bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes and the prognostic significance of clinicopathological features in patients with endometrial clear cell carcinoma: a 35-year single-center retrospective study
Authors: Ma Xiao , Cao Dongyan , Zhou Huimei , Wang Tao , Wang Jinhui , Zhang Ying , Yu Mei , Cheng Ninghai , Peng Peng , Yang Jiaxin , Huang Huifang , Shen Keng 
Published: March 2023

AbstractBackgroundTo evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes.MethodsMedical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used.ResultsIn total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS.ConclusionsECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors.
A framework for sustainable capacity-building for collaborative North–South translational health research and training in a resource-constrained setting
Authors: Maponga Charles C. , Mhazo Alison T. , Morse Gene D. 
Published: March 2023

AbstractIntroductionSuccess with highly active antiretroviral therapy (ART) for the human immunodeficiency virus (HIV) in developing countries has been attributed to collaborative North–South resource-sharing and capacity-building. Academic research and training programmes have contributed towards policy entrepreneurship in a manner that influenced capacity-building within health systems. However, the documented capacity-building frameworks rarely elucidate how such programmes can be designed and implemented efficiently and sustainably.MethodWe implemented the University of Zimbabwe (UZ)–State University of New York at Buffalo (UB) collaborative HIV clinical pharmacology capacity-building programme in Zimbabwe in 1998. We intuitively operationalized the programme around a mnemonic acronym, “RSTUVW”, which spells out a supportive framework consisting of “room (space), skills, tools (equipment)”, underpinned by a set of core values, “understanding, voice (clout) and will”. Subsequent to our two decades of successful collaborative experience, we tested the general validity and applicability of the framework within a prospective programme aimed at expanding the role of health professionals.Results and conclusionBased on this collaborative North–South research and training capacity-building programme which has been positively validated in Zimbabwe, we propose this novel mnemonic acronym-based framework as an extra tool to guide sustainable capacity-building through collaborative North–South implementation research. Its extended use could also include assessment and evaluation of health systems within resource-constrained settings.
Digital behaviour change interventions to increase vegetable intake in adults: a systematic review
Authors: Livingstone Katherine M. , Rawstorn Jonathan C. , Partridge Stephanie R. , Godrich Stephanie L. , McNaughton Sarah A. , Hendrie Gilly A. , Blekkenhorst Lauren C. , Maddison Ralph , Zhang Yuxin , Barnett Scott , Mathers John C. , Packard Maria , Alston Laura 
Published: March 2023

Abstract
Background
Digital interventions may help address low vegetable intake in adults, however there is limited understanding of the features that make them effective. We systematically reviewed digital interventions to increase vegetable intake to 1) describe the effectiveness of the interventions; 2) examine links between effectiveness and use of co-design, personalisation, behavioural theories, and/or a policy framework; and 3) identify other features that contribute to effectiveness.

Methods
A systematic search strategy was used to identify eligible studies from MEDLINE, Embase, PsycINFO, Scopus, CINAHL, Cochrane Library, INFORMIT, IEEE Xplore and Clinical Trial Registries, published between January 2000 and August 2022. Digital interventions to increase vegetable intake were included, with effective interventions identified based on statistically significant improvement in vegetable intake. To identify policy-action gaps, studies were mapped across the three domains of the NOURISHING framework (i.e., behaviour change communication, food environment, and food system). Risk of bias was assessed using Cochrane tools for randomized, cluster randomized and non-randomized trials.

Results
Of the 1,347 records identified, 30 studies were included. Risk of bias was high or serious in most studies (n = 25/30; 83%). Approximately one quarter of the included interventions (n = 8) were effective at improving vegetable intake. While the features of effective and ineffective interventions were similar, embedding of behaviour change theories (89% vs 61%) and inclusion of stakeholders in the design of the intervention (50% vs 38%) were more common among effective interventions. Only one (ineffective) intervention used true co-design. Although fewer effective interventions included personalisation (67% vs 81%), the degree of personalisation varied considerably between studies. All interventions mapped across the NOURISHING framework behaviour change communication domain, with one ineffective intervention also mapping across the food environment domain.

Conclusion
Few digital interventions identified in this review were effective for increasing vegetable intake. Embedding behaviour change theories and involving stakeholders in intervention design may increase the likelihood of success. The under-utilisation of comprehensive co-design methods presents an opportunity to ensure that personalisation approaches better meet the needs of target populations. Moreover, future digital interventions should address both behaviour change and food environment influences on vegetable intake.
Comprehensive analysis of scRNA-Seq and bulk RNA-Seq reveals dynamic changes in the tumor immune microenvironment of bladder cancer and establishes a prognostic model
Authors: Tan Zhiyong , Chen Xiaorong , Zuo Jieming , Fu Shi , Wang Haifeng , Wang Jiansong 
Published: March 2023

Abstract
Background
The prognostic management of bladder cancer (BLCA) remains a great challenge for clinicians. Recently, bulk RNA-seq sequencing data have been used as a prognostic marker for many cancers but do not accurately detect core cellular and molecular functions in tumor cells. In the current study, bulk RNA-seq and single-cell RNA sequencing (scRNA-seq) data were combined to construct a prognostic model of BLCA.

Methods
BLCA scRNA-seq data were downloaded from Gene Expression Omnibus (GEO) database. Bulk RNA-seq data were obtained from the UCSC Xena. The R package "Seurat" was used for scRNA-seq data processing, and the uniform manifold approximation and projection (UMAP) were utilized for downscaling and cluster identification. The FindAllMarkers function was used to identify marker genes for each cluster. The limma package was used to obtain differentially expressed genes (DEGs) affecting overall survival (OS) in BLCA patients. Weighted gene correlation network analysis (WGCNA) was used to identify BLCA key modules. The intersection of marker genes of core cells and genes of BLCA key modules and DEGs was used to construct a prognostic model by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, and chemotherapeutic drug sensitivity between the high and low-risk groups were also investigated.

Results
scRNA-seq data were analyzed to identify 19 cell subpopulations and 7 core cell types. The ssGSEA showed that all 7 core cell types were significantly downregulated in tumor samples of BLCA. We identified 474 marker genes from the scRNA-seq dataset, 1556 DEGs from the Bulk RNA-seq dataset, and 2334 genes associated with a key module identified by WGCNA. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of 3 signature genes, namely MAP1B, PCOLCE2, and ELN. The feasibility of the model was validated by an internal training set and two external validation sets. Moreover, patients with high-risk scores are predisposed to experience poor OS, a larger prevalence of stage III-IV, a greater TMB, a higher infiltration of immune cells, and a lesser likelihood of responding favorably to immunotherapy.

Conclusion
By integrating scRNA-seq and bulk RNA-seq data, we constructed a novel prognostic model to predict the survival of BLCA patients. The risk score is a promising independent prognostic factor that is closely correlated with the immune microenvironment and clinicopathological characteristics.
Closed reduction of dorsally displaced distal radius fractures in the elderly provided improved final radiographic results
Authors: Hassellund Sondre Stafsnes , Oftebro Ingrid , Williksen John Haakon , Søreide Endre , Madsen Jan Erik , Frihagen Frede 
Published: March 2023

Abstract
Background
Recent guidelines recommend non-operative treatment as primary treatment in elderly patients with displaced distal radius fractures. Most of these fractures are closely reduced. We aimed to evaluate the radiological results of closed reduction and casting of dorsally displaced distal radius fractures in patients 65 years or older.

Methods
A total of 290 patients treated during the years 2015, 2018 and 2019 in an urban outpatient fracture clinic with complete follow-up at least 5 weeks post-reduction were available for analysis. Closed fracture reduction was performed by manual traction under hematoma block. A circular plaster of Paris cast was used. Radiographs pre- and post-reduction and at final follow-up were analyzed.

Results
Mean age was 77 years (SD 8) and 258 (89%) were women. Dorsal tilt improved from mean 111° (range 83–139) to 89° (71–116) post-reduction and fell back to mean 98° (range 64–131) at final follow-up. Ulnar variance was 2 mm ((-1)-12) pre-reduction, 0 mm ((-3)-5) post-reduction and ended at mean 2 mm (0–8). Radial inclination went from 17° ((-6)-30) to 23° (SD 7–33), and then back to 18° (0–32) at final follow-up. 41 (14%) patients had worse alignment at final follow-up compared to pre-reduction. 48 (17%) obtained a position similar to the starting point, while 201 (69%) improved. Fractures with the volar cortex aligned after reduction retained 0.4 mm (95% Confidence Interval (CI) 0.1 to 0.7; p = 0,022) more radius length during immobilization. In a regression analysis, less ulnar variance in initial radiographs (OR 1.8 (95% CI 1.4 to 2.3) per mm, p < 0.001) and lower age (OR 1.06 (95% CI 1.02 to 1.09) per year, p < 0.003) protected against loss of reduction.

Conclusion
Subsequent loss of reduction after initial closed reduction was seen in most distal radius fractures. Reduction improved overall alignment in 2/3 of the patients at final follow-up. An aligned volar cortex seemed to protect partially against loss of radial length.
LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia
Authors: Wang Dong , Li Xiaohui , Jiao Defeng , Cai Ying , Qian Liting , Shen Yiqing , Lu Yichen , Zhou Yonggang , Fu Binqing , Sun Rui , Tian Zhigang , Zheng Xiaohu , Wei Haiming 
Published: March 2023

Abstract
Background
Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome.

Methods
First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting.

Results
Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice.

Conclusions
Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.
Current sequence-based models capture gene expression determinants in promoters but mostly ignore distal enhancers
Authors: Karollus Alexander , Mauermeier Thomas , Gagneur Julien 
Published: March 2023

Abstract
Background
The largest sequence-based models of transcription control to date are obtained by predicting genome-wide gene regulatory assays across the human genome. This setting is fundamentally correlative, as those models are exposed during training solely to the sequence variation between human genes that arose through evolution, questioning the extent to which those models capture genuine causal signals.

Results
Here we confront predictions of state-of-the-art models of transcription regulation against data from two large-scale observational studies and five deep perturbation assays. The most advanced of these sequence-based models, Enformer, by and large, captures causal determinants of human promoters. However, models fail to capture the causal effects of enhancers on expression, notably in medium to long distances and particularly for highly expressed promoters. More generally, the predicted impact of distal elements on gene expression predictions is small and the ability to correctly integrate long-range information is significantly more limited than the receptive fields of the models suggest. This is likely caused by the escalating class imbalance between actual and candidate regulatory elements as distance increases.

Conclusions
Our results suggest that sequence-based models have advanced to the point that in silico study of promoter regions and promoter variants can provide meaningful insights and we provide practical guidance on how to use them. Moreover, we foresee that it will require significantly more and particularly new kinds of data to train models accurately accounting for distal elements.
Workload and procedures used by European data protection authorities related to personal data protection: a cross-sectional study
Authors: Puljak Livia , Mladinić Anamarija , Koporc Zvonimir 
Published: March 2023

Abstract
Objective
Data protection authorities (DPAs) are independent public authorities supervising the application of the data protection law. There is one DPA in each European Union (EU) Member State. Workload and procedures used by European DPAs were analyzed via a cross-sectional study.

Results
DPAs from 13 countries participated: Austria, Bulgaria, Croatia, Estonia, Finland, Greece, Italy, Latvia, Liechtenstein, Lithuania, Norway, Romania, and Slovakia. Responding to opinion/guidance requests in DPAs was highly heterogeneous. Procedure types used by DPAs varied, from telephone-based advisory service in Norway to a formal legal opinion in Austria. The deadline for responding to the requests varied considerably in DPAs. The number of opinion/guidance requests sent by data controllers and processors, and the number of opinion/guidance requests and complaints sent by data subjects, increased from 2015 to 2018 when the General Data Protection Regulation (GDPR) came into full effect; it decreased in 2019. Few DPAs organized education about data protection for the research community. In conclusion, the procedures and workload of DPAs in the EU were highly variable. It is important to study these aspects further, as they may assist in tailoring future data protection policies and procedures at the EU level.
Induction of antitoxic antibody and preventive effect against porcine edema disease by the pentameric Stx2eB subunit vaccine
Authors: Yoshimura Masaya , Honda Youko , Yonemitsu Emi , Takahashi Ryota , Suenaga Kiyotaka , Waki Takashi 
Published: March 2023

AbstractPorcine edema disease (ED) is an enterotoxaemia that frequently occurs in 4–12 week-old piglets and results in high mortality. ED is caused by Shiga toxin 2e (Stx2e), produced by host-adapted Shiga toxin-producing Escherichia coli (STEC) strains. We constructed a recombinant protein in which the B subunit of Stx2e (Stx2eB) was linked to Cartilage Oligomeric Matrix Protein (COMP)’s pentameric domain to enhance antigenicity to induce neutralizing antibodies against Stx2e. We evaluated the efficacy of this antigen as a vaccine on the farm where ED had occurred. The suckling piglets were divided into two groups. The pigs in the vaccinated group were intramuscularly immunized with the vaccine containing 30 µg/head of Stx2eB-COMP at 1 and 4 weeks of age. The control pigs were injected with saline instead of the vaccine. The neutralizing antibody titer to Stx2e, mortality, clinical score, and body weight was evaluated up to 11 weeks after the first vaccination. In the vaccinated group, the Stx2e neutralizing antibody was detected 3 weeks after the first vaccination, its titer increased during the following weeks. The antibody was not detected in the control group during the test period. The STEC gene was detected in both groups during the test period, but a typical ED was observed only in control pigs; the mortality and clinical score were significantly lower in the vaccinated group than in the control group. These data indicate that the pentameric B subunit vaccine is effective for preventing ED and offers a promising tool for pig health control.
Rethinking the path from evidence to decision-making
Authors: Rasooly Alon , Ben-Sheleg Eliana , Davidovitch Nadav , Ellen Moriah 
Published: March 2023

AbstractEvidence-informed decision-making is increasingly recognized as a standard for policymaking in many fields, including public health. However, many challenges exist in identifying the appropriate evidence, disseminating it to different stakeholders, and implementing it in various settings. The Israel Implementation Science and Policy Engagement Centre (IS-PEC) was established at Ben-Gurion University of the Negev to “bridge the gap” between scientific research and policy. As an illustrative case study, IS-PEC is conducting a scoping review on strategies to engage senior citizens in Israel when developing health policy. In May 2022, IS-PEC brought together international experts and Israeli stakeholders to increase knowledge in the field of evidence-informed policy, develop a research agenda, strengthen international collaborations, and create a community for sharing experience, research, and best practices. Panelists presented the importance of communicating clear, accurate bottom-line messages with the media. Also, they highlighted the once-in-a-generation opportunity to promote the uptake of evidence in public health due to the increased public interest in evidence-informed policymaking post-COVID-19 pandemic and the need to build systems and centers to support the systematic use of evidence. Group discussions focused on various aspects of communication, including challenges and strategies when communicating to policymakers, understanding the nuances of communication between scientists, journalists, and the public, and some ethical issues surrounding data visualization and infographics. Panelists participated in a passionate debate regarding whether and how values play a role when conducting, analyzing, and communicating evidence. Takeaway lessons from the workshop included that going forward, Israel must create lasting systems and a sustainable environment for evidence-informed policy. Novel and interdisciplinary academic programs must be developed to train future policymakers in various fields, including public health, public policy, ethics, communication, social marketing, and infographics. Sustainable professional relationships between journalists, scientists, and policymakers must be fostered and strengthened based on mutual respect and a shared commitment to creating, synthesizing, implementing, and communicating high-quality evidence to serve the public and individual wellbeing.
Novel secure data protection scheme using Martino homomorphic encryption
Authors: Rupa Ch. , Greeshmanth  , Shah Mohd Asif 
Published: March 2023

AbstractGlobally, data maintenance and its security are vital tasks due to the rapid development of advanced technologies. Users now utilise Cloud computing technique and security techniques to preserve their data securely from intruders and hackers. Even yet, because of the technology's rapid advancement and inherent insecurity, attackers are conducting assaults on the cloud data. Hence, a homomorphic encryption technique was proposed based on Matrix Transformations with shifts, rotations, and transpositions of Binary converted ASCII values of each character in the plain text. For both encryption and decryption, symmetric cryptography employs the same secret key. The “avalanche effect” is a desirable feature of symmetric encryption in which two distinct keys generate separate cipher texts for the same message. As there are different conditions for the key, it helps to achieve this effect in this technique. The suggested algorithm's cryptanalysis reveals that it is more powerful than the existing encryption methods and resistant to a variety of attacks. So that an attacker cannot easily predict a plaintext through a statistical analysis.