Patient-derived organoids for precision oncology: a platform to facilitate clinical decision making.

BACKGROUND: Despite recent advances in research, there are still critical lacunae in our basic understanding of the cause, pathogenesis, and natural history of many cancers, especially heterogeneity in patient response to drugs and mediators in the transition from malignant to invasive phenotypes. The explication of the pathogenesis of cancer has been constrained by limited access to patient samples, tumor heterogeneity and lack of reliable biological models. Amelioration in cancer treatment depends on further understanding of the etiologic, genetic, biological, and clinical heterogeneity of tumor microenvironment. Patient-derived organoids recapitulate the basic features of primary tumors, including histological complexity and genetic heterogeneity, which is instrumental in predicting patient response to drugs. METHODS: Human iPSCs from healthy donors, breast and ovarian cancer patients were successfully differentiated towards isogenic hepatic, cardiac, neural and endothelial lineages. Multicellular organoids were established using Primary cells isolated from tumor tissues, histologically normal tissues adjacent to the tumors (NATs) and adipose tissues (source of Mesenchymal Stem Cells) from ovarian and breast cancer patients. Further these organoids were propagated and used for drug resistance/sensitivity studies. RESULTS: Ovarian and breast cancer patients' organoids showed heterogeneity in drug resistance and sensitivity. iPSCs-derived cardiomyocytes, hepatocytes and neurons showed donor-to-donor variability of chemotherapeutic drug sensitivity in ovarian cancer patients, breast cancer patients and healthy donors. CONCLUSION: We report development of a novel integrated platform to facilitate clinical decision-making using the patient's primary cells, iPSCs and derivatives, to clinically relevant models for oncology research.

Gamut of Extratesticular Scrotal Masses: Anatomic Approach to Sonographic Differential Diagnosis.

The commonly taught tenet that intratesticular lesions are always malignant and extratesticular scrotal lesions are always benign is a simplistic statement that erroneously minimizes the significance of extratesticular scrotal masses and their diagnosis. Yet, disease in the extratesticular space is commonly encountered by clinicians and radiologists and is often a source of uncertainty in diagnosis and management. Given the embryologically rooted complex anatomy of this region, a wide range of pathologic conditions is possible. Radiologists may not be familiar with some of these conditions; further, many of these lesions can have a specific sonographic appearance, allowing accurate diagnosis that can minimize surgical intervention. Lastly, malignancies can occur in the extratesticular space-although this is less common than in the testicles-and proper recognition of findings that warrant additional imaging or surgery is critical in optimizing outcomes. The authors present a compartmental anatomic framework for differential diagnosis of extratesticular scrotal masses and provide a comprehensive illustrative display of many of the pathologic conditions that can be encountered to familiarize radiologists with the sonographic appearances of these lesions. They also review management of these lesions and scenarios where US may not be definitive in diagnosis and selective use of scrotal MRI can be helpful. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Multimodality Imaging after Liver Transplant: Top 10 Important Complications.

Patients who have undergone liver transplant are now regularly seen in day-to-day radiology practice. All surgical techniques for liver transplant require arterial, portal venous, hepatic venous and caval, and biliary anastomoses. This review is focused on the 10 "not to be missed" complications of liver transplant that affect the health and life of the graft and graft recipient. Arterial complications are the most common and devastating. Early hepatic artery thrombosis may be catastrophic because the biliary tree is solely dependent on the hepatic artery after transplant and collateral vessels have not yet formed. In contrast, delayed hepatic artery thrombosis may be more insidious as collateral arteries develop. US findings of delayed hepatic artery thrombosis may be similar to those of hepatic artery stenosis and celiac artery stenosis. Splenic artery steal syndrome is an increasingly recognized cause of graft ischemia. Venous complications are much less common. Hepatic venous and caval complications are notable for their increased incidence in living-donor and pediatric transplants. Biliary complications often result from arterial ischemia. Biliary cast syndrome is a notable example in which ischemic biliary mucosa sloughs into and obstructs the duct lumens. Neoplasms also may occur within the hepatic graft and may be due to recurrent malignancy, posttransplant lymphoproliferative disorder, or metastases. US is the initial imaging modality of choice, particularly in the acute postoperative setting. Further evaluation with contrast-enhanced US, CT, or MRI; catheter angiography; endoscopic retrograde cholangiopancreatography; and/or nuclear medicine studies is performed as needed. An invited commentary by Bhargava is available online. Online supplemental material is available for this article. ©RSNA, 2022.

Undetectable equals untransmittable (U = U): implications for preconception counseling for human immunodeficiency virus serodiscordant couples.

Although limited by society guidelines from the American Society for Reproductive Medicine and the Centers for Disease Control and Prevention in the past, many human immunodeficiency virus serodiscordant American couples who desired future childbearing were referred to reproductive endocrinology and infertility specialists for in vitro fertilization. The access to and cost of assisted reproductive technology created a significant barrier to reproductive care in this patient population. New evidence-based guidelines by the Centers for Disease Control and Prevention, however, endorse condomless intercourse timed to ovulation for human immunodeficiency virus serodiscordant couples with undetectable viral loads on antiretroviral therapy. In parallel, the Prevention Access Campaign's undetectable equals untransmittable initiative advocates increasing awareness of the favorable prognosis of persons living with human immunodeficiency virus to remove the associated stigma of the disease and promote the safety of condomless intercourse in the setting of undetectable viral loads. With these new guidelines, human immunodeficiency virus serodiscordant couples may not require an automatic referral to the reproductive endocrinology and infertility specialist. Rather, providers of preconception care could recommend timed intercourse for these couples after confirmation of an undetectable viral load and discussion with the interdisciplinary team of health care professionals caring for persons living with human immunodeficiency virus.

Human proton coupled folic acid transporter is a monodisperse oligomer in the lauryl maltose neopentyl glycol solubilized state.

The human proton coupled folic acid transporter PCFT is the major import route for dietary folates. Mutations in the gene encoding PCFT cause hereditary folic acid malabsorption, which manifests itself by compromised folate absorption from the intestine and also in impaired folate transport into the central nervous system. Since its recent discovery, PCFT has been the subject of numerous biochemical studies aiming at understanding its structure and mechanism. One major focus has been its oligomeric state, with some reports supporting oligomers and others a monomer. Here, we report the overexpression and purification of recombinant PCFT. Following detergent screening, n-Dodecyl ß-D-maltoside (DDM) and lauryl maltose neopentyl glycol (LMNG) were chosen for further work as they exhibited the most optimal solubilization. We found that purified detergent solubilized PCFT was able to bind folic acid, thus indicating a functionally active protein. Size exclusion chromatography showed that PCFT in DDM was polydisperse; the LMNG preparation was clearly monodisperse but with shorter retention time than the major DDM peak. To assess the oligomeric state negative stain electron microscopy was performed which showed a particle with the size of a PCFT dimer.

Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics.

Compensatory islet response is a distinct feature of the prediabetic insulin-resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from 5 month old male control, high-fat diet fed (HFD), or obese ob/ob mice by LC-MS/MS and quantified ~1100 islet proteins (at least two peptides) with a false discovery rate < 1%. Significant alterations in abundance were observed for ~350 proteins among groups. The majority of alterations were common to both models, and the changes of a subset of ~40 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and western blots, respectively. The insulin-resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin-resistant models. In summary, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin-resistant rodent models that are not overtly diabetic. These data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing ß-cell mass in patients with diabetes. The data are available via the MassIVE repository, under accession no. MSV000079093.

Characterizing morphological alterations in blood related disorders through Atomic Force Microscopy.

Atomic Force Microscopy (AFM) is a very flexible method that can create topographical images from a range of materials and image surfaces. Significantly, AFM has emerged as an invaluable tool for dissecting the morphology and biochemical aspects of body cells and tissues. The high-resolution imaging capabilities of AFM enable researchers to discern alterations in cell morphology and understand the underlying mechanisms of diseases. It contributes to understanding disease etiology and progression. In the context of this review, our focus will be directed towards elucidating the pivotal role of AFM in analysis of blood related disorders. Through detailed comparisons with normal cells, we delve into the alterations in size, shape, and surface characteristics induced by conditions such as cancer, diabetes, anaemia, and infections caused by pathogens. In essence, various work described in this article highlights to bridge the gap between traditional microscopy and in-depth analysis of blood-related pathologies, which in turn offers valuable perspectives for both research and clinical applications in the field.

Surface engineered nanohybrids in plasmonic photothermal therapy for cancer: Regulatory and translational challenges.

Plasmonic materials as non-invasive and selective treatment strategies are gaining increasing attention in the healthcare sector due to their remarkable optical and electronic properties, where the interface between matter and light becomes enhanced and highly localized. Some attractive applications of plasmonic materials in healthcare include drug delivery to target specific tissues or cells, hence reducing the side effects of the drug and improving their efficacy; enhancing the contrast and resolution in bioimaging; and selectively heating and destroying the cancerous cells while parting the healthy cells. Despite such advancements in photothermal therapy for cancer treatment, some limitations are still challenging. These include poor photothermal conversion efficiency, heat resistance, less accumulation in the tumor microenvironment, poor biosafety of photothermal agents, damage to the surrounding healthy tissues, post-treatment inflammatory responses, etc. Even though the clinical application of photothermal therapy is primarily restricted due to poor tissue penetration of excitation light, enzyme therapy is hindered due to less therapeutic efficacy. Several multimodal strategies, including chemotherapy, radiotherapy, photodynamic therapy, and immunotherapy were developed to circumvent these side effects associated with plasmonic photothermal agents for effective mild-temperature photothermal therapy. It can be prophesied that the nanohybrid platform could pave the way for developing cutting-edge multifunctional precise nanomedicine via an ecologically sustainable approach towards cancer therapy. In the present review, we have highlighted the significant challenges of photothermal therapy from the laboratory to the clinical setting and their struggle to get approval from the Food and Drug Administration (FDA).

What do healthy women know about the consequences of delayed childbearing?

Female fertility declines dramatically with age, and childbearing at older maternal ages has significant medical consequences for mother and infant that are well-known to health professionals. Despite this, the average maternal age in the United States continues to rise. Many factors likely contribute to this secular trend; to date, no research has examined whether American women are aware of the complications of deferring conception and how this correlates with health literacy. The purpose of this study was to evaluate women's knowledge of the implications of delaying pregnancy. A structured, in-person interview was administered to 300 women between 20 and 50 years of age attending 1 of 2 gynecologic clinics at a single institution. Demographic information, medical history, and gynecologic history were obtained; and participants answered questions about the implications of aging for fertility and pregnancy outcome. Health literacy and numeracy were assessed. Participants demonstrated knowledge deficits about the implications of aging on fertility and pregnancy, and many were unfamiliar with success rates of infertility treatments. Several demographic factors correlated with knowledge; health literacy and numeracy were both important predictive variables. To the authors' knowledge, this is the first study of women's knowledge about fertility, aging, and their health literacy. Awareness of the importance of health literacy and numeracy should inform future educational efforts about fertility.

Derivation of Breast Cancer Patient Derived Human Induced Pluripotent Stem Cell Line (YBLi006-A) with FANC-BRCA Gene Mutations: A Resource for Precision & Personalized Medicine.

Fanconi anemia complementation group I (FANCI) is located on the chromosome 15q26.1 locus and becomes ubiquitinated following DNA damage. 3.06% of patients with breast cancer have altered FANCI gene. We generated an iPSC line (YBLi006-A) from peripheral blood mononuclear cells (PBMCs) of a patient carrying a mutation in FANCIgene (NM_001376911.1, NM_001376910.1, NM_001113378.2; c.80G > T, c.257C > T, c.2225G > C; p.Gly27Val, p.Ala86Val, p.Cys742Ser) using non-integrating Sendai virus technology. This unique breast cancer patient-derived-iPSC line will be resourceful to analyze the entire coding sequence and splicing sites ofFANCIin high-risk familial breast cancer.

Preference Signaling for the Diagnostic Radiology Match: A Single Institution Experience.

The Association of American Medical Colleges announced the addition of preference signaling to the 2022-2023 residency match cycle for Diagnostic and Interventional Radiology. This new offering provided applicants the option to indicate their specific interest in up to 6 residency programs during initial application submission. Our institutional diagnostic radiology residency program received a total of 1294 applications. One hundred and eight applicants signaled the program. Interview invitations were sent to 104 applicants, 23 of which signaled the program. Out of the top 10 ranked applicants, 6 applicants signaled the program. Out of the 5 matched applicants, 80% used the program signal, and 100% did the geographic preference. Opting to signal programs during the initial application submission may be beneficial for both the applicants and the programs in finding the optimal match.

A pictorial review of ultrasonography of the FIGO classification for uterine leiomyomas.

Uterine leiomyomas are the most common gynecological and pelvic neoplasm, reported in up to 80 percent of women by age 50. While the majority are asymptomatic, uterine leiomyomas, depending on size, number, and location can result in bulk symptoms, abnormal uterine bleeding (AUB), infertility or recurrent pregnancy loss. Ultrasonography (USG) remains first-line for the diagnosis of leiomyomas and is the most appropriate imaging modality for the initial assessment of abnormal uterine bleeding. In an effort to standardize nomenclature and identify causes of AUB, the International Federation of Gynecology and Obstetrics (FIGO) developed a classification system based on the acronym PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified). For the L category of leiomyoma, when present, a secondary and tertiary subclassification system is described distinguishing submucosal masses from others and categorizing the relationship of the mass to the endometrium and serosa. With advancements in newer minimally to non-invasive techniques developed for the management of leiomyomas, uniform characterization, mapping, and classification of leiomyomas is necessary to decide the optimal therapeutic approach. While this classification system has recently been reviewed on MR, to our knowledge, it has not been reviewed on ultrasound in the radiology literature. We hereby present a pictorial review of USG images of all the FIGO categories of leiomyomas to provide a standard guide for radiology reporting.

Multimodality imaging of renal lymphoma and its mimics.

Lymphomatous involvement of the genitourinary system, particularly the kidneys, is commonly detected on autopsies; yet on conventional diagnostic imaging renal lymphoma is significantly underestimated and underreported, in part due to its variable imaging appearance and overlapping features with other conditions. We present a spectrum of typical and atypical appearances of renal lymphoma using multimodality imaging, while reviewing the roles of imaging in the detection, diagnosis, staging, and surveillance of patients with lymphoma. We also illustrate a breadth of benign and malignant entities with similar imaging features confounding the diagnosis of renal lymphoma, emphasizing the role of percutaneous image-guided biopsy. Understanding the spectrum of appearances of renal lymphoma and recognizing the overlapping entities will help radiologists improve diagnostic confidence and accuracy.

Resident Scholarly Activity for Diagnostic Radiology Residency - A Point System Approach.

Scholarly activity is an important aspect of diagnostic radiology residency training, however, there is no clear standard for what is expected and deemed appropriate for scholarly activity. This article discusses the rationale and development of a point system approach for resident scholarly activity at our diagnostic radiology residency program.

Reductions in anxiety, depression and insomnia in health care workers using a non-pharmaceutical intervention.

The COVID-19 pandemic has caused significant medical and psychological challenges worldwide, and not only exceeded the capacity of hospitals and intensive care units but also an individuals' ability to cope with life. Health-care workers have continued to provide care for patients despite exhaustion, fear of transmission to themselves and their family, illness or death of friends and colleagues, and losing many patients. They have also faced additional stress and anxiety due to long shifts combined with unprecedented population restrictions, including personal isolation. In this study, we study the effect of an app-based Yoga of Immortals (YOI) intervention on mental health of healthcare workers. In this study, the health care workers were digitally recruited, and their psychological parameters were measured using validated questionaries. The participants were randomly grouped into control and test groups. The validated psychological measures were the Patient Health Questionnaire-8 (PHQ-8), Insomnia Severity Index (ISI) and generalized anxiety disorder (GAD-7) scales. The digital YOI intervention significantly reduced the anxiety, depression symptoms, and insomnia in healthcare workers of all age groups. In contrast, there was no improvement in the control group. This study details the effectiveness of an app-based YOI intervention in healthcare workers.

Imaging features of solitary fibrous tumors.

OBJECTIVE: The goal of this pictorial essay is to illustrate the multimodality imaging features of pleural and extrapleural solitary fibrous tumors. CONCLUSION: Solitary fibrous tumors tend to be well-defined, ovoid, heterogeneously enhancing lesions. MRI characteristically depicts areas of low signal intensity that correspond to dense collagen. The findings of lesion multiplicity and hypermetabolism on PET images should raise the suspicion of malignancy.

Spontaneous intratesticular hemorrhage: two case descriptions and brief review of the literature.

Spontaneous intratesticular hemorrhage is an extremely rare entity with few prior reports in the literature. Although intratesticular hemorrhage in the setting of trauma or malignancy is common, spontaneous intratesticular hemorrhage has no identifiable risk factors. The sonographic appearance of spontaneous intratesticular hemorrhage poses a diagnostic dilemma because of its similarity to testicular malignancy. We present 2 cases of spontaneous intratesticular hemorrhage that were confirmed after unilateral orchiectomy and histologic examination.