Transparency of Results Reporting in Cancer Clinical Trials.

This cross-sectional study investigates rates of results reporting among oncology clinical trials across trial registries, medical journals, and medical conferences.

Drug Repurposing During The COVID-19 Pandemic: Lessons For Expediting Drug Development And Access.

The COVID-19 pandemic created a large, sudden unmet public health need for rapid access to safe and effective treatments. Against this backdrop, policy makers and researchers have looked to drug repurposing-using a drug previously approved for one indication to target a new indication-as a means to accelerate the identification and development of COVID-19 treatments. Using detailed data on US clinical trials initiated during the pandemic, we examined the trajectory and sources of drug repurposing initiatives for COVID-19. We found a rapid increase in repurposing efforts at the start of the pandemic, followed by a transition to greater de novo drug development. The drugs tested for repurposing treat a wide range of indications but were typically initially approved for other infectious diseases. Finally, we documented substantial variation by trial sponsor (academic, industry, or government) and generic status: Industry sponsorship for repurposing occurred much less frequently for drugs with generic competitors already on the market. Our findings inform drug repurposing policy for both future emerging diseases and drug development in general.

COVID fog demystified.

Acute mild respiratory SARS-CoV-2 infection can lead to a more chronic cognitive syndrome known as "COVID fog." New findings from Fernández-Castañeda et al. reveal how glial dysregulation and consequent neural circuit dysfunction may contribute to cognitive impairments in long COVID.

Regionally defined proteomic profiles of human cerebral tissue and organoids reveal conserved molecular modules of neurodevelopment.

Cerebral organoids have emerged as robust models for neurodevelopmental and pathological processes, as well as a powerful discovery platform for less-characterized neurobiological programs. Toward this prospect, we leverage mass-spectrometry-based proteomics to molecularly profile precursor and neuronal compartments of both human-derived organoids and mid-gestation fetal brain tissue to define overlapping programs. Our analysis includes recovery of precursor-enriched transcriptional regulatory proteins not found to be differentially expressed in previous transcriptomic datasets. To highlight the discovery potential of this resource, we show that RUVBL2 is preferentially expressed in the SOX2-positive compartment of organoids and that chemical inactivation leads to precursor cell displacement and apoptosis. To explore clinicopathological correlates of this cytoarchitectural disruption, we interrogate clinical datasets and identify rare de novo genetic variants involving RUVBL2 in patients with neurodevelopmental impairments. Together, our findings demonstrate how cell-type-specific profiling of organoids can help nominate previously unappreciated genes in neurodevelopment and disease.

Three-dimensional modeling of human neurodegeneration: brain organoids coming of age.

The prevalence of dementia and other neurodegenerative diseases is rapidly increasing in aging nations. These relentless and progressive diseases remain largely without disease-modifying treatments despite decades of research and investments. It is becoming clear that traditional two-dimensional culture and animal model systems, while providing valuable insights on the major pathophysiological pathways associated with these diseases, have not translated well to patients' bedside. Fortunately, the advent of induced-pluripotent stem cells and three-dimensional cell culture now provide tools that are revolutionizing the study of human diseases by permitting analysis of patient-derived human tissue with non-invasive procedures. Specifically, brain organoids, self-organizing neural structures that can mimic human fetal brain development, have now been harnessed to develop alternative models of Alzheimer's disease, Parkinson's disease, motor neuron disease, and Frontotemporal dementia by recapitulating important neuropathological hallmarks found in these disorders. Despite these early breakthroughs, several limitations need to be vetted in brain organoid models in order to more faithfully match human tissue qualities, including relative tissue immaturity, lack of vascularization and incomplete cellular diversity found in this culture system. Here, we review current brain organoid protocols, the pathophysiology of neurodegenerative disorders, and early studies with brain organoid neurodegeneration models. We then discuss the multiple engineering and conceptual challenges surrounding their use and provide possible solutions and exciting avenues to be pursued. Altogether, we believe that brain organoids models, improved with classical and emerging molecular and analytic tools, have the potential to unravel the opaque pathophysiological mechanisms of neurodegeneration and devise novel treatments for an array of neurodegenerative disorders.

Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry.

Molecular characterization of diffuse gliomas has thus far largely focused on genomic and transcriptomic interrogations. Here, we utilized mass spectrometry and overlay protein-level information onto genomically defined cohorts of diffuse gliomas to improve our downstream molecular understanding of these lethal malignancies. Bulk and macrodissected tissues were utilized to quantitate 5,496 unique proteins over three glioma cohorts subclassified largely based on their IDH and 1p19q codeletion status (IDH wild type (IDHwt), n = 7; IDH mutated (IDHmt), 1p19q non-codeleted, n = 7; IDH mutated, 1p19q-codeleted, n = 10). Clustering analysis highlighted proteome and systems-level pathway differences in gliomas according to IDH and 1p19q-codeletion status, including 287 differentially abundant proteins in macrodissection-enriched tumor specimens. IDHwt tumors were enriched for proteins involved in invasiveness and epithelial to mesenchymal transition (EMT), while IDHmt gliomas had increased abundances of proteins involved in mRNA splicing. Finally, these abundance changes were compared with IDH-matched GBM stem-like cells (GSCs) to better pinpoint protein patterns enriched in putative cellular drivers of gliomas. Using this integrative approach, we outline specific proteins involved in chloride transport (e.g. chloride intracellular channel 1, CLIC1) and EMT (e.g. procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, PLOD3, and serpin peptidase inhibitor clade H member 1, SERPINH1) that showed concordant IDH-status-dependent abundance differences in both primary tissue and purified GSC cultures. Given the downstream position proteins occupy in driving biology and phenotype, understanding the proteomic patterns operational in distinct glioma subtypes could help propose more specific, personalized, and effective targets for the management of patients with these aggressive malignancies.

Proteomic analysis of meningiomas reveals clinically distinct molecular patterns.

BACKGROUND: Meningiomas represent one of the most common brain tumors and exhibit a clinically heterogeneous behavior, sometimes difficult to predict with classic histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored. METHODS: We utilize liquid chromatography tandem mass spectrometry with an Orbitrap mass analyzer to quantify global protein abundances of a clinically well-annotated formalin-fixed paraffin embedded (FFPE) cohort (n = 61) of meningiomas spanning all World Health Organization (WHO) grades and various degrees of clinical aggressiveness. RESULTS: In total, we quantify 3042 unique proteins comparing patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n = 106 proteins, Welch's t-test, P < 0.01) and pathway-level (eg, Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (grade I) and atypical/malignant (grades II‒III) meningiomas with specific oncogenes enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas that rapidly recurred (<3 y) had distinctive protein patterns converging on mRNA processing and impaired activation of the matrisome complex. Larger sized meningiomas (>3 cm maximum tumor diameter) and those with previous radiation exposure revealed perturbed pro-proliferative (eg, epidermal growth factor receptor) and metabolic as well as inflammatory response pathways (mitochondrial activity, interferon), respectively. CONCLUSIONS: Our proteomic study demonstrates that meningiomas of different grades and clinical parameters present distinct proteomic profiles. These proteomic variations offer potential future utility in helping better predict patient outcome and in nominating novel therapeutic targets for personalized care.

Food insecurity, mental distress and suicidal ideation in rural Africa: Evidence from Nigeria, Uganda and Ghana.

BACKGROUND: In sub-Saharan Africa, mental and substance-related disorders account for 19% of all years lived with disability, yet the intersection between poverty and mental distress is poorly understood since most psychiatric research is conducted in high-income countries. AIMS: To examine the prevalence of and associations between food insecurity, mental distress and suicidal ideation in three rural village clusters in sub-Saharan Africa. METHOD: Cross-sectional multivariate analysis of sociodemographic variables associated with mental distress and suicidal ideation in three countries. The sample included 1,142 individuals from three rural village clusters in Nigeria ( n = 380), Uganda ( n = 380) and Ghana ( n = 382). Food insecurity was measured based on the number of months in the previous year that the respondent's family reported being 'unable to eat two square meals per day'. Mental distress was assessed using the Kessler non-specific psychological distress scale (K6) and suicidal ideation was measured using an item from PRIME-MD. Other sociodemographic variables included gender, age, literacy and occupation. RESULTS: The prevalence of individuals with moderate or severe mental distress in Nigeria, Uganda and Ghana were higher than previously reported in the literature: 35.5%, 30.8% and 30.4%, respectively, and suicidal ideation rates were 29.7%, 21.3% and 10.9%. No differences were observed in mental distress between men and women in any of the sites. Being a farmer (vs student or other) was protective for mental distress in two sites (Uganda and Ghana) but no other social indicators, such as age, gender, literacy and food insecurity, were significantly associated with mental distress. Risk for suicidal ideation differed across sites: it was associated with food insecurity in Nigeria, female gender in Uganda, and older age in Uganda. CONCLUSIONS: Mental distress and suicidal ideation were highly prevalent in three settings of extreme poverty across all groups, in ways that were not always consistent with the global literature. These findings suggest that more research is needed in to better understand the social etiology of mental distress in sub-Saharan Africa.

STAT3 signaling stimulates miR-21 expression in bovine cumulus cells during in vitro oocyte maturation.

MicroRNAs are potent regulators of gene expression that have been widely implicated in reproduction and embryo development. Recent studies have demonstrated that miR-21, a microRNA extensively studied in the context of disease, is important in multiple facets of reproductive biology including folliculogenesis, ovulation, oocyte maturation and early mammalian development. Surprisingly, little is known about the mechanisms that regulate miR-21 and no studies have characterized these regulatory pathways in cumulus-oocyte complexes (COCs). We therefore investigated miR-21 in an in vitro model of bovine oocyte maturation. Levels of the primary transcript of miR-21 (pri-miR-21) and mature miR-21 increased markedly in COCs over the maturation period. Cloning of the bovine pri-miR-21 gene and promoter by 5'3'RACE (rapid amplification of cDNA ends) revealed a highly conserved region immediately upstream of the transcription start site and two alternatively-spliced variants of pri-miR-21. The promoter region contained several putative transcription factor binding sites, including two for signal transducer and activator of transcription 3 (STAT3). Mutation of these sites significantly decreased both the intrinsic activity of pri-miR-21 promoter-luciferase constructs and the response to leukemia inhibitory factor (LIF) (a STAT3 activator) in cultured MCF7 cells. In COCs, treatment with a STAT3 pathway inhibitor markedly decreased pri-miR-21 expression and prevented cumulus expansion. Pri-miR-21 expression was also inhibited by the protein synthesis inhibitor cycloheximide, suggesting that a protein ligand or signaling cofactor synthesized during maturation is necessary for transcription. Together these studies represent the first investigation of signaling pathways that directly influence miR-21 expression in bovine oocytes and cumulus cells.

Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay.

We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations. Cellular heterogeneity in 3D genome organization allowed unequivocal identification of RDCs on 14 different chromosomes using HTGTS baits on three mouse chromosomes. Additional candidate RDCs were also implicated, however, suggesting that some RDCs were missed. To more completely identify RDCs, we exploited our finding that joining of two DSBs occurs more frequently if they lie on the same cis chromosome. Thus, we used CRISPR/Cas9 to introduce specific DSBs into each mouse chromosome in NSPCs that were used as bait for HTGTS libraries. This analysis confirmed all 27 previously identified RDCs and identified many new ones. NSPC RDCs fall into three groups based on length, organization, transcription level, and replication timing of genes within them. While mostly less robust, the largest group of newly defined RDCs share many intriguing characteristics with the original 27. Our findings also revealed RDCs in NSPCs in the absence of induced replication stress, and support the idea that the latter treatment augments an already active endogenous process.

DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions.

Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical nonhomologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining that is more biased to use longer junctional microhomologies (MHs). Deficiency for DSB response (DSBR) factors, including ataxia telangiectasia-mutated (ATM) and 53BP1, variably impair CSR end-joining, with 53BP1 deficiency having the greatest impact. However, studies of potential impact of DSBR factor deficiencies on MH-mediated CSR end-joining have been technically limited. We now use a robust DSB joining assay to elucidate impacts of deficiencies for DSBR factors on CSR and chromosomal translocation junctions in primary mouse B cells and CH12F3 B-lymphoma cells. Compared with wild-type, CSR and c-myc to S region translocation junctions in the absence of 53BP1, and, to a lesser extent, other DSBR factors, have increased MH utilization; indeed, 53BP1-deficient MH profiles resemble those associated with C-NHEJ deficiency. However, translocation junctions between c-myc DSB and general DSBs genome-wide are not MH-biased in ATM-deficient versus wild-type CH12F3 cells and are less biased in 53BP1- and C-NHEJ-deficient cells than CSR junctions or c-myc to S region translocation junctions. We discuss potential roles of DSBR factors in suppressing increased MH-mediated DSB end-joining and features of S regions that may render their DSBs prone to MH-biased end-joining in the absence of DSBR factors.

Interpersonal psychotherapy (IPT) for major depression following perinatal loss: a pilot randomized controlled trial.

This randomized controlled pilot trial examined the feasibility, acceptability, and preliminary efficacy of an adapted interpersonal psychotherapy (IPT) for major depressive disorder (MDD) following perinatal loss (miscarriage, stillbirth, or early neonatal death). Fifty women who experienced a perinatal loss within the past 18 months, whose current depressive episode onset occurred during or after the loss, were randomized to the group IPT adapted for perinatal loss (the Group IPT for Major Depression Following Perinatal Loss manual developed for this study is available at no cost by contacting either of the first two authors) or to the group Coping with Depression (CWD), a cognitive behavioral treatment which did not focus on perinatal loss nor social support. Assessments occurred at baseline, treatment weeks 4 and 8, post-treatment, and 3 and 6 months after the end of treatment. IPT was feasible and acceptable in this population. Although some participants were initially hesitant to discuss their losses in a group (as occurred in IPT but not CWD), end of treatment satisfaction scores were significantly (p = 0.001) higher in IPT than in CWD. Confidence intervals around between-groups effect sizes favored IPT for reductions in depressive symptoms during treatment as well as for improvement in mode-specific targets (social support, grief symptoms) and recovery from a post-traumatic stress disorder over follow-up. This group IPT treatment adapted for MDD after perinatal loss is feasible, acceptable, and possibly efficacious.

Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells.

High-throughput, genome-wide translocation sequencing (HTGTS) studies of activated B cells have revealed that DNA double-strand breaks (DSBs) capable of translocating to defined bait DSBs are enriched around the transcription start sites (TSSs) of active genes. We used the HTGTS approach to investigate whether a similar phenomenon occurs in primary neural stem/progenitor cells (NSPCs). We report that breakpoint junctions indeed are enriched around TSSs that were determined to be active by global run-on sequencing analyses of NSPCs. Comparative analyses of transcription profiles in NSPCs and B cells revealed that the great majority of TSS-proximal junctions occurred in genes commonly expressed in both cell types, possibly because this common set has higher transcription levels on average than genes transcribed in only one or the other cell type. In the latter context, among all actively transcribed genes containing translocation junctions in NSPCs, those with junctions located within 2 kb of the TSS show a significantly higher transcription rate on average than genes with junctions in the gene body located at distances greater than 2 kb from the TSS. Finally, analysis of repair junction signatures of TSS-associated translocations in wild-type versus classical nonhomologous end-joining (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alternative end-joining pathways can generate translocations by joining TSS-proximal DSBs to DSBs on other chromosomes. Our studies show that the generation of transcription-associated DSBs is conserved across divergent cell types.

Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells.

Repair of DNA double-strand breaks (DSBs) by non-homologous end joining is critical for neural development, and brain cells frequently contain somatic genomic variations that might involve DSB intermediates. We now use an unbiased, high-throughput approach to identify genomic regions harboring recurrent DSBs in primary neural stem/progenitor cells (NSPCs). We identify 27 recurrent DSB clusters (RDCs), and remarkably, all occur within gene bodies. Most of these NSPC RDCs were detected only upon mild, aphidicolin-induced replication stress, providing a nucleotide-resolution view of replication-associated genomic fragile sites. The vast majority of RDCs occur in long, transcribed, and late-replicating genes. Moreover, almost 90% of identified RDC-containing genes are involved in synapse function and/or neural cell adhesion, with a substantial fraction also implicated in tumor suppression and/or mental disorders. Our characterization of NSPC RDCs reveals a basis of gene fragility and suggests potential impacts of DNA breaks on neurodevelopment and neural functions.

A respiratory chain controlled signal transduction cascade in the mitochondrial intermembrane space mediates hydrogen peroxide signaling.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases and many other signaling molecules through oxidation of critical cysteine residues, which led to the notion that initiation of ROS signaling is broad and nonspecific, and thus fundamentally distinct from other signaling pathways. Here, we report that H2O2 signaling bears hallmarks of a regular signal transduction cascade. It is controlled by hierarchical signaling events resulting in a focused response as the results place the mitochondrial respiratory chain upstream of tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk), and Syk upstream of numerous targets involved in signaling, transcription, translation, metabolism, and cell cycle regulation. The active mediators of H2O2 signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial intermembrane space. Finally, the same intermediaries control the signaling response in tissues and species responsive to H2O2 as the respiratory chain, Lyn, and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts, and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is coexpressed across tissues, is of early metazoan origin, and displays evidence of evolutionary constraint in the human. These results suggest that H2O2 signaling is under control of a signal transduction pathway that links the respiratory chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient Syk pathway in hematopoietic and nonhematopoietic cells.

The Positive Effect of a Group Intervention to Reduce Postpartum Depression on Breastfeeding Outcomes in Low-Income Women.

This study examined, as a secondary analysis, whether a group interpersonal psychotherapy (IPT) intervention focused on preventing postpartum depression by strengthening social support and building interpersonal skills during the transition to motherhood positively affected breastfeeding outcomes among low-income women. The intervention-Reach Out, Stand strong, Essentials for new mothers (ROSE)-taught participants the importance of self-care and assertive help seeking to be better able to sustain breastfeeding practices. Ninety-nine pregnant women were randomized to ROSE plus standard care or to standard care alone. Though women in both conditions had similar breastfeeding initiation rates, women in ROSE had longer breastfeeding duration (median days breastfed: 54 vs. 21). Results suggest ROSE may positively affect breastfeeding.

Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients.

BACKGROUND: Pretreatment evaluation of axillary lymph nodes (ALNs) and marking of biopsied nodes in patients with newly diagnosed breast cancer is becoming routine practice. We sought to test tattooing of biopsied ALNs with a sterile black carbon suspension (Spot™). The intraoperative success of identifying tattooed ALNs and their concordance to sentinel nodes was determined. METHODS: Women with suspicious ALNs and newly diagnosed breast cancer underwent palpation and/or ultrasound-guided fine needle aspiration or core needle biopsy, followed by injection of 0.1 to 0.5 ml of Spot™ ink into the cortex of ALNs and adjacent soft tissue. Group I underwent surgery first, and group II underwent neoadjuvant therapy followed by surgery. Identification of black pigment and concordance between sentinel and tattooed nodes was evaluated. RESULTS: Twenty-eight patients were tattooed, 16 in group I and 12 in group II. Seventeen cases had evidence of atypia or metastases, 8 (50 %) in group I and 9 (75 %) in group II. Average number of days from tattooing to surgery was 22.9 (group I) and 130 (group II). Black tattoo ink was visualized intraoperatively in all cases, except one case with microscopic black pigment only. Fourteen group I and 10 group II patients had black pigment on histological examination of ALNs. Sentinel nodes corresponded to tattooed nodes in all except one group I patient with a tattooed non-sentinel node. CONCLUSION: Tattooed nodes are visible intraoperatively, even months later. This approach obviates the need for additional localization procedures during axillary staging.

Rim sign in breast lesions on diffusion-weighted magnetic resonance imaging: diagnostic accuracy and clinical usefulness.

PURPOSE: To investigate the diagnostic accuracy and clinical usefulness of the rim sign in breast lesions observed in diffusion-weighted magnetic resonance imaging (DWI). MATERIALS AND METHODS: The magnetic resonance imaging (MRI) findings of 98 pathologically confirmed lesions (62 malignant and 36 benign) in 84 patients were included. Five breast radiologists were asked to independently review the breast MRI results, to grade the degree of high peripheral signal, the "rim sign," in the DWI, and to confirm the mean apparent diffusion coefficient (ADCmean ) values. We analyzed the diagnostic accuracy and compared the consensus (when ≥ 4 of 5 independent reviewers agreed) results of the rim sign with the ADCmean values. Additionally, we evaluated the correlation between the dynamic contrast-enhanced (DCE)-MRI morphologic appearance and DWI rim sign. RESULTS: According to the consensus results, the rim sign in DWI was observed on 59.7% of malignant lesions and 19.4% of benign lesions. The sensitivity, specificity, and area under the curve (AUC) value for the rim sign in DWI were 59.7%, 80.6%, and 0.701, respectively. The sensitivity, specificity, and AUC value for the ADCmean value (criteria ≤ 1.46 × 10(-3) mm(2) /sec) were 82.3%, 63.9%, and 0.731, respectively. Based on consensus, no correlation was observed between the DCE-MRI and DWI rim signs. CONCLUSION: In DWI, a high-signal rim is a valuable morphological feature for improving specificity in DWI.

3D T2-weighted spin echo imaging in the breast.

PURPOSE: To evaluate the performance of 2D versus 3D T2-weighted spin echo imaging in the breast. MATERIALS AND METHODS: 2D and 3D T2-weighted images were acquired in 25 patients as part of a clinically indicated breast magnetic resonance imaging (MRI) exam. Lesion-to-fibroglandular tissue signal ratio was measured in 16 identified lesions. Clarity of lesion morphology was assessed through a blinded review by three radiologists. Instances demonstrating the potential diagnostic contribution of 3D versus 2D T2-weighted imaging in the breast were noted through unblinded review by a fourth radiologist. RESULTS: The lesion-to-fibroglandular tissue signal ratio was well correlated between 2D and 3D T2-weighted images (R(2) = 0.93). Clarity of lesion morphology was significantly better with 3D T2-weighted imaging for all observers based on a McNemar test (P ≤ 0.02, P ≤ 0.01, P ≤ 0.03). Instances indicating the potential diagnostic contribution of 3D T2-weighted imaging included improved depiction of signal intensity and improved alignment between DCE and T2-weighted findings. CONCLUSION: In this pilot study, 3D T2-weighted imaging provided comparable contrast and improved depiction of lesion morphology in the breast in comparison to 2D T2-weighted imaging. Based on these results further investigation to determine the diagnostic impact of 3D T2-weighted imaging in breast MRI is warranted.