RNA transcripts circulating in peripheral blood represent an important source of non-invasive biomarkers. To accurately quantify the levels of circulating transcripts, one needs to normalize the data ...with internal control reference genes, which are detected at relatively constant levels across blood samples. A few reference gene candidates have to be selected from transcriptome data before the validation of their stable expression by reverse-transcription quantitative polymerase chain reaction. However, there is a lack of transcriptome, let alone whole-transcriptome, data from maternal blood. To overcome this shortfall, we performed RNA-sequencing on blood samples from women presenting with preterm labor. The
(
) of expression levels was calculated. Of 11,215 exons detected in the maternal blood whole-transcriptome, a panel of 395 genes, including
,
,
, and
, were identified to comprise exons with considerably less variable expression level (
, 7.75-17.7%) than any
exon (minimum
, 27.3%). Upon validation, the selected genes from this panel remained more stably expressed than
in maternal blood. This panel is over-represented with genes involved with the actin cytoskeleton, macromolecular complex, and integrin signaling. This groundwork provides a starting point for systematically selecting reference gene candidates for normalizing the levels of circulating RNA transcripts in maternal blood.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Perineural invasion (PNI) is associated with aggressive tumor behavior, recurrence, and metastasis, and can influence the administration of adjuvant treatment. However, standard histopathologic ...examination has limited sensitivity in detecting PNI and does not provide insights into its mechanistic underpinnings.
A multivariate Cox regression was performed to validate associations between PNI and survival in 2,029 patients across 12 cancer types. Differential expression and gene set enrichment analysis were used to learn PNI-associated programs. Machine learning models were applied to build a PNI gene expression classifier. A blinded re-review of hematoxylin and eosin (H&E) slides by a board-certified pathologist helped determine whether the classifier could improve occult histopathologic detection of PNI.
PNI associated with both poor overall survival HR, 1.73; 95% confidence interval (CI), 1.27-2.36;
< 0.001 and disease-free survival (HR, 1.79; 95% CI, 1.38-2.32;
< 0.001). Neural-like, prosurvival, and invasive programs were enriched in PNI-positive tumors (
< 0.001). Although PNI-associated features likely reflect in part the increased presence of nerves, many differentially expressed genes mapped specifically to malignant cells from single-cell atlases. A PNI gene expression classifier was derived using random forest and evaluated as a tool for occult histopathologic detection. On a blinded H&E re-review of sections initially described as PNI negative, more specimens were reannotated as PNI positive in the high classifier score cohort compared with the low-scoring cohort (
= 0.03, Fisher exact test).
This study provides salient biological insights regarding PNI and demonstrates a role for gene expression classifiers to augment detection of histopathologic features.
Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and ...gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.
Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light microscopy, and myenteric plexus neurochemistry by whole-mount immunostaining.
Regional gastric sampling revealed site-specific differences in contractile patterns and myenteric plexus structure. In neonatal mice, TmSep prolonged gastric emptying. In the forestomach, TmSep increased contractile responses to carbachol, decreased muscularis externa and mucosa thickness, and increased the relative proportion of myenteric plexus nNOS+ neurons. Germ-free conditions did not appreciably alter the structure or function of the neonatal mouse stomach and did not impact the changes caused by TmSep.
A regional sampling approach facilitates site-specific investigations of murine gastric motor physiology and histology to identify site-specific alterations that may impact gastrointestinal function. Delayed gastric emptying in TmSep is associated with a thinner muscle wall, exaggerated cholinergic contractile responses, and increased proportions of inhibitory myenteric plexus nNOS+ neurons in the forestomach. Gut microbes do not profoundly affect the development of the neonatal mouse stomach or the gastric pathophysiology that results from TmSep.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
► Class size has an impact on the rhetorical structure of lecture closings. ► Lecturers use a wide variety of strategies yet with great variation. ► Strategies concentrate at Ending Stage in large ...classes. ► Strategies concentrate at Pre-ending and Post-ending Stages in small classes. ► Personal pronouns are used to enhance engagement and mitigate potential disfavor.
The present study investigates the rhetorical structure of academic lecture closings, and the impact of class size on this part genre. A framework of stages and strategies is developed to analyze the rhetorical structure of lecture closings. Large and small classes are further compared to find how class size may influence the ways lecturers close their lectures. Personal pronouns I, you, and we are also examined to explore interpersonal dynamics. Results show that lecturers use a wide range of strategies in closings, yet with great variation. Three strategies—explicitly indicating the end of lecture, explaining course plans for the next class, and dismissing the class—are most frequently used. Large and small classes differ in both stages and strategies. Strategies tend to concentrate at the Ending Stage in large classes, but at the Pre-ending and Post-ending Stages in small classes. Interestingly, students and lecturers in small classes have frequent, informal interaction on non-course-related issues. Lecturers may use personal pronouns flexibly and strategically, referring to a variety of semantic referents, to enhance student engagement and mitigate potential disfavor. These findings demonstrate the impact of class size on lecture closings, which provide an opportunity for lecturers to establish close rapport with students.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Prognostication for patients with cancer is important for clinical planning and management, but remains challenging given the large number of factors that can influence outcomes. As such, there is a ...need to identify features that can robustly predict patient outcomes. We evaluated 8608 patient tumor samples across 16 cancer types from The Cancer Genome Atlas and generated distinct survival classifiers for each using clinical and histopathological data accessible to standard oncology workflows. For cancers that had poor model performance, we deployed a random-forest-embedded sequential forward selection approach that began with an initial subset of the 15 most predictive clinicopathological features before sequentially appending the next most informative gene as an additional feature. With classifiers derived from clinical and histopathological features alone, we observed cancer-type-dependent model performance and an area under the receiver operating curve (AUROC) range of 0.65 to 0.91 across all 16 cancer types for 1- and 3-year survival prediction, with some classifiers consistently outperforming those for others. As such, for cancers that had poor model performance, we posited that the addition of more complex biomolecular features could enhance our ability to prognose patients where clinicopathological features were insufficient. With the inclusion of gene expression data, model performance for 3 select cancers (glioblastoma, stomach/gastric adenocarcinoma, ovarian serous carcinoma) markedly increased from initial AUROC scores of 0.66, 0.69, and 0.67 to 0.76, 0.77, and 0.77, respectively. As a whole, this study provides a thorough examination of the relative contributions of clinical, pathological, and gene expression data in predicting overall survival and reveals cancer types for which clinical features are already strong predictors and those where additional biomolecular information is needed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Mindfulness-based interventions (MBIs) are supported by clinical practice guidelines as effective non-pharmacologic interventions for common symptoms experienced by cancer patients, ...including anxiety, depression, and fatigue. However, the evidence predominately derives from White breast cancer survivors. Racial and ethnic minority patients have less access to integrative oncology care and worse cancer outcomes. To address these gaps, we designed and piloted a series of mindfulness-based group medical visits (MB-GMVs), embedded into comprehensive cancer care, for racially and ethnically diverse patients in cancer treatment. Methods As a quality improvement project, we launched a telehealth MB-GMV series for patients undergoing cancer treatment, delivered as four weekly 2-hour visits billable to insurance. Content was concordant with evidence-based guidelines and established MBIs and adapted to improve cultural relevance and fit (eg, access-centered, trauma-informed, with inclusive communication practices). Program structure was adapted to address barriers to participation, with ≥50% slots per series reserved for racial and ethnic minority patients. Intake surveys incorporated a demographic questionnaire and symptom assessments. Evaluations were sent following the visits. Results In our first ten cohorts (n = 78), 80% of referred patients enrolled. Participants were: 22% Asian, 14% Black, 17% Latino, 45% non-Latino White; 65% female; with a median age of 54 years (range 27-79); and 80% had metastatic cancer. Common baseline symptoms included lack of energy, difficulty sleeping, and worrying. Most patients (90%) attended ≥3 visits. On final evaluations, 87% patients rated the series as “excellent”; 81% “strongly agreed” that they liked the GMV format; and 92% would “definitely” recommend the series to others. Qualitative themes included empowerment and connectedness. Conclusion Telehealth GMVs are a feasible, acceptable, and financially sustainable model for increasing access to MBIs. Diverse patients in active cancer treatment were able to participate and reported high levels of satisfaction with this series that was tailored to center health equity and inclusion.
To determine whether optical imaging can be used for in vivo therapy response monitoring as an alternative to radionuclide techniques. For this, we evaluated the known Her2 response to ...17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG) treatment, an Hsp90 inhibitor.
After in vitro 17-DMAG treatment response evaluation of MCF7 parental cells and 2 HER2-transfected clones (clone A medium, B high Her2 expression), we established human breast cancer xenografts in nude mice (only parental and clone B) for in vivo evaluation. Mice received 120 mg/kg of 17-DMAG in 4 doses at 12-hour intervals intraperitonially (n = 14) or PBS as carrier control (n = 9). Optical images were obtained both pretreatment (day 0) and posttreatment (day 3, 6, and 9), always 5 hours postinjection of 500 pmol of anti-Her2 Affibody-AlexaFluor680 via tail vein (with preinjection background subtraction). Days 3 and 9 in vivo optical imaging signal was further correlated with ex vivo Her2 levels by Western blot after sacrifice.
Her2 expression decreased with 17-DMAG dose in vitro. In vivo optical imaging signal was reduced by 22.5% in clone B (P = 0.003) and by 9% in MCF7 parental tumors (P = 0.23) 3 days after 17-DMAG treatment; optical imaging signal recovered in both tumor types at days 6 to 9. In the carrier group, no signal reduction was observed. Pearson correlation of in vivo optical imaging signal with ex vivo Her2 levels ranged from 0.73 to 0.89.
Optical imaging with an affibody can be used to noninvasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in positron emission tomography imaging studies.
本論文利用語料庫來檢視以英語爲母語的人士如何在現實生活中表示感激。本論文使用兩個著名的口語語料庫，一是密西根學術口語語料庫(Michigan Corpus of Academic Spoken English, or MICASE)，以及英國國家語料庫的口語部分British National Corpus (BNC, the spoken ...part)。這兩個口語語料庫都包括了各種類型的情境和說話者，與各種不同形式的互動。本文以質性與量性的方式分析以英語爲母語的人士在各種情境中表達感激的方式，並將感激用語分爲六大類。分析結果顯示以英語爲母語的人士最常使用thanks和thank you兩種感激用語。另外，研究成果亦歸納出thanks和thank you的各種不同的功用。例如，他們可以用於表示禮貌，回覆別人的感激，回絕他人的贈與或邀請，以及當作是對話的結束語，這類的用法多出現在BNC語料庫。MICASE語料庫則有較多的appreciate用法，感謝第三者，以及在正式演講場合所使用的較爲正式的感謝用語。對外語學習者而言，表達感激的方式就像其他語言行爲一樣需要加強學習。尤其要學習在適當的時間與情境下，表達適宜的感激方式, The present study takes a corpus-based approach to investigate the speech act of thanking. Two well-known spoken corpora MICASE and BNC (the spoken part) were used for quantitative and qualitative analysis. Six major categories were identified: (a) thanking, (b) appreciation, (c) non-gratitude, (d) combinations, (e) thanking a 3(superscript rd) person, and (f) formal speech. The results of the study indicate that the thanking strategy constituted the majority of the coded expressions; nevertheless, the second most frequent strategy is the non-gratitude strategy, which performs the illocutionary functions of relief, rejection of an offer, politeness, greetings, and conversation endings. Results also revealed that thank you is much more frequently used than thanks. In addition, data from MICASE show more varieties of strategies than BNC, particularly the more formal strategies such as appreciation, thanking a 3(superscript rd) person, and formal speech whereas BNC contains much more instances of the non-gratitude strategy than MICASE, reflecting register differences of the two corpora. In sum, the wide variety of thanking strategies, the numerous formulaic linguistic realizations, and the expected appropriate responses when being thanked, as shown from the corpora, suggest potential problems the speech act of thanking poses for second language learners.
e13717 Background: The 2023 Society for Integrative Oncology-ASCO joint guideline recommends mindfulness-based interventions (MBIs) as the non-pharmacologic therapy with the highest level of evidence ...to improve anxiety and depression symptoms experienced by adults with cancer. However, the evidence predominately derives from White breast cancer survivors. Racial and ethnic minority patients have less access to integrative symptom support and worse cancer outcomes. To address these gaps, we designed and piloted a series of mindfulness-based group medical visits (MB-GMVs), embedded into comprehensive cancer care, for racially and ethnically diverse patients in cancer treatment. Methods: As a quality improvement project, we launched a telehealth MB-GMV series for patients undergoing cancer treatment, delivered as four weekly 2-hour visits billable to insurance. Content was concordant with evidence-based guidelines and established MBIs and adapted to improve cultural relevance and fit (e.g., access-centered, trauma-informed, with inclusive communication practices). Program structure was adapted to address barriers to participation, with ≥50% slots per series reserved for racial and ethnic minority patients. Intake surveys incorporated a demographic questionnaire and symptom assessments. Evaluations were sent following the visits. Results: In our first ten cohorts (n=78), 80% of referred patients enrolled. Participants were: 22% Asian, 14% Black, 17% Latino, 45% non-Latino White; 65% female; with median age 54 years (range 27-79); and 80% had metastatic cancer. Common baseline symptoms included lack of energy, difficulty sleeping, and worrying. Most patients (90%) attended ≥3 visits. On final evaluations, 87% patients rated the series as “excellent”; 81% “strongly agreed” that they liked the GMV format; and 92% would “definitely” recommend the series to others. Qualitative themes included empowerment and connectedness. Conclusions: Telehealth GMVs are a feasible, acceptable, and financially sustainable model for increasing access to MBIs. Diverse patients in active cancer treatment were able to participate and reported high levels of satisfaction with this series that was tailored to center health equity and inclusion.
With increasing diversification of research, a research article depends much upon the title to encapsulate its distinctive content. The present study examines the syntactic structures and functions ...of research article titles in applied linguistics. Using a corpus of 796 titles from four journals that are included in the Social Sciences Citation Index, it identified five syntactic structures, namely, compound, nominal, full-sentence, V-ing phrase, and prepositional phrase. Of the five structures, compound titles, which enable research article writers to present dual foci of studies, constitute more than half of the occurrences, followed by nominal titles, which can concisely summarise the essence of studies. Each of the other three structures accounts for a very small percentage. A second-phase analysis was performed on the two constituent elements of the compound titles and on the heads and modifiers of the nominal titles. For the former, a total of eleven categories were found, revealing a wide variety of crucial aspects of research in applied linguistics, including mainly topic-scope, topic-method, topic-description, topic-source, metaphor-topic, and topic-question. For the nominal titles, both discipline-specific and non-discipline-specific heads were recognised. A majority of the discipline-specific heads are compound nouns, and prepositional phrases are widely used as post-modifiers. The analysis results provide useful information for the academic writing pedagogy. Author abstract, ed
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