What Is Actually Affected by the Scrambling of Objects When Localizing the Lateral Occipital Complex?

The lateral occipital complex (LOC), the cortical region critical for shape perception, is localized with fMRI by its greater BOLD activity when viewing intact objects compared with their scrambled versions (resembling texture). Despite hundreds of studies investigating LOC, what the LOC localizer accomplishes-beyond distinguishing shape from texture-has never been resolved. By independently scattering the intact parts of objects, the axis structure defining the relations between parts was no longer defined. This led to a diminished BOLD response, despite the increase in the number of independent entities (the parts) produced by the scattering, thus indicating that LOC specifies interpart relations, in addition to specifying the shape of the parts themselves. LOC's sensitivity to relations is not confined to those between parts but is also readily apparent between objects, rendering it-and not subsequent "place" areas-as the critical region for the representation of scenes. Moreover, that these effects are witnessed with novel as well as familiar intact objects and scenes suggests that the relations are computed on the fly, rather than being retrieved from memory.

The Lateral Occipital Complex shows no net response to object familiarity.

In 1995, Malach et al. discovered an area whose fMRI BOLD response was greater when viewing intact, familiar objects than when viewing their scrambled versions (resembling texture). Since then hundreds of studies have explored this late visual region termed the Lateral Occipital Complex (LOC), which is now known to be critical for shape perception (James, Culham, Humphrey, Milner, & Goodale, 2003). Malach et al. (1995) discounted a role of familiarity by showing that "abstract" Henry Moore sculptures, unfamiliar to the subjects, also activated this region. This characterization of LOC as a region that responds to shape independently of familiarity has been accepted but never tested with control of the same low-level features. We assessed LOC's response to objects that had identical parts in two different arrangements, one familiar and the other novel. Malach was correct: There is no net effect of familiarity in LOC. However, a multivoxel correlation analysis showed that LOC does distinguish familiar from novel objects.

A neurocomputational account of the face configural effect.

A striking phenomenon in face perception is the configural effect in which a difference in a single part appears more distinct in the context of a face than it does by itself. The face context would be expected to increase search complexity, rendering discrimination more--not less--difficult. Remarkably, there has never been a biologically plausible explanation of this fundamental signature of face recognition.We show that the configural effect can be simply derived from a model composed of overlapping receptive fields (RFs) characteristic of early cortical simple-cell tuning but also present in face-selective areas. Because of the overlap in RFs, the difference in a single part is not only represented in the RFs centered on it but also propagated to larger RFs centered on distant parts of the face. Dissimilarity values computed from the model between pairs of faces and pairs of face parts closely matched the recognition accuracy of human observers who had learned a set of faces composed of composite parts and were tested on wholes (Which is Larry?) and parts (Which is Larry's nose?). When stimuli were high versus low passed the contributions of different spatial frequency (SF) bands to the configural effect were largely comparable. Therefore, it was the larger RFs rather than the low SFs that accounted for most of the configural effect. The representation explains why, relative to objects, face recognition is so adversely affected by inversion and contrast reversal and why distinctions between similar faces are ineffable.

Patient-reported distress at a cancer center during the COVID-19 pandemic.

Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.

Targeting Acquired and Intrinsic Resistance Mechanisms in Epidermal Growth Factor Receptor Mutant Non-Small-Cell Lung Cancer.

Over the past 2 decades, rapid advances in molecular profiling and the development of targeted therapies have dramatically improved the clinical course of advanced non-small-cell lung cancer (NSCLC). Mutations in the epidermal growth factor receptor (EGFR) gene are found in about a third of patients with advanced NSCLC, and the approval of first-generation EGFR targeted kinase inhibitors significantly improved survival when compared with platinum-based doublet chemotherapy (PBC), the previous standard of care. Inevitably, selective pressure from first-generation EGFR inhibitors led to acquired resistance mechanisms, such as the T790M mutation. The advent of third-generation EGFR inhibitors (e.g., osimertinib) successfully overcame the T790M resistance mechanism, and osimertinib subsequently became the first-line therapy for EGFR mutant NSCLC. Currently, research in EGFR mutant NSCLC is primarily focused on targeting resistance mechanisms to osimertinib. Over the past several years, many important acquired and intrinsic mechanisms of resistance to osimertinib have been identified. Acquired resistance mechanisms include C797X, mesenchymal epithelial transition factor (MET) amplification, HER2/HER3 amplification, phosphoinositide 3-kinase (PI3K) pathway mutations, RAS/mitogen-activated protein kinase (MAPK) pathway mutations, cell-cycle gene alterations, oncogenic fusions, and histologic transformations. An important intrinsic resistance mechanism to osimertinib is the EGFR exon 20 insertion mutation, which is sensitive to the newly Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor mobocertinib and the EGFR/MET bispecific antibody amivantamab. This review article aims to (1) summarize the advances in the treatment of EGFR mutant NSCLC, (2) delineate known resistance mechanisms to the current first-line therapy, osimertinib, and (3) describe the development of targeted drugs that aim to overcome these resistance mechanisms.

EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy.

INTRODUCTION: In classical EGFR mutant non-small-cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitor (TKI) therapy yields better outcomes than platinum-based chemotherapy. However, EGFR exon 20 insertion (ex20ins) NSCLC is relatively resistant to currently available EGFR TKIs. Though platinum-based chemotherapy is the frontline standard of care for EGFR ex20ins NSCLC, its efficacy is not fully described. STUDY DESIGN: A retrospective, single-center, case series METHODS: Patients were identified through an electronic research database at a single institution and included if they had advanced EGFR ex20ins NSCLC, received platinum-based chemotherapy for metastatic disease, and had scans evaluable for response. Each patient's demographics, tumor characteristics, and clinical course were recorded. Treatment response was evaluated using RECIST v1.1 criteria, and the PFS was calculated by the Kaplan-Meier method. RESULTS: Among 27 patients identified with EGFR ex20ins NSCLC at our institution, 18 (67%) received platinum-based chemotherapy for metastatic disease and had scans evaluable for response. These patients received platinum-based chemotherapy in the first-line (N = 17, 94%) and second-line settings (N = 1, 6%). The objective response rate (ORR) to platinum-based chemotherapy was 39% (7 of 18 patients; 95% confidence interval [CI] 16-61). The median PFS with platinum-based chemotherapy was 7.1 months (95% CI, 6.3 -13.7), and the median overall survival was 3.2 years (95% CI, 1.92 - NR). CONCLUSIONS: The efficacy of platinum-based chemotherapy in EGFR ex20ins NSCLC is similar to that expected for TKI sensitive EGFR mutant NSCLC. Novel agents designed to specifically target ex20ins mutant EGFR should additionally improve outcomes.

Relative Impact of Anticancer Therapy on Unplanned Hospital Care in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: In lung cancer, unplanned hospital care is a significant driver of costs. While toxicities of cancer therapies are well-known, there are little data on their relative contribution to unplanned care. This study aims to (1) determine the relative impact of tyrosine-kinase inhibitor (TKI) therapy, immune checkpoint inhibitor immunotherapy, and cytotoxic chemotherapy on unplanned hospital care and (2) identify potential strategies to prevent unplanned hospital encounters in patients with non-small-cell lung cancer (NSCLC). METHODS: A research database search of the electronic health record was used to identify 97 patients with established NSCLC who were undergoing either TKI therapy, immunotherapy, or chemotherapy at our institution and visited our emergency department (ED) in 2018. The resulting 173 ED encounters were reviewed to determine (1) the cause (cancer, therapy, other, or rule-out) of each encounter and (2) whether the encounter was preventable. RESULTS: A small portion (9%) of all unplanned hospital encounters were therapy related (2% in the TKI therapy group, 12% in the immunotherapy group, and 21% in the chemotherapy group). Cancer itself was the leading cause (54%) of the encounters. Over 20% of all encounters were classified as preventable, and half of those encounters were deemed unnecessary. DISCUSSION: TKI therapy, immunotherapy, and, to a lesser extent, chemotherapy are relatively small drivers of unplanned acute hospital care for patients with NSCLC. A significant share of unplanned hospital encounters may be prevented through proactive evidence-based initiatives.

Student-Written Multiple-Choice Questions-a Practical and Educational Approach.

The purpose of our student-led project was to fulfill junior medical students' demand for instructive, curriculum-specific practice questions while providing a learning experience and teaching opportunity for participating senior students. Eleven second-year students were taught how to write high-quality multiple-choice questions through an interactive workshop. Subsequently, they were instructed to write questions with detailed explanations for their assigned lecture topics. Thirty-four student-written and faculty-reviewed questions were combined with 16 purely faculty-written questions to create a 50-question exam. No significant difference was found in question difficulty between the student-written (79.5%) and faculty-written (84.0%) questions (p = 0.37). The discrimination index and point biserial correlation were higher for student-written (0.29, 0.32) vs. faculty-written (0.17, 0.25) questions (p < .01, < .05). The test-takers learned key course topics, while the test-writers reviewed key first-year objectives and refined their test-taking strategies. The project provided a model for feasibly developing comprehensive, high-quality, and curriculum-specific questions.

Greater sensitivity to nonaccidental than metric shape properties in preschool children.

Nonaccidental properties (NAPs) are image properties that are invariant over orientation in depth and allow facile recognition of objects at varied orientations. NAPs are distinguished from metric properties (MPs) that generally vary continuously with changes in orientation in depth. While a number of studies have demonstrated greater sensitivity to NAPs in human adults, pigeons, and macaque IT cells, the few studies that investigated sensitivities in preschool children did not find significantly greater sensitivity to NAPs. However, these studies did not provide a principled measure of the physical image differences for the MP and NAP variations. We assessed sensitivity to NAP vs. MP differences in a nonmatch-to-sample task in which 14 preschool children were instructed to choose which of two shapes was different from a sample shape in a triangular display. Importantly, we scaled the shape differences so that MP and NAP differences were roughly equal (although the MP differences were slightly larger), using the Gabor-Jet model of V1 similarity (Lades & et al., 1993). Mean reaction times (RTs) for every child were shorter when the target shape differed from the sample in a NAP than an MP. The results suggest that preschoolers, like adults, are more sensitive to NAPs, which could explain their ability to rapidly learn new objects, even without observing them from every possible orientation.