Resection of NAFLD/NASH-related Hepatocellular Carcinoma (HCC): Clinical Features and Outcomes Compared with HCC Due to Other Etiologies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies. METHODS: Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients. RESULTS: Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant. CONCLUSIONS: Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs.

Patient Navigation Increases Linkage to Care and Receipt of Direct-acting Antiviral Therapy in Patients with Hepatitis C.

BACKGROUND & AIMS: Patient navigation interventions can improve health outcomes in underserved, low-income, and racial and ethnic minority groups, who often experience health disparities. We examined the effectiveness of patient navigation to improve linkage to hepatitis C virus (HCV) treatment receipt in a socioeconomically disadvantaged, racially diverse patient population. METHODS: We performed a pre-post analysis evaluating the effectiveness of a patient navigation program among baby boomers who tested positive for HCV in a safety-net health system. The usual care group (June 2013 to May 2015) and patient navigation group (January 2016 to December 2017) were balanced using a stabilized inverse probability of treatment weighting approach. We used logistic regression analyses to evaluate associations between patient navigation and linkage to care for HCV treatment evaluation, treatment initiation, and sustained virologic response. RESULTS: Among 1353 patients (62% black, 61% uninsured, 16% homeless), 769 were in the usual care group, and 584 were in the patient navigation group. The patient navigation group had significantly higher odds of linkage to care (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.9-4.8) and treatment initiation (OR, 3.2; 95% CI, 2.3-4.2) within 6 months. The patient navigation group continued to have increased linkage to care (OR, 3.4; 95% CI, 2.7-4.3) and treatment initiation (OR 2.3; 95% CI, 1.7-3.0) at 12 months. However, there was no significant difference in sustained virologic response between the groups (86.9% vs 86.1%; P = .78). CONCLUSIONS: Patient navigation was associated with significantly increased linkage to care and treatment initiation among patients with HCV infection. Patient navigation programs can be used to promote HCV elimination among traditionally difficult-to-reach patient populations.

Pilot Study of Quantitative Methods for Differentiating Pharyngeal Swallowing Mechanics by Dysphagia Etiology.

Quantitative analysis of modified barium swallow (MBS) imaging is useful to determine the impact of various disease states on pharyngeal swallowing mechanics. In this retrospective proof of concept study, kinematic analysis and computational analysis of swallowing mechanics (CASM) were used to demonstrate how these methods differentiate swallowing dysfunction by dysphagia etiology. Ten subjects were randomly selected from four cohorts of dysphagic patients including COPD, head and neck cancer (HNC), motor neuron disease, and stroke. Each subject was age- and gender-matched with healthy, non-dysphagic controls. MBS videos of 5 ml thin and 5 ml thick bolus trials from each subject were used. A MATLAB tracker tool was adapted and updated to collect and compile data for each video (n = 160). For kinematic measurements, a MANOVA was performed with post-hoc analyses to determine group differences. For CASM measurements, a morphometric canonical variate analysis with post hoc analysis was performed to determine group differences. Kinematic analyses indicated statistically significant differences between HNC cohort and controls in distance measurements for hyolaryngeal approximation (p = .001), laryngeal elevation (p = 0.0001), pharyngeal shortening (p = 0.0002), and stage transition duration timing (p = 0.002). Timing differences were noted between the stroke cohort and controls for pharyngeal transit time (p = 0.007). Multivariate morphometric canonical variate analysis showed significant differences between etiology groups (p < 0.0001) with eigenvectors indicating differing patterns of swallowing mechanics. This study demonstrated that swallowing mechanics among cohorts of dysphagic patients can be differentiated using kinematics and CASM, providing different but complementary quantitative methods for investigating the impact of various disease states on swallowing function.

Development of a Mobile Application to Enhance Knowledge, Awareness and Communication of Dry Mouth Amongst Dental Practitioners and Patients: A South Texas Oral Health Network Study.

BACKGROUND: Dry mouth, also commonly known as "xerostomia", is a prominent symptom that is often overlooked by dental practitioners and patients. The purpose of this study was to pilot the development of a mobile application for assessing dry mouth symptoms. The application will allow patients to self-assess and enhance knowledge, awareness and communication with dental practitioners in their management of dry mouth. METHOD: The first phase of the study was to draw on common knowledge and awareness by conducting two focus groups of dental professionals and community members on content, practicality, functionality, design, and effectiveness. The second phase of the study was the development of the dry mouth mobile application followed by the third phase of the study that consisted of face-validity interviews to obtain feedback on the application. RESULTS: Fifty two percent (n=15) of the dental professionals estimated being aware of the prevalence of dry mouth in 40% or more of their patients. Thirty Nine percent of (n=9) community estimated being aware of the prevalence of dry mouth in 40% or more of the community. When asked about their awareness of the etiologies of dry mouth, 100% (n=29) of dental professionals reported that multiple medications and smoking were primary factors whereas the community members indicated that illness and dehydration (87%, n=20) were primary factors in dry mouth. Dental professional's (25% n=7) were very confident in recognizing symptoms and 28% (n=8) were very confident they knew how to manage dry mouth symptoms. Furthermore, 22% (n=5) of the community members were also very confident about recognizing dry mouth symptoms and 13% (n=3) were very confident knowing how managing it. The ToP report generated from the discussions identified "themes" that were utilized in the development of the mobile application. Most individuals who participated in the validity interviews agreed that the dry mouth mobile application was useful, appealing, easy to use and the self-assessment test gave clear and concise information. The application was made available to download from the iTunes Appstore (2019-2020). CONCLUSION: The dry mouth pilot study indicated that the mobile application was beneficial for self-assessment and easy to use. Development of advanced technology tools such as the dry mouth application can promote communication between patients and their dental practitioners to discuss management options for dry mouth.

Training experiences regarding pain management, addiction, and drug diversion of dentists enrolled in the National Dental Practice-Based Research Network.

Background: The purpose of this study was to describe dentists' training experiences relevant to pain management, addiction, and prescription opioid drug diversion and examine associations between these training experiences and dentists' opioid prescribing practices. Methods: A Web-based, cross-sectional survey was conducted among practicing dentist members of the National Dental Practice-Based Research Network (PBRN; N = 822). The survey assessed pain management prescribing practices and training experiences related to pain management and assessment for addiction and drug diversion. Survey data were linked with National Dental PBRN Enrollment Questionnaire data regarding practitioner demographics and practice characteristics. Results: The majority of dentists (67%) reported prior training in pain management; however, a minority of dentists reported prior training regarding identification and assessment of drug abuse or addiction (48%) or identification of prescription drug diversion (25%). The majority of training experiences across all topics occurred through continuing dental education participation. Dental school training relevant to pain management, addiction, and identification of drug diversion was more prevalent among more recent dental school graduates. Training experiences were associated with prescribing practices. Conclusions: Results suggest that across multiple levels of training, many dentists are not receiving training specific to addiction assessment and identification of drug diversion. Such training is associated with greater consistency of risk mitigation implementation in practice.

Tooth Fairy Study- The South Texas Oral Health Network Collaboration.

PURPOSE: This study's purpose was to examine the processes and the potential for dental practitioners to address environmental health exposure risks to their patients through dental practice-based research participation. To explore this, the South Texas Oral Health Network (STOHN) initiated a collaboration with The Tooth Fairy National Study investigating toxicants stored in deciduous teeth as a potential neurodevelopmental risk factor. BACKGROUND: Neurodevelopmental disorders (ND), like Autism Spectrum Disorder (ASD), affect 1 in 68 live births. Evidence suggests that environmental chemicals may play a role in ASD risk and/or etiology by acting independently or through interactions with genetic vulnerabilities. Provider awareness of environmental exposure risk during pregnancy and early childhood in South Texas is low. Therefore, it is important to increase provider knowledge and awareness to enable greater communication with patients. STOHN serves as a conduit reaching large numbers of patients. This study also engaged practitioners in an ongoing national study with minimal impact on their practice. METHODS: The goal was to enroll twenty parents with children via ten dental practitioners. STOHN pediatric and general practitioners were recruited for the study. Practitioners were contacted by phone and in person. Upon completion of Human Subject Protection training, each practitioner participated in a study training taught by a public health educator in the department of Family and Community Medicine at University of Texas Health Science Center in San Antonio (UTHSCSA). Training topics included NDs, environmental health exposures, patient engagement, survey administration, and how to collect donated teeth. This collaboration allowed STOHN to gather control teeth as well as demographic and health information for the Tooth Fairy Study repository for future analyses. Participants received a thank you card from the Tooth Fairy and participating providers were highlighted in the monthly STOHN newsletter. EVALUATION RESULTS: Evaluation was threefold: Practitioner enrollment and retention; practitioner confidence in educating their patients about potential environmental risk exposures and completed surveys with donated teeth. CONCLUSION: The interdisciplinary collaboration between dental practitioners and medical researchers through STOHN provided an opportunity to increase practitioner knowledge and awareness of a novel health concern, while also raising their confidence and willingness to educate their patients about potential environmental exposure risks. UTHSCSA IRB Protocol # HSC20170132E.

Management of Dentin Hypersensitivity by National Dental Practice-Based Research Network practitioners: results from a questionnaire administered prior to initiation of a clinical study on this topic.

BACKGROUND: Dentin hypersensitivity (DH) is a common problem encountered in clinical practice. The purpose of this study was to identify the management approaches for DH among United States dentists. METHODS: One hundred eighty five National Dental Practice-Based Research Network clinicians completed a questionnaire regarding their preferred methods to diagnose and manage DH in the practice setting, and their beliefs about DH predisposing factors. RESULTS: Almost all dentists (99%) reported using more than one method to diagnose DH. Most frequently, they reported using spontaneous patient reports coupled with excluding other causes of oral pain by direct clinical examination (48%); followed by applying an air blast (26%), applying cold water (12%), and obtaining patient reports after dentist's query (6%). In managing DH, the most frequent first choice was desensitizing, over-the-counter (OTC), potassium nitrate toothpaste (48%), followed by fluorides (38%), and glutaraldehyde/HEMA (3%). A total of 86% of respondents reported using a combination of products when treating DH, most frequently using fluoride varnish and desensitizing OTC potassium nitrate toothpaste (70%). The most frequent predisposing factor leading to DH, as reported by the practitioners, was recessed gingiva (66%), followed by abrasion, erosion, abfraction/attrition lesions (59%) and bruxism (32%). CONCLUSIONS: The majority of network practitioners use multiple methods to diagnose and manage DH. Desensitizing OTC potassium nitrate toothpaste and fluoride formulations are the most widely used products to manage DH in dental practice setting.

Connecting and Collaborating: Developing National Dental PBRN Study Concepts Through POD Engagement.

PURPOSE: This article illustrates the process by which the Southwest Region of the National Dental Practice-Based Research Network (www.NationalDentalPBRN.org) fosters collaboration among practitioners and researchers in study concept development through protocol development groups (PODs). The Southwest Region begins this process by engaging PODs, which comprise dentists, hygienists, and/or academic faculty who share research interests related to improving dental care. METHOD: The PODs use the Tuckman four-stage model of group development (forming, storming, norming, and performing) to develop study concepts. This well-structured model encourages engagement among group members and enables quality discussion through organized sessions. This model provides milestones for the group's progression and for the members' interactions. The Southwest Region Directors play a crucial role in guiding and directing the development of PODs by aligning the members' research interests with the goals of the National Network. RESULTS: POD engagement using Tuckman's stages has been successful in developing study concepts for submission to the National Network. Between 2012 and 2014, the Southwest Region has developed 14 PODs from 275 research ideas. Five of these study concepts have been submitted to the National Network for approval, including the Novel Tobacco Products POD, which showcases the applicability of Tuckman's model. CONCLUSION: Overall, the POD concept is a collaborative effort that brings together practitioners and academicians through shared research interests and capitalizes on participants' expertise and experiences. The Southwest Region will continue to develop PODs to foster new ideas for future studies in the Network.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. METHODS: This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided. RESULTS: Among 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P < .00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver-directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%) (all P < .001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months; P < .001). CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

FGFR mRNA Expression in Cholangiocarcinoma and Its Correlation with FGFR2 Fusion Status and Immune Signatures.

PURPOSE: Selective FGFR inhibitors are effective against cholangiocarcinomas that harbor gene alterations in FGFR2. Clinical trials suggest that expression of wild-type FGFR mRNA can predict sensitivity to FGFR inhibitors, but this biomarker has not been well characterized in cholangiocarcinoma. This study explores the prevalence of FGFR mRNA overexpression in cholangiocarcinoma, its role in predicting sensitivity to FGFR inhibitors, and its association with immune markers. EXPERIMENTAL DESIGN: Tissue microarrays of intrahepatic (ICC) and extrahepatic cholangiocarcinomas (ECC) resected between 2004 and 2015 were used to evaluate FGFR1-4 mRNA expression levels by RNA in situ hybridization (ISH). Expression levels of FGFR2 mRNA were correlated with FGFR2 fusion status and with patient outcomes. Immune markers expression was assessed by IHC and CSF1 and CSF1 receptor expression were examined by RNA ISH. RESULTS: Among 94 patients with resected cholangiocarcinoma, the majority had ICC (77%). FGFR2 fusions were identified in 23% of ICCs and 5% of ECCs. High levels of FGFR mRNA in FGFR2 fusion-negative ICC/ECC were seen for: FGFR1 (ICC/ECC: 15%/0%), FGFR2 (ICC/ECC: 57%/0%), FGFR3 (ICC/ECC: 53%/18%), and FGFR4 (ICC/ECC: 32%/0%). Overall, 62% of fusion-negative cholangiocarcinomas showed high levels of FGFR mRNA. In patients with advanced FGFR2 fusion-positive ICC, high levels of FGFR2 mRNA did not correlate with clinical benefit. FGFR2 fusion-positive tumors showed a paucity of PD-L1 on tumor cells. CONCLUSIONS: FGFR mRNA overexpression occurs frequently in cholangiocarcinoma in the absence of genetic alterations in FGFR. This study identifies a molecular subpopulation in cholangiocarcinoma for which further investigation of FGFR inhibitors is merited outside currently approved indications.

Aspiration Screening in Motor Neuron Disease: Preliminary Results From Utilization of the Yale Swallow Protocol.

Purpose Dysphagia is a common symptom experienced by patients with motor neuron disease (MND). The Yale Swallow Protocol (YSP) is a validated screening instrument for identifying patients at risk for aspiration. The purpose of this exploratory cross-sectional, multicenter study was to investigate how the YSP results in identifying aspiration risk in patients with MND in comparison with aspiration observed during a videofluoroscopic swallow study (VFSS). Method Participants referred for VFSS as part of clinical management were recruited from four specialized MND clinics. All participants were administered the YSP immediately prior to the VFSS by a speech-language pathologist, with results recorded as pass or fail. Aspiration on VFSS was determined using the Penetration-Aspiration Scale (scores 6-8). A 2 × 2 contingency table was constructed to compare results of YSP with those on VFSS. Results Thirty-one patients with MND (13 males, 18 females; M age = 64 ± 12 years) referred for VFSS participated in this study. Of the 22 patients who failed the YSP, interrupted drinking was the most frequent reason (65%). Compared to the VFSS, the YSP yielded a sensitivity of 80%, a specificity of 33%, positive predictive value of 36%, and negative predictive value of 78%. Conclusions The YSP is a simple tool and easy to utilize and has a high sensitivity in identifying aspiration risk in amyotrophic lateral sclerosis. A future investigation with a larger sample size is needed to better investigate the utility of YSP as a screening tool for this population.

Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer.

In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment of a cancer's mutational profile when analyzing a single tumor biopsy. In this study, we perform sequencing of cell-free DNA (cfDNA) and distinct metastatic tissue samples from ten rapid autopsy cases with pre-treated metastatic cancer. We show that levels of heterogeneity in genetic biomarkers vary between patients but that gene expression signatures representative of the tumor microenvironment are more consistent. Across nine patients with plasma samples available, we are able to detect 62/62 truncal and 47/121 non-truncal point mutations in cfDNA. We observe that mutation clonality in cfDNA is correlated with the number of metastatic lesions in which the mutation is detected and use this result to derive a clonality threshold to classify truncal and non-truncal driver alterations with reasonable specificity. In contrast, mutation truncality is more often incorrectly assigned when studying single tissue samples. Our results demonstrate the utility of a single cfDNA sample relative to that of single tissue samples when treating patients with metastatic cancer.

An Association Between the Inflammatory Biomarker GlycA and Depressive Symptom Severity.

OBJECTIVE: The underlying mechanisms of depression remain unclear; however, current literature suggests a relationship between inflammation and depression. The association between the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) and depression has been previously investigated, but the relationship between GlycA, a novel spectroscopic inflammatory biomarker, and depression does not appear to have been examined. METHODS: Data were obtained from The Dallas Heart Study (DHS, conducted between 2000 and 2002), which consisted of a large community-based sample of Dallas County residents (N = 3,033). Depressive symptom severity was assessed with the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR). It was hypothesized that the serum GlycA level would be a statistically significant predictor of QIDS-SR scores after control for demographic covariates. Multiple linear regression was used to assess the relationship between GlycA level and QIDS-SR scores. The role of hs-CRP in predicting QIDS-SR scores was also explored. RESULTS: GlycA level was a statistically significant positive predictor of QIDS-SR score (ß = .053, P = .038) with control for sex, age, antidepressant use, ethnicity, smoking status, drinking status, body mass index, and years of education. In a subset of adults with moderate-to-severe depression, GlycA level was not associated with QIDS-SR scores. Additionally, hs-CRP level was not a statistically significant predictor of QIDS-SR scores. CONCLUSIONS: This study found a positive association between the inflammatory biomarker GlycA, but not hs-CRP, and depressive symptom severity in a large multiethnic and multiracial community-based sample. Thus, these results provide the first indication that GlycA may be a potentially useful novel biomarker of depression.

Practitioner Engagement in Activities of the National Dental Practice-Based Research Network (PBRN): 7-Year Results.

PURPOSE: To 1) quantify practitioner activities of the National Dental Practice-Based Research Network (Network) for which Continuing Education (CE) credits were received (study training, videos, webinars, meetings, and symposia); 2) quantify practitioner coauthoring Network publications and presentations; and 3) test whether practitioner characteristics were associated with participation in these activities. METHODS: A retrospective analysis of 4361 practitioners who enrolled in the Network between April 12, 2012 and October 12, 2018. RESULTS: Overall, 59% (n = 2586) of practitioners earned CE credit from the Network; among these, 68% (n = 1757) from a video, 38% (n = 993) attended an annual Network meeting, 31% (n = 798) due to training for a Network clinical study, 9% (n = 226) attended a national symposium, and 7% (n = 170) participated in a Network webinar. Members of 2 large group practices earned on average more CEs than practitioners from other practice settings. Four percent (n = 159) of practitioners coauthored a Network presentation or publication. Practitioners who received their dental degree before 2000, were general practitioners, or were members of 2 large group practices, were more likely to have coauthored a publication or presentation. CONCLUSION: This Network used a broad range of activities to engage community practitioners. These activities were successful in sustaining a high level of practitioner engagement in clinical research and its relevance to everyday clinical practice.

Attitudes and beliefs concerning sexual relationships among minority adolescent women.

Learning about one's sexuality is an important developmental task for the adolescent and has implications for a lifelong process of becoming a sexual being and reaching sexual maturity. Learning about intimacy in relationship with others is another important developmental task for the adolescent. The occurrence of interpersonal violence, particularly sexual, physical, or psychological violence, disrupts the development of intimacy which informs the process for becoming a sexual being. Society can assist adolescent females experiencing interpersonal violence to understand their sexual nature and make informed sexual decisions throughout their lifetime. This assistance requires a contextual understanding of the relationship between adolescent sexual development and the effects of interpersonal violence on this process. This study presents the groundwork needed to understand the contextual meanings of sexual relationships of adolescent females with a history of interpersonal violence and discusses the evolution of these adolescents' attitudes and beliefs for sexual health promotion.

Association between telomere length and cognitive ability in a community-based sample.

Prior research suggests that telomere length is a biomarker of cognitive aging; however, literature has demonstrated conflicting findings to date. The present study uses data from the Dallas Heart Study, N = 2606, to assess the association between telomere length and cognitive ability on the Montreal Cognitive Assessment. The data do not support a relationship between telomere length and general cognitive functioning, (ß = 0.016, SE = 0.31, p = 0.407). The data further replicate the negative findings within current literature.

Electronic and paper mode of data capture when assessing patient-reported outcomes in the National Dental Practice-Based Research Network.

AIM: Our objectives were to describe the approach used in the National Dental Practice-Based Research Network to capture patient-reported outcomes and to compare electronic and paper modes of data capture in a specific network study. METHODS: This was a prospective, multicenter cohort study of 1862 patients with dentin hypersensitivity. Patient-reported outcomes were assessed based on patients' perception of pain using Visual Analog Scales and Labeled Magnitude scales at baseline and at 1, 4 and 8 weeks post-baseline. RESULTS: Eighty-five percent of study patients chose to complete follow-up assessments via an electronic mode; 15% completed them via a paper mode. There was not a significant difference in the proportions of patients who completed the 8-week assessment when comparing the electronic mode to the paper mode (92% vs. 90.8%, P = 0.31, Rao-Scott clustered χ2 -test). CONCLUSION: The electronic mode of data capture was as operational as the traditional paper mode, while also providing the advantage of eliminating data entry errors, not involving site research coordinators in measuring the patient-reported outcomes, and not incurring cost and potential delays due to mailing study forms. Electronic data capture of patient reported outcomes could be successfully implemented in the community dental practice setting.

TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic Cholangiocarcinoma.

ATP-competitive fibroblast growth factor receptor (FGFR) kinase inhibitors, including BGJ398 and Debio 1347, show antitumor activity in patients with intrahepatic cholangiocarcinoma (ICC) harboring activating FGFR2 gene fusions. Unfortunately, acquired resistance develops and is often associated with the emergence of secondary FGFR2 kinase domain mutations. Here, we report that the irreversible pan-FGFR inhibitor TAS-120 demonstrated efficacy in 4 patients with FGFR2 fusion-positive ICC who developed resistance to BGJ398 or Debio 1347. Examination of serial biopsies, circulating tumor DNA (ctDNA), and patient-derived ICC cells revealed that TAS-120 was active against multiple FGFR2 mutations conferring resistance to BGJ398 or Debio 1347. Functional assessment and modeling the clonal outgrowth of individual resistance mutations from polyclonal cell pools mirrored the resistance profiles observed clinically for each inhibitor. Our findings suggest that strategic sequencing of FGFR inhibitors, guided by serial biopsy and ctDNA analysis, may prolong the duration of benefit from FGFR inhibition in patients with FGFR2 fusion-positive ICC. SIGNIFICANCE: ATP-competitive FGFR inhibitors (BGJ398, Debio 1347) show efficacy in FGFR2-altered ICC; however, acquired FGFR2 kinase domain mutations cause drug resistance and tumor progression. We demonstrate that the irreversible FGFR inhibitor TAS-120 provides clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomes several FGFR2 mutations in ICC models.This article is highlighted in the In This Issue feature, p. 983.

Patterns of FOS expression in the spinal cord and periaqueductal grey matter of 6OHDA-lesioned rats.

A less well-known feature of Parkinson disease is that up to 40% of patients experience distinct sensory disturbances, including hyperalgesia and chronic pain. There is a limited understanding of the neural mechanisms that generate these symptoms, however. This study explores the patterns of Fos expression (a well-known marker for changes in cell activity) in the spinal cord and periaqueductal grey matter (PaG), two major sensory (nociceptive) centers, of hemiParkinsonian rats. The medial forebrain bundle (mfb; major tract carrying dopaminergic nigrostriatal axons) was injected with either 6OHDA or saline (controls). A week later, some rats were subjected to mechanical stimulation (pinching) of the hindpaw for 2 h, whereas others received no stimulation. Thereafter, brains were processed using routine tyrosine hydroxylase (marker for dopaminergic cells) or Fos immunocytochemistry. In the PaG, there were many more Fos(+) cells in the 6OHDA-lesioned than in the Control group, in both the stimulation and, in particular, the non-stimulation cases. In the spinal cord, there were also more Fos(+) cells in the 6OHDA-lesioned than in the Control group, but in the stimulation cases only. Overall, the results show distinct changes in Fos expression in the spinal cord and PaG of 6OHDA-lesioned rats, suggesting a substrate for some of the abnormal sensory (nociceptive) circuits that may be evident in parkinsonian cases.