bluuebunny/crossref_metadata_2025 huggingface dataset:
A rare case of concomitant endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis
Authors: Zhou Cailu , Luo Xiaojing , Tang Mengjie , Luo Fangyuan , Liao Zhi
Published: August 2024

Background

Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium.

Case presentation

This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy.

Conclusion

We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.
Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut
Authors: Nagai Hiroki , Adachi Yuya , Nakasugi Tenki , Takigawa Ema , Ui Junichiro , Makino Takashi , Miura Masayuki , Nakajima Yu-ichiro
Published: August 2024

Background

The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.

Results

Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.

Conclusions

These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.
Semi-field evaluation of aquatic predators for the control of Anopheles funestus in rural south-eastern Tanzania
Authors: Mahenge Herieth H. , Muyaga Letus L. , Nkya Joel D. , Kafwenji Andrew D. , Mwalugelo Yohana A. , Kahamba Najat F. , Ngowo Halfan S. , Kaindoa Emmanuel W.
Published: August 2024

Background

Biological control is a promising alternative or complementary approach for controlling vector populations in response to the spread of insecticide resistance in malaria vectors. This study evaluated the efficacy of three selected potential predators on the density and fitness parameters of Anopheles funestus larvae in rural Tanzania.

Methods

Common predator families Aeshnidae (dragonflies), Coenagrionidae (damselflies), and Notonectidae (backswimmers) and An. funestus group larvae were collected from natural aquatic habitats in rural south-eastern Tanzania. Predators were starved for 12-h while An. funestus larvae were given fish food before starting the experiment. Anopheles funestus larvae were placed into artificial habitats containing predators, exposing them to potential predation. The number of surviving An. funestus larvae were counted every 24-h. An emergence traps were placed at the top of artificial habitats to capture emerging mosquitoes. Emerged mosquitoes were monitored until they died. Female wings were measured and used as a proxy for body size. Generalized linear mixed models (GLMM) with binomial variates at 95% CI and Cox proportional hazard models were used to assess the proportion of dead mosquitoes and the daily survival determined.

Results

There were significant differences in the number of emerged mosquitoes between the treatment and control groups (P < 0.001). Thus, all predator species played a significant role in reducing the density of An. funestus mosquitoes (P < 0.001). Furthermore, these predators had notable effects on the fitness parameters and survival of emerged mosquitoes (P < 0.001). Among the three predators studied, Coenagrionidae (damselflies) were most efficient followed by Notonectidae (backswimmers), with Aeshnidae (dragonflies) being the least efficient.

Conclusion

Selected aquatic predators have the potential to reduce the survival and density of An. funestus larvae. They might eventually be included within an integrated malaria vector control strategy, ultimately leading to a reduction in malaria transmission.
Cancer, metastasis, and the epigenome
Authors: Kiri Saurav , Ryba Tyrone
Published: August 2024

Cancer is the second leading cause of death worldwide and disease burden is expected to increase globally throughout the next several decades, with the majority of cancer-related deaths occurring in metastatic disease. Cancers exhibit known hallmarks that endow them with increased survival and proliferative capacities, frequently as a result of de-stabilizing mutations. However, the genomic features that resolve metastatic clones from primary tumors are not yet well-characterized, as no mutational landscape has been identified as predictive of metastasis. Further, many cancers exhibit no known mutation signature. This suggests a larger role for non-mutational genome re-organization in promoting cancer evolution and dissemination. In this review, we highlight current critical needs for understanding cell state transitions and clonal selection advantages for metastatic cancer cells. We examine links between epigenetic states, genome structure, and misregulation of tumor suppressors and oncogenes, and discuss how recent technologies for understanding domain-scale regulation have been leveraged for a more complete picture of oncogenic and metastatic potential.
Genetic insights into the complexity of premature ovarian insufficiency
Authors: Nie Linhang , Wang Xiaojie , Wang Songyuan , Hong Zhidan , Wang Mei
Published: August 2024

Premature Ovarian Insufficiency (POI) is a highly heterogeneous condition characterized by ovarian dysfunction in women occurring before the age of 40, representing a significant cause of female infertility. It manifests through primary or secondary amenorrhea. While more than half of POI cases are idiopathic, genetic factors play a pivotal role in all instances with known causes, contributing to approximately 20–25% of cases. This article comprehensively reviews the genetic factors associated with POI, delineating the primary candidate genes. The discussion delves into the intricate relationship between these genes and ovarian development, elucidating the functional consequences of diverse mutations to underscore the fundamental impact of genetic effects on POI. The identified genetic factors, encompassing gene mutations and chromosomal abnormalities, are systematically classified based on whether the resulting POI is syndromic or non-syndromic. Furthermore, this paper explores the genetic interplay between mitochondrial genes, such as Required for Meiotic Nuclear Division 1 homolog Gene (RMND1), Mitochondrial Ribosomal Protein S22 Gene (MRPS22), Leucine-rich Pentapeptide Repeat Gene (LRPPRC), and non-coding RNAs, including both microRNAs and Long non-coding RNAs, with POI. The insights provided serve to consolidate and enhance our understanding of the etiology of POI, contributing to establishing a theoretical foundation for diagnosing and treating POI patients, as well as for exploring the mechanisms underlying the disease.
Are physical activity referral scheme components associated with increased physical activity, scheme uptake, and adherence rate? A meta-analysis and meta-regression
Authors: Mino Eriselda , Pfeifer Klaus , Hanson Coral L. , Schuler Michael , Brandmeier Anna , Klamroth Sarah , Naber Inga , Weissenfels Anja , McHale Sheona , Abu-Omar Karim , Gelius Peter , Whiting Stephen , Wickramasinghe Kremlin , Galea Gauden , Geidl Wolfgang
Published: August 2024

Background

Physical activity referral schemes (PARS) are composed of various components, such as a written prescription or a person-centered approach. The role of these components in their effectiveness is yet to be understood. Therefore, we aimed to explore the relationships between PARS components and physical activity, scheme uptake, and adherence rate; and to estimate the effect of PARS.

Methods

We searched Scopus, PubMed, Web of Science, CINAHL, ScienceDirect, SpringerLink, HTA, Wiley Online Library, SAGE Journals, Taylor & Francis, Google Scholar, OpenGrey, and CORE. Eligible studies were published between 1990 and November 2023 in English or German, investigated PARS with participants aged ≥ 16 years, and reported physical activity, scheme uptake, or scheme adherence. Separate random-effects meta-analysis by comparison group were conducted for physical activity. Scheme uptake and adherence rates were pooled using proportional meta-analysis. The components were analyzed via univariate meta-regression. We rated the risk of bias using RoB2 and ROBINS-I, and the certainty of evidence using GRADE.

Results

Fifty-two studies were included. PARS were more effective in increasing physical activity than usual care (k = 11, n = 5046, Hedges’ g = 0.18, 95%CI 0.12 to 0.25; high certainty of evidence). When PARS were compared with physical activity advice or enhanced scheme versions, the pooled Hedges’ g values for physical activity were -0.06 (k = 5, n = 1082, 95%CI -0.21 to 0.10; low certainty of evidence), and 0.07 (k = 9, n = 2647, 95%CI -0.03 to 0.18; low certainty of evidence) respectively. Scheme uptake was 87% (95%CI 77% to 94%, k = 14, n = 5000) across experimental studies and 68% (95%CI 51% to 83%, k = 14, n = 25,048) across non-experimental studies. Pooled scheme adherence was 68% (95%CI 55% to 80%, k = 16, n = 3939) and 53% (95%CI 42% to 63%, k = 18, n = 14,605). The meta-regression did not detect any significant relationships between components and physical activity or scheme uptake. A person-centered approach, screening, and brief advice were positively associated with scheme adherence, while physical activity sessions were negatively associated.

Conclusion

PARS are more effective in increasing physical activity than usual care only. We did not identify any components as significant predictors of physical activity and scheme uptake. Four components predicted scheme adherence, indicating that the component-effectiveness relationship warrants further research.
FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis
Authors: Lin Jing , Lin Hong-wei , Wang Yu-xing , Fang Yan , Jiang Hui-mian , Li Ting , Huang Jia , Zhang Hua-dong , Chen Da-zhi , Chen Yong-ping
Published: August 2024

Background

The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH.

Methods

We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages.

Results

We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation.

Conclusion

We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K–AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.
Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless
Authors: Wallis Mathew , Bodek Simon D. , Munro Jacob , Rafehi Haloom , Bennett Mark F. , Ye Zimeng , Schneider Amy , Gardiner Fiona , Valente Giulia , Murdoch Emma , Uebergang Eloise , Hunter Jacquie , Stutterd Chloe , Huq Aamira , Salmon Lucinda , Scheffer Ingrid , Eratne Dhamidhu , Meyn Stephen , Fong Chun Y. , John Tom , Mullen Saul , White Susan M. , Brown Natasha J. , McGillivray George , Chen Jesse , Richmond Chris , Hughes Andrew , Krzesinski Emma , Fennell Andrew , Chambers Brian , Santoreneos Renee , Le Fevre Anna , Hildebrand Michael S. , Bahlo Melanie , Christodoulou John , Delatycki Martin , Berkovic Samuel F.
Published: August 2024

Background

Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program. The main objectives were to identify the causal mutation for a variety of diseases of individuals and families enrolled, and to discover novel disease genes.

Methods

Unsolved patients in whom standard genomic diagnostic techniques such as targeted gene panel, exome-wide next generation sequencing, and/or chromosomal microarray, had already been performed were recruited. Genome sequencing and enhanced genomic analysis from the research setting were applied to aid novel gene discovery.

Results

In total, 16/50 (32%) families/cases were solved. One or more candidate variants of uncertain significance were detected in 18/50 (36%) families. No candidate variants were identified in 16/50 (32%) families. Two novel disease genes (TOP3B, PRKACB) and two novel genotype–phenotype correlations (NARS, and KMT2C genes) were identified. Three out of eight patients with suspected mosaic tuberous sclerosis complex had their diagnosis confirmed which provided reproductive options for two patients. The utility of confirming diagnoses for patients with mosaic conditions (using high read depth sequencing and ddPCR) was not specifically envisaged at the onset of the project, but the flexibility to offer recruitment and analyses on an as-needed basis proved to be a strength of the AHA-UDP.

Conclusion

AHA-UDP demonstrates the utility of a UDP approach applying genome sequencing approaches in diagnosing adults with rare diseases who have had uninformative conventional genetic analysis, informing clinical management, recurrence risk, and recommendations for relatives.
The 26 S proteasome in Entamoeba histolytica: divergence of the substrate binding pockets from host proteasomes
Authors: Joshi Nidhi , Hosen SK Yasir , Fahad Mohd. , Narooka Anil Raj , Gourinath S. , Tiwari Swati
Published: August 2024

Objective

Proteasomes are conserved proteases crucial for proteostasis in eukaryotes and are promising drug targets for protozoan parasites. Yet, the proteasomes of Entamoeba histolytica remain understudied. The study’s objective was to analyse the differences in the substrate binding pockets of amoeba proteasomes from those of host, and computational modelling of β5 catalytic subunit, with the goal of finding selective inhibitors.

Results

Comparative sequence analysis revealed differences in substrate binding sites of E. histolytica proteasomes, especially in the S1 and S3 pockets of the catalytic beta subunits, implying differences in substrate preference and susceptibility to inhibitors from host proteasomes. This was strongly supported by significantly lower sensitivity to MG132 mediated inhibition of amoebic proteasome β5 subunit’s chymotryptic activity compared to human proteasomes, also reflected in lower sensitivity of E. histolytica to MG132 for inhibition of proliferation. Computational models of β4 and β5 subunits, and a docked β4-β5 model revealed a binding pocket between β4-β5, similar to that of Leishmania tarentolae. Selective inhibitors for visceral leishmaniasis, LXE408 and compound 8, docked well to this pocket. This functional and sequence-based analysis predicts differences between amoebic and host proteasomes that can be utilized to develop rationally designed, selective inhibitors against E. histolytica.
Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer
Authors: Karunakara Shreyas Hulusemane , Eswaran Sangavi , Mallya Sandeep , Suresh Padmanaban S. , Chakrabarty Sanjiban , Kabekkodu Shama Prasada
Published: August 2024

Objective

miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets.

Results

In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.
A case of an Angelman-syndrome caused by an intragenic duplication of UBE3A uncovered by adaptive nanopore sequencing
Authors: Holthöfer Laura , Diederich Stefan , Haug Verena , Lehmann Lioba , Hewel Charlotte , Paul Norbert W. , Schweiger Susann , Gerber Susanne , Linke Matthias
Published: August 2024

Adaptive nanopore sequencing as a diagnostic method for imprinting disorders and episignature analysis revealed an intragenic duplication of Exon 6 and 7 in UBE3A (NM_000462.5) in a patient with relatively mild Angelman-like syndrome. In an all-in-one nanopore sequencing analysis DNA hypomethylation of the SNURF:TSS-DMR, known contributing deletions on the maternal allele and point mutations in UBE3A could be ruled out as disease drivers. In contrast, breakpoints and orientation of the tandem duplication could clearly be defined. Segregation analysis in the family showed that the duplication derived de novo in the maternal grandfather. Our study shows the benefits of an all-in-one nanopore sequencing approach for the diagnostics of Angelman syndrome and other imprinting disorders.
METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium
Authors: Huang Meimei , Wang Xiaodan , Zhang Mengxian , Liu Yuan , Chen Ye-Guang
Published: August 2024

Intestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated m6A modification maintains intestinal homeostasis by impeding epithelial cell death. Mettl3 knockout induces both apoptosis and necroptosis in IECs. Targeting different modes of cell death with specific inhibitors unveils that RIPK1 kinase activity is critical for the cell death triggered by Mettl3 knockout. Mechanistically, this occurs via the m6A-mediated transcriptional regulation of Atf3, a transcription factor that directly binds to Cflar, the gene encoding the anti-cell death protein cFLIP. cFLIP inhibits RIPK1 activity, thereby suppressing downstream apoptotic and necroptotic signaling. Together, these findings delineate the essential role of the METTL3-ATF3-cFLIP axis in homeostatic regulation of the intestinal epithelium by blocking RIPK1 activity.
Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease
Authors: Lu Huiying , Suo Zhimin , Lin Jian , Cong Yingzi , Liu Zhanju
Published: August 2024

Background

Monocytes and macrophages play an indispensable role in maintaining intestinal homeostasis and modulating mucosal immune responses in inflammatory bowel disease (IBD). Although numerous studies have described macrophage properties in IBD, the underlying mechanisms whereby the monocyte-macrophage lineage modulates intestinal homeostasis during gut inflammation remain elusive.

Main body

In this review, we decipher the cellular and molecular mechanisms governing the generation of intestinal mucosal macrophages and fill the knowledge gap in understanding the origin, maturation, classification, and functions of mucosal macrophages in intestinal niches, particularly the phagocytosis and bactericidal effects involved in the elimination of cell debris and pathogens. We delineate macrophage-mediated immunoregulation in the context of producing pro-inflammatory and anti-inflammatory cytokines, chemokines, toxic mediators, and macrophage extracellular traps (METs), and participating in the modulation of epithelial cell proliferation, angiogenesis, and fibrosis in the intestine and its accessory tissues. Moreover, we emphasize that the maturation of intestinal macrophages is arrested at immature stage during IBD, and the deficiency of MCPIP1 involves in the process via ATF3-AP1S2 signature. In addition, we confirmed the origin potential of IL-1B+ macrophages and defined C1QB+ macrophages as mature macrophages. The interaction crosstalk between the intestine and the mesentery has been described in this review, and the expression of mesentery-derived SAA2 is upregulated during IBD, which contributes to immunoregulation of macrophage. Moreover, we also highlight IBD-related susceptibility genes (e.g., RUNX3, IL21R, GTF2I, and LILRB3) associated with the maturation and functions of macrophage, which provide promising therapeutic opportunities for treating human IBD.

Conclusion

In summary, this review provides a comprehensive, comprehensive, in-depth and novel description of the characteristics and functions of macrophages in IBD, and highlights the important role of macrophages in the molecular and cellular process during IBD.
Adoption of smart watches as wearable technology in TESOL education among university students
Authors: Wardat Saja , Akour Mohammed
Published: August 2024

This research explores the key motivating factors that influence student engagement with wearable technology (WT) in teaching English to speakers of other languages (TESOL) education. The study employs a novel, integrated framework that merges elements from the established technology acceptance model (TAM), Flow Theory, and additional factors pivotal to WT's efficacy, namely content richness and personal innovativeness. TAM and Flow Theory are utilized to identify the variables that drive WT adoption. Data for the research was gathered through an online survey comprising 23 questions, distributed among students in the KSA, with a total of 468 participants. Analysis of the data was conducted using Smart PLS Software to evaluate the research model, constructs, and hypotheses. The findings reveal varying contributions of the model's main constructs to WT acceptance. Specifically, content richness and innovativeness significantly enhance the perceived usefulness of WT. Additionally, perceived ease of use is a strong predictor of perceived usefulness and behavioral intention. The results underscore a growing demand for WT in TESOL Education, highlighting its role in streamlining information exchange among students. The study underscores the significance of certain external factors in technology acceptance, offering a fresh perspective by incorporating a framework that links TAM's perceived usefulness and ease of use with user satisfaction, content richness, and innovativeness. Moreover, the inclusion of Flow Theory adds a unique dimension by assessing engagement and control over WT. The research contributes to understanding the underlying motivations for employing WT in TESOL Education, primarily aimed at enhancing the effectiveness of both instructors and students. A limitation of this study is its focused application of TAM and Flow Theory within a specific educational context, which may not fully capture the complex societal, psychological, and gender-specific factors influencing WT adoption across diverse settings.
Unpacking the role of AI ethics online education for science and engineering students
Authors: Usher Maya , Barak Miri
Published: August 2024

Background

As artificial intelligence (AI) technology rapidly advances, it becomes imperative to equip students with tools to navigate through the many intricate ethical considerations surrounding its development and use. Despite growing recognition of this necessity, the integration of AI ethics into higher education curricula remains limited. This paucity highlights an urgent need for comprehensive ethics education initiatives in AI, particularly for science and engineering students who are at the forefront of these innovations. Hence, this research investigates the role of an online explicit-reflective learning module in fostering science and engineering graduate students' ethical knowledge, awareness, and problem-solving skills. The study’s participants included 90 graduate students specializing in diverse science and engineering research tracks. Employing the embedded mixed-methods approach, data were collected from pre- and post-intervention questionnaires with closed-ended and open-ended questions.

Results

The study's results indicate that the online explicit-reflective learning module significantly enhanced students' knowledge of AI ethics. Initially, students exhibited a medium–high level of perceived ethical awareness, which saw a modest but statistically significant enhancement following the participation. Notably, a more distinct increase was observed in students' actual awareness of ethical issues in AI, before and after the intervention. Content analysis of students’ responses to the open-ended questions revealed an increase in their ability to identify and articulate concerns relating to privacy breaches, the utilization of flawed datasets, and issues of biased social representation. Moreover, while students initially displayed limited problem-solving abilities in AI ethics, a considerable enhancement in these competencies was evident post-intervention.

Conclusions

The study results highlight the important role of explicit-reflective learning in preparing future professionals in science and engineering with the skills necessary for ethical decision-making. The study highlights the need for placing more emphasis not only on students’ ability to identify AI-related ethical issues but also on their capacity to resolve and perhaps mitigate the impact of such ethical dilemmas.
A retrospective study examining the association between polypharmacy and complications after laparoscopic surgery for colorectal cancer
Authors: Watanabe Takashi , Kashiwagura Shota , Ouchi Ryusuke , Usui Kensuke , Shibata Chikashi , Okada Kouji
Published: August 2024

Background

Polypharmacy is an escalating public health concern across various healthcare settings worldwide. We aimed to comprehensively investigate postoperative complications after laparoscopic surgery for colorectal cancer and explore their association with polypharmacy. As laparoscopic surgery is widespread, clarifying the association between polypharmacy and postoperative complications is clinically important.

Methods

We retrospectively surveyed the medical charts of adult inpatients who underwent laparoscopic surgery for colorectal cancer at Tohoku Medical and Pharmaceutical University Hospital between April 2019 and March 2023. Postoperative complications were determined using the Clavien–Dindo classification. We explored the factors related to postoperative complications and calculated the cut-off values for the number of medication ingredients.

Results

Among the 236 patients, 32 (13.6%) developed postoperative complications. On multivariable logistic regression analysis, the number of regularly used medication ingredients (odds ratio = 1.160, 95% confidence interval 1.050–1.270, p = 0.002) was identified as a factor related to postoperative complications. The identified cut-off value for complications was 10 ingredients. Patients using 10 or more ingredients had approximately 3.5 times higher occurrence of postoperative complications than those using fewer than 10 ingredients (33.3% vs. 9.3%, p < 0.001, Fisher’s exact test).

Conclusions

Our study comprehensively investigated postoperative complications and examined their association with polypharmacy. We found that the number of regularly used medication ingredients may be linked to complications following laparoscopic surgery for colorectal cancer. These findings have important implications for perioperative management and patient care, providing valuable insights that may influence clinical practices and enhance patient outcomes.
A novel robust method for estimating the covariance matrix of financial returns with applications to risk management
Authors: Leccadito Arturo , Staino Alessandro , Toscano Pietro
Published: August 2024

This study introduces the dynamic Gerber model (DGC) and evaluates its performance in the prediction of Value at Risk (VaR) and Expected Shortfall (ES) compared to alternative parametric, non-parametric and semi-parametric methods for estimating the covariance matrix of returns. Based on ES backtests, the DGC method produces, overall, accurate ES forecasts. Furthermore, we use the Model Confidence Set procedure to identify the superior set of models (SSM). For all the portfolios and VaR/ES confidence levels we consider, the DGC is found to belong to the SSM.
Cyclotron production of manganese-52: a promising avenue for multimodal PET/MRI imaging
Authors: Porto Francesca , Cisternino Sara , Cazzola Emiliano , Speltri Giorgia , Mou Liliana , Boschi Alessandra , Marvelli Lorenza , Di Domenico Giovanni , Pagnoni Antonella , De Dominicis Lucia , Calliari Irene , Gennari Claudio , Uccelli Licia , Pupillo Gaia , Gorgoni Giancarlo , Esposito Juan , Martini Petra
Published: August 2024

Background

The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) holds promise for advancing diagnostic imaging capabilities. The METRICS project aims to develop cyclotron-driven production of 52Mn for PET/MRI imaging.

Results

Using the 52Cr(p,n)52Mn reaction, we designed chromium metal targets via Spark Plasma Sintering and developed a separation procedure for isolating 52Mn. Labeling tests were conducted with traditional chelators (i.e. S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid) and the 1.4-dioxa-8-azaspiro[4.5]decane-8- carbodithioate ligand to produce radioactive complexes suitable for PET/MRI applications. Our methodology yielded high-quality 52Mn suitable for PET radiopharmaceuticals and PET/MRI imaging. Preliminary studies on phantom imaging using microPET and clinical MRI demonstrated the efficacy of our approach.

Conclusions

The developed technology offers a promising avenue for producing 52Mn and enhancing PET/MRI imaging capabilities. Further in vivo investigations are warranted to evaluate the potential advantages of this hybrid imaging technique.
Grewia flava twig extracts: phytochemical, antioxidant, and antimicrobial evaluations
Authors: Coin Gofaone , Lekutlane Disang , Masisi Kabo , Muzila Mbaki , Mazimba Ofentse
Published: August 2024

Background

Grewia flava infusions are consumed to assist with kidney problems and stomach ailments. However, there are no scientific data on the phytochemical profile or biological properties to validate its folklore use. Thus, the study aimed to assess the phytochemical profile, antioxidant, and antimicrobial activities of Grewia flava twig extracts.

Methodology

The antioxidant activities of the extracts were assayed using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, reducing power, metal chelation, and total phenolic and flavonoid content assays. The agar well diffusion and microdilution methods were used for crude extracts and fractions (from 80% methanol extract) for antimicrobial screening against P. aeruginosa, S. aureus, E. coli, B. subtilis, A. niger, and R. oryzae.

Results

The 80% methanol twig extract (250.00 ± 2 GAE/g) exhibited a high concentration of phenolic content, followed by the distilled water extract (192.00 ± 2 mg GAE/g) and the hexane extract (43.10 ± 0.2 mg GAE/g). Fraction 14 of the methanol twig extract exhibited MIC values of 0.21–0.31 mg/mL against all test microorganisms. The root and twig extracts exhibited significant antioxidant and antimicrobial activities, which were attributed to the extracts of bioactive phytochemical compounds such as alkaloids, flavonoids, saponins, steroids, glycosides, anthraquinones, and tannins that were detected in the extracts. Also, the root and twig non-polar extracts were subjected to gas chromatography–mass spectrometry analysis, which identified several bioactive compounds like betulin, β-amyrin, palmitic acid, lupenone, and phytol, highlighting the potential of the plant species as a botanical drug.

Conclusions

The study supports the traditional use of plant roots and twigs for treating various ailments, indicating their medicinal value. The twigs can be used in place of the roots to guarantee Grewia flava harvesting that is sustainable. However, a comparison of the quantities of the active compound in the twigs and roots using LC–MS is crucial.
Classification of DDoS attack traffic on SDN network environment using deep learning
Authors: Clinton Urikhimbam Boby , Hoque Nazrul , Robindro Singh Khumukcham
Published: August 2024

Distributed Denial of Service (DDoS) attack is a major threat to the Internet of Things (IoT), Software Defined Networks (SDN), and Cloud Computing Networks. Due to the tremendous applications of IoT networks, the number of DDoS attacks is increasing significantly, and most sophisticated DDoS attacks are generated through IoT botnets. An IoT botnet-based DDoS attack can disrupt the network quickly with a surge of malicious traffic. Especially in an SDN network, it is important to detect the DDoS attack before it occurs to the SDN controller. DDoS attacks on the centralized controller of the SDN can disrupt the whole network. So, identifying DDoS attacks at the earliest is a critical security measure for network experts and practitioners. In this paper, we analyze the DDoS attack on an SDN environment and develop a method to identify the DDoS attack using Deep Learning (DL). The proposed method converts the captured raw network traffic to image data and classifies the malicious data from normal data. The method is evaluated on our test-bed simulated dataset and two other benchmark datasets. The experimental comparison shows that the proposed method performs better on all three datasets, giving more than 99% classification accuracy.
Patterns in the spatial configuration of Sultani Mosques in the Qajar period: a comparative study using space syntax and layout-based analysis
Authors: Fadakari Mohammad Moein , Andaroodi Elham
Published: August 2024

The pattern of built heritage provides insights into spatial organisation principles, revealing recurring traits among buildings of a similar type. Such constructions illuminate how building components are aligned and interconnected to embody a unified design ethos. However, well-preserved instances of a sequential series of similar buildings that were built in the same period based on historical evidence are rarely located. Thus, the Sultani Mosques, a prominent collection of mosques built in Iran between 1806 and 1840 under King Fath-Ali Shah of the Qajar dynasty's auspices, are particularly noteworthy, attracting scholarly attention from figures such as Ritter, Hillenbrand, and Scarce for their distinctive spatial organisation of architectural elements such as iwans, domes, naves, and courtyards. To comprehensively study the shared spatial organisation concept within these mosques through a comparative study, this research aimed to verify the spatial layout using analytical techniques such as space syntax and layout-based justified graphs. By juxtaposing these graphs and depth values, this research elucidated the spatial integration and privacy delineation within these religious structures. Moreover, an examination of layout-based graphs and immersive three-dimensional assessments reinforced and confirmed the prevailing layout configuration. The research findings reveal a cohesive architectural concept in Sultani mosques, as multifaceted accessibility was emphasised, and spatial layouts were structured to facilitate movement and interactions. Qajar architects likely established a consistent design approach across these mosques, integrating essential elements while accommodating educational spaces. When schools were included, courtyard dynamics were reshaped, which impacted spatial connections and access routes. Variations in building division configurations, vault spans, and spatial relations tailored to local contexts highlight the unique design and spatial value of each mosque. Preserving these spatial relationships in restoration efforts is crucial for maintaining the intrinsic spatial language and historical design significance of these mosques.
Reflections on the future of psychiatry
Authors: Elkholy Hussien
Published: August 2024

The new Deputy Editor of BJPsych International introduces articles in the current issue on topics as diverse as metacommunity psychiatry, child and adolescent mental health services in Australia and the Philippines, the mental health of the UK's Gypsy, Roma and Traveller populations, Indigenous mental health professionals in Bangladesh, and the relationship between spirituality and behavioural addictions.
11β-Hydroxysteroid dehydrogenase type 2 may mediate the stress-specific effects of cortisol on brain cell proliferation in adult zebrafish (Danio rerio)
Authors: Flatt E. Emma , Alderman Sarah L.
Published: August 2024

Stress-induced increases in cortisol can stimulate or inhibit brain cell proliferation, but the mechanisms behind these opposing effects are unknown. We tested the hypothesis that 11β-hydroxysteroid dehydrogenase type 2 (Hsd11b2), a glucocorticoid-inactivating enzyme expressed in neurogenic regions of the adult zebrafish brain, mitigates cortisol-induced changes to brain cell proliferation, using one of three stress regimes: a single 1 min air exposure (acute stress), two air exposures spaced 24 h apart (repeat acute stress) or social subordination (chronic stress). Plasma cortisol was significantly elevated 15 min after air exposure and recovered within 24 h after acute and repeat acute stress, whereas subordinate fish exhibited significant and sustained elevations relative to dominant fish for 24 h. Following acute stress, brain hsd11b2 transcript abundance was elevated up to 6 h after a single air exposure but was unchanged by repeat acute stress or social subordination. A sustained increase in brain Hsd11b2 protein levels occurred after acute stress, but not after repeat or chronic stress. Following acute and repeat acute stress, brain pcna transcript abundance (a marker of cell proliferation) exhibited a prolonged elevation, but was unaffected by social subordination. Interestingly, the number of telencephalic BrdU+ cells increased in fish after a single air exposure but was unchanged by repeat acute stress. Following acute and repeat acute stress, fish expressed lower brain glucocorticoid and mineralocorticoid receptor (gr and mr) transcript abundance while subordinate fish exhibited no changes. Taken together, these results demonstrate stressor-specific regulation of Hsd11b2 in the zebrafish brain that could modulate rates of cortisol catabolism contributing to observed differences in brain cell proliferation.
Are Opportunity Zones an Effective Place-Based Policy?
Authors: Corinth Kevin , Feldman Naomi
Published: August 2024

We evaluate the Opportunity Zones provision of the Tax Cuts and Jobs Act, focusing on its targeting and effects on investment and resident outcomes. The policy allowed substantial discretion for state governors to designate Opportunity Zones that were not necessarily the most distressed, though we find that in aggregate their ultimate selections were still somewhat well-targeted. However, we show that the policy is insufficient to encourage investment with a significantly below-market rate of return and provides the largest tax benefits to investment that would have occurred regardless of the policy. Consistent with these features of the policy’s design, a substantial amount of Opportunity Zone investment has been made, including in many lower-income areas. However, it appears that much of the investment would have occurred anyway, and the evidence to date mostly points to limited effects on resident wellbeing.
What Went Wrong with Federal Student Loans?
Authors: Looney Adam , Yannelis Constantine
Published: August 2024

At a time when the returns to college and graduate school are at historic highs, why do so many students struggle with their student loans? The increase in aggregate student debt and the struggles of today’s student loan borrowers can be traced to changes in federal policies intended to broaden access to federal aid and educational opportunities, and which increased enrollment and borrowing in higher-risk circumstances. Starting in the late 1990s, policymakers weakened regulations that had constrained institutions from enrolling aid-dependent students. This led to rising enrollment of relatively disadvantaged students, but primarily at poor-performing, low-value institutions whose students systematically failed to complete a degree, struggled to repay their loans, defaulted at high rates, and foundered in the job market. As these new borrowers experienced similarly poor outcomes, their loans piled up, loan performance deteriorated, and with it the finances of the federal program. The crisis illustrates the important role that educational institutions play in access to postsecondary education and student outcomes, and difficulty of using broadly-available loans to subsidize investments in education when there is so much heterogeneity in outcomes across institutions and programs and in the ability to repay of students.
Remote work for the public administration of a country of origin under the EU Temporary Protection Directive
Authors: Sadowski Piotr
Published: August 2024

This research focuses on the legal situation of displaced persons who benefit from Directive 2001/55/EC regulating the EU temporary protection mechanism. This law can be activated in cases of mass arrivals of persons in need of international protection. The research examines whether displaced persons can work remotely for the authorities of their country of origin. The analysis has shown that the answer to the research questions depends on the nature of the activities performed by a displaced person, but not on the type of contract that this beneficiary concludes with the authorities.
Joking to learn
Authors: Hoicka Elena
Published: August 2024

Associate professor of psychology in education at Bristol University, Elena Hoicka, discusses research into how humour develops in children under three and why it might be important
Practice-based education: a scoping review
Authors: Godley Nicola D , Devlin Lauren , Watson Jay , Davidson Tom
Published: August 2024

Background:

Apprenticeships are key to ensuring that private and public employers can recruit and develop workforces. The degree apprenticeship in paramedic practice allows learners to continue academic study while participating in on-the-job training.

Objectives:

The aim of this UK-based scoping review is to identify the barriers and challenges in practice-based education, and link the findings to paramedic degree apprenticeships.

Methods:

A scoping review was undertaken to examine the literature on degree apprenticeships and the barriers and challenges within practice-based education.

Findings:

Six studies were reviewed. None were specific to paramedicine, so analysis and evaluation were drawn from other professions. Three main themes were identified: role of the mentor/practice-based educator; stakeholder collaboration; and apprentice support.

Conclusion:

Employers are key to the collaborative design of apprenticeship, yet multiple issues in terms of their working with higher education institutions exist. The interpretation of apprenticeship-specific terminology used to assess competence, and the subjective definition of expected standards were key concerns of practice educators. Employers need to provide education to practice educators to support the facilitation of learning and assessment. Responsibility for the success of apprentices lies with both employer and learner. More research is needed on barriers for each stakeholder. Employers require clearer guidance regarding funding and expectations.