Effects of conflicting emotional cues on toddlers' emotion perception.

The communication of emotion is dynamic and occurs across multiple channels, such as facial expression and tone of voice. When cues are in conflict, interpreting emotion can become challenging. Here, we examined the effects of incongruent emotional cues on toddlers' interpretation of emotions. We presented 33 children (22-26 months, Mage = 23.8 months, 15 female) with side-by-side images of faces along with sentences spoken in a tone of voice that conflicted with semantic content. One of the two faces matched the emotional tone of the audio, whereas the other matched the semantic content. For both congruent and incongruent trials, toddlers showed no overall looking preference to either type of face stimuli. However, during the second exposure to the sentences of incongruent trials, older children tended to look longer to the face matching semantic content when listening to happy vs. angry content. Results inform our understanding of the early development of complex emotion understanding.

Stat5 induces androgen receptor (AR) gene transcription in prostate cancer and offers a druggable pathway to target AR signaling.

Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regulated Stat5-inducible genes as well as AR and AR-regulated genes and suppressed PC growth. This work introduces the concept of Stat5 as an inducer of AR gene transcription in PC. Pharmacological Stat5 inhibitors may represent a new strategy for suppressing AR and CRPC growth.

Unraveling the complex relationship between mRNA and protein abundances: a machine learning-based approach for imputing protein levels from RNA-seq data.

The correlation between messenger RNA (mRNA) and protein abundances has long been debated. RNA sequencing (RNA-seq), a high-throughput, commonly used method for analyzing transcriptional dynamics, leaves questions about whether we can translate RNA-seq-identified gene signatures directly to protein changes. In this study, we utilized a set of 17 widely assessed immune and wound healing mediators in the context of canine volumetric muscle loss to investigate the correlation of mRNA and protein abundances. Our data reveal an overall agreement between mRNA and protein levels on these 17 mediators when examining samples from the same experimental condition (e.g. the same biopsy). However, we observed a lack of correlation between mRNA and protein levels for individual genes under different conditions, underscoring the challenges in converting transcriptional changes into protein changes. To address this discrepancy, we developed a machine learning model to predict protein abundances from RNA-seq data, achieving high accuracy. Our approach also effectively corrected multiple extreme outliers measured by antibody-based protein assays. Additionally, this model has the potential to detect post-translational modification events, as shown by accurately estimating activated transforming growth factor ß1 levels. This study presents a promising approach for converting RNA-seq data into protein abundance and its biological significance.

Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions.

The multi-target stool DNA (mt-sDNA) test screens for colorectal cancer by analyzing DNA methylation/mutation and hemoglobin markers to algorithmically derive a qualitative result. A new panel of highly discriminant candidate methylated DNA markers (MDM) was recently developed. Performance of the novel MDM panel, with hemoglobin, was evaluated in a simulated screening population using archived stool samples weighted to early-stage colorectal cancer and prospectively collected advanced precancerous lesions (APL). Marker selection study (MSS) and separate preliminary independent verification studies (VS) were conducted utilizing samples from multi-center, case-control studies. Sample processing included targeted MDM capture, bisulfite conversion, and MDM quantitation. Fecal hemoglobin was quantified using ELISA. Samples were stratified into 75%/25% training-testing sets; model outcomes were cross-validated 1,000 times. All laboratory operators were blinded. The MSS included 232 cases (120 colorectal cancer/112 APLs) and 490 controls. The VS featured 210 cases (112 colorectal cancer/98 APLs) and 567 controls; APLs were 86.7% adenomas and 13.3% sessile serrated lesions (SSL). Average age was 65.5 (cases) and 63.2 (controls) years. Mean sensitivity in the VS from cross-validation was 95.2% for colorectal cancer and 57.2% for APLs, with specificities of 89.8% (no CRC/APLs) and 92.4% (no neoplasia). Subgroup analyses showed colorectal cancer sensitivities of 93.4% (stage I) and 94.2% (stage II). APL sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSLs. These data support high sensitivity and specificity for a next-generation mt-sDNA test panel. Further evaluation of assay performance will be characterized in a prospective, multi-center clinical validation study (NCT04144738). PREVENTION RELEVANCE: This study highlights performance of the next-generation mt-sDNA test, which exhibits high sensitivity and specificity for detecting colorectal cancer and APLs. This noninvasive option has potential to increase screening participation and clinical outcomes. A multi-center, clinical validation trial is underway. See related commentary by Bresalier, p. 93.

Is chest imaging needed as part of pT1a renal cell carcinoma surveillance after surgical resection?

INTRODUCTION: Following surgical excision of pT1a renal cell carcinoma (RCC), 2% to 5% will recur, with 50% to 60% being lung metastases. The ideal surveillance strategy to identify recurrences is unclear. Guidelines are mixed, with NCCN and AUA recommending surveillance via chest x-ray (CXR) at least annually for 5 years, while EAU guidelines do not specifically recommend the use of CXR. In an effort to clarify the utility of surveillance CXR, we retrospectively evaluated pT1a patients following surgical treatment at a single institution. METHODS: We performed retrospective analysis of unique patients who underwent surgical excision of pT1 RCC between January 2000 and January 2020. In addition to demographic information, we collected RCC pathology, recurrence details, and most recent chest imaging. We excluded non-RCC pathology, and patients with pulmonary nodules on baseline imaging. RESULTS: We identified 463 unique patients (mean age 58.3 years, range 23-87) that underwent surgical excision of pT1a RCC with mean follow-up of 47.6 months (range 1-201). On the most recent pulmonary surveillance imaging, 72.4% (335/463) had CXR while 27.6% (128/463) had chest CT performed. Regardless of modality, pulmonary recurrence was not detected on any surveillance imaging (0/463). CONCLUSION: In patients without baseline preoperative lung pathology, we found that there is questionable clinical value in surveillance for pulmonary recurrence after resection of pT1a RCC.

Benign mature teratoma of the cecum: a case report.

A teratoma is a typically benign tumor derived from more than one embryonic cell line, and it is characterized by presence of tissue foreign to the tumor location site. With the unlikely primary location in the gastrointestinal tract and no history of malignancy, we present a rare case of a primary mature cystic teratoma of the cecum. The patient is a 66-year-old male with imaging demonstrating an extraluminal, seemingly fat-containing mass abutting the cecum. The patient underwent resection, and final pathology revealed a mature cystic teratoma. Primary mature teratoma of the cecum is exceptionally rare; thus, diagnosis can be challenging. As he had no primary testicular or retroperitoneal mass, this cystic lesion likely represents a developmental abnormality and not a true neoplasm. The radiographic features, presentation, differential diagnoses, and treatment recommendations are discussed.

A prospective Canadian gastroesophageal cancer database: What have we learned?

BACKGROUND: Minimal literature exists on outcomes for Canadian patients with gastroesophageal adenocarcinoma (GEA). The objective of our study was to establish a prospective clinical database to evaluate demographic characteristics, presentation and outcomes of patients with GEA. METHODS: Patients diagnosed with GEA were recruited from Jan. 30, 2017, to Aug. 30, 2020. Data collected included demographic characteristics, presentation, treatment and survival. A multivariable model for overall survival in patients treated with curative intent was created using sex, lymph node status, resection margin status, age and tumour location as variables. RESULTS: A total of 122 patients with adenocarcinoma of the stomach or gastroesophageal junction were included. Median age was 65 years (interquartile range [IQR] 59-74), 70% of patients were male and 26% were born outside of Canada. Median follow-up time was 14.5 (IQR 8.0-31.0) months. Following staging computed tomography scanning, 88% of patients were deemed to have potentially resectable disease. Eighty-one (76%) received staging laparoscopy and 74 (61%) were treated with curativeintent surgery. Forty-six (62%) patients had nodal metastases. The median number of nodes harvested was 22 (IQR 18-30). The R0 resection margin rate was 82%. The 3-year overall survival for patients who received curative-intent treatment was 63% and 38% for all patients. On multivariable analysis, female sex (hazard ratio [HR] 3.88, p = 0.01), positive nodal status (HR 3.58, p = 0.02), positive margins (HR 3.11, p = 0.03) and tumour location (HR 3.00, p = 0.03) were associated with decreased overall survival. CONCLUSION: Many of the patients with GEA in this study presented with advanced disease, and only 61% were offered curative-intent surgery. A prospective multicentre national GEA database is now being established.

Artificial Intelligence Optical Biopsy for Evaluating the Functional State of Wounds.

INTRODUCTION: The clinical characterization of the functional status of active wounds in terms of their driving cellular and molecular biology remains a considerable challenge that currently requires excision via a tissue biopsy. In this pilot study, we use convolutional Siamese neural network (SNN) architecture to predict the functional state of a wound using digital photographs of wounds in a canine model of volumetric muscle loss (VML). METHODS: Digital images of VML injuries and tissue biopsies were obtained in a standardized fashion from an established canine model of VML. Gene expression profiles for each biopsy site were obtained using RNA sequencing. These profiles were converted to functional profiles by a manual review of validated gene ontology databases in which we determined a hierarchical representation of gene functions based on functional specificity. An SNN was trained to regress functional profile expression values, informed by an image segment showing the surface of a small tissue biopsy. RESULTS: The SNN was able to predict the functional expression of a range of functions based with error ranging from ∼5% to ∼30%, with functions that are most closely associated with the early state of wound healing to be those best-predicted. CONCLUSIONS: These initial results suggest promise for further research regarding this novel use of machine learning regression on medical images. The regression of functional profiles, as opposed to specific genes, both addresses the challenge of genetic redundancy and gives a deeper insight into the mechanistic configuration of a region of tissue in wounds.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia.

BACKGROUND & AIMS: The prevalence of non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is rising rapidly, yet its underlying mechanisms remain unclear. Herein, we aim to determine the role of hypoxia-inducible lipid droplet associated protein (HILPDA)/hypoxia-inducible gene 2 (HIG2), a selective inhibitor of intracellular lipolysis, in NASH-driven HCC. METHODS: The clinical significance of HILPDA was assessed in human NASH-driven HCC specimens by immunohistochemistry and transcriptomics analyses. The oncogenic effect of HILPDA was assessed in human HCC cells and in 3D epithelial spheroids upon exposure to free fatty acids and either normoxia or hypoxia. Lipidomics profiling of wild-type and HILPDA knockout HCC cells was assessed via shotgun and targeted approaches. Wild-type (Hilpdafl/fl) and hepatocyte-specific Hilpda knockout (HilpdaΔHep) mice were fed a Western diet and high sugar in drinking water while receiving carbon tetrachloride to induce NASH-driven HCC. RESULTS: In patients with NASH-driven HCC, upregulated HILPDA expression is strongly associated with poor survival. In oxygen-deprived and lipid-loaded culture conditions, HILPDA promotes viability of human hepatoma cells and growth of 3D epithelial spheroids. Lack of HILPDA triggered flux of polyunsaturated fatty acids to membrane phospholipids and of saturated fatty acids to ceramide synthesis, exacerbating lipid peroxidation and apoptosis in hypoxia. The apoptosis induced by HILPDA deficiency was reversed by pharmacological inhibition of ceramide synthesis. In our experimental mouse model of NASH-driven HCC, HilpdaΔHep exhibited reduced hepatic steatosis and tumorigenesis but increased oxidative stress in the liver. Single-cell analysis supports a dual role of hepatic HILPDA in protecting HCC cells and facilitating the establishment of a pro-tumorigenic immune microenvironment in NASH. CONCLUSIONS: Hepatic HILPDA is a pivotal oncometabolic factor in the NASH liver microenvironment and represents a potential novel therapeutic target. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH, chronic metabolic liver disease caused by buildup of fat, inflammation and damage in the liver) is emerging as the leading risk factor and the fastest growing cause of hepatocellular carcinoma (HCC), the most common form of liver cancer. While curative therapeutic options exist for HCC, it frequently presents at a late stage when such options are no longer effective and only systemic therapies are available. However, systemic therapies are still associated with poor efficacy and some side effects. In addition, no approved drugs are available for NASH. Therefore, understanding the underlying metabolic alterations occurring during NASH-driven HCC is key to identifying new cancer treatments that target the unique metabolic needs of cancer cells.

Radiation necrosis or tumor progression? A review of the radiographic modalities used in the diagnosis of cerebral radiation necrosis.

PURPOSE: Cerebral radiation necrosis is a complication of radiation therapy that can be seen months to years following radiation treatment. Differentiating radiation necrosis from tumor progression on standard magnetic resonance imaging (MRI) is often difficult and advanced imaging techniques may be needed to make an accurate diagnosis. The purpose of this article is to review the imaging modalities used in differentiating radiation necrosis from tumor progression following radiation therapy for brain metastases. METHODS: We performed a review of the literature addressing the radiographic modalities used in the diagnosis of radiation necrosis. RESULTS: Differentiating radiation necrosis from tumor progression remains a diagnostic challenge and advanced imaging modalities are often required to make a definitive diagnosis. If diagnostic uncertainty remains following conventional imaging, a multi-modality diagnostic approach with perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single photon emission spectroscopy (SPECT), and radiomics may be used to improve diagnosis. CONCLUSION: Several imaging modalities exist to aid in the diagnosis of radiation necrosis. Future studies developing advanced imaging techniques are needed.

Clinical Validation of the Canada Lymph Node Score for Endobronchial Ultrasound.

BACKGROUND: The Canada Lymph Node Score (CLNS) uses 4 sonographic criteria to predict the risk of malignancy in lymph nodes during endobronchial ultrasound. The CLNS may play a role in identifying targets for biopsy or rebiopsy during invasive mediastinal staging for lung cancer. However the CLNS has not yet been prospectively validated in routine clinical practice. METHODS: CLNSs for each lymph node biopsied during endobronchial ultrasound were prospectively captured for 1 year (2019). The CLNS and the presence of malignancy in each node were compared. Univariate binary logistic regression was completed for each ultrasonographic feature and multivariate logistic regression model. RESULTS: CLNSs and diagnostic pathology results were available for 367 lymph nodes. Incidence of malignancy increased with higher scores. Scores ≥ 3 were significantly associated with malignancy (specificity, 84.4%; positive likelihood ratio, 4.0). Area under the curve was 0.76, indicating a good ability of the model to predict presence or absence of malignancy. Nodes scoring < 2 and negative on computed tomography and positron emission tomography were malignant in 10.1%. CONCLUSIONS: The CLNS correlates with the presence or absence of malignancy in thoracic lymph nodes and may serve as an adjunct to currently available methods of invasive and noninvasive mediastinal staging. The CLNS may be most helpful in selecting which nondiagnostic lymph nodes require rebiopsy. There is a significant risk of a false-negative result even with a score of 0, and using a combination of low CLNSs and negative conventional radiology to obviate the need for any initial biopsy remains to be studied in prospective trials.

Impact of Acetazolamide on Perioperative Pain Control in Robotic Assisted Laparoscopic Prostatectomy.

OBJECTIVE: To evaluate the efficacy of peri-operative acetazolamide for pain control in robotic assisted laparoscopic prostatectomy (RALP). Prior studies have demonstrated that preoperative acetazolamide decreased postoperative referred pain in the postsurgical period for laparoscopic procedures. The proposed mechanism is acetazolamide mediated inhibition of carbonic anhydrase, thereby preventing formation of carbonic acid and subsequent peritoneal acidosis with referred pain. This has yet to be demonstrated in the setting of RALP. METHODS AND MATERIALS: Patients undergoing RALP were randomized to receive either preoperative saline or acetazolamide prior to the procedure. Overall pain scores were recorded at multiple time points post operatively, as well as total morphine equivalents administered for adjunctive pain control. RESULTS: Thirty-one patients were included in the study: 16 patients (51.6%) received perioperative acetazolamide, and 15 patients (48.4%) received perioperative saline as placebo. Overall pain scores were similar for patients receiving acetazolamide compared to placebo at various time points: first responsive (3.5 ± 3.1 vs 4.1 ± 1.7, P = .28), immediately prior to leaving PACU (2.8 ± 2.9 vs 2.9 ± 2.9, P = .48), at 4 hours post-procedure (3.1 ± 3.0 vs 2.9 ± 1.8, P = .362), or at 24 hours post-procedure (2.3 ± 1.7 vs 2.2 ± 1.6, P = .5). Shoulder tip pain was not present in either cohort. No statistically significant difference was observed for total morphine equivalents delivered between acetazolamide and placebo (17.3 vs 20.5, P= .2, respectively). CONCLUSION: Acetazolamide does not appear to impact overall pain or shoulder tip pain in the observed cohort of patients undergoing RALP.

Indirect treatment comparison of oral versus injectable azacitidine as maintenance therapy for acute myeloid leukemia.

Aim: Evaluate the relative efficacy of oral versus injectable azacitidine (AZA) maintenance therapy in acute myeloid leukemia (AML) after complete remission. Materials & methods: Systematic literature review identified QUAZAR AML-001, HOVON 97 AML, UK NCRI AML16 and QoLESS-AZA-AMLE (sensitivity analysis) trials. Network meta-analysis and matching-adjusted indirect comparisons assessed survival outcomes. Results: In the network meta-analysis, combining the HOVON 97 and UK NCRI trials, oral AZA (QUAZAR) was associated with significantly improved overall survival (OS) versus injectable AZA (hazard ratio: 0.744; 95% credible interval: 0.557-0.998). After matching-adjusted indirect comparisons, to address differences in patient characteristics across trials, OS improvements were maintained with oral versus injectable AZA (hazard ratio: 0.753; credible interval: 0.563-0.998). Conclusion: In AML, maintenance therapy with oral AZA was associated with improved OS versus injectable AZA.

Older people with acute myeloid leukemia (AML) may have remission with or without blood count recovery, after first-line chemotherapy; however, remission is short lived and overall survival is limited (7­12 months). Ongoing treatment (maintenance therapy) after response to initial chemotherapy may prolong remission. Maintenance therapy with azacitidine (AZA) given by injection beneath the skin (subcutaneous) or into a vein (intravenous) can extend disease-free survival compared with no further treatment and best supportive care. However, treatment with intravenous AZA may only extend overall survival in certain patients. ONUREG^® is a novel formulation of AZA that can be taken by mouth (orally), remains in the body for longer periods and has the potential for significant clinical benefits compared with intravenous AZA. Presently, there are no studies directly comparing outcomes of maintenance therapy with oral and injectable AZA in older people with AML. In this analysis, we used an indirect treatment comparison method including four clinical trials to explore the survival benefit associated with ONUREG and injectable AZA when used as maintenance therapies after response to initial chemotherapy in older people with AML. Findings showed ONUREG significantly improved overall survival compared with injectable AZA, with an almost 26% reduction in the risk of death. These results suggest that maintenance therapy with ONUREG significantly improves overall survival compared with injectable AZA in older people with AML who may have remission with or without blood count recovery, after first-line chemotherapy.

3D Bioprinted Patient-Specific Extracellular Matrix Scaffolds for Soft Tissue Defects.

Soft tissue injuries such as volumetric muscle loss (VML) are often too large to heal normally on their own, resulting in scar formation and functional deficits. Decellularized extracellular matrix (dECM) scaffolds placed into these wounds have shown the ability to modulate the immune response and drive constructive healing. This provides a potential solution for functional tissue regeneration, however, these acellular dECM scaffolds are challenging to fabricate into complex geometries. 3D bioprinting is uniquely positioned to address this, being able to create patient-specific scaffolds based on clinical 3D imaging data. Here, a process to use freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting and computed tomography (CT) imaging to build large volume, patient-specific dECM patches (≈12 × 8 × 2 cm) for implantation into canine VML wound models is developed. Quantitative analysis shows that these dECM patches are dimensionally accurate and conformally adapt to the surface of complex wounds. Finally, this approach is extended to a human VML injury to demonstrate the fabrication of clinically relevant dECM scaffolds with precise control over fiber alignment and micro-architecture. Together these advancements represent a step towards an improved, clinically translatable, patient-specific treatment for soft tissue defects from trauma, tumor resection, and other surgical procedures.

Lung lobectomy surgical approach and resource utilization differ by anatomic lobe in a statewide discharge registry.

Background: Anatomic lobe-specific differences with respect to pulmonary lobectomy have been suggested in the thoracic surgery literature but hard data has been lacking in larger population studies in part due to coding systems that do not distinguish pulmonary lobectomy by anatomic lobe. International Classification of Diseases, Tenth Revision (ICD-10) procedure codes, adopted in the United States in 2015, may provide novel methodologic accessibility for pulmonary lobectomy studies as they classify lobectomy operations by specific anatomic lobe. We queried the Texas Inpatient Public Use Data File (TPUDF) ICD-10 codes for both open and endoscopic approach lobectomy with a specific view to differences based on anatomic lobes. Methods: Between fourth fiscal quarter (Q4) 2015 and Q4 2017, all pulmonary lobectomy operations performed in Texas state-licensed hospitals were identified by querying the TPUDF for ICD-10 procedure codes for pulmonary lobectomy as classified by anatomic lobe. Surgical approach, additional procedures and diagnosis codes, length of hospital stay (LOS), and discharge status were recorded with aggregate values undergoing statistical analysis. Results: Right and left upper versus lower lobe resections were more prevalent however minimally invasive surgery was less commonly performed for upper than right lower lobectomy. LOS, irrespective of surgical approach, was longer for upper versus lower lobe resection as was need for transfer to additional inpatient facilities. LOS was longer and need for additional surgical or procedural interventions days after the primary procedure of lobectomy was greater for right versus left upper lobe resection, suggesting some differential properties of the right versus left pleural space. Conclusions: The marked clinical differences between anatomic lobes in the setting of pulmonary lobectomy observed in this study have the potential to translate to differences in expected hospital and health system costs and surgeon time-expenditure and experience premium that currently have no mechanism for their accounting. These findings highlight the value of ICD-10 coding for analysis of pulmonary lobectomy in administrative databases and suggest a possible path to more informed patient counseling and equitable hospital and surgeon reimbursement based on payment adjustment by anatomic lobe in pulmonary lobectomy operations.

Lead optimization of cathepsin K inhibitors for the treatment of Osteoarthritis.

Cathepsin K (Cat K) is a cysteine protease involved in bone remodeling. In addition to its role in bone biology, Cat K is upregulated in osteoclasts, chondrocytes and synoviocytes in osteoarthritic (OA) disease states making it a potential therapeutic target for disease-modifying OA. Starting from a prior preclinical compound, MK-1256, lead optimization efforts were carried out in the search for potent Cat K inhibitors with improved selectivity profiles with an emphasis on cathepsin F. Herein, we report the SAR studies which led to the discovery of the highly selective oxazole compound 23, which was subsequently shown to inhibit cathepsin K in vivo as measured by reduced levels of urinary C-telopeptide of collagen type I in dog.

Bilateral Pleural Mesothelioma In Situ and Peritoneal Mesothelioma In Situ Associated With BAP1 Germline Mutation: A Case Report.

Mesothelioma in situ is a recently described precursor to invasive mesothelioma. Thus far, all cases in the literature have involved one pleural cavity or the peritoneal cavity. We describe a patient with biopsy-proven mesothelioma in situ involving both pleural cavities and the peritoneal cavity. Genetic analysis results revealed that the patient had a BAP1 germline mutation. This is the first report of mesothelioma in situ involving multiple body cavities and raises a question of whether such patients will all have BAP1 germline mutations.

Performance of the Neck Imaging Reporting and Data System as applied by general neuroradiologists to predict recurrence of head and neck cancers.

BACKGROUND: The Neck Imaging Reporting and Data System (NI-RADS) is used to assess imaging after head and neck cancer treatment. We evaluated NI-RADS with general neuroradiologists rather than with head and neck subspecialists. METHODS: Computed tomography and magnetic resonance imaging examinations with/without positron emission tomography from May 2018 to September 2020 were retrospectively identified. NI-RADS scores at the primary site and lymph nodes were provided by 21 neuroradiologists. Recurrence status was based on clinical and imaging findings. Area under the curve (AUC) was used to assess accuracy. RESULTS: We assessed 608 scans from 464 patients. For NI-RADS categories 1, 2, and 3, primary site recurrence rates were 5%, 29%, and 65% with AUC of 0.765, while lymph node recurrence rates were 3%, 10%, and 80% with AUC of 0.820. CONCLUSIONS: NI-RADS as used by general neuroradiologists is effective in separating head and neck cancers into discrete categories for predicting recurrent disease.