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Organizational tasks and processes are preconditions for organizing professional learning teams but are often neglected in research. In nine schools, we examined which organizational tasks and processes were set up for lesson study, a form of a professional learning team, and in what way. Schools set up three organizational tasks and processes: recruiting participants, giving credit for time-investment, and scheduling meetings. Recruitment of participants was sometimes difficult when potential participants worked autonomously within their departments or teams. Credit for time-investment was often constrained as schools gave credit in a way that made lesson study an additional workload. Scheduling meetings was very challenging. The scheduled meetings were considered satisfactory in only one school. Here, the school leader collaborated and communicated with her teachers to plan useful and uninterrupted meetings in the timetable. Our results show that organizational work is not mundane and simple but complex and vital for embedding professional development in schools.

This research shares insights into the results of a three-year process of re-engineering general education at Brigham Young University--Hawaii (BYU--Hawaii), a private university, and the impact this change has conveyed to our students, curriculum, and faculty. The authors first describe the background of traditional general education, then describe the impetus for change. This is followed by a detailed explanation of the new general education program and the resulting impact on students, specifically those perusing degrees in computer science, information systems, and information technology.

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte- derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD., Introduction Crohn's disease (CD) is a chronic inflammatory condition affecting the gastrointestinal tract, characterized by transmural inflammation that often leads to complications such as strictures, fistulas, and abscesses. The disease [...]

Abstract Introduction Severe immune‐related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center. Methods All patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan–Meier method. Results Over the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti‐PD‐1 plus anti‐CTLA‐4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes‐related ketoacidosis (n = 8), immune‐related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2–6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0—NA). Conclusion The incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long‐term survival.

In this research project we describe the legacy software landscape, its current state, and challenges associated with aging information systems and access to its data. We briefly describe the popularity of dynamic languages and how a specific dynamic programming language, Ruby on Rails (RoR or Rails), is used to create a system to extract data from a legacy system to increase efficiency and productivity in an academic class scheduling system. As an example, we describe, first, how a system developed in Rails, called Class Scheduler, pulls data from a legacy student management system (MAPPER) developed in Tcl (pronounced "tickle") and uses this data to vastly increase the efficiency of the scheduling process and, second, how it reduces conflicts in class schedules. We discuss the advantages of automatically extracting and processing the data from the legacy system and the limitations associated with this process.

Abstract CD8+ T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against microsatellite stable (MSS) CRC is limited. Little is known about the most critical features of CRC CD8+ T cells that together determine the diverse immune landscapes and contrasting ICB responses. Hence, we pursued a deep single cell mapping of CRC CD8+ T cells on transcriptomic and T cell receptor (TCR) repertoire levels in a diverse patient cohort, with additional surface proteome validation. This revealed that CRC CD8+ T cell dynamics are underscored by complex interactions between interferon-γ signaling, tumor reactivity, TCR repertoire, (predicted) TCR antigen-specificities, and environmental cues like gut microbiome or colon tissue-specific ‘self-like’ features. MSI CRC CD8+ T cells showed tumor-specific activation reminiscent of canonical ‘T cell hot’ tumors, whereas the MSS CRC CD8+ T cells exhibited tumor unspecific or bystander-like features. This was accompanied by inflammation reminiscent of ‘pseudo-T cell hot’ tumors. Consequently, MSI and MSS CRC CD8+ T cells showed overlapping phenotypic features that differed dramatically in their TCR antigen-specificities. Given their high discriminating potential for CD8+ T cell features/specificities, we used the single cell tumor-reactive signaling modules in CD8+ T cells to build a bulk tumor transcriptome classification for CRC patients. This “Immune Subtype Classification” (ISC) successfully distinguished various tumoral immune landscapes that showed prognostic value and predicted immunotherapy responses in CRC patients. Thus, we deliver a unique map of CRC CD8+ T cells that drives a novel tumor immune landscape classification, with relevance for immunotherapy decision-making.

Abstract Background Due to the nursing shortage, positive work environments are needed to retain (student) nurses. More and attractive internships for students need to be ensured. In order to provide more internship places learning departments were developed, which are characterized by a buddy system and supervisors who coaches at least two students during a shift. Gaining knowledge about career perspectives and job satisfaction is essential within the context of learning departments, as both will contribute to quality and safety of care and will support lifelong learning. The current study aimed to investigate how nurses and nursing students working and learning in learning departments experience preconditions for career opportunities. Methods Using a generic qualitative approach, semi-structured interviews were conducted through videocalls between March and April 2021 in the Netherlands. Inductive qualitative analysis based on ‘The Data Analysis Spiral’ was used. Results Career perspective is explored among six students and seven nurses. Five main themes were generated for both nurses and students; (1) personal goals; (2) skills and self-efficacy; (3) mentoring; (4) job satisfaction; and (5) career perspectives. Within the five main themes, subcategories were developed from 198 codes related to career opportunities. Results show career perspective is experienced differently. For students, the requirements to experience career perspective seem largely existing, as learning departments fits with personal goals, increases self-efficacy and provide coaching mentoring. Students felt learning departments contributed positively to becoming more skilled in working independently and collaborating with fellow students. This resulted in students feeling well prepared for the future. Nurses’ career perspectives varied from wanting more personal development to experiencing opportunities due to having great colleagues, a challenging patient category, satisfaction from sharing knowledge and a decreasing physical workload. Nurses who had affinity with coaching students experience more career perspective on learning departments. Conclusion Interviews provided in-depth insights. Interviews gave in-depth insight into the elements of learning departments that contribute to career perspectives of (student)nurses. The results can be used by nursing supervisors, teachers and policymakers to optimize nurses’ work environment, to eliminate leave intentions and improve quality of patientcare. The results should be taken into consideration when coaching students, developing manuals and implementing or optimizing learning departments. Future research is recommended to investigate which tools/interventions are effective for nurses and other healthcare professionals to support career guidance.

In this research study, we performed a "content analysis" of selected introductory programming textbooks for three languages to examine which software development concepts are emphasized in these books. Our goal was to determine which concepts are considered to be most representative of software development based on the topics emphasized by the textbook authors. We counted how often programming words appeared in samples of C++, Java, and Python books. We discovered which concepts are consistently supported for all three languages. We also noted those concepts that are favored by just one or two languages. Our summarized results lead to several conclusions that are relevant to the choice of a language for an introductory programming course.

الملخص: أهداف البحث: هدفت هذه الدراسة إلى استكشاف تجارب سلامة المرضى المنومين في المستشفيات في أقسام تعليمية حيث يقدم الطلاب والممرضات الرعاية معا. طرق البحث: أجريت هذه الدراسة الاستكشافية النوعية العامة في المركز الطبي الجامعي في هولندا. تم أخذ عينات المرضى الذين تم تنويمهم في قسم تعليمي باستخدام طريقة العينة الهادفة. تم إجراء مقابلات فردية شبه منظمة. تم جمع البيانات بين فبراير وأبريل 2021. تم استخدام التحليل الموضوعي لتحليل البيانات. النتائج: ظهرت خمسة موضوعات رئيسة عند إجراء مقابلات مع المرضى (العدد = 13): وجود ممرضات خاضعات للمساءلة، والثقة من خلال الاستقلالية والدعم، وأخذ الوقت للتواصل، وبيئة تعليمية آمنة مع الدعم، وعدم الوعي بالتواجد في قسم تعليمي. أشار جميع المرضى إلى أنهم يشعرون بالأمان في القسم التعليمي. الاستنتاجات: شعر المرضى بالأمان عند تنويمهم في قسم تعليمي ولم يواجهوا أي اختلافات في الشعور بالأمان بين الممرضات والطلاب. يمكن أن يشعر المرضى بمزيد من الأمان في القسم إذا تم إبلاغهم مسبقا بقبولهم في قسم تعليمي، لكي يكونوا على دراية بوجود الطلاب. Abstract: Objectives: This study aimed to explore experiences of the safety of hospital-admitted patients in learning departments where students and nurses provide care together. Methods: This general qualitative explorative study was conducted in a University Medical Center in the Netherlands. Patients admitted to a learning department were purposefully sampled. Semi-structured individual interviews were conducted. Data was collected between February and April 2021. Thematic analysis was used to analyse the data. Results: Five main themes emerged after interviewing patients (n = 13): having accountable nurses, trust through autonomy and support, taking time to communicate, a safe learning environment with backup, and being unaware of being in a learning department. All patients indicated that they feel safe in a learning department. Conclusion: Patients felt safe being admitted to a learning department and experienced no differences in feeling safe between nurses and students. Patients can feel safer in the department if they are informed in advance that they have been admitted to a learning department, so they are aware of the presence of students.

Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

This review examines the concept of organizational routines and its potential for investigating educational initiatives in practice. The studies in our review revealed three different approaches to routines: (1) examining organizational routines as entities, (2) (also) examining conversational routines, and (3) examining the internal structure of organizational routines. Current definitions, operationalizations, and examinations can lack clarity and validity. At present, the concept of organizational routines not only holds potential but is also ambiguous. To bolster the potential of the concept, two working definitions of organizational routines are formalized that best allow researchers to investigate initiatives in practice. These working definitions are needed to create clarity regarding the concept and for it to be able to deliver on its promise for providing meaningful and relevant information on how new initiatives actually work and unfold in practice.

This study examines which school factors schools report influence their (dis)continuation of lesson study, a professional development initiative, and how after a four-year, cross-school lesson study project ends. To examine this, the framework on three types of school factors (features of employment, malleable school processes and fixed school characteristics) and the concept of organisational routines are used. Semistructured interviews were held with 21 teachers and 15 school leaders from the 14 schools who participated in the project. Findings show schools reported nine school factors that influenced their (dis)continuation of lesson study after the project: five features of employment (part-time appointment, turnover, (un)planned leave of absence, work location and beginning teachers), three malleable processes (policies on improvement, scheduling and school finances), and one fixed school characteristic (school size). School factors were reported to constrain schools from making lesson study a repeated practice in the school, performing its core features, and ensuring collective attendance. Two narrative portraits revealed that the simultaneous occurrence of school factors made continuing with lesson study especially complex and limited schools' ability to move beyond shortened and simplified initiatives to more rich and meaningful professional development.

This research study provides an examination of the relatively new fields of Data Analytics and Data Science. We compare word rates in Data Analytics and Data Science documents to determine which concepts are mentioned most often. The most frequent concept in both fields is "data." The word rate for "data" is more than twice the next highest word rate, which is for "model." This contrasts sharply with how often the word "data" appears in most Mathematics books. Overall, we observed substantial agreement on important concepts in Data Analysis and Data Science. Eighteen of the 25 most frequent concepts are shared by both fields. One difference is that the words "problem" and "solution" had Top 25 word rates for Data Science, but not for Data Analytics. A close look at Statistics concepts suggests that Data Analytics is more focused on "exploratory" concerns, such as searching for patterns in data. Data Science retains more of the classical inferential activities that use sample data to draw conclusions about populations. Both fields deal with Big Data situations, but Data Scientists must continue to be prepared for traditional small sample applications.

Abstract Background CRISPR screens provide large-scale assessment of cellular gene functions. Pooled libraries typically consist of several single guide RNAs (sgRNAs) per gene, for a large number of genes, which are transduced in such a way that every cell receives at most one sgRNA, resulting in the disruption of a single gene in that cell. This approach is often used to investigate effects on cellular fitness, by measuring sgRNA abundance at different time points. Comparing gene knockout effects between different cell populations is challenging due to variable cell-type specific parameters and between replicates variation. Failure to take those into account can lead to inflated or false discoveries. Results We propose a new, flexible approach called ShrinkCRISPR that can take into account multiple sources of variation. Impact on cellular fitness between conditions is inferred by using a mixed-effects model, which allows to test for gene-knockout effects while taking into account sgRNA-specific variation. Estimates are obtained using an empirical Bayesian approach. ShrinkCRISPR can be applied to a variety of experimental designs, including multiple factors. In simulation studies, we compared ShrinkCRISPR results with those of drugZ and MAGeCK, common methods used to detect differential effect on cell fitness. ShrinkCRISPR yielded as many true discoveries as drugZ using a paired screen design, and outperformed both drugZ and MAGeCK for an independent screen design. Although conservative, ShrinkCRISPR was the only approach that kept false discoveries under control at the desired level, for both designs. Using data from several publicly available screens, we showed that ShrinkCRISPR can take data for several time points into account simultaneously, helping to detect early and late differential effects. Conclusions ShrinkCRISPR is a robust and flexible approach, able to incorporate different sources of variations and to test for differential effect on cell fitness at the gene level. These improve power to find effects on cell fitness, while keeping multiple testing under the correct control level and helping to improve reproducibility. ShrinkCrispr can be applied to different study designs and incorporate multiple time points, making it a complete and reliable tool to analyze CRISPR screen data.

A genome-wide siRNA screen on patient-derived Fanconi anemia pathway-deficient head-and-neck squamous-cell-carcinoma (HNSCC) cell lines identifies RBBP9 as a candidate therapeutic target.

Abstract Dairy calves, including surplus calves, are typically separated from their dam within hours of birth. The aim of this study was to assess the welfare impacts of raising surplus calves destined for veal with their dam for 2 or 4 weeks until transport. Surplus calves from one dairy farm were separated from their dam at birth (n = 39) or kept with the dam (n = 37) until transport to the veal farm at either 2 (n = 50) or 4 (n = 26) weeks of age, with abrupt separation for dam-reared calves. Calf measures of body weight, health, immunity, haematology and behaviour were recorded at the dairy and veal farms. Dam-reared calves had higher body weights in weeks 3, 4 and 5 at the DF, as well as at arrival at the veal farm, but by slaughter this advantage was lost. More dam-reared calves had fever in week 3 and showed signs of disease in week 5 at the dairy farm. Dam-reared calves did not differ in IgG, IgA or IgM levels but had higher counts of white blood cells, which could reflect a higher pathogen exposure rather than improved immunity. Dam-reared calves displayed more fear towards humans in a human approach test at 5 and 7 weeks after arrival at the veal farm, and more frequent social behaviours at the veal farm at 9 and 16 weeks of age. In conclusion, it seems that there may be both advantages and disadvantages to keeping veal calves with the dam in terms of welfare in the current system.

Aim: Pleural dissemination of pseudomyxoma peritonei (PMP) is an extremely rare diagnosis, for which no standard therapy is available.Methods: We describe the successful treatment of a 67-year-old male diagnosed with left-sided intrapleural dissemination of PMP (low-grade appendiceal mucinous neoplasm), 2 years after treatment of abdominal PMP with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy. Treatment consisted of extended pleural decortication (ePD) and oxaliplatin-based hyperthermic intrathoracic chemotherapy (HITHOC). The patient is doing well without complications or signs of recurrence, 26 months after thoracic surgery.Conclusion: ePD in combination with HITHOC is a valuable treatment for thoracic PMP.

Purpose: To report on organ preservation following chemoradiotherapy (CRT) in a prospective cohort of locally advanced rectal cancer patients. Methods and materials: Fifty-two patients received CRT. MRI and 18F-FDG-PET/CT were performed prior to CRT. Response assessment was done 6 and 12 weeks after CRT using digital rectal examination, MRI, 18F-FDG-PET/CT and endoscopy. For clinical complete response or minimal residual disease, a watch-and-wait (W&W) protocol was started.Regrowth-free survival (ReFS), Total Mesorectal Excision-free disease-free survival, distant metastasis-free survival (DMFS) and overall survival (OS) were evaluated using Kaplan-Meier method. Functional outcome was compared with the Wilcoxon signed-rank test using EORTC QLQ-C30, MSKCC BFI, LARS and IIEF-5/FSFI-5 questionnaires. A previously developed prediction model performance was tested using receiver operating characteristic analysis. Results: 29/52 patients entered a W&W protocol. There was no difference in two-year DMFS (81.1 % vs 78.8 %, p = 0.82), two-year OS (96.4 % vs 100 %, p = 0.38) and two-year DFS (77.5 % vs 78.8 %, p = 0.87) between W&W patients and those who underwent surgery at 12 weeks after CRT. Two-year DMFS differed between W&W with local regrowth, W&W with sustained response and patients who had surgery (66.7 % vs 88.0 % vs 78.8 %; p = 0.04). At 6 and 12 months, W&W patients reported good QoL and bowel function. The model validation reached an AUC of 0.627. Conclusion: Good functional outcome in patients with rectal cancer allocated to surveillance after CRT needs to be balanced against potentially worse DMFS in a subset of patients without sustained clinical complete response. Reliable prediction of patients eligible for surveillance programs needs further investigation.

In this research, we compare two languages, Java and Python, by performing a content analysis of words in textbooks that describe important programming concepts. Our goal is to determine which language has better textbook support for teaching introductory programming courses. We used the TextSTAT program to count how often our list of concept words appear in a sample of Java and Python textbooks. We summarize and compare the results, leading to several conclusions that relate to the choice of language for a CS0 or CS1 course.

Host genotype, early post-hatch feeding, and pre- and probiotics are factors known to modulate the gut microbiome. However, there is a knowledge gap on the effect of both chicken genotype and these dietary strategies and their interplay on fecal microbiome composition and diversity, which, in turn, can affect the release of endotoxins in the excreta of broilers. Endotoxins are a major concern as they can be harmful to both animal and human health. The main goal of the current study was to investigate whether it was possible to modulate the fecal microbiome, thereby reducing endotoxin concentrations in the excreta of broiler chickens. An experiment was carried out with a 2 × 2 × 2 factorial arrangement including the following three factors: 1) genetic strain (fast-growing Ross 308 vs. slower growing Hubbard JA757); 2) no vs. combined use of probiotics and prebiotics in the diet and drinking water; and 3) early feeding at the hatchery vs. non-early feeding. A total of 624 Ross 308 and 624 Hubbard JA757 day-old male broiler chickens were included until d 37 and d 51 of age, respectively. Broilers (N = 26 chicks/pen) were housed in a total of 48 pens, and there were six replicate pens/treatment groups. Pooled cloacal swabs (N = 10 chickens/pen) for microbiome and endotoxin analyses were collected at a target body weight (BW) of 200 g, 1 kg, and 2.5 kg. Endotoxin concentration significantly increased with age (p = 0.01). At a target BW of 2.5 kg, Ross 308 chickens produced a considerably higher amount of endotoxins (Δ = 552.5 EU/mL) than the Hubbard JA757 chickens (p < 0.01). A significant difference in the Shannon index was observed for the interaction between the use of prebiotics and probiotics, and host genotype (p = 0.02), where Ross 308 chickens with pre-/probiotics had lower diversity than Hubbard JA757 chickens with pre-/probiotics. Early feeding did not affect both the fecal microbiome and endotoxin release. Overall, the results suggest that the chicken genetic strain may be an important factor to take into account regarding fecal endotoxin release, although this needs to be further investigated under commercial conditions.