Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type-Specific Attribution.

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

Dynamic functional connectivity in anorexia nervosa: alterations in states of low connectivity and state transitions.

BACKGROUND: The onset of anorexia nervosa (AN) frequently occurs during adolescence and is associated with preoccupation with body weight and shape and extreme underweight. Altered resting state functional connectivity in the brain has been described in individuals with AN, but only from a static perspective. The current study investigated the temporal dynamics of functional connectivity in adolescents with AN and how it relates to clinical features. METHOD: 99 female patients acutely ill with AN and 99 pairwise age-matched female healthy control (HC) participants were included in the study. Using resting-state functional MRI data and an established sliding-window analytic approach, we identified dynamic resting-state functional connectivity states and extracted dynamic indices such as dwell time (the duration spent in a state), fraction time (the proportion of the total time occupied by a state), and number of transitions (number of switches) from one state to another, to test for group differences. RESULTS: Individuals with AN had relatively reduced fraction time in a mildly connected state with pronounced connectivity within the default mode network (DMN) and an overall reduced number of transitions between states. CONCLUSIONS: These findings revealed by a dynamic, but not static analytic approach might hint towards a more "rigid" connectivity, a phenomenon commonly observed in internalizing mental disorders, and in AN possibly related to a reduction in energetic costs as a result of nutritional deprivation.

Reliably making the primary diagnosis of mesothelioma utilizing serous fluid cytology specimens: an institutional experience.

INTRODUCTION: The diagnosis of mesothelioma has historically been challenging, especially on serous fluid cytology (SFC). Distinguishing between reactive and neoplastic mesothelial cells can be difficult on cytomorphology alone. However, additional ancillary tests, such as BRCA1 associated protein-1 immunohistochemistry and fluorescence in situ hybridization for cyclin-dependent kinase inhibitor 2A deletion, can provide a sensitive and highly specific method of proving malignancy. MATERIALS AND METHODS: SFC specimens diagnosed as mesothelioma, suspicious for mesothelioma (SM), and atypical mesothelial cells (AMCs) since 2012 were identified by querying the laboratory information system. Clinical data and pathologic parameters were gathered. RESULTS: One hundred ten cases of mesothelioma, SM, and AMC were identified. Of these, 61 cases had a definitive diagnosis of mesothelioma on SFC. Average age at SFC diagnosis was 67 years (26-87 years), with most patients being male (67%). Out of the 61 cases, 11 cases (18%) had an initial diagnosis of mesothelioma made on SFC specimens, with 5 of these 11 cases being in patients that never received a histologic diagnosis of mesothelioma. Ancillary studies were utilized in all 11 cases. An initial diagnosis of metastatic mesothelioma was made on SFC in 9 cases (15%). For 6 of these 9 cases, the SFC diagnosis was the sole diagnosis of metastatic mesothelioma without a companion histologic diagnosis. In addition, 15 cases were diagnosed as SM, with 11 of these cases following a definitive mesothelioma diagnosis. Thirty-four cases were diagnosed as AMC, with 27 cases following a definitive mesothelioma diagnosis. CONCLUSIONS: The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.

Dynamic Changes in Local Brain Connectivity and Activity: A Longitudinal Study in Adolescent Anorexia Nervosa.

BACKGROUND: Resting-state functional connectivity analysis has been used to study disruptions in neural circuitries underlying eating disorder symptoms. Research has shown resting-state functional connectivity to be altered during the acute phase of anorexia nervosa (AN), but little is known about the biological mechanisms underlying neural changes associated with weight restoration. The goal of the current study was to investigate longitudinal changes in regional homogeneity (ReHo) among neighboring voxels, degree centrality (DC) (a voxelwise whole brain correlation coefficient), voxel-mirrored homotopic connectivity (VMHC) (measuring the synchronization between hemispheres), and the fractional amplitude of low-frequency fluctuations associated with weight gain during AN treatment. METHODS: Resting-state functional connectivity data were acquired and analyzed from a sample of 174 female volunteers: 87 underweight patients with AN that were scanned before treatment and again after at least 12% body mass index increase, as well as 87 age-matched healthy control participants. RESULTS: Longitudinal changes in ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations were observed in most regions identified to differ between patients with AN before treatment and healthy control participants. However, the degree of normalization varied for each parameter, ranging from 9% of all clusters in DC to 66% in VMHC. Longitudinal changes in ReHo and VMHC showed a linear association weight gain. CONCLUSIONS: Resting-state functional magnetic resonance imaging measures, including ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations, show varying degrees of recovery after short-term weight restoration. Although only some of these changes were related to weight gain, our results provide an overall positive message, suggesting that weight restoration is associated with changes in functional brain measures that point toward normalization.

Effect of serum concentrations of IL-6 and TNF-α on brain structure in anorexia nervosa: a combined cross-sectional and longitudinal study.

Previous studies of brain structure in anorexia nervosa (AN) have reported reduced gray matter in underweight patients, which largely normalizes upon weight gain. One underlying biological mechanism may be glial cell alterations related to low-grade inflammation. Here, we investigated relationships between brain structure as measured by magnetic resonance imaging and serum concentrations of two pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) cross-sectionally in 82 underweight adolescent and young adult female patients (mean age 16.8 years; 59 of whom were observed longitudinally after short-term weight restoration; mean duration 2.8 months), 20 individuals long-term weight-recovered from AN (mean age 22.7 years) and 105 healthy control (HC) participants (mean age 17.2 years). We measured cortical thickness, subcortical volumes and local gyrification index, a measure of cortical folding. In contrast to most previous studies of cytokine concentrations in AN, we found no cross-sectional group differences (interleukin-6: p = 0.193, tumor necrosis factor alpha: p = 0.057) or longitudinal changes following weight restoration (interleukin-6: p = 0.201, tumor necrosis factor alpha: p = 0.772). As expected, widespread gray matter reductions (cortical thickness, subcortical volumes, cortical folding) were observed in underweight patients with AN compared to HC. However, we found no evidence of associations between cytokine concentrations and structural brain measures in any participant group. Furthermore, longitudinal changes in cytokine concentrations were unrelated to changes in gray matter. In conclusion, we did not identify any association between (sub-)inflammatory processes and structural brain changes in AN. Future studies are needed to elucidate which other factors besides nutritional status may contribute to brain morphological alterations.