bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency
Authors: Kwon Jong-Wan , Oh Jeong-Seop , Seok Sang Hyeok , An Hyeok-Won , Lee Yu Jin , Lee Na Yun , Ha Taehun , Kim Hyeon Ah , Yoon Gyeong Min , Kim Sung Eun , Oh Pu-Reum , Lee Su-Hyung , Voon Dominic C. , Kim Dae-Yong , Park Jun Won
Published: September 2023

Background

Targetable molecular drivers of gastric cancer (GC) metastasis remain largely unidentified, leading to limited targeted therapy options for advanced GC. We aimed to identify molecular drivers for metastasis and devise corresponding therapeutic strategies.

Methods

We performed an unbiased in vivo genome-wide CRISPR/Cas9 knockout (KO) screening in peritoneal dissemination using genetically engineered GC mouse models. Candidate genes were validated through in vivo transplantation assays using KO cells. We analyzed target expression patterns in GC clinical samples using immunohistochemistry. The functional contributions of target genes were studied through knockdown, KO, and overexpression approaches in tumorsphere and organoid assays. Small chemical inhibitors against Bcl-2 members and YAP were tested in vitro and in vivo.

Results

We identified Nf2 and Rasa1 as metastasis-suppressing genes through the screening. Clinically, RASA1 mutations along with low NF2 expression define a distinct molecular subtype of metastatic GC exhibiting aggressive traits. NF2 and RASA1 deficiency increased in vivo metastasis and in vitro tumorsphere formation by synergistically amplifying Wnt and YAP signaling in cancer stem cells (CSCs). NF2 deficiency enhanced Bcl-2-mediated Wnt signaling, conferring resistance to YAP inhibition in CSCs. This resistance was counteracted via synthetic lethality achieved by simultaneous inhibition of YAP and Bcl-2. RASA1 deficiency amplified the Wnt pathway via Bcl-xL, contributing to cancer stemness. RASA1 mutation created vulnerability to Bcl-xL inhibition, but the additional NF2 deletion conferred resistance to Bcl-xL inhibition due to YAP activation. The combined inhibition of Bcl-xL and YAP synergistically suppressed cancer stemness and in vivo metastasis in RASA1 and NF2 co-deficiency.

Conclusion

Our research unveils the intricate interplay between YAP and Bcl-2 family members, which can lead to synthetic lethality, offering a potential strategy to overcome drug resistance. Importantly, our findings support a personalized medicine approach where combined therapy targeting YAP and Bcl-2, tailored to NF2 and RASA1 status, could effectively manage metastatic GC.
Prevalence of blood stream infections and associated factors among febrile neutropenic cancer patients on chemotherapy at Ocean Road Cancer Institute, Tanzania
Authors: Safari Lambert C. , Mloka Doreen , Minzi Omary , Dharsee Nazima J. , Reuben Rabson
Published: September 2023

Background

Febrile Neutropenia (FN) caused by bacteria in cancer patients is associated with poor prognosis. The aim of this study was to determine the prevalence of FN and associated factors among cancer patients on chemotherapy at Ocean Road Cancer Institute (ORCI), Tanzania.

Methods

A cross-sectional study was conducted from June to September 2019. Study participants were conveniently recruited. A desk review of participants medical records was performed. Standard microbiological procedures used to culture and identify the bacterial isolates from the positive blood cultures of participants that presented with FN. Kirby-Bauer disc diffusion was used to perform the antibiotics susceptibility testing. SPSS version 20.0 and MS Excel were used in data entry and analysis. Chi-Square was used as a measure of association between various factors and neutropenia. P-value less than 0.05 was considered statistically significant.

Results

A total 213 participants were enrolled. Of these 76.1% were female. Most of the participants came from the Coast region. Majority of participants presented with breast Cancer (36.2%) and GIT (20.2%). The prevalence of FN and bacteremia was 5.6% and 35.3% respectively. Staphylococcus Aureus (60%) and Coagulase-Negative Staphylococci (40%) were the main isolates. Of the 6 isolates tested most were resistant to Co-Trimoxazole 4/6 (66.7%) and Doxycycline 3/6 (50%). FN was positively associated with chemotherapy regimen (P = 0.0001), platelets count (P = 0.0001) and use of G-CSF (P = 0.0001).

Conclusion

The prevalence of FN among the cancer patients on chemotherapy in Tanzania is low but associated with drug-resistant bacteria.
A Novel pyroptosis-related signature for predicting prognosis and evaluating tumor immune microenvironment in ovarian cancer
Authors: Yang Jiani , Wang Chao , Zhang Yue , Cheng Shanshan , Xu Yanna , Wang Yu
Published: September 2023

Ovarian cancer (OV) is the most fatal gynecological malignant tumor worldwide, with high recurrence rates and great heterogeneity. Pyroptosis is a newly-acknowledged inflammatory form of cell death with an essential role in cancer progression, though studies focusing on prognostic patterns of pyroptosis in OV are still lacking. Our research filtered 106 potential pyroptosis-related genes (PRGs) among the 6406 differentially expressed genes (DEGs) between the 376 TCGA-OV samples and 180 normal controls. Through the LASSO-Cox analysis, the 6-gene prognostic signature, namely CITED2, EXOC6B, MIA2, NRAS, SETBP1, and TRPV46, was finally distinguished. Then, the K-M survival analysis and time-dependent ROC curves demonstrated the promising prognostic value of the 6-gene signature (p-value < 0.0001). Furthermore, based on the signature and corresponding clinical features, we constructed and validated a nomogram model for 1-year, 2-year, and 3-year OV survival, with reliable prognostic values in TCGA-OV (p-value < 0.001) and ICGC-OV cohort (p-value = 0.040). Pathway analysis enriched several critical pathways in cancer, refer to the pyroptosis-related signature, while the m6A analysis indicated greater m6A level in high-risk group. We assessed tumor immune microenvironment through the CIBERSORT algorithm, which demonstrated the upregulation of M1 Macrophages and activated DCs and high expression of key immune checkpoint molecules (CTLA4, PDCD1LG2, and HAVCR2) in high-risk group. Interestingly, the high-risk group exhibited poor sensitivity towards immunotherapy and better sensitivity towards chemotherapies, including Vinblastine, Docetaxel, and Sorafenib. Briefly, the pyroptosis-related signature was a promising tool to predict prognosis and evaluate immune responses, in order to assist decision-making for OV patients in the realm of precision medicine.
The potential influence of follicle diameter on natural cycle in vitro fertilization among women with diminished ovarian reserve: a retrospective cohort study
Authors: Tian Tian , Li Yu , Lv Jiaxin , Chen Lixue , Wang Yuanyuan , Yang Rui , Liu Ping , Li Rong , Qiao Jie
Published: September 2023

Background

Natural cycle- in vitro fertilization (NC-IVF) is particularly recommended for women with decreased ovarian reserve (DOR) or poor response to controlled ovarian hyperstimulation. In these cases, it can be challenging to determine the optimal timing for a trigger, and follicles of varying sizes are typically obtained. The influence of follicular size on IVF outcomes in women with DOR remains uncertain. This study aims to investigate the association between different follicular sizes and NC-IVF outcomes in women with DOR.

Methods

A retrospective cohort study involving 477 NC-IVF cycles from 2015 to 2021 was conducted at one of the largest reproductive medical centers in China. Follicular growth was monitored using transvaginal ultrasonography, and the follicles were categorized into three groups based on their diameters:12–15 mm; 16–17 mm and ≥ 18 mm. Laboratory outcomes were evaluated, including the number of canceled cycles, number of oocytes retrieved, 2PN fertilization, embryo and good-quality embryo, fresh embryo transfers, and frozen embryo. Additionally, clinical outcomes, such as the rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth, were investigated and compared among the different follicular size groups.

Results

A total of 68 cycles with follicles sizes of 12-15 mm, 171 cycles with follicles sizes of 16-17 mm, and 236 cycles with follicles sizes ≥ 18 mm were included in this study. The basic characteristics, including female age, male age, infertility duration, infertility type, and parity, were comparable among the groups. The rate of cycle cancellation in the 12–15 mm group (27.9%) was higher compared to the other two groups. The 2PN fertilization rate for follicles with a diameter of 16-17 mm (75.0%) was higher than that of follicles with a diameter of 12-15 mm (61.3%) and ≥ 18 mm (56.6%) (P = 0.031). Other clinical outcomes, such as the number of oocytes retrieved, good-quality embryos, fresh embryo transfers, and frozen embryos, did not show significant differences between groups. Further analysis revealed no significant difference in the rates of clinical pregnancy, ongoing pregnancy, and live birth rate among the three groups.

Conclusions

This study indicates that in women with DOR undergoing NC-IVF, if a premature LH surge occurs and small follicles are retrieved, these follicles can still be used in subsequent treatment and provide a comparable chance of clinical pregnancy to normal-sized follicles. These findings have important implications for guiding NC-IVF treatment in patients with severe DOR.

Trial registration number

N/A.
DISCERN: deep single-cell expression reconstruction for improved cell clustering and cell subtype and state detection
Authors: Hausmann Fabian , Ergen Can , Khatri Robin , Marouf Mohamed , Hänzelmann Sonja , Gagliani Nicola , Huber Samuel , Machart Pierre , Bonn Stefan
Published: September 2023

Background

Single-cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering and cell type identification.

Results

Here, we present DISCERN, a novel deep generative network that precisely reconstructs missing single-cell gene expression using a reference dataset. DISCERN outperforms competing algorithms in expression inference resulting in greatly improved cell clustering, cell type and activity detection, and insights into the cellular regulation of disease. We show that DISCERN is robust against differences between batches and is able to keep biological differences between batches, which is a common problem for imputation and batch correction algorithms. We use DISCERN to detect two unseen COVID-19-associated T cell types, cytotoxic CD4+ and CD8+ Tc2 T helper cells, with a potential role in adverse disease outcome. We utilize T cell fraction information of patient blood to classify mild or severe COVID-19 with an AUROC of 80% that can serve as a biomarker of disease stage. DISCERN can be easily integrated into existing single-cell sequencing workflow.

Conclusions

Thus, DISCERN is a flexible tool for reconstructing missing single-cell gene expression using a reference dataset and can easily be applied to a variety of data sets yielding novel insights, e.g., into disease mechanisms.
Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer’s disease
Authors: Delgado-Peraza Francheska , Nogueras-Ortiz Carlos , Simonsen Anja Hviid , Knight De’Larrian DeAnté , Yao Pamela J. , Goetzl Edward J. , Jensen Camilla Steen , Høgh Peter , Gottrup Hanne , Vestergaard Karsten , Hasselbalch Steen Gregers , Kapogiannis Dimitrios
Published: September 2023

Background

Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RCT) of exercise ADEX.

Methods

proBDNF, BDNF, and humanin were quantified in NDEVs immunocaptured from the plasma of 95 ADEX participants, randomized into exercise and control groups, and collected at baseline and 16 weeks. Exploratorily, we also quantified NDEV levels of putative exerkines known to respond to exercise in peripheral tissues.

Results

NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group, especially in APOE ε4 carriers, but remained unchanged in the control group. Inter-correlations between NDEV biomarkers observed at baseline were maintained after exercise. NDEV levels of putative exerkines remained unchanged.

Conclusions

Findings suggest that the cognitive benefits of exercise could be mediated by the upregulation of neuroprotective factors in NDEVs. Additionally, our results indicate that AD subjects carrying APOE ε4 are more responsive to the neuroprotective effects of physical activity. Unchanged NDEV levels of putative exerkines after physical activity imply that exercise engages different pathways in neurons and peripheral tissues. Future studies should aim to expand upon the effects of exercise duration, intensity, and type in NDEVs from patients with early AD and additional neurodegenerative disorders.

Trial registration

The Effect of Physical Exercise in Alzheimer Patients (ADEX) was registered in ClinicalTrials.gov on April 30, 2012 with the identifier NCT01681602.

Graphical abstract
The relationship between methodological quality and the use of retracted publications in evidence syntheses
Authors: Bakker Caitlin J. , Theis-Mahon Nicole , Brown Sarah Jane , Zeegers Maurice P.
Published: September 2023

Background

Evidence syntheses cite retracted publications. However, citation is not necessarily endorsement, as authors may be criticizing or refuting its findings. We investigated the sentiment of these citations—whether they were critical or supportive—and associations with the methodological quality of the evidence synthesis, reason for the retraction, and time between publication and retraction.

Methods

Using a sample of 286 evidence syntheses containing 324 citations to retracted publications in the field of pharmacy, we used AMSTAR-2 to assess methodological quality. We used scite.ai and a human screener to determine citation sentiment. We conducted a Pearson’s chi-square test to assess associations between citation sentiment, methodological quality, and reason for retraction, and one-way ANOVAs to investigate association between time, methodological quality, and citation sentiment.

Results

Almost 70% of the evidence syntheses in our sample were of critically low quality. We found that these critically low-quality evidence syntheses were more associated with positive statements while high-quality evidence syntheses were more associated with negative citation of retracted publications. In our sample of 324 citations, 20.4% of citations to retracted publications noted that the publication had been retracted.

Conclusion

The association between high-quality evidence syntheses and recognition of a publication’s retracted status may indicate that best practices are sufficient. However, the volume of critically low-quality evidence syntheses ultimately perpetuates the citation of retracted publications with no indication of their retracted status. Strengthening journal requirements around the quality of evidence syntheses may lessen the inappropriate citation of retracted publications.
Expression of miR-138 in cryopreserved bovine sperm is related to their fertility potential
Authors: Salas-Huetos Albert , Ribas-Maynou Jordi , Mateo-Otero Yentel , Tamargo Carolina , Llavanera Marc , Yeste Marc
Published: September 2023

Background

MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules of 22–24 nucleotides that regulate gene expression. In the last decade, miRNAs have been described in sperm of several mammals, including cattle. It is known that miRNAs can act as key gene regulators of early embryogenesis in mice and humans; however, little is known about the content, expression, and function of sperm-borne miRNAs in early bovine embryo. In this study, total sperm RNA was isolated from 29 cryopreserved sperm samples (each coming from a separate bull) using a RNeasy kit and treatment with DNase I. RNA concentration and purity were determined through an Epoch spectrophotometer and an Agilent Bioanalyzer. The expression of 10 candidate miRNAs in bovine sperm (bta-miR-10a, bta-miR-10b, bta-miR-138, bta-miR-146b, bta-miR-19b, bta-miR-26a, bta-miR-34a, bta-miR-449a, bta-miR-495 and bta-miR-7), previously identified in testis and/or epididymis, was evaluated with RT-qPCR. The cel-miR-39-3p was used as a spike-in exogenous control. Nonparametric Mann–Whitney tests were run to evaluate which miRNAs were differentially expressed between bulls with high fertility [HF; non-return rates (NRR) ranging from 39.5 to 43.5] and those with subfertility (SF; NRR ranging from 33.3 to 39.3). Several sperm functionality parameters (e.g., viability, membrane stability or oxygen consumption, among others) were measured by multiplexing flow cytometry and oxygen sensing technologies.

Results

RNA concentration and purity (260/280 nm ratio) (mean ± SD) from the 29 samples were 99.3 ± 84.6 ng/µL and 1.97 ± 0.72, respectively. Bioanalyzer results confirmed the lack of RNA from somatic cells. In terms of the presence or absence of miRNAs, and after applying the Livak method, 8 out of 10 miRNAs (bta-miR-10b, -138, -146b, -19b, -26a, -449a, -495, -7) were consistently detected in bovine sperm, whereas the other two (bta-miR-10a, and -34a) were absent. Interestingly, the relative expression of one miRNA (bta-miR-138) in sperm was significantly lower in the SF than in the HF group (P = 0.038). In addition to being associated to fertility potential, the presence of this miRNA was found to be negatively correlated with sperm oxygen consumption. The expression of three other miRNAs (bta-miR-19b, bta-miR-26a and bta-miR-7) was also correlated with sperm function variables.

Conclusions

In conclusion, although functional validation studies are required to confirm these results, this study suggests that sperm bta-miR-138 is involved in fertilization events and beyond, and supports its use as a fertility biomarker in cattle.
Exploring the synergy between Karst World Heritage site's OUV conservation and buffer zone’s tourism industry development: a case study of the Libo-Huanjiang Karst
Authors: Zhang Juan , Xiong Kangning , Liu Zhaojun , He Lixiang , Zhang Ning , Gu Xinyan , Chen Dong
Published: September 2023

Karst World Heritage Site (KWHS) combines high-grade landscape resources and a fragile ecological environment. As an essential tool for heritage conservation and maintaining local interests, its buffer zone is primarily located in remote villages, a crucial and challenging area for rural revitalization. The conflict between heritage conservation and development is particularly acute at the site. How to deal with the relationship between the heritage site’s OUV conservation and the buffer zone's tourism industry development and realize the synergy between the two subsystems? Few studies have focused on it. There is an urgent need to explore the synergistic mechanism of the KWHS's OUV conservation and the buffer zone's tourism industry development. Accordingly, this study takes the Libo-Huanjiang KWHS, one of the 'South China Karst' series of heritage sites, as a case study. The coupling coordination degree model, gray correlation analysis (GCA), and Geographic Information System (GIS) spatial analysis are used. The results show that: (1) There is a synergistic effect between the Libo-Huanjiang KWHS's OUV conservation and its buffer zone's tourism industry development, showing a favorable trend. The mean value of the coupling coordination degree increased from 0.57 in 2015 to 0.63 in 2020, and the overall situation improved from barely coupling coordination state to primary coupling coordination. (2) Influenced by the main driving factors, such as NDVI, landscape dominance, government support for tourism development, tourists' satisfaction, and residents' support, the coupling coordination of the four tourist scenic areas in the study area differed slightly in 2015 and 2020. Yaoshan Ancient Village Scenic Area is the highest in both years, increasing from 0.69 to 0.81, followed by the Mengliu Buyi Scenic Area (0.59), Wanmu Meiyuan Scenic Area is relatively stable with a slight increase, and Lianshanwan Scenic Area (0.45) is the lowest. (3) The four dimensions of ecological resources, policy drivers, economy drivers, and social facilitators work together to create a synergistic mechanism between the KWHS's OUV conservation and the buffer zone's tourism industry development. Future research can promote synergy between the two by formulating a comprehensive plan, encouraging sustainable tourism, establishing a diversified tourism industry, strengthening heritage education and training, enhancing community participation, and reinforcing stakeholder cooperation.
The sequence of the 2017–2018 eruptions and seismo-acoustic activity at Kirishima volcano group
Authors: Ichihara Mie , Kobayashi Tsukasa , Maeno Fukashi , Ohminato Takao , Watanabe Atsushi , Nakada Setsuya , Kaneko Takayuki
Published: September 2023

Kirishima volcano consists of more than 20 eruptive centers. Among them, Shinmoe-dake had magmatic eruptions in October 2017 and March 2018. Subsequently, another active cone, Iwo-yama, had phreatic eruptions in April 2018. These events were unique in that the 2018 eruption was the first effusion-dominated eruption of Shinmoe-dake and the first simultaneous activity of two cones of the Kirishima volcanic group ever documented. We report the detailed sequence of the events by combining areal photos, satellite images, and seismo-acoustic data analyses with the other published information. The seismo-acoustic data clarify the eruption onset and the transitions of the behaviors in three stages for each of the 2017 and 2018 eruptions. For both eruptions, we present regularly repeated tremors or ’drumbeat’ earthquakes in the second stage, which interpret as gas separation from magma, leading to the ash-poor plume in the 2017 eruption or the effusive eruption in the 2018 event. We also propose that the 2017 and 2018 eruptions of Shinmoe-dake and the 2018 eruption of Iwo-yama are sequential events linked by the degassing of magma beneath Shinmoe-dake. An eruption like the 2017–2018 eruptions of Shinmoe-dake would leave few geological records and could be captured only by modern techniques. Although Shinmoe-dake has been believed to be an example of less-frequent eruptions, effusive eruptions like the 2018 case might have occurred more frequently in the past , but the following eruptions had obscured their records. The timelines summarized in this study will be useful in future studies of Kirishima volcanoes and world equivalences.

Graphical Abstract
Subsurface magma movement inferred from extensometer and tiltmeter records during the early stage of the 2018 Shinmoe-dake eruptions, Japan
Authors: Yoshinaga Koki , Matsushima Takeshi , Shimizu Hiroshi , Yamashita Yusuke , Yamazaki Ken’ichi , Komatsu Shintaro , Fujiwara Satoshi
Published: September 2023

We infer the temporal changes in the pressure sources that induced crustal deformation during the 2018 Shinmoe-dake eruption using strain and tilt observations and discern that the deep magmatic activity associated with the early stage of this eruption began approximately 19 h earlier than the previously defined onset of magmatic activity. Distinct tilt changes were observed from around 09:00 on 6 March to 12:00 on 8 March 2018 (JST), coincident with observed lava outflow into the crater and lava dome formation. Existing studies have attributed this tilt change to the onset of the deflation of a spherical pressure source located at ~ 7 km bsl (below sea level) to the northwest of Shinmoe-dake. Here we examine strain and tilt data that were acquired in the Kirishima volcanic group, and we find that the distinct changes in the measured strain at Isa-Yoshimatsu Observatory began at around 14:00 on 5 March. This change can be explained by the deflation of a spherical pressure source, thereby suggesting that the onset of magma ascent was earlier than previously thought. The time variation in the spherical pressure source is estimated using the time-dependent inversion of the Ensemble Kalman Filter; the deflation source ascended from ~ 11 to 7 km bsl during Phase 1 (14:00 on 5 March to 06:00 on 6 March) and descended from 7 to 8 km bsl during Phase 2 (06:00 on 6 March to 12:00 on 8 March). Interferometric synthetic aperture radar analysis suggests that a dike intrusion had occurred just below Shinmoe-dake crater until 5 March, and this inflatable crustal deformation is attributed to the emplacement of residual volcanic fluids from the 2011 eruption. It is also known that the surface eruptive activity increased during Phase 1, including an increase in ash venting from the night of 5 March. These strain and tilt observations, therefore, suggest that magma ascended from ~ 11 km bsl to the magma reservoir at 7 km bsl during Phase 1, followed by a deflation of the magma reservoir during Phase 2 due to the large magma supply to the surface.

Graphical Abstract
Giant adrenal metastasis of malignant melanoma: impact of 18F-FDG PET/CT in early assessment of dramatic response to immunotherapy: case report
Authors: Kalantari Forough , Schweighofer-Zwink Gregor , Rendl Gundula , Pirich Christian , Beheshti Mohsen
Published: September 2023

Background

This case represents one of the largest adrenal metastases in the literature and highlights the importance of accurate imaging in clinical management of patients with advanced malignant melanoma.

Case presentation

A 67-year-old female with an ulcerated malignant melanoma presented with an asymptomatic 18-cm left adrenal mass on 18F-FDG PET/CT staging. After two cycles of combined systemic immunotherapy, an impressive shrinkage of the adrenal metastatic tumor was observed on 18F-FDG PET/CT imaging.

Conclusions

The case emphasizes the potential of 18F-FDG PET/CT as a functional imaging modality for accurate staging and precise early assessment of response to immunotherapy. Overall, this report highlights the importance of accurate imaging for the effective management of adrenal metastases in melanoma patients.
Implementation strategies in the Exploration and Preparation phases of a colorectal cancer screening intervention in community health centers
Authors: Ferrari Renée M. , Leeman Jennifer , Brenner Alison T. , Correa Sara Y. , Malo Teri L. , Moore Alexis A. , O’Leary Meghan C. , Randolph Connor M. , Ratner Shana , Frerichs Leah , Farr Deeonna , Crockett Seth D. , Wheeler Stephanie B. , Lich Kristen Hassmiller , Beasley Evan , Hogsed Michelle , Bland Ashley , Richardson Claudia , Newcomer Mike , Reuland Daniel S.
Published: September 2023

Background

Adoption of colorectal cancer (CRC) screening has lagged in community health center (CHC) populations in the USA. To address this implementation gap, we developed a multilevel intervention to improve screening in CHCs in our region. We used the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to guide this effort. Here, we describe the use of implementation strategies outlined in the Expert Recommendations for Implementing Change (ERIC) compilation in both the Exploration and Preparation phases of this project. During these two EPIS phases, we aimed to answer three primary questions: (1) What factors in the inner and outer contexts may support or hinder colorectal cancer screening in North Carolina CHCs?; (2) What evidence-based practices (EBPs) best fit the needs of North Carolina CHCs?; and (3) How can we best integrate the selected EBPs into North Carolina CHC systems?

Methods

During the Exploration phase, we conducted local needs assessments, built a coalition, and conducted local consensus discussions. In the Preparation phase, we formed workgroups corresponding to the intervention’s core functional components. Workgroups used cyclical small tests of change and process mapping to identify implementation barriers and facilitators and to adapt intervention components to fit inner and outer contexts.

Results

Exploration activities yielded a coalition of stakeholders, including two rural CHCs, who identified barriers and facilitators and reached consensus on two EBPs: mailed FIT and navigation to colonoscopy. Stakeholders further agreed that the delivery of those two EBPs should be centralized to an outreach center. During Preparation, workgroups developed and refined protocols for the following centrally-delivered intervention components: a registry to identify and track eligible patients, a centralized system for mailing at-home stool tests, and a process to navigate patients to colonoscopy after an abnormal stool test.

Conclusions

This description may be useful both to implementation scientists, who can draw lessons from applied implementation studies such as this to refine their implementation strategy typologies and frameworks, as well as to implementation practitioners seeking exemplars for operationalizing strategies in early phases of implementation in healthcare.
A postgraduate training programme in child and adolescent mental health in a lower-middle-income country: a partnership model from Nigeria
Authors: Omigbodun Olayinka , Ani Cornelius
Published: September 2023

This paper describes a postgraduate training programme in child and adolescent mental health (CAMH) in Nigeria. It explains the background, curriculum development, teaching, evaluation and outcomes. By its 10th year the programme had trained 166 CAMH professionals from 14 African countries. Many of the graduates are running clinical CAMH services in their countries, mostly pioneered by them. They are also conducting CAMH training, including as faculty on the programme, and some are in international CAMH leadership roles. Key success elements of the programme that can be replicated in other low- and middle-income countries include international partnership, adopting a train-the-trainer approach, using a curriculum that covers clinical aspects of CAMH while also developing leadership and research skills, use of free-access training resources, and access to seed funding.
Clicking Away to Capture Cancer Staging—The Benefits and Challenges of Completing Standardized Staging Modules
Authors: Vidula Neelima , Peppercorn Jeffrey
Published: September 2023

This article by Neelima Vidula and Jeffrey Peppercorn @MGHCancerCenter explores the benefits and challenges of completing standardized modules for cancer staging, and opportunities to improve module compliance while reducing burnout
Medieval Engagement with Authorial Intention
Authors: Pasnau Robert
Published: September 2023

The Middle Ages developed a rigorous semantic account of how thought mediates between words and things. Modern literary theory, in contrast, has been characteristically skeptical about whether anything is gained by attempting to discover the thoughts of the author that lie behind the words. For medieval readers, connecting with an author's thoughts mattered, above all, because they understood reading to be a form of interpersonal engagement. The text is not simply an impersonal artifact, good for stimulating certain sorts of responses, but it is an expression of the thoughts of another mind. Ultimately, it is the value of minds connecting with other minds that led medieval readers to care about authorial intention.
Making or Declaring Law? Legislative Intent and Privileged Speech in Anglo-Saxon England
Authors: Jurasinski Stefan
Published: September 2023

Celebrated by a generation of literature scholars, lamented by E. D. Hirsch, the disappearance of the author and authorial intentions as means of interpretation has a history with branches in the study of pre-Conquest England. Long before the twentieth century, Anglo-Saxon legislators were disappearing from their laws, as discussion of their intentions in establishing them was viewed by historians with increasing disfavor. Even today, commentary on early English royal legislation seldom acknowledges that these texts enjoyed (or were intended to enjoy) the force of law in any meaningful sense. Only in the past decade have cracks emerged in the consensus that such legislation was meant for anything beyond symbolic purposes, a view backed by a much older consensus that pre-Conquest law could do no more than “declare” what had always been custom, thus revealing little about the purposes of kings and their counselors. This essay traces commentators’ reticence about acknowledging the legislative purposes behind early English legislation to disputes over codification that agitated German-speaking parts of Europe in the early nineteenth century. Yet the earliest editors and commentators prized these materials specifically because they exhibited the lawmaking powers of kings and their councils. The article examines neglected evidence afforded by early English legislation itself, finding that this earlier tradition was by no means exhausted when abandoned.
Who Has Intention? Chaucer Studies and the Search for Meaning
Authors: von Contzen Eva
Published: September 2023

Chaucer criticism has always grappled with the question of intentionality. While early critics saw no trouble in identifying the voices in Chaucer's texts with the author's intention, authorial intention—not to be confused with autobiographical readings—became the elephant in the room from the early twentieth century onward. This article reviews the various approaches critics have put forward within Chaucer studies to avoid ascribing intention to Chaucer the poet. Starting with the concept of the narrator (a twentieth-century invention), three different approaches to the Canterbury Tales and their narrative situations are discussed, in which authorial intention looms large: the “dramatic,” the “detached,” and the “animated.” Then a case is made for the unavoidability of intentionalist readings by drawing on cognitive literary theories, in particular the intentional stance. When engaging with Chaucer, critics need to embrace intention as a key generator in the meaning-making activity of interpretation.
Translational control byTrypanosoma bruceiDRBD18 contributes to the maintenance of the procyclic state
Authors: Ciganda Martin , Sotelo-Silveira José , Dubey Ashutosh P. , Pandey Parul , Smith Joseph T. , Shen Shichen , Qu Jun , Smircich Pablo , Read Laurie K.
Published: September 2023

Trypanosoma bruceioccupies distinct niches throughout its life cycle, within both the mammalian and tsetse fly hosts. The immunological and biochemical complexity and variability of each of these environments require a reshaping of the protein landscape of the parasite both to evade surveillance and face changing metabolic demands. In kinetoplastid protozoa, includingT. brucei, posttranscriptional control mechanisms are the primary means of gene regulation, and these are often mediated by RNA-binding proteins. DRBD18 is aT. bruceiRNA-binding protein that reportedly interacts with ribosomal proteins and translation factors. Here, we tested a role for DRBD18 in translational control. We validate the DRBD18 interaction with translating ribosomes and the translation initiation factor, eIF3a. We further show that DRBD18 depletion by RNA interference leads to altered polysomal profiles with a specific depletion of heavy polysomes. Ribosome profiling analysis reveals that 101 transcripts change in translational efficiency (TE) upon DRBD18 depletion: 41 exhibit decreased TE and 60 exhibit increased TE. A further 66 transcripts are buffered, that is, changes in transcript abundance are compensated by changes in TE such that the total translational output is expected not to change. In DRBD18-depleted cells, a set of transcripts that codes for procyclic form-specific proteins is translationally repressed while, conversely, transcripts that code for bloodstream form- and metacyclic form-specific proteins are translationally enhanced. RNA immunoprecipitation/qRT-PCR indicates that DRBD18 associates with members of both repressed and enhanced cohorts. These data suggest that DRBD18 contributes to the maintenance of the procyclic state through both positive and negative translational control of specific mRNAs.
The numbers game of nature in cities
Authors: Laspidou Chrysi
Published: September 2023

Various catchy rules, such as the “3-30-300 rule”, or the “15-minute city” are becoming increasingly popular on how to green a city and allow easy access to green public spaces. These rules of thumb focus mostly on the instrumental value of nature, less on its intrinsic value, but none on its relational value—Nature as Culture. Focusing on humans reconnecting with nature and feeling as “One with Nature” is critical for developing ecological identities and sustaining a caring, committed and everlasting relationship with nature.
Incidence and risk factors of deep vein thrombosis and pulmonary thromboembolism after spinal cord disease at a rehabilitation unit: a retrospective study
Authors: Kim Yoonhee , Jeong Minjae , Park Myung Woo , Shin Hyun Iee , Lee Byung Chan , Kim Du Hwan
Published: September 2023

Background: Deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) are major complications of spinal cord disease. However, studies of their incidence in Korean patients are limited. Thus, this study investigated the incidence and risk factors of DVT and PTE in Korean patients with spinal cord disease.Methods: We retrospectively analyzed the medical records of 271 patients with spinal cord disease who were admitted to a rehabilitation unit within 3 months of disease onset at a tertiary hospital. The presence of DVT and PTE was mainly determined using Doppler ultrasonography and chest embolism computed tomography. Risk factor analysis included variables such as sex, age, obesity, completeness of motor paralysis, neurological level of injury, cause of injury, lower extremity fracture, active cancer, and functional ambulation category (FAC) score.Results: The incidences of DVT and PTE in the patients with spinal cord disease were both 6.3%. Risk factor analysis revealed that age of ≥65 years (p=0.031) and FAC score of ≤1 (p=0.023) were significantly associated with DVT development. Traumatic cause of injury (p=0.028) and DVT (p<0.001) were significant risk factors of PTE. Conclusion: Patients with spinal cord disease developed DVT and PTE within 3 months of disease onset with incidence rates of 6.3% and 6.3%, respectively. Age of ≥65 years and an FAC of score ≤1 were risk factors for DVT. Traumatic cause of injury and DVT were risk factors for PTE. However, given the inconsistent results of previous studies, the risk factors for DVT and PTE remain inconclusive. Therefore, early screening for DVT and PTE should be performed in patients with acute-to-subacute spinal cord disease regardless of the presence or absence of these risk factors.
Education and Fertility: A Review of Recent Research in Europe
Authors: Vasireddy Sindhu , Berrington Ann , Kuang Bernice , Kulu Hill
Published: September 2023

This paper reviews research on education and childbearing in Europe over the last decade. Early demographic research attributed declining fertility in advanced economies in the second half of the twentieth century to increasing female educational levels. The twenty-first century has witnessed further increases in educational attainment coupled with trend reversals in fertility. The relationship between education and fertility has become more complex, sparking renewed interest in the interplay between the two life domains. We examine how educational enrolment and attainment influence individuals’ fertility behaviour – both fertility timing and level – and how the relationship between education and fertility is shaped by contextual factors such as family policies, macroeconomic shocks, and normative changes in gender attitudes. We also summarise the recent literature on educational gradients in male fertility and review methodological developments to address issues of self-selection and unmeasured heterogeneity in the study of education and fertility. Finally, this paper identifies and discusses challenges and important areas for future research.
Problemas, modelos, grafos y algoritmos
Authors: Toro Bonilla Miguel
Published: September 2023

Este libro está diseñado como material complementario de la asignatura Análisis y Diseño de Datos y Algoritmos, que constituye la continuación natural de Fundamentos de Programación. Para abordar el diseño de algoritmos, es necesario tener asimilados los elementos de la programación en algún lenguaje previo; en este sentido, conocer Java y sus peculiaridades es indispensable para poder asimilar el contenido, en el que se aborda un conjunto de técnicas algorítmicas de uso general: Programación Lineal Entera, Algoritmos Genéticos, Algoritmos A*, Backtracking, Programación Dinámica, entre otras.
Algoritmos y tipos de datos en C
Authors: Toro Bonilla Miguel
Published: September 2023

Los lenguajes de programación tienden a compartir las mismas ideas básicas, dado que unos y otros van tomando prestadas recíprocamente las más novedosas. Aunque existen particularidades, podemos decir que los lenguajes de programación van convergiendo hacia elementos comunes a todos ellos. En este manual, en el que el diseño de tipos ocupa un lugar central, se abordan algoritmos y estructuras de datos en el lenguaje C; en la última sección, se incluyen varios ejemplos diseñados con estas ideas. El material que conforma el texto procede de la experiencia acumulada durante varios años en la enseñanza de la asignatura Análisis de Datos y Algoritmos en la Universidad de Sevilla.
Carga cognitiva y esfuerzo mental durante el cambio de contexto en entornos de realidad aumentada con fines de aprendizaje procedimental
Authors: Maradei García Fernanda , Bautista Rojas Luis Eduardo , Pedraza Gabriel
Published: September 2023

La Realidad Aumentada es usada en el aprendizaje procedimental por su capacidad de mostrar información registrada en el espacio. Sin embargo, algunos autores argumentan que podría incrementar el esfuerzo mental de los usuarios, al requerir cambios continuos en el enfoque de atención entre el contenido real y el contenido virtual. El objetivo es conocer la presencia de carga cognitiva y esfuerzo mental, cuando se presentan cambios de contexto en el uso de realidad aumentada en tareas de aprendizaje procedimental, especialmente en el espacio peri-personal del participante. Se ejecutó un experimento para evaluar la carga cognitiva subjetiva y el esfuerzo mental, durante actividades de aprendizaje procedimental de anatomía de superficie de la rodilla humana. Se combinaron medidas subjetivas basadas en auto-reportes, y medidas objetivas, basadas en pupilometría y rastreo ocular. Se evaluó la actividad de aprendizaje en treinta y cuatro participantes sin experiencia en la actividad. Los resultados generales mostraron que la medida de Carga Cognitiva Subjetiva y las medidas de rastreo ocular, evidencian diferencias significativas entre los tratamientos. Sin embargo, la medida de pupilometría no mostró diferencias.
Indicadores de agencia en experiencias educativas Agile: una revisión panorámica
Authors: Torres-Blasco Celia , Pérez-Garcias Adolfina
Published: September 2023

Agile fue creado inicialmente para la gestión de proyectos de software. No obstante, se ha extendido a campos como la educación, porque favorece el aprendizaje activo del estudiante (Krehbiel et al., 2017). Así pues, Agile podría facilitar la agencia del estudiante al intervenir en la responsabilidad del aprendizaje. A través de esta revisión panorámica bajo el protocolo PRISMA, se quiere identificar si las estrategias didácticas Agile contribuyen al desarrollo de la agencia estudiantil en estudios superiores, y si dichas estrategias se despliegan con el apoyo de recursos tecnológicos. A partir de los 116 documentos seleccionados, hemos obtenido resultados que indican el creciente interés sobre estas estrategias. Scrum es el marco ágil más utilizado y su uso principal es en Ciencias de la Informática. Asimismo, hemos identificado numerosos recursos tecnológicos para la comunicación, la colaboración y la gestión de los proyectos ágiles. En cuanto a la relación con la agencia, existen factores coincidentes como el aprendizaje autorregulado, la propiedad del aprendizaje, la autonomía o la colaboración (Marín et al., 2020). El trabajo futuro implicaría un análisis cualitativo, para desarrollar un modelo con los principios de diseño didáctico basados en Agile que dan soporte a la agencia.
A Stochastic Optimization Approach to Energy-Efficient Underground Timetabling Under Uncertain Dwell and Running Times
Authors: Gemander Patrick , Bärmann Andreas , Martin Alexander
Published: September 2023

We consider a problem from the context of energy-efficient underground railway timetabling, in which an existing timetable draft is improved by slightly changing departure and running times. In practice, synchronization between accelerating and braking trains to utilize regenerative braking plays a major role for the energy efficiency of a timetable. Because deviations from a planned timetable may lead to unnecessarily high energy consumption during actual operation, we include operational uncertainties in our model to create a timetable that remains energy efficient, even if deviations from the nominal timetable occur. To solve the problem, we use a scenario expansion model in conjunction with a Benders decomposition approach. As an alternative to solving the Benders subproblems, we present a heuristic sparse cut that can be computed efficiently. The resulting sparse-cut heuristic produces high-quality solutions on a set of real-world instances stemming from the Nürnberg underground system, outperforming the integrated mixed-integer programming approach as well as the basic Benders approach. Additionally, we evaluate two static recovery strategies—shortening dwell times as well as shortening dwell and running times—to determine the cost and benefit of handling delays using a simple static rule. In our experiments, we are able to reduce the energy consumption by up to 9.4% and confirm that delay recovery via shortening dwell times is an energy-efficient and effective way to increase punctuality at low cost in terms of energy.

Funding: This research was supported by the Bavarian Ministry of Economic Affairs, Regional Development and Energy through the Center for Analytics – Data – Applications (ADA-Center) within the framework of “BAYERN DIGITAL II” (20-3410-2-9-8).
A–Z of prescribing for children
Authors: Davies Kate
Published: September 2023

This series focuses on aspects of prescribing for neonates, children and young people, from A–Z. Aspects of pharmacokinetics will be considered, alongside legal considerations, consent and medications in schools
Groundhoppers (Orthoptera: Tetrigidae) of the wetlands of Ramaroshan, Achham (Nepal) with description of a new species
Authors: SUBEDI MADAN
Published: September 2023

This paper presents a list of groundhoppers (Orthoptera: Tetrigidae) from Ramaroshan, Achham, Nepal, along with the description of a new species, Hedotettix samitae sp. nov. A total of 7 species were recorded from the study area. The new species is brachypronotal with anterior margin of pronotum slightly rounded; robust hind femora; and antennal grooves with top margin above bottom margin of eyes and bottom margin slightly below. The new species is in many ways similar to Hedotettix gracilis. Hedotettix (gracilis) species group is described to include these two species, which differ mainly in the shape of the hind femora, scutellum, and anterior margin of pronotum. The taxonomy of the genus Hedotettix is problematic, and it is likely to be paraphyletic. Future works involving molecular studies would solve the taxonomic problems. Bolivaritettix insignis (Kirby, 1914) is recorded for the first time from Nepal.