Strategies for enhancing Chinese students' engagement in a large class learning environment: An interpretative phenomenological approach.

AIM: It is common for Chinese students to sit quietly during classroom lectures, attentively following teachers' instructions without interacting or asking questions, viewed as passive engagement. This study aims to understand further the passive engagement of Chinese students in relation to classroom questioning, just-in-time feedback and collaborative activities. With objectives to formulate strategies to enhance Chinese students' engagement in a large class learning environment without undermining the cultural dimension of "face". BACKGROUND: Engaging in collaborative educational activities between teachers and students can be challenging in a large classroom learning environment. Within the Chinese context, Confucian-heritage culture may further exacerbate the challenges teachers face. Chinese students often appear passive when responding to questions. In this situation, educators may receive insufficient student feedback to modify and optimise their teaching and learning approaches. DESIGN: A qualitative research method, with an interpretative phenomenological approach was employed in a self-financed institute of higher education in Hong Kong. METHODS: Eight nursing graduates were invited to participate in two focus group interviews to generate teaching and learning strategies. In addition, individual in-depth interviews were conducted with twelve nursing teachers recruited through a snowballing sampling strategy. The narratives were coded, categorised, themed, analysed and interpreted through thematic analysis. RESULTS: Chinese students are concerned with "losing face" and the fear of being teased by their peers in a collectivist culture. Based on these findings, three teaching and learning strategies for engaging students in classroom questioning and collaborative activities were generated. These strategies include using digital learning platforms, the promotion of communication and fostering interpersonal relationships. CONCLUSIONS: In higher education, academic managers and teachers must critically reflect on teaching and learning strategies tailor-made to different cultural and contextual settings. Collaborating on pedagogical reforms can provide solid guidance and insight on implementing student-centred learning for Chinese students in large class learning environments while respecting the cultural dimension of "face".

The prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. MATERIALS AND METHODS: In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. RESULTS: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. CONCLUSIONS: A high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.

Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Nutri-score is now widely available in food packages in Europe. AIM: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort METHODS: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake. RESULTS: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24-3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69-1.21; p-trend: 0.76). CONCLUSIONS: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Genomic structures and regulation patterns at HPV integration sites in cervical cancer.

Human papillomavirus (HPV) integration has been implicated in transforming HPV infection into cancer, but its genomic consequences have been difficult to study using short-read technologies. To resolve the dysregulation associated with HPV integration, we performed long-read sequencing on 63 cervical cancer genomes. We identified six categories of integration events based on HPV-human genomic structures. Of all HPV integrants, defined as two HPV-human breakpoints bridged by an HPV sequence, 24% contained variable copies of HPV between the breakpoints, a phenomenon we termed heterologous integration. Analysis of DNA methylation within and in proximity to the HPV genome at individual integration events revealed relationships between methylation status of the integrant and its orientation and structure. Dysregulation of the human epigenome and neighboring gene expression in cis with the HPV-integrated allele was observed over megabase-ranges of the genome. By elucidating the structural, epigenetic, and allele-specific impacts of HPV integration, we provide insight into the role of integrated HPV in cervical cancer.

The genome and sex-dependent responses to temperature in the common yellow butterfly, Eurema hecabe.

BACKGROUND: Lepidoptera (butterflies and moths) is one of the most geographically widespread insect orders in the world, and its species play important and diverse ecological and applied roles. Climate change is one of the biggest challenges to biodiversity this century, and lepidopterans are vulnerable to climate change. Temperature-dependent gene expression differences are of relevance under the ongoing climate crisis. However, little is known about how climate affects gene expression in lepidopterans and the ecological consequences of this, particularly with respect to genes with biased expression in one of the sexes. The common yellow butterfly, Eurema hecabe (Family Pieridae), is one of the most geographically widespread lepidopterans that can be found in Asia, Africa, and Australia. Nevertheless, what temperature-dependent effects there may be and whether the effects differ between the sexes remain largely unexplored. RESULTS: Here, we generated high-quality genomic resources for E. hecabe along with transcriptomes from eight developmental stages. Male and female butterflies were subjected to varying temperatures to assess sex-specific gene expression responses through mRNA and microRNA transcriptomics. We find that there are more temperature-dependent sex-biased genes in females than males, including genes that are involved in a range of biologically important functions, highlighting potential ecological impacts of increased temperatures. Further, by considering available butterfly data on sex-biased gene expression in a comparative genomic framework, we find that the pattern of sex-biased gene expression identified in E. hecabe is highly species-specific, rather than conserved across butterfly species, suggesting that sex-biased gene expression responses to climate change are complex in butterflies. CONCLUSIONS: Our study lays the foundation for further understanding of differential responses to environmental stress in a widespread lepidopteran model and demonstrates the potential complexity of sex-specific responses of lepidopterans to climate change.

Tetraplegic spinal cord injury as a presentation of multiple myeloma: A case report.

Spinal cord injury is a devastating complication of cancers that exert physical compression on the spinal cord. Multiple myeloma is known predominantly as a condition that involves bony structures and can manifest with complications such as pathological fractures. However, involvement of other structures including spinal cord is a possible complication, with potentially catastrophic consequences. We describe a case of multiple myeloma presenting initially as severe paraplegia secondary to spinal cord compression in a 79-year-old man.

Food Processing and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. METHODS: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. RESULTS: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I2 = 0%). CONCLUSIONS: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.

Defining the heterogeneity of unbalanced structural variation underlying breast cancer susceptibility by nanopore genome sequencing.

Germline structural variants (SVs) are challenging to resolve by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at cancer susceptibility loci has not been reported. Nanopore long-read genome sequencing was performed for nineteen individuals with pathogenic copy number alterations in BRCA1, BRCA2, CHEK2 and PALB2 identified by prior clinical testing. Fourteen variants, which spanned single exons to whole genes and included a tandem duplication, were accurately represented. Defining the precise breakpoints of SVs in BRCA1 and CHEK2 revealed unforeseen allelic heterogeneity and informed the mechanisms underlying the formation of recurrent deletions. Integrating read-based and statistical phasing further helped define extended haplotypes associated with founder alleles. Long-read sequencing is a sensitive method for characterizing private, recurrent and founder SVs underlying breast cancer susceptibility. Our findings demonstrate the potential for nanopore sequencing as a powerful genetic testing assay in the hereditary cancer setting.

Diet Quality and Risk of Older-onset Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to assess the relationship between diet quality and risk of older-onset Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: We conducted a prospective cohort study of 83 147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaires to calculate adherence scores to multiple derived healthy diet patterns: Alternate Healthy Eating Index [AHEI], Healthy Eating Index-2015 [HEI-2015], Healthful Plant-Based Diet Index [HPDI], and modified Mediterranean Diet Score [mMED] at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modelling to estimate the adjusted hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest with the lowest quartiles, the adjusted HRs of CD were 0.73 [95% CI, 0.48, 1.12, ptrend = 0.123] for AHEI; 0.90 [0.57, 1.41, ptrend = 0.736] for HEI 2015; 0.52 [95% CI 0.32, 0.85, ptrend = 0.011] for HPDI; and 0.58 [95% CI 0.32, 1.06, ptrend = 0.044] for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC. CONCLUSIONS: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions in designing future prevention strategies for IBD.

Food Processing and Risk of Crohn's Disease and Ulcerative Colitis: A European Prospective Cohort Study.

BACKGROUND & AIMS: Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption. RESULTS: During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend < .01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks. CONCLUSIONS: In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.

Meat Intake Is Associated with a Higher Risk of Ulcerative Colitis in a Large European Prospective Cohort Studyø.

BACKGROUND AND AIMS: We aimed to investigate the association between protein intake and risk of inflammatory bowel disease [IBD] in the European Prospective Investigation into Cancer and Nutrition. METHODS: A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins [total, animal, and vegetable] or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models. RESULTS: After a mean follow-up of 16 years, 177 patients with Crohn's disease [CD] and 418 with ulcerative colitis [UC], were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio [HR] for the 4th vs 1st quartile = 1.40, 95% confidence interval [CI] = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively]. There was no association between other food sources of animal protein [processed meat, fish, shellfish, eggs, poultry] and UC. We found no association between food sources of animal proteins and CD risk. CONCLUSIONS: Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.

Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia.

Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.

Oro-pharyngo-esophageal radionuclide scintigraphy predicts aspiration pneumonia risk and associated survival in post-irradiated nasopharyngeal carcinoma patients.

OBJECTIVE: To demonstrate that oro-pharyngo-esophageal radionuclide scintigraphy (OPERS) not only detects tracheobronchial aspiration after swallowing, but also quantifies the amount of aspiration and subsequent clearance. METHODS: Data collected between 2014 and 2019 were reviewed for aspiration pneumonia at 12 and 24-months after OPERS. The predictive value for aspiration pneumonia on flexible endoscopic evaluation of swallowing (FEES), videofluoroscopic swallowing study (VFSS), and OPERS, and the overall survival of patients with or without aspiration were determined. RESULTS: Thirty-seven patients treated with radiotherapy for nasopharyngeal carcinoma (NPC) were reviewed. The incidence of aspiration detected on FEES, VFSS, and OPERS was 78.4%, 66.7%, and 44.4%, respectively. Using VFSS as a gold standard, the sensitivity and specificity of OPERS for aspiration was 73.7% and 100%. The positive and negative predictive values for aspiration were 100% and 66.7%, respectively, with an overall accuracy of 82.8%. A history of aspiration pneumonia was one factor associated with a higher chance of subsequent aspiration pneumonia within 12 months (odds ratio: 15.5, 95% CI 1.67-145.8, p < .05) and 24 months (odds ratio: 23.8, 95% CI 3.69-152.89, p < .01) of the swallowing assessment. Aspiration detected by OPERS was a significant risk factor for future aspiration pneumonia at 12 and 24 months respectively. Significantly, better survival was associated with an absence of aspiration on OPERS only, but not on FEES or VFSS. CONCLUSION: OPERS predicts the safety of swallowing, the incidence of subsequent aspiration pneumonia, and the survival prognosis in post-irradiated NPC dysphagia patients. LEVEL OF EVIDENCE: 3.

Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies.

BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.

Lifestyle factors for the prevention of inflammatory bowel disease.

OBJECTIVE: To estimate the proportion of cases of Crohn's disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors. DESIGN: In a prospective cohort study of US adults from the Nurses' Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0-6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0-9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144). RESULTS: Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986-2016; NHSII: 1991-2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%-51.2% and 48.8%-60.4% of CD cases and 20.6%-27.8% and 46.8%-56.3% of UC cases. CONCLUSIONS: Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

Epigenetically mismatched parental centromeres trigger genome elimination in hybrids.

Wide crosses result in postzygotic elimination of one parental chromosome set, but the mechanisms that result in such differential fate are poorly understood. Here, we show that alterations of centromeric histone H3 (CENH3) lead to its selective removal from centromeres of mature Arabidopsis eggs and early zygotes, while wild-type CENH3 persists. In the hybrid zygotes and embryos, CENH3 and essential centromere proteins load preferentially on the CENH3-rich centromeres of the wild-type parent, while CENH3-depleted centromeres fail to reconstitute new CENH3-chromatin and the kinetochore and are frequently lost. Genome elimination is opposed by E3 ubiquitin ligase VIM1. We propose a model based on cooperative binding of CENH3 to chromatin to explain the differential CENH3 loading rates. Thus, parental CENH3 polymorphisms result in epigenetically distinct centromeres that instantiate a strong mating barrier and produce haploids.

Assessment of pharyngeal motor function using a novel velopharyngeal squeeze maneuver and a novel endoscopic pharyngeal contraction grade scale in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: To investigate a novel velopharyngeal squeeze maneuver (VPSM) and novel endoscopic pharyngeal contraction grade (EPCG) scale for the evaluation of pharyngeal motor function. METHODS: During endoscopic examination of 77 post-irradiated nasopharyngeal carcinoma patients and control subjects, VPSM was rated and lateral pharyngeal wall movement graded with EPCG scale during swallowing. Pharyngeal constriction ratio (PCR) measured by videofluoroscopy was used for correlation. RESULTS: VPSM and EPCG scale showed almost perfect intra-rater and inter-rater reliability (Kappa: >0.90). VPSM was present in 61% of patients suggesting good pharyngeal motor function. VPSM was predictive of EPCG scale (Wald statistic = 29.99, p < 0.001). EPCG scale also correlated strongly with PCR (r: 0.812) and was predictive for aspiration (odds ratio: 22.14 [95% CI 5.01-97.89, p < 0.001]). CONCLUSIONS: VPSM and EPCG scale are two novel tools to assess pharyngeal motor function, and both correlate well with pharyngeal contractility and aspiration.

A clinical transcriptome approach to patient stratification and therapy selection in acute myeloid leukemia.

As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.