The Emotional Content of Children's Writing: A Data-Driven Approach.

Emotion is closely associated with language, but we know very little about how children express emotion in their own writing. We used a large-scale, cross-sectional, and data-driven approach to investigate emotional expression via writing in children of different ages, and whether it varies for boys and girls. We first used a lexicon-based bag-of-words approach to identify emotional content in a large corpus of stories (N>100,000) written by 7- to 13-year-old children. Generalized Additive Models were then used to model changes in sentiment across age and gender. Two other machine learning approaches (BERT and TextBlob) validated and extended these analyses, converging on the finding that positive sentiments in children's writing decrease with age. These findings echo reports from previous studies showing a decrease in mood and an increased use of negative emotion words with age. We also found that stories by girls contained more positive sentiments than stories by boys. Our study shows the utility of large-scale data-driven approaches to reveal the content and nature of children's writing. Future experimental work should build on these observations to understand the likely complex relationships between written language and emotion, and how these change over development.

The nature and frequency of relative clauses in the language children hear and the language children read: A developmental cross-corpus analysis of English complex grammar.

As written language contains more complex syntax than spoken language, exposure to written language provides opportunities for children to experience language input different from everyday speech. We investigated the distribution and nature of relative clauses in three large developmental corpora: one of child-directed speech (targeted at pre-schoolers) and two of text written for children - namely, picture books targeted at pre-schoolers for shared reading and children's own reading books. Relative clauses were more common in both types of book language. Within text, relative clause usage increased with intended age, and was more frequent in nonfiction than fiction. The types of relative clause structures in text co-occurred with specific lexical properties, such as noun animacy and pronoun use. Book language provides unique access to grammar not easily encountered in speech. This has implications for the distributional lexical-syntactic features and associated discourse functions that children experience and, from this, consequences for language development.

Boys Write About Boys: Androcentrism in Children's Reading Experience and Its Emergence in Children's Own Writing.

Gender bias exists in our language environment. We investigated personal name usage in two large corpora of language written for and by U.K. children aged 5-13. Study 1 found an overrepresentation of male names in children's books, largely attributable to male authors. In stories written by over 100,000 children, Study 2 found an overall male bias that interacted with age. Younger children wrote more about their own gender. With age, girls became more balanced yet boys continued to show a strong male bias. Our findings demonstrate a male-centered bias in both children's books and their own writing. We consider the power of written language to both shape and be shaped by cultural stereotypes via systematic biases in gender associations.

The Role of T-box Transcription Factor in a Pituitary Adenoma Diagnostic Algorithm.

CONTEXT.­: We previously examined pituitary adenomas with immunohistochemical (IHC) stains for steroidogenic factor 1, Pit-1, anterior pituitary hormones, cytokeratin CAM 5.2, and the α-subunit of human chorionic gonadotropin and found that a screening panel comprising stains for steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone successfully classified most cases and reduced the overall number of stains required. OBJECTIVES.­: To examine the potential role of IHC stain for T-box transcription factor (Tpit) in the classification of our series of pituitary adenomas and to update our screening panel as necessary. DESIGN.­: We collected 157 pituitary adenomas from 2 institutions and included these in tissue microarrays. Immunostains for Tpit were scored in a blinded fashion using the Allred system. Adenomas were assigned to a gold standard class based on IHC pattern followed by application of available clinical and serologic information. Test characteristics were calculated. Correlation analyses, cluster analyses, and classification tree analyses were used to see whether IHC staining patterns reliably reflected adenoma class. RESULTS.­: Of the cases collected, 147 (93.6%) had sufficient material for Tpit analysis. IHC stain for Tpit identified 8 null cell adenomas (all nonfunctioning clinically) as silent corticotrophs; Tpit stains showed better sensitivity, specificity, positive predictive value, and negative predictive value than IHC for adrenocorticotropic hormone and cytokeratin CAM 5.2. Correlation analyses continued to show the expected relationships among IHC stains. Cluster analyses showed grouping of adenomas into clinically consistent groups. Classification tree analysis underscored the central role of transcription factor IHC stains, including Tpit, in adenoma classification. CONCLUSIONS.­: Substitution of Tpit stain for the adrenocorticotropic hormone stain improves our prior algorithm by reducing the number of false-negatives and false-positives. As a result, fewer adenomas are classified as null cell adenoma, and more adenomas are classified as silent corticotroph adenoma.

Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage: A Safety and Tolerability Study.

BACKGROUND: Perihematomal edema (PHE) growth in intracranial hemorrhage (ICH) is a biomarker for worse outcomes. Although the management of PHE is potentially beneficial for ICH patients, there is currently no proven clinical therapy that both reduces PHE and improves outcomes in this population. OBJECTIVE: To examine the safety and tolerability of conivaptan, a non-peptide vasopressin (AVP) receptor antagonist, for the management of PHE in ICH patients. METHODS: We performed a single-center, open-label, phase I study in seven patients with ICH at risk for developing PHE. Conivaptan (20 mg) was administered every 12 h for 2 days, along with the standard ICH management. Electrolyte levels, renal and cardiac function, and vital signs were monitored throughout treatment. Neurological status, ICH, and PHE volumes were assessed at study baseline, 24 h, 72 h, and 7 days from the first conivaptan administration, as well as at the 3-month follow-up. RESULTS: Conivaptan was well tolerated in our patients. We observed the expected increase in sodium levels following conivaptan administration (p = 0.01), with no change in cardiac or renal function. All patients survived to follow-up, and adverse event rates were comparable with those of the neurocritical care unit overall. CONCLUSIONS: These data indicate that conivaptan can be safely administered to ICH patients and support further clinical investigation into the efficacy of this drug for ICH treatment. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT03000283, 22 December 2016.

Physical Therapy-Based Exercise Protocol for Cancer Patients: Evaluating Outcomes for Cardiopulmonary Performance and Cancer-Related Fatigue.

BACKGROUND: Studies have shown that rehabilitation and fitness throughout cancer treatment interventions have been linked to improved outcomes for morbidity and mortality of cancer patients. This study serves to detail the efficacy of the Cancer Rehabilitation Physical Therapy Fitness and Debility (Ca PT) Program in cancer patients. OBJECTIVE: To describe the clinical population of cancer patients referred to the Ca PT Program and evaluate the efficacy of the program's therapy protocol in improving cardiopulmonary performance and cancer-related fatigue and pain. DESIGN: Retrospective study. SETTING: Outpatient clinics. PATIENTS: One hundred two adults who had been referred from a variety of referral sources and supervised individualized exercise programs. METHODS: Participation in the Ca PT Program. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was a change in baseline-to-discharge scores in the 6-Minute Walk Test (6MWT), a cardiopulmonary performance measure. The secondary measures were changes in baseline-to-discharge scores of cancer-related fatigue and general pain, measured by patient self-report using a visual analogue scale. RESULTS: 6MWT values were significantly higher at discharge (mean 523 yards) than at baseline (mean 436), (P < .001, r = 0.57). Ninety-two percent of cases showed improvement and 58% of cases had a change on the 6MWT that met threshold for minimal important difference. Quality of life factors, fatigue (P < .001) and pain (P < .001) also significantly improved. CONCLUSIONS: The results indicate the Ca PT Program yields significant improvement in cardiovascular fitness, fatigue, and pain in people with cancer history. Personalized physical therapy fitness programs for individuals recovering from cancer treatment should be a standard component of cancer intervention. LEVEL OF EVIDENCE: III.

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

CONTEXT: -Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. OBJECTIVE: -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. DESIGN: -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. RESULTS: -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. CONCLUSIONS: -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

High incidence of triple negative breast cancers following pregnancy and an associated gene expression signature.

Breast cancer risk increases transiently in the period following pregnancy; pregnancy-associated breast cancers (PABC) are more aggressive than cases diagnosed in nulliparous women. We have previously reported that in the normal human breast pregnancy results in the upregulation of a number of inflammation related genes, suggesting a pro-tumorigenic environment as well as downregulation of ESR1 (ERα) and ERBB2 (HER2) and upregulation of ESR2 (ERß), suggesting a protective effect. In this study, we aimed to investigate the possibility of differential regulation of the same gene set modulated in the normal breast, in human breast tumors following pregnancy. Gene expression was measured by real-time PCR on tumor regions isolated by laser capture microdissection from paraffin sections. Immunohistochemistry was performed on tissue microarrays (TMA) for protein expression. Hierarchical clustering was performed using the average linkage method to determine coordinate expression of sets of genes. We find that breast cancers detected within 10 years following pregnancy display a different gene expression pattern than those detected in nulliparous breast cancer patients. The gene expression difference is mainly attributable to a triple negative (TNBC) subgroup found to be more frequent in PABCs up to 10 years following a pregnancy. We also show that protein and mRNA expression levels correlate in half of the proteins tested by TMA. Despite the fact that this is a small study of 53 patients, we identified a gene expression signature that is differentially expressed in pregnancy-associated TNBC.

PTK6/BRK is expressed in the normal mammary gland and activated at the plasma membrane in breast tumors.

Protein Tyrosine kinase 6 (PTK6/BRK) is overexpressed in the majority of human breast tumors and breast tumor cell lines. It is also expressed in normal epithelial linings of the gastrointestinal tract, skin, and prostate. To date, expression of PTK6 has not been extensively examined in the normal human mammary gland. We detected PTK6 mRNA and protein expression in the immortalized normal MCF-10A human mammary gland epithelial cell line, and examined PTK6 expression and activation in a normal human breast tissue microarray, as well as in human breast tumors. Phosphorylation of tyrosine residue 342 in the PTK6 activation loop corresponds with its activation. Similar to findings in the prostate, we detect nuclear and cytoplasmic PTK6 in normal mammary gland epithelial cells, but no phosphorylation of tyrosine residue 342. However, in human breast tumors, striking PTK6 expression and phosphorylation of tyrosine 342 is observed at the plasma membrane. PTK6 is expressed in the normal human mammary gland, but does not appear to be active and may have kinase-independent functions that are distinct from its cancer promoting activities at the membrane. Understanding consequences of PTK6 activation at the plasma membrane may have implications for developing novel targeted therapies against this kinase.

Rare presentation of a gastrointestinal stromal tumor with spontaneous esophageal perforation: A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) of the alimentary canal are malignant tumors with <1% of cases diagnosed in esophagus. These cases require special consideration given their close proximity to vital structures and propensity to be highly aggressive. Management of patients with GISTs has been transformed since the introduction of tyrosine kinase inhibitors. In this report, we present an unusual case of GIST with spontaneous esophageal perforation. PRESENTATION OF CASE: A 39-year-old Caucasian male presented to our hospital with complaints of severe chest and abdominal pain. A diagnostic chest radiograph revealed a moderate right-sided pleural effusion. Subsequently, an esophagram demonstrated a perforation proximal to an elongated stricture in the distal esophagus. A left thoracotomy was performed whereby a large mediastinal mass firmly attached to the esophagus and gastroesophageal junction was encountered. The neoplasm involved proximal one-third of the stomach and perforated into the right hemithorax. Histopathological evaluation of the tumor led to a diagnosis of GIST. DISCUSSION: GISTs of the gastroesophageal junction are uncommon and may rarely present with esophageal perforation. The standard of care for treating GIST at present includes tyrosine kinase inhibitors. This pharmacologic agent, along with improved surgical techniques and understanding of molecular markers for accurate diagnosis, will assuredly continue to improve overall survival of patients with GISTs. CONCLUSION: When stricture or achalasia is detected on imaging, GIST should be considered in the differential diagnosis for individual patients. Additionally, chest and abdomen CT scans of may be performed to confirm presence of a tumor mass, thereby ruling out achalasia.

Postoperative incidence of incarcerated hiatal hernia and its prevention after robotic transhiatal esophagectomy.

BACKGROUND: Transhiatal robot-assisted total esophagectomy (RE) has gained acceptance as a minimally invasive procedure with several clinical benefits. In this report, the authors describe their experience with the incidence of incarcerated hiatal hernia after RE. METHODS: Between March 2007 and July 2009, 36 patients underwent RE at the authors' institution. A retrospective chart review was performed, and data were abstracted including gender, age, weight at surgery, presenting symptoms, pathologic diagnosis, operative time, estimated blood loss, mortality, and postoperative complications. RESULTS: The study cohort consisted of 28 men and 8 women undergoing RE. Their average age was 65.4±10.5 years, and their mean body weight was 86.2±24.8 kg at surgery. A review of medical records indicated that 7 (19.4%) of the 36 patients had postoperative incarcerated hiatal hernias. Two of these patients had experienced two episodes of incarceration, which required reoperation. One patient died of complications related to hernia repair. Six (85.7%) of 7 patients had a preexisting diagnosis of hiatus hernia which was significantly higher in comparison to the incidence of this complication within the group of 29 patients without post-operative hernia incarcerations (11 of 29, 37.9%; Fisher's exact p=0.04). CONCLUSIONS: The results indicate that postoperative incarcerated hiatal hernia after RE is an infrequently reported, albeit serious, complication. A preexisting hiatal hernia may put patients at a higher risk of incarceration. According to the authors' experience, a primary closure and reinforcement with mesh sutured to the gastric wall is recommended as a preventive measure. Diligent follow-up evaluation with regular computed tomography (CT) scans investigating likelihoods for incarceration is advisable, especially for patients with preexisting hernias.

FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic and pathologic correlations, including cuplike blast morphology.

CONTEXT: Acquired mutations in the fms-like tyrosine kinase 3 gene (FLT3) adversely impact relapse risk after chemotherapy in patients with acute myeloid leukemia (AML). The FLT3 mutation status may differ at diagnosis and relapse, suggesting a potential role in chemoresistance, yet few reports have addressed the cytogenetic and pathologic correlates of FLT3 mutations in relapsed AML. OBJECTIVES: To determine FLT3 mutations at diagnosis and relapse in a cohort of adult patients with chemoresistant AML and to correlate mutation status with multiple variables. DESIGN: We retrospectively determined FLT3 internal tandem duplication (FLT3/ITD) and FLT3 tyrosine kinase domain mutations in 50 diagnosis/relapse pairs. We correlated FLT3 status with karyotype, World Health Organization 2008 subtype, white blood cell count, biopsy cellularity, blast percentage, and the presence of invaginated ("cuplike") blast nuclei. RESULTS: In 11 of 50 patients (22%) the FLT3 mutation status differed at relapse and diagnosis, with a trend toward gain of FLT3/ITD (n = 7) and loss of FLT3 tyrosine kinase domain (n = 5) mutations. FLT3-mutated AMLs correlated with the World Health Organization 2008 subtype, AML, not otherwise specified, hyperproliferative features at diagnosis and relapse, and cytogenetic evolution. FLT3-wild type AMLs correlated with the subtype AML with myelodysplasia-related changes and frequently had adverse presentation karyotypes. Cuplike blast morphology was associated with FLT3/ITD+ status and with high mutation levels. Four of 7 patients with relapse-only FLT3/ITD mutations exhibited cuplike blasts at relapse after being noncuplike at diagnosis. CONCLUSIONS: In addition to well-known correlates in pretreatment specimens, FLT3 mutation status has pathologic and cytogenetic significance at relapse. A shift to cuplike blast morphology at relapse may herald emergence of a previously undetected FLT3/ITD mutation.

Association of germ-line polymorphisms in the feline p53 gene with genetic predisposition to vaccine-associated feline sarcoma.

A case-control study was conducted in order to investigate the association of polymorphisms in the genomic sequence of the feline p53 gene with a predisposition to vaccine-associated feline sarcoma (VAFS). In the study, 50 domestic short hair cats with a confirmed histopathologic diagnosis of VAFS were matched to disease-free controls (1:2) by age, sex, and breed. Cats from both the diseased (case) and control groups were also negative for feline leukemia virus and feline immunodeficiency virus. Germ-line DNA was prepared from blood samples from cats in both groups and analyzed for sequence variation at 8 polymorphic sites in the p53 gene. A strong association was found between VAFS and the presence of specific nucleotides at 2 of the polymorphic sites. The strongest association was observed for a single-base insertion in intron 7 of the gene with an odds ratio of 8.99 (95% confidence interval = 3.42-23.57, P < 0.0001). The results of the study indicate that analysis of the presence or absence of the identified genetic markers in apparently healthy disease-free cats may help in predicting which individual animals are at greater risk of developing the disease.

Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma.

OBJECTIVE: To determine somatic alterations in p53 in vaccine-associated feline sarcoma (VAFS). Animals-27 domestic shorthair cats undergoing first surgical treatment for primary VAFS with no history of chemotherapy or gamma radiation. PROCEDURES: Sequence analysis was performed on the genomic sequence of p53 (between exons 5 through 9) from tumor and blood samples obtained from the cats. Cats were monitored for 3 years and disease-free intervals and survival times calculated. RESULTS: Eight single nucleotide polymorphisms were detected within the genomic sequence of p53, with 20 of 27 cats (74%) having heterozygosity at > or = 1 polymorphic site. Somatic loss of heterozygosity at p53 was detected in the primary tumors of 12 of these 20 (60%) cats. Such allelic deletion was significantly associated with rapid tumor recurrence and reduced overall survival. Point mutations were rare, occurring in 3 of 27 primary tumors. The finding of malignant cells in the surgical margins was significantly associated with disease recurrence, but clear margins (with no detectable malignant cells) were not predictive of positive outcome. CONCLUSIONS AND CLINICAL RELEVANCE: p53 status is an indicator of postsurgical recurrence and overall survival in cats with VAFS. Careful follow-up is important in treating vaccine-site tumors containing allelic deletion of p53, whereas aggressive surgical treatment may be sufficient to control primary vaccination site tumors without the allelic loss.

The complete genome sequence of Mycobacterium avium subspecies paratuberculosis.

We describe here the complete genome sequence of a common clone of Mycobacterium avium subspecies paratuberculosis (Map) strain K-10, the causative agent of Johne's disease in cattle and other ruminants. The K-10 genome is a single circular chromosome of 4,829,781 base pairs and encodes 4,350 predicted ORFs, 45 tRNAs, and one rRNA operon. In silico analysis identified >3,000 genes with homologs to the human pathogen, M. tuberculosis (Mtb), and 161 unique genomic regions that encode 39 previously unknown Map genes. Analysis of nucleotide substitution rates with Mtb homologs suggest overall strong selection for a vast majority of these shared mycobacterial genes, with only 68 ORFs with a synonymous to nonsynonymous substitution ratio of >2. Comparative sequence analysis reveals several noteworthy features of the K-10 genome including: a relative paucity of the PE/PPE family of sequences that are implicated as virulence factors and known to be immunostimulatory during Mtb infection; truncation in the EntE domain of a salicyl-AMP ligase (MbtA), the first gene in the mycobactin biosynthesis gene cluster, providing a possible explanation for mycobactin dependence of Map; and Map-specific sequences that are likely to serve as potential targets for sensitive and specific molecular and immunologic diagnostic tests. Taken together, the availability of the complete genome sequence offers a foundation for the study of the genetic basis for virulence and physiology in Map and enables the development of new generations of diagnostic tests for bovine Johne's disease.

Evaluation of in vitro chemosensitivity of vaccine-associated feline sarcoma cell lines to vincristine and paclitaxel.

OBJECTIVE: To determine the in vitro sensitivity of 4 vaccine-associated feline sarcoma (VAFS) cell lines to the chemotherapeutic agents vincristine and paclitaxel. SAMPLE POPULATION: Cell lines derived from 4 VAFS specimens. PROCEDURES: Cell lines were cultured in vitro and individually exposed to various concentrations of vincristine and paclitaxel. Survival was estimated after 24 and 72 hours of exposure to each drug, and the drug concentrations that resulted in 50 and 90% reduction in number of viable cells (IC50 and IC90, respectively) were calculated. RESULTS: Both vincristine and paclitaxel had significant dose-dependent effects on the viability of the VAFS cell lines. After 72 hours of drug exposure, the IC50 and IC90 of vincristine for the 4 cell lines were between 0.005 to 0.039 microg/ml and 0.045 to 1.027 microg/ml, respectively. The IC50 and IC90 values for paclitaxel were between 0.037 to 0.092 microg/ml and 2.450 to 15.413 microg/ml, respectively. CONCLUSIONS: Results of pharmacokinetic studies on vincristine and paclitaxel in other species suggest that concentrations greater than the IC50 values may be possible for both drugs in feline patients as well. The drug concentrations at which viable cell numbers were reduced by 90% may also be attained in vivo for some cases, but detailed information is needed regarding the distribution, concentration, duration of availability, and toxicity of various drugs in cats. Carefully chosen combinations of antineoplastic agents need to be screened to identify treatment protocols that may be further evaluated clinically for the treatment of VAFS.