bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized Merkel cell carcinoma treatment considerations: a response to the forty-year experience at the Peter MacCallum cancer centre
Authors: Leigh James , Gebauer Kurt
Published: June 2024

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin with poor prognosis and rising global incidence. A recently published article in BMC Cancer, titled “Merkel cell carcinoma: a forty-year experience at the Peter MacCallum Cancer Centre” (Wang et al.), provides a contemporary analysis of locoregional disease outcomes in Australia which highlights the comparative effectiveness of radiotherapy for excisions with involved margins versus wide local excision. There is a persistent lack of clear, well-defined guidelines to manage MCC in Australia despite experiencing the highest rates globally. The advanced age at onset also provides inherent challenges for optimal management and often, a case-by-case approach is necessary based on patient preferences, baseline function and fitness for surgery. This paper responds to the recently published article by Wang et al. and will expand the discourse regarding management of localized MCC. Specifically, we will discuss the surgical excision approaches; alternative treatment options for MCC including radiotherapy, Mohs micrographic surgery and novel immunotherapy agents being investigated through several clinical trials.
A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda
Authors: Okello Clement D. , Orem Jackson , Nabwana Martin , Kiwanuka Noah , Shih Andrew W. , Heddle Nancy , Mayanja-Kizza Harriet
Published: June 2024

Background

Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting.

Methods

An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality.

Results

There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1–3) unit and 2 (IQR, 1–3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1–10) and was 6.2% (95% CI, 3.2–12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86–0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00–0.31, p < 0.01) were associated with reduced 30-day mortality.

Conclusions

The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed.

Trial registration

Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.
Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma
Authors: Yang Kyungmi , Ahn Joong Hyun , Woo Sook-Young , Jung Sang Hoon , Sung Ki Woong , Lee Ji Won , Lim Do Hoon
Published: May 2024

Background

To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma.

Methods

Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae.

Results

The follow-up was a median of 53.5 months (range, 21–81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular.

Conclusion

The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.
Review of clinical characteristics and mortality outcomes in patients on maintenance hemodialysis during the Omicron surge: a single center experience
Authors: Xue Yiyang , Feng Weiwei , Shi Ling , Cui Ning , Zhang Wei , Dong Junxiu , Li Chunying , Hu Jinjin , Wei Junjun
Published: June 2024

Background

This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge.

Methods

According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison.

Results

366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group.

Conclusions

Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities.
The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility
Authors: Diao Shitong , Li Shan , Dong Run , Jiang Wei , Wang Chunyao , Chen Yan , Wang Jingyi , He Shuhua , Wang Yifan , Du Bin , Weng Li
Published: May 2024

Backgrounds

Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure.

Methods

We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min.

Results

Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively).

Conclusions

EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation.

Trial Registration

Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).
The effect of educational intervention according to mindfulness on the psychological well-being of female heads of households
Authors: Mahmoudi Fataneh , Zarnaghash Maryam , Shegefti Nadere Sohrabi , Barzegar Majid
Published: June 2024

Objective

The low level of psychological well-being is one of the most common problems of the women who are the heads of households, and various educational programs have been conducted to improve the psychological well-being of such a group. The present study was conducted to outline the effectiveness of mindfulness-based educational intervention in the psychological well-being of women as the heads of households.

Methods

This research as a semi-experimental study was done by pretest–posttest design and control group. The study statistical population included all women as the heads of households in Shiraz, who had a file in the Shiraz based welfare office and at the same time their children were studying in schools covered by the 2nd district educational department of Shiraz in 2022–2023. Out of the female heads of the households in the statistical community, 30 women were selected as Purposive sampling and then randomly divided into two 15-individual groups, including experimental group (training on mindfulness-based therapy) and control group. The research tool included Ryff’s psychological well-being scale (Ryff, 1989). The experimental group was subjected to training on mindfulness-based therapy (Baer et al., 2006) during eight 90-min sessions. However, the control group did not receive any intervention.

Result

After running the intervention, a significant difference was seen between the components of autonomy, personal growth, purpose in life, self-acceptance, positive relationship with others, and psychological well-being after running the educational intervention between the experimental and control groups (P < 0.05), while no meaningful difference popped up between the experimental and control groups in terms of environmental mastery as one of the aspects measured in psychological well-being scale after the educational intervention (P = 0.602).

Conclusion

According to the results, it seems that psychologists can benefit from the method of training on mindfulness-based therapy in order to increase the psychological well-being of women as the heads of households.
Ethanolic extract from Sophora moorcroftiana inhibit cell proliferation and alter the mechanical properties of human cervical cancer
Authors: Guo Manli , Guo Dingcheng , Liao Lingzi , Zhang Xiao , Wang Zhilong , Zhou Qiaozhen , Chen Ping , Li Ruiping , Han Bing , Bao Guangjie , Zhang Baoping
Published: June 2024

Background

Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation.

Methods

The proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS.

Results

EESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes.

Conclusion

This study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.
Understanding the integration of artificial intelligence in healthcare organisations and systems through the NASSS framework: a qualitative study in a leading Canadian academic centre
Authors: Alami Hassane , Lehoux Pascale , Papoutsi Chrysanthi , Shaw Sara E. , Fleet Richard , Fortin Jean-Paul
Published: June 2024

Background

Artificial intelligence (AI) technologies are expected to “revolutionise” healthcare. However, despite their promises, their integration within healthcare organisations and systems remains limited. The objective of this study is to explore and understand the systemic challenges and implications of their integration in a leading Canadian academic hospital.

Methods

Semi-structured interviews were conducted with 29 stakeholders concerned by the integration of a large set of AI technologies within the organisation (e.g., managers, clinicians, researchers, patients, technology providers). Data were collected and analysed using the Non-Adoption, Abandonment, Scale-up, Spread, Sustainability (NASSS) framework.

Results

Among enabling factors and conditions, our findings highlight: a supportive organisational culture and leadership leading to a coherent organisational innovation narrative; mutual trust and transparent communication between senior management and frontline teams; the presence of champions, translators, and boundary spanners for AI able to build bridges and trust; and the capacity to attract technical and clinical talents and expertise.

Constraints and barriers include: contrasting definitions of the value of AI technologies and ways to measure such value; lack of real-life and context-based evidence; varying patients’ digital and health literacy capacities; misalignments between organisational dynamics, clinical and administrative processes, infrastructures, and AI technologies; lack of funding mechanisms covering the implementation, adaptation, and expertise required; challenges arising from practice change, new expertise development, and professional identities; lack of official professional, reimbursement, and insurance guidelines; lack of pre- and post-market approval legal and governance frameworks; diversity of the business and financing models for AI technologies; and misalignments between investors’ priorities and the needs and expectations of healthcare organisations and systems.

Conclusion

Thanks to the multidimensional NASSS framework, this study provides original insights and a detailed learning base for analysing AI technologies in healthcare from a thorough socio-technical perspective. Our findings highlight the importance of considering the complexity characterising healthcare organisations and systems in current efforts to introduce AI technologies within clinical routines. This study adds to the existing literature and can inform decision-making towards a judicious, responsible, and sustainable integration of these technologies in healthcare organisations and systems.
“Let’s put it this way: you can’t really live without it” - digital technologies in routine palliative care delivery: an explorative qualitative study with patients and their family caregivers in Germany
Authors: May Susann , Gehlhaar Anne , Stahlhut Kerstin , Kamp Marcel-Alexander , Heinze Martin , Allsop Matthew , Muehlensiepen Felix
Published: June 2024

Background

Despite ongoing efforts to integrate palliative care into the German healthcare system, challenges persist, particularly in areas where infrastructure does not fully support digital technologies (DT). The increasing importance of digital technology (DT) in palliative care delivery presents both opportunities and challenges.

Objective

This study aimed to explore the perspectives and preferences of palliative care patients and their family caregivers regarding the use of DT in care delivery.

Methods

An exploratory qualitative study was conducted using semi-structured interviews with palliative care patients and their family caregivers across various settings. Participants were selected through gatekeeper-supported purposive sampling. Interviews were analysed using structured qualitative content analysis.

Results

Nineteen interviews were conducted.Three themes emerged: (1) Application of DTs in palliative care; (2) Potential of DTs; (3) Barriers to the use of DTs. Key findings highlighted the preference for real-time communication using DTs that participants are familiar with. Participants reported limited perceived value for digital transformation in the presence of in-person care. The study identified requirements for DT development and use in palliative care, including the need for direct and immediate functionality, efficiency in healthcare professional (HCP) work, and continuous access to services.

Conclusion

The findings highlight a demonstrate the importance of familiarity with DTs and real-time access for patients and their families. While DT can enhance palliative care efficiency and accessibility, its integration must complement, not replace, in-person interaction in palliative care. As DTs continue to grow in scope and use in palliative care, maintaining continued user engagement is essential to optimise their adoption and ensure they benefit patients and their caregivers.
High-affinity monoclonal antibodies against the porcine epidemic diarrhea virus S1 protein
Authors: Lang Qiaoli , Huang Nan , Guo Jincao , Ge Liangpeng , Yang Xi
Published: June 2024

The porcine epidemic diarrhea virus (PEDV) infection inflicted substantial economic losses upon the global pig-breeding industry. This pathogen can infect all pigs and poses a particularly high fatality risk for suckling piglets. The S1 subunit of spike protein is a crucial target protein for inducing the particularly neutralizing antibodies that can intercept the virus-host interaction and neutralize virus infectivity. In the present study, the HEK293F eukaryotic expression system was successfully utilized to express and produce recombinant S1 protein. Through quantitative analysis, five monoclonal antibodies (mAbs) specifically targeting the recombinant S1 protein of PEDV were developed and subsequently evaluated using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and flow cytometry assay (FCA). The results indicate that all five mAbs belong to the IgG1 isotype, and their half-maximal effective concentration (EC50) values measured at 84.77, 7.42, 0.89, 14.64, and 7.86 pM. All these five mAbs can be utilized in ELISA, FCA, and IFA for the detection of PEDV infection. MAb 5-F9 exhibits the highest sensitivity to detect as low as 0.3125 ng/mL of recombinant PEDV-S1 protein in ELISA, while only 0.096 ng/mL of mAb 5-F9 is required to detect PEDV in FCA. The results from antigen epitope analysis indicated that mAb 8-G2 is the sole antibody capable of recognizing linear epitopes. In conclusion, this study has yielded a highly immunogenic S1 protein and five high-affinity mAbs specifically targeting the S1 protein. These findings have significant implications for early detection of PEDV infection and provide a solid foundation for further investigation into studying virus-host interactions.
The small tumor antigen of Merkel cell polyomavirus accomplishes cellular transformation by uniquely localizing to the nucleus despite the absence of a known nuclear localization signal
Authors: Thevenin Kaira R. , Tieche Isabella S. , Di Benedetto Cody E. , Schrager Matt , Dye Kristine N.
Published: June 2024

Background

Merkel Cell Carcinoma (MCC) is an aggressive skin cancer that is three times deadlier than melanoma. In 2008, it was found that 80% of MCC cases are caused by the genomic integration of a novel polyomavirus, Merkel Cell Polyomavirus (MCPyV), and the expression of its small and truncated large tumor antigens (ST and LT-t, respectively). MCPyV belongs to a family of human polyomaviruses; however, it is the only one with a clear association to cancer.

Methods

To investigate the role and mechanisms of various polyomavirus tumor antigens in cellular transformation, Rat-2 and 293A cells were transduced with pLENTI MCPyV LT-t, MCPyV ST, TSPyV ST, HPyV7 ST, or empty pLENTI and assessed through multiple transformation assays, and subcellular fractionations. One-way ANOVA tests were used to assess statistical significance.

Results

Soft agar, proliferation, doubling time, glucose uptake, and serum dependence assays confirmed ST to be the dominant transforming protein of MCPyV. Furthermore, it was found that MCPyV ST is uniquely transforming, as the ST antigens of other non-oncogenic human polyomaviruses such as Trichodysplasia Spinulosa-Associated Polyomavirus (TSPyV) and Human Polyomavirus 7 (HPyV7) were not transforming when similarly assessed. Identification of structural dissimilarities between transforming and non-transforming tumor antigens revealed that the uniquely transforming domain(s) of MCPyV ST are likely located within the structurally dissimilar loops of the MCPyV ST unique region. Of all known MCPyV ST cellular interactors, 62% are exclusively or transiently nuclear, suggesting that MCPyV ST localizes to the nucleus despite the absence of a canonical nuclear localization signal. Indeed, subcellular fractionations confirmed that MCPyV ST could achieve nuclear localization through a currently unknown, regulated mechanism independent of its small size, as HPyV7 and TSPyV ST proteins were incapable of nuclear translocation. Although nuclear localization was found to be important for several transforming properties of MCPyV ST, some properties were also performed by a cytoplasmic sequestered MCPyV ST, suggesting that MCPyV ST may perform different transforming functions in individual subcellular compartments.

Conclusions

Together, these data further elucidate the unique differences between MCPyV ST and other polyomavirus ST proteins necessary to understand MCPyV as the only known human oncogenic polyomavirus.
Efficacy and safety of ultrasound-guided thermal ablation of graves’ disease: a retrospective cohort study
Authors: Cai Guangzhen , Luo Beilin , Wang Maolin , Su Jiqin , Lin Luping , Li Guibin , Chen Xiangru , Huang Zhishu , Lin Peiyi , Liu Shengwei , Yan Huidi , Zhou Lixin
Published: June 2024

Background

Ultrasound-guided thermal ablation (TA) has emerged as a robust therapeutic approach for treating solid tumors in multiple organs, including the thyroid. Yet, its efficacy and safety profile in the management of Graves’ Disease (GD) remains to be definitively established.

Methods

A retrospective study was conducted on 50 GD patients treated with TA between October 2017 and December 2021. Key metrics like thyroid volume, volume reduction rate (VRR), thyroid hormones, and basal metabolic rate (BMR) were evaluated using paired Wilcoxon tests.

Results

The intervention of ultrasound-guided TA yielded a statistically significant diminution in total thyroid volume across all postoperative follow-up intervals—1, 3, 6, and 12 months—relative to pre-intervention baselines (p < 0.001). The median VRR observed at these time points were 17.5%, 26.5%, 34.4%, and 39.8%, respectively. Euthyroid status was corroborated in 96% of patients at the one-year follow-up milestone. Transient tachycardia and dysphonia were observed in three patients, while a solitary case of skin numbness was noted. Crucially, no instances of enduring injury to the recurrent laryngeal nerve (RLN) were documented.

Conclusions

Our investigation substantiates ultrasound-guided TA as a pragmatic, well-tolerated, and safe therapeutic modality for GD. It effectively improves symptoms of hyperthyroidism, engenders a substantial reduction in thyroid volume, and restores thyroid hormone and BMR to physiological levels. Given its favorable safety profile, enhanced cosmetic outcomes, and minimally invasive nature, ultrasound-guided TA is a compelling alternative to thyroidectomy for GD patients.
Targeting FGFR for cancer therapy
Authors: Zhang Pei , Yue Lin , Leng QingQing , Chang Chen , Gan Cailing , Ye Tinghong , Cao Dan
Published: June 2024

The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current state of clinical research in this field. Then, we highlight four drugs that have been approved for marketing by the FDA, offering insights into their molecular mechanisms and clinical achievements. Our discussion encompasses the intricate landscape of FGFR-driven tumorigenesis, current techniques for pinpointing FGFR anomalies, and clinical experiences with FGFR inhibitor regimens. Furthermore, we discuss the inherent challenges of targeting the FGFR pathway, encompassing resistance mechanisms such as activation by gatekeeper mutations, alternative pathways, and potential adverse reactions. By synthesizing the current evidence, we underscore the potential of FGFR-centric therapies to enhance patient prognosis, while emphasizing the imperative need for continued research to surmount resistance and optimize treatment modalities.
Deep learning-based risk stratification of preoperative breast biopsies using digital whole slide images
Authors: Boissin Constance , Wang Yinxi , Sharma Abhinav , Weitz Philippe , Karlsson Emelie , Robertson Stephanie , Hartman Johan , Rantalainen Mattias
Published: June 2024

Background

Nottingham histological grade (NHG) is a well established prognostic factor in breast cancer histopathology but has a high inter-assessor variability with many tumours being classified as intermediate grade, NHG2. Here, we evaluate if DeepGrade, a previously developed model for risk stratification of resected tumour specimens, could be applied to risk-stratify tumour biopsy specimens.

Methods

A total of 11,955,755 tiles from 1169 whole slide images of preoperative biopsies from 896 patients diagnosed with breast cancer in Stockholm, Sweden, were included. DeepGrade, a deep convolutional neural network model, was applied for the prediction of low- and high-risk tumours. It was evaluated against clinically assigned grades NHG1 and NHG3 on the biopsy specimen but also against the grades assigned to the corresponding resection specimen using area under the operating curve (AUC). The prognostic value of the DeepGrade model in the biopsy setting was evaluated using time-to-event analysis.

Results

Based on preoperative biopsy images, the DeepGrade model predicted resected tumour cases of clinical grades NHG1 and NHG3 with an AUC of 0.908 (95% CI: 0.88; 0.93). Furthermore, out of the 432 resected clinically-assigned NHG2 tumours, 281 (65%) were classified as DeepGrade-low and 151 (35%) as DeepGrade-high. Using a multivariable Cox proportional hazards model the hazard ratio between DeepGrade low- and high-risk groups was estimated as 2.01 (95% CI: 1.06; 3.79).

Conclusions

DeepGrade provided prediction of tumour grades NHG1 and NHG3 on the resection specimen using only the biopsy specimen. The results demonstrate that the DeepGrade model can provide decision support to identify high-risk tumours based on preoperative biopsies, thus improving early treatment decisions.
Protein target similarity is positive predictor of in vitro antipathogenic activity: a drug repurposing strategy for Plasmodium falciparum
Authors: Mogire Reagan M. , Miruka Silviane A. , Juma Dennis W. , McNamara Case W. , Andagalu Ben , Burrows Jeremy N. , Chenu Elodie , Duffy James , Ogutu Bernhards R. , Akala Hoseah M.
Published: June 2024

Drug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases. By leveraging publicly available biomedical information, it is possible to predict compounds’ activity and identify their potential targets across diverse organisms. In this study, we aimed to assess the antiplasmodial activity of compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library using in vitro and bioinformatics approaches. We assessed the in vitro antiplasmodial activity of the compounds using blood-stage and liver-stage drug susceptibility assays. We used protein sequences of known targets of the ReFRAME compounds with high antiplasmodial activity (EC50 < 10 uM) to conduct a protein-pairwise search to identify similar Plasmodium falciparum 3D7 proteins (from PlasmoDB) using NCBI protein BLAST. We further assessed the association between the compounds' in vitro antiplasmodial activity and level of similarity between their known and predicted P. falciparum target proteins using simple linear regression analyses. BLAST analyses revealed 735 P. falciparum proteins that were similar to the 226 known protein targets associated with the ReFRAME compounds. Antiplasmodial activity of the compounds was positively associated with the degree of similarity between the compounds’ known targets and predicted P. falciparum protein targets (percentage identity, E value, and bit score), the number of the predicted P. falciparum targets, and their respective mutagenesis index and fitness scores (R2 between 0.066 and 0.92, P < 0.05). Compounds predicted to target essential P. falciparum proteins or those with a druggability index of 1 showed the highest antiplasmodial activity.
Unveiling the entrepreneurial mindset: exploring orientation and intentions among students of prominent engineering disciplines
Authors: Pinto Prakash , Pallikkara Vinish , Pinto Slima , Hawaldar Iqbal Thonse
Published: June 2024

The advent of Industry 4.0 presents a spectrum of challenges for entrepreneurs in India, demanding specific skills and resources. Within this transformative landscape, engineering disciplines assume a pivotal role in navigating the complexities of the new industrial revolution yet pose challenges in instilling entrepreneurial skills. While universities are recognised for fostering entrepreneurial skills, a gap persists in comprehending students’ intentions to pursue entrepreneurship after completing their studies, especially within technical education systems. This emphasises the necessity for a comprehensive examination of variations in entrepreneurial orientation among diverse engineering disciplines. The study employed cross-sectional research and surveyed 370 final-year engineering students from leading engineering colleges in Karnataka, India. The data analysis included Exploratory Factor Analysis (EFA) and Structural Equation Modeling (SEM). The findings demonstrate a significant propensity for entrepreneurship among engineering students, highlighting attributes such as innovativeness, risk-taking, and proactiveness. However, contrary to expectations, the study does not discern distinct entrepreneurial orientations across different engineering disciplines. Importantly, it unveils that college education has minimal influence on students’ entrepreneurial intentions.
Microstructural differences in the cingulum and the inferior longitudinal fasciculus are associated with (extinction) learning
Authors: Nostadt Alina , Schlaffke Lara , Merz Christian J. , Wolf Oliver T. , Nitsche Michael A. , Tegenthoff Martin , Lissek Silke
Published: June 2024

Cognitive functions, such as learning and memory processes, depend on effective communication between brain regions which is facilitated by white matter tracts (WMT). We investigated the microstructural properties and the contribution of WMT to extinction learning and memory in a predictive learning task. Forty-two healthy participants completed an extinction learning paradigm without a fear component. We examined differences in microstructural properties using diffusion tensor imaging to identify underlying neural connectivity and structural correlates of extinction learning and their potential implications for the renewal effect. Participants with good acquisition performance exhibited higher fractional anisotropy (FA) in WMT including the bilateral inferior longitudinal fasciculus (ILF) and the right temporal part of the cingulum (CNG). This indicates enhanced connectivity and communication between brain regions relevant to learning and memory resulting in better learning performance. Our results suggest that successful acquisition and extinction performance were linked to enhanced structural connectivity. Lower radial diffusivity (RD) in the right ILF and right temporal part of the CNG was observed for participants with good acquisition learning performance. This observation suggests that learning difficulties associated with increased RD may potentially be due to less myelinated axons in relevant WMT. Also, participants with good acquisition performance were more likely to show a renewal effect. The results point towards a potential role of structural integrity in extinction-relevant WMT for acquisition and extinction.
An investigation on the craft of Tianche: traditional timber salt well structures of the Sichuan Basin, China
Authors: Zhu Zhenyu , Li Haiqing , Yu Jingwei
Published: June 2024

This study investigates the craft of Tianche, an ancient towering timber structure used in well salt production in Sichuan Province, China. Originating in the Han Dynasty and maturing in the late Qing Dynasty, Tianches can reach heights of up to 110 m and represent a unique craft and structural system that is rare worldwide, yet remains largely unexplored in scholarly research. The Tianches are under threat due to a lack of maintenance and extinction of the craft. This study aims to document and elucidate the procedure and principles of the Tianche craft to help conserve this heritage. The key question is how to employ traditional craft to assemble over 100-m-tall structures from small-sized logs using pre-industrial technology. The study combines anthropological fieldwork and principles of mechanics to analyze the scientific validity and rationality of traditional crafts. The study reveals the principles of the Tianche craft, including mature craft procedure and reliable binding joints. Its advantages, namely self-locking structure, frictional force transmission, and hollow cylindrical columns, enhance the structure’s strength and stability and are fundamental for constructing 100-m-tall timber structures. Additionally, the study identifies two limitations of the craft: restricted column diameters and the tendency of the inverted dragon member’s tenon to break. This study investigated Tianche timber structures featuring hollow, bundle-like columns with frictional force transmission mechanism, presenting new possibilities beyond mainstream timber structural systems. The findings may contribute to enhancing research on the Tianche craft and could lay the foundation for future conservation practices related to Tianche heritage.
Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults
Authors: Lim Zhi Wei , Li Jonathan , Wong Damon , Chung Joey , Toh Angeline , Lee Jia Ling , Lam Crystal , Balakrishnan Maithily , Chia Audrey , Chua Jacqueline , Girard Michael , Hoang Quan V. , Chong Rachel , Wong Chee Wai , Saw Seang Mei , Schmetterer Leopold , Brennan Noel , Ang Marcus
Published: June 2024

Background

Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems.

Methods

Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland–Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement.

Results

A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of − 26.7 µm (95% CI: − 29.7 to − 23.7, P < 0.001) and proportional bias of − 0.090 (P < 0.001).

Conclusion

We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.
Reflections on the benefits and challenges of using co-produced artistic workshops to engage with young people in community settings
Authors: Tinner Laura
Published: June 2024

Background

Despite increased focus on adolescence, young people’s voices are often undervalued and underrepresented in health inequalities research and policy. Through exploring young people’s priorities for their health and their community, we may begin to understand how public health interventions and policies can be more effective and equitable. Engaging with youth using art enables empowerment and self-expression on these complex topics.

Methods

Creative workshops, co-produced with a young artist, were delivered at three youth centres to participants aged 11–18 years (n = 30) in disadvantaged areas of Bristol, UK. Participants engaged in art and were guided by a semi-structured topic guide through focus group discussion. Thematic analysis, supported by the young artist, was used to distil key policy priorities for young people to be delivered to the local authority.

Results

The young people identified a list of key priorities. These were: (1) mental health, (2) feeling ‘forgotten’ as an age group and having safe city spaces to socialise, (3) the need for greater support for their education and career aspirations. I provide a brief summary of these priorities, but the focus of this article is on the critical reflections on this innovative way of engaging with young people about local policy. I provide key learning points for researchers looking to do creative public health work in community settings and involve marginalised young people.

Conclusions

Art is a promising way of engaging with young people in community settings and elevating marginalised voices. Co-producing with a local young artist enriched the project and partially alleviated power imbalances. This approach has potential for involving different groups within local policymaking and priority setting around health inequalities.
Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications
Authors: Tago Tetsuro , Toyohara Jun
Published: June 2024

Background

Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general.

Results

In the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%.

Conclusions

Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study.
Increase in choroidal thickness after blue light stimulation of the blind spot in young adults
Authors: Hoseini-Yazdi Hosein , Read Scott A. , Collins Michael J. , Bahmani Hamed , Ellrich Jens , Schilling Tim
Published: June 2024

Background

Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness.

Methods

The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460 nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620 nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups.

Results

Compared with sham control (2 ± 1 μm, n = 20) and red light (−1 ± 2 μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60 min after blue light stimulation of the blind spot (7 ± 1 μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2 μm, p < 0.001) but not in myopes (4 ± 2 μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation.

Conclusions

These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.