatal outcomes in patients with pregnancy-associated cancer (PAC). This study was conducted from February 13, 2021, through July 24, 2023. A systematic search of MEDLINE, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials was conducted to identify studies reporting outcomes for patients with PAC. The study was registered on PROSPERO. Two reviewers independently conducted screening, data extraction, and quality assessment. The associations were quantified using random-effects meta-analysis. The initial search produced 29,401 titles and abstracts, after which 147 unique full-text articles were screened, of which 22 articles with 59,190 pregnancies with PAC from 70,097,167 births were included in the meta-analysis. Women with PAC were at significantly increased risk of cesarean deliveries (risk ratio [RR], 1.58; 95% CI, 1.31-1.89), preterm birth (RR, 3.07; 95% CI, 2.37-3.98), venous thromboembolism (RR, 6.76; 95% CI, 5.08-8.99), and maternal death (RR, 41.58; 95% CI, 20.38-84.83). The only outcome with reduced risk was instrumental mode of delivery (RR, 0.67; 95% CI, 0.52-0.87). Pregnancy-associated cancer increases risk of adverse outcomes, including a 7-fold risk of venous thromboembolism and a 42-fold risk of maternal death. Further research is required to better understand the mechanisms leading to these adverse outcomes, especially for women who are not diagnosed until the postpartum period. Affected women should have counseling regarding their increased risk of adverse outcomes.

For the past 2 decades, pathologists have been accustomed to reporting the HER2 status of breast cancer as either positive or negative, based on HER2 IHC. Today, however, there is a clinical imperative to employ a 3-tier approach to interpreting HER2 IHC that can also identify tumours categorised as HER2-low. Meeting this need for a finer degree of discrimination may be challenging, and in this article, we consider the potential for the integration of computational approaches to support pathologists in achieving accurate and reproducible HER2 IHC scoring as well as outlining some of the practicalities involved.

BackgroundPercutaneous interventional left atrial appendage occlusion (LAAO) is a reliable, safe, and effective alternative for stroke prevention in selected patients with atrial fibrillation (AF).MethodsIn a retrospective observational study, 149 patients underwent LAAO between 2016 and 2022 at the Department of Cardiology of the Charité—Universitätsmedizin Berlin, Campus Virchow, with AF for prevention of thromboembolic complications. We compared patient characteristics, intraoperative details and postoperative outcomes between single-occlusive plug-type (SOPT) and dual-occlusive disc-type (DODT) devices.ResultsIn all patients, the device implantation was successful. 60 patients received a SOPT occluder, including Watchman (35%) and Watchman FLX Occluders (65%), while 89 patients received a DODT occluder, including Amplatzer Cardiac Plug (37.1%), the Amplatzer Amulet (25.8%), and the LAmbre occluder (37.1%) systems. Procedure duration was significantly longer for DODT occluder implantation (49 ± 33 vs. 41 ± 25 min, p = 0.018). There were no in-hospital deaths or thromboembolic events reported after LAAO in both groups. Beyond that, a low rate of bleeding or access-side-related complications and pericardial tamponades were observed. Anticoagulation at discharge varied. About 60.8% of patients received dual antiplatelet therapy at hospital discharge, and 33.1% received direct oral anticoagulants. A 6-month follow-up was obtained in 85% of the patients. All implanted devices were in the desired position. However, in 5.7% of the patients, a device-related thrombus formation was detected in the SOPT group, while no thrombus was seen in the DODT group (p = 0.11). Thromboembolic events were noticed in 3.1%, without any difference between the device types. There was a statistically non-significant trend for less residual device leaks after SOPT vs. DODT implantation (no leak in 71.7% vs. 62.2%, p = 0.07; minor leaks

Background: The American Heart Association's (AHA) Life's Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. We sought to assess sex differences in relation to LE8 and its components along with association with mortality. Methods: The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult participants > age 18, stratified by sex. We categorized overall CVH, health factors, and health behaviors into 3 levels (low:

* Context.--Increasing implementation of whole slide imaging together with digital workflow and advances in computing capacity enable the use of artificial intelligence (AI) in pathology, including breast pathology. Breast pathologists often face a significant workload, with diagnosis complexity, tedious repetitive tasks, and semi-quantitative evaluation of biomarkers. Recent advances in developing AI algorithms have provided promising approaches to meet the demand in breast pathology. Objective.--To provide an updated review of AI in breast pathology. We examined the success and challenges of current and potential AI applications in diagnosing and grading breast carcinomas and other pathologic changes, detecting lymph node metastasis, quantifying breast cancer biomarkers, predicting prognosis and therapy response, and predicting potential molecular changes. Data Sources.--We obtained data and information by searching and reviewing literature on AI in breast pathology from PubMed and based our own experience. Conclusions.--With the increasing application in breast pathology, AI not only assists in pathology diagnosis to improve accuracy and reduce pathologists' workload, but also provides new information in predicting prognosis and therapy response., Pathology is the gold standard for disease diagnosis. Pathologists are committed to assisting clinicians in the precise treatment of various diseases, especially malignant tumors. The advance in individualized treatment requires [...]

Abstract This review discusses the profound impact of artificial intelligence (AI) on breast cancer (BC) diagnosis and management within the field of pathology. It examines the various applications of AI across diverse aspects of BC pathology, highlighting key findings from multiple studies. Integrating AI into routine pathology practice stands to improve diagnostic accuracy, thereby contributing to reducing avoidable errors. Additionally, AI has excelled in identifying invasive breast tumors and lymph node metastasis through its capacity to process large whole-slide images adeptly. Adaptive sampling techniques and powerful convolutional neural networks mark these achievements. The evaluation of hormonal status, which is imperative for BC treatment choices, has also been enhanced by AI quantitative analysis, aiding interobserver concordance and reliability. Breast cancer grading and mitotic count evaluation also benefit from AI intervention. AI-based frameworks effectively classify breast carcinomas, even for moderately graded cases that traditional methods struggle with. Moreover, AI-assisted mitotic figures quantification surpasses manual counting in precision and sensitivity, fostering improved prognosis. The assessment of tumor-infiltrating lymphocytes in triple-negative breast cancer using AI yields insights into patient survival prognosis. Furthermore, AI-powered predictions of neoadjuvant chemotherapy response demonstrate potential for streamlining treatment strategies. Addressing limitations, such as preanalytical variables, annotation demands, and differentiation challenges, is pivotal for realizing AI’s full potential in BC pathology. Despite the existing hurdles, AI’s multifaceted contributions to BC pathology hold great promise, providing enhanced accuracy, efficiency, and standardization. Continued research and innovation are crucial for overcoming obstacles and fully harnessing AI’s transformative capabilities in breast cancer diagnosis and assessment. Graphical Abstract

Abstract Background The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation. Methods A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature. Results The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals’ autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation. Conclusion The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine.

Coronary dominance describes the anatomic variation of coronary arterial supply, notably as it relates to perfusion of the inferior cardiac territories. Differences in the development and outcome in select disease states between coronary dominance patterns are increasingly recognized. In particular, observational studies have identified higher prevalence of poor outcomes in left coronary dominance in the setting of ischemic, conduction, and valvular disease. In this qualitative literature review, we summarize anatomic, physiologic, and clinical implications of differences in coronary dominance to highlight current understanding and gaps in the literature that should warrant further studies.

Abstract Digital pathology (DP) is being increasingly employed in cancer diagnostics, providing additional tools for faster, higher-quality, accurate diagnosis. The practice of diagnostic pathology has gone through a staggering transformation wherein new tools such as digital imaging, advanced artificial intelligence (AI) algorithms, and computer-aided diagnostic techniques are being used for assisting, augmenting and empowering the computational histopathology and AI-enabled diagnostics. This is paving the way for advancement in precision medicine in cancer. Automated whole slide imaging (WSI) scanners are now rendering diagnostic quality, high-resolution images of entire glass slides and combining these images with innovative digital pathology tools is making it possible to integrate imaging into all aspects of pathology reporting including anatomical, clinical, and molecular pathology. The recent approvals of WSI scanners for primary diagnosis by the FDA as well as the approval of prostate AI algorithm has paved the way for starting to incorporate this exciting technology for use in primary diagnosis. AI tools can provide a unique platform for innovations and advances in anatomical and clinical pathology workflows. In this review, we describe the milestones and landmark trials in the use of AI in clinical pathology with emphasis on future directions.

Prostate cancer (PCa) remains a leading cause of mortality among American men, with metastatic and recurrent disease posing significant therapeutic challenges due to a limited comprehension of the underlying biological processes governing disease initiation, dormancy, and progression. The conventional use of PCa cell lines has proven inadequate in elucidating the intricate molecular mechanisms driving PCa carcinogenesis, hindering the development of effective treatments. To address this gap, patient-derived primary cell cultures have been developed and play a pivotal role in unraveling the pathophysiological intricacies unique to PCa in each individual, offering valuable insights for translational research. This review explores the applications of the conditional reprogramming (CR) cell culture approach, showcasing its capability to rapidly and effectively cultivate patient-derived normal and tumor cells. The CR strategy facilitates the acquisition of stem cell properties by primary cells, precisely recapitulating the human pathophysiology of PCa. This nuanced understanding enables the identification of novel therapeutics. Specifically, our discussion encompasses the utility of CR cells in elucidating PCa initiation and progression, unraveling the molecular pathogenesis of metastatic PCa, addressing health disparities, and advancing personalized medicine. Coupled with the tumor organoid approach and patient-derived xenografts (PDXs), CR cells present a promising avenue for comprehending cancer biology, exploring new treatment modalities, and advancing precision medicine in the context of PCa. These approaches have been used for two NCI initiatives (PDMR: patient-derived model repositories; HCMI: human cancer models initiatives).

This clinical trial investigated the efficacy of platelet-rich fibrin (PRF) as an adjunct to conventional scaling and root planing (SRP) in non-surgical periodontal therapy. In a split-mouth randomized controlled trial with 13 patients and 26 periodontal pocket sites, PRF was inserted in test group pockets alongside SRP, while control group pockets received SRP alone. Measurements at baseline and six weeks included probing pocket depths (PPDs), clinical attachment loss (CAL), gingival recession (GR), the plaque index, and the gingivitis index. The wound healing index was assessed at six weeks. The results show statistically significant improvements in the SRP+PRF group compared to SRP alone, demonstrating a better CAL gain (SRP+PRF group: 2.69 ± 0.63; SRP alone group: 4.15 ± 0.69—p-value: 0.001), PPD reduction (SRP+PRF group: 2.62 ± 0.65; SRP alone group: 3.85 ± 0.80—p-value: 0.001), and GR minimization (SRP+PRF group: 0.46 ± 0.62; SRP alone group: 0.81 ± 0.72—p-value: 0.21). The adjunctive use of PRF enhanced healing, reduced pocket depths, decreased tissue morbidity, and minimized gingival recession. This study concludes that PRF placement is effective in 5–6 mm pockets, potentially reducing the number of periodontal treatment sessions needed for pocket closure.

BackgroundThe coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known.ObjectivesThis study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia.MethodsThe International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison.ResultsProcedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020.ConclusionsThe COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

ObjectivesThis study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-U.S. institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.BackgroundThe COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.MethodsData were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.ResultsReductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p

Context.--Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. Objective.--To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. Data Sources.--Sources were a literature review and the personal experience of authors and educators. Conclusions.--High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development. doi: 10.5858/arpa.2021-0473-RA, We could just as well be writing this paper with a manually powered typewriter, or with ink drawn from a well by a quill pen, had not a series of [...]

Introduction: Acute Myocardial injury defined by increased troponin I level is associated with poor in-hospital outcomes and cardiovascular complications in patients with COVID-19. The current study was designed to determine the implications and clinical outcome of myocardial injury in COVID-19. Methods: This retrospective study included hospitalized COVID-19 patients. Myocardial injury was defined by high sensitivity Troponin I (hs-TNI)≥26ng/l. Cardiac biomarkers, inflammatory markers and clinical data were systemically collected and analyzed. Hazard ratio for in-hospital mortality and logistic regression for predictors of acute myocardial injury were analyzed. Results: Of the 1821 total patients with COVID-19, 293(16.09%) patients died and 1528 (83.91%) patients survived. Patients who died had significantly higher association with presence of cardiovascular risk factors, severe CTSS ( CT severity score ) and myocardial injury as compared to survived group. 628 (34.5%) patients had evidence of myocardial injury and they had statistically significant association with cardiovascular risk factors, in-hospital mortality, procalcitonin; higher hospital, and ICCU stay. We found significant hazard ratio of diabetes (HR=2.66, (CI:1.65-4.29)), Severe CT score (HR=2.81, (CI:1.74-4.52)), hs-TNI≥26 ng/l (HR=4.68, (CI:3.81-5.76)) for mortality. Severe CTSS score (OR=1.95, CI: 1.18-3.23, P=0.01) and prior CVD history (OR=1.65, CI:1.00-2.73, P=0.05) were found significant predictors of myocardial injury in regression analysis. Conclusion: Almost one third of hospitalized patients had evidence of acute myocardial injury during hospitalization. Acute myocardial injury is associated with higher hospital and ICCU stay, mortality, higher in-hospital infection which indicates more severe disease and the poor in-hospital outcomes.

Vγ9Vδ2 T cells represent a promising cancer therapy platform because the implementation of allogenic, off-the-shelf product candidates is possible. However, intravenous administration of human Vγ9Vδ2 T cells manufactured under good manufacturing practice (GMP)-compliant, serum-free conditions are not tested easily in most mouse models, mainly because they lack the ability to migrate from the blood to tissues or tumors. We demonstrate that these T cells do not migrate from the circulation to the mouse bone marrow (BM), the site of many malignancies. Thus, there is a need to better characterize human γδ T-cell migration in vivo and develop strategies to direct these cells to in vivo sites of therapeutic interest. To better understand the migration of these cells and possibly influence their migration, NSG mice were conditioned with agents to clear BM cellular compartments, i.e., busulfan or total body irradiation (TBI), or promote T-cell migration to inflamed BM, i.e., incomplete Freund’s adjuvant (IFA), prior to administering γδ T cells. Conditioning with TBI, unlike busulfan or IFA, increases the percentage and number of γδ T cells accumulating in the mouse BM, and cells in the peripheral blood (PB) and BM display identical surface protein profiles. To better understand the mechanism by which cells migrate to the BM, mice were conditioned with TBI and administered γδ T cells or tracker-stained red blood cells. The mechanism by which γδ T cells enter the BM after radiation is passive migration from the circulation, not homing. We tested if these ex vivo-expanded cells can migrate based on chemokine expression patterns and showed that it is possible to initiate homing by utilizing highly expressed chemokine receptors on the expanded γδ T cells. γδ T cells highly express CCR2, which provides chemokine attraction to C-C motif chemokine ligand 2 (CCL2)-expressing cells. IFNγ-primed mesenchymal stromal cells (MSCs) (γMSCs) express CCL2, and we developed in vitro and in vivo models to test γδ T-cell homing to CCL2-expressing cells. Using an established neuroblastoma NSG mouse model, we show that intratumorally-injected γMSCs increase the homing of γδ T cells to this tumor. These studies provide insight into the migration of serum-free, ex vivo-expanded Vγ9Vδ2 T cells in NSG mice, which is critical to understanding the fundamental properties of these cells.

Background Although individuals with cancer experience high rates of cardiovascular morbidity, there are limited data on the potential differences in cardiovascular health (CVH) metrics between individuals with and without cancer. Methods and Results The National Health and Nutrition Examination Survey between 2015 and 2020 was queried to evaluate the prevalence of health metrics that comprise the American Heart Association Life's Essential 8 construct of cardiovascular health among adult individuals with and without cancer in the United States. Health metric scores were also evaluated according to important patient demographics including age, sex, race and ethnicity, and socioeconomic status. Among 4370 participants representing >180 million US adults, 9.4% had a history of cancer. Individuals with cancer had lower overall cardiovascular health scores (67.1 versus 69.1, P

Mucormycosis is an invasive fungal infection associated with high death rates. Poorly controlled diabetes mellitus, organ transplantation, hematological malignancies, and immunosuppression are the known predisposing factors for mucormycosis (1). During [...]

Abstract Low- and middle-income countries (LMICs) represent a big source of data not only for endemic diseases but also for neoplasms. Data is the fuel which drives the modern era. Data when stored in digital form can be used for constructing disease models, analyzing disease trends and predicting disease outcomes in various demographic regions of the world. Most labs in developing countries don’t have resources such as whole slide scanners or digital microscopes. Owing to severe financial constraints and lack of resources, they don’t have the capability to handle large amounts of data. Due to these issues, precious data cannot be saved and utilized properly. However, digital techniques can be adopted even in low resource settings with significant financial constraints. In this review article, we suggest some of the options available to pathologists in developing countries which can enable them to start their digital journey and move forward despite resource-poor health system.

Abstract The risk of alcoholic liver disease (ALD) is increased by excessive ethanol drinking. For the prevention of ALD, the effects of ethanol on the liver, adipose tissue, and gut are crucial. Interestingly, garlic and a few probiotic strains can protect against ethanol-induced hepatotoxicity. However, the relationship between adipose tissue inflammation, Kyolic aged garlic extract (AGE), and Lactobacillus rhamnosus MTCC1423 in developing ALD is unknown. Therefore, the present study explored the effect of synbiotics (a combination of prebiotics and probiotics) on adipose tissue to prevent ALD. To investigate the efficacy of synbiotics administration on adipose tissue in preventing ALD, in vitro (3T3-L1 cells, N = 3) groups: control, control + LPS (lipopolysaccharide), ethanol, ethanol + LPS, ethanol + synbiotics, ethanol + synbiotics + LPS; in vivo (Wistar male rats, N = 6) groups: control, ethanol, pairfed, ethanol + synbiotics and in silico experiments were conducted. Lactobacillus multiplies in accordance with the growth curve when exposed to AGE. Additionally, Oil red O staining and scanning electron microscopy (SEM) demonstrated that synbiotics therapy maintained the morphology of adipocytes in the alcoholic model. In support of the morphological changes, quantitative real-time PCR demonstrated overexpression of adiponectin and downregulation of leptin, resistin, PPARγ, CYP2E1, iNOS, IL-6, and TNF-α after administration of synbiotics compared to the ethanol group. In addition, MDA estimation by high-performance liquid chromatography (HPLC) indicated that the synbiotics treatment reduced oxidative stress in rat adipose tissue. Consequently, the in-silico analysis revealed that AGE inhibited the C-D-T networks as PPARγ acting as the main target protein. The current study demonstrates that using synbiotics improves adipose tissue metabolism in ALD. Graphical Abstract