bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of proteomic markers for prediction of the response to 5-Fluorouracil based neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients
Authors: Wang Jianan , Liu Jiayu , Wang Jinyang , Wang Shijian , Li Feifei , Li Ruibing , Liu Peng , Li Mianyang , Wang Chengbin 
Published: March 2022

Abstract
Background
Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is the standard treatment for patients with locally advanced rectal cancer (LARC), while parts of them show poor therapeutic response accompanied by therapy adverse effects. Predictive biomarkers for nCRT response could facilitate the guidance on treatment decisions but are still insufficient until now, which limits the clinical applications of nCRT in LARC patients.

Methods
In our study, 37 formalin-fixed paraffin-embedded tumor biopsies were obtained from patients with LARC before receiving 5-fluorouracil based nCRT. Proteomics analyses were conducted to identify the differentially expressed proteins (DEPs) between total responders (TR) and poor responders (PR). The DEPs were validated via ROC plotter web tool and their predictive performance was evaluated by receiver operating characteristic analysis. Functional enrichment analyses were performed to further explore the potential mechanisms underlying nCRT response.

Results
Among 3,998 total proteins, 91 DEPs between TR and PR were screened out. HSPA4, NIPSNAP1, and SPTB all with areas under the curve (AUC) ~ 0.8 in the internal discovery cohort were independently validated by the external mRNA datasets (AUC ~ 0.7), and their protein levels were linearly correlated with the graded responses to nCRT in the internal cohort. The combination of HSPA4 and SPTB could distinctly discriminate the TR and PR groups (AUC = 0.980, p < 0.0001). Moreover, multiple combinations of the three proteins realized increased specificity and/or sensitivity, while achieving favorable predictive value when moderate responders were introduced into the ROC analysis. Pathways including DNA damage repair, cell cycle, and epithelial mesenchymal transition were involved in nCRT response according to the enrichment analysis results.

Conclusions
HSPA4, SPTB and NIPSNAP1 in tumor biopsies and/or their optional combinations might be potential predictive markers for nCRT response in patients with LARC. The DEPs and their related functions have implications for the potential mechanisms of treatment response to nCRT in patients with LARC.
Key factors associated with malaria infection among patients seeking care through the public sector in endemic townships of Ayeyarwady Region, Myanmar
Authors: Dunning Jillian , Aung Nang Khaing Zar , Ward Abigail , Aye Moe Moe , Lourenço Christopher , Gallalee Sarah , Lavenberg Stephen , Le Menach Arnaud , Tun Myat Min , Thi Aung 
Published: March 2022

Abstract
Background
Ayeyarwady Region in Myanmar has made significant progress towards malaria elimination, with cases decreasing from 12,312 in 2015 to 122 in 2019. As transmission declines, malaria becomes increasingly focalized both in geographic hotspots and among population groups sharing certain risk factors. Developing a thorough profile of high-risk activities associated with malaria infections is critical to ensure intervention approaches are evidence-based.

Methods
A test-negative study was conducted from September 2017 to May 2018 in Ngaputaw, Pathein and Thabaung townships in Ayeyarwady Region. Patients that presented to selected public facilities or community health volunteers with fever answered survey questions on demographic and behavioural risk factors, including exposure to malaria interventions, and were assigned to case and control groups based on the result of a malaria rapid diagnostic test. A random-effects logistic regression model adjusted for clustering at the facility level, as well as any variables along the causal pathway described by a directed acyclic graph, was used to determine odds ratios and association with malaria infections.

Results
A total of 119 cases and 1744 controls were recruited from 41 public facilities, with a mean age of 31.3 and 63.7% male. Higher risk groups were identified as males (aOR 1.8, 95% CI 1.2–2.9) and those with a worksite located within the forest (aOR 2.8, 95% CI 1.4–5.3), specifically working in the logging (aOR 2.7, 95% CI 1.5–4.6) and rubber plantation (aOR 3.0, 95% CI 1.4–6.8) industries. Additionally, links between forest travel and malaria were observed, with risk factors identified to be sleeping in the forest within the past month (aOR 2.6, 95% CI 1.1–6.3), and extended forest travel with durations from 3 to 14 days (aOR 8.6, 95% CI 3.5–21.4) or longer periods (aOR 8.4, 95% CI 3.2–21.6).

Conclusion
Malaria transmission is highly focalized in Ayeyarwady, and results illustrate the need to target interventions to the most at-risk populations of working males and forest goers. It will become increasingly necessary to ensure full intervention coverage of at-risk populations active in forested areas as Myanmar moves closer to malaria elimination goals.
Developing a tool for the measurement of social exclusion in healthcare settings
Authors: O’Donnell Patrick , Hannigan Ailish , Ibrahim Nuha , O’Donovan Diarmuid , Elmusharaf Khalifa 
Published: March 2022

Abstract
Background
Social exclusion is a complex concept that is recognised as a key determinant of health. Many measurement tools developed looked at people from single excluded groups in isolation. We know from experience and literature that exclusion is often intersectional and multi-layered. Therefore, the aim of this research was to develop a social exclusion measurement tool for use in healthcare settings with individuals from any excluded group that would include questions to investigate socioeconomic elements and subjective experiences in their lives.

Methods
Inductive and deductive methods were used to develop the tool. Early drafts were tested with experts (both academic and experts by experience) and modified in line with feedback received. The tool was then piloted with people in the community, and this allowed us to assess the internal consistency and validity of the tool. Exploratory factor analysis was carried out as part of this evaluation.

Results
The measurement tool was initially evaluated by 17 academic and ‘real world’ experts. It was then piloted with seven experts by experience, two gatekeepers and two participants who were presumed not to be excluded, resulting in the development of the final tool. This was then tested with 276 participants (127 presumed excluded, 149 presumed not excluded). The socioeconomic characteristics of these participants were documented, and exploratory factor analysis was carried out on data relating to subjective items. A four-factor structure emerged comprising 22 items. Internal consistency of the factors was high, and their ability to discriminate between the two groups was notable.

Conclusions
A tool for measuring the social exclusion of individuals has been developed by engaging with people from a variety of excluded groups. Socioeconomic indicators were combined with subjective items. The input of experts by experience, academics and others was sought to enhance the tool. The tool was applied to two distinct samples, showing obvious differences both in the socioeconomic items, and the items included in the factor analysis. The potential use of this tool could have positive implications for people who are excluded.
Early diagnosis of breast cancer lung metastasis by nanoprobe-based luminescence imaging of the pre-metastatic niche
Authors: Zheng Hanwen , Yuan Chunsen , Cai Jiajun , Pu Wendan , Wu Peng , Li Chenwen , Li Gang , Zhang Yang , Zhang Jianxiang , Guo Jiawei , Huang Dingde 
Published: March 2022

Abstract
Background
Early detection of breast cancer lung metastasis remains highly challenging, due to few metastatic cancer cells at an early stage. Herein we propose a new strategy for early diagnosis of lung metastasis of breast cancer by luminescence imaging of pulmonary neutrophil infiltration via self-illuminating nanoprobes.

Methods
Luminescent nanoparticles (LAD NPs) were engineered using a biocompatible, neutrophil-responsive self-illuminating cyclodextrin material and an aggregation-induced emission agent. The chemiluminescence resonance energy transfer (CRET) effect and luminescence properties of LAD NPs were fully characterized. Using mouse peritoneal neutrophils, in vitro luminescence properties of LAD NPs were thoroughly examined. In vivo luminescence imaging and correlation analyses were performed in mice inoculated with 4T1 cancer cells. Moreover, an active targeting nanoprobe was developed by surface decoration of LAD NPs with a neutrophil-targeting peptide, which was also systemically evaluated by in vitro and in vivo studies.

Results
LAD NPs can generate long-wavelength and persistent luminescence due to the CRET effect. In a mouse model of 4T1 breast cancer lung metastasis, we found desirable correlation between neutrophils and tumor cells in the lungs, demonstrating the effectiveness of early imaging of the pre-metastatic niche by the newly developed LAD NPs. The active targeting nanoprobe showed further enhanced luminescence imaging capability for early detection of pulmonary metastasis. Notably, the targeting nanoprobe-based luminescence imaging strategy remarkably outperformed PET/CT imaging modalities in the examined mouse model. Also, preliminary tests demonstrated good safety of LAD NPs.

Conclusions
The neutrophil-targeting imaging strategy based on newly developed luminescence nanoparticles can serve as a promising modality for early diagnosis of lung metastasis of breast cancers.

Graphical Abstract
Enhanced tumor accumulation and therapeutic efficacy of liposomal drugs through over-threshold dosing
Authors: Ao Hui , Wang Zhuo , Lu Likang , Ma Hongwei , Li Haowen , Fu Jingxin , Li Manzhen , Han Meihua , Guo Yifei , Wang Xiangtao 
Published: March 2022

Abstract
Background
Most intravenously administered drug-loaded nanoparticles are taken up by liver Kupffer cells, and only a small portion can accumulate at the tumor, resulting in an unsatisfactory therapeutic efficacy and side effects for chemotherapeutic agents. Tumor-targeted drug delivery proves to be the best way to solve this problem; however, the complex synthesis, or surface modification process, together with the astonishing high cost make its clinical translation nearly impossible.

Methods
Referring to Ouyang’s work and over-threshold dosing theory in general, blank PEGylated liposomes (PEG-Lipo) were prepared and used as tumor delivery enhancers to determine whether they could significantly enhance the tumor accumulation and in vivo antitumor efficacy of co-injected liposomal ACGs (PEG-ACGs-Lipo), a naturally resourced chemotherapeutic. Here, the phospholipid dose was used as an indicator of the number of liposomes particles with similar particle sizes, and the liposomes was labelled with DiR, a near-red fluorescent probe, to trace their in vivo biodistribution. Two mouse models, 4T1-bearing and U87-bearing, were employed for in vivo examination.

Results
PEG-Lipo and PEG-ACGs-Lipo had similar diameters. At a low-threshold dose (12 mg/kg equivalent phospholipids), PEG-Lipo was mainly distributed in the liver rather than in the tumor, with the relative tumor targeting index (RTTI) being ~ 0.38 at 72 h after administration. When over-threshold was administered (50 mg/kg or 80 mg/kg of equivalent phospholipids), a much higher and quicker drug accumulation in tumors and a much lower drug accumulation in the liver were observed, with the RTTI increasing to ~ 0.9. The in vivo antitumor study in 4T1 tumor-bearing mice showed that, compared to PEG-ACGs-Lipo alone (2.25 mg/kg phospholipids), the co-injection of a large dose of blank PEG-Lipo (50 mg/kg of phospholipids) significantly reduced the tumor volume of the mice by 22.6% (P < 0.05) and enhanced the RTTI from 0.41 to 1.34. The intravenous injection of a low drug loading content (LDLC) of liposomal ACGs (the same dose of ACGs at 50 mg/kg of equivalent phospholipids) achieved a similar tumor inhibition rate (TIR) to that of co-injection. In the U87 MG tumor-bearing mouse model, co-injection of the enhancer also significantly promoted the TIR (83.32% vs. 66.80%, P < 0.05) and survival time of PEG-ACGs-Lipo.

Conclusion
An over-threshold dosing strategy proved to be a simple and feasible way to enhance the tumor delivery and antitumor efficacy of nanomedicines and was benefited to benefit their clinical result, especially for liposomal drugs.

Graphical Abstract
Changes in cannabis use and associated correlates during France’s first COVID-19 lockdown in daily cannabis users: results from a large community-based online survey
Authors: Mezaache Salim , Donadille Cécile , Martin Victor , Le Brun Gadelius Maëla , Appel Laurent , Spire Bruno , Briand Madrid Laelia , Bastien Martin , Roux Perrine 
Published: March 2022

AbstractBackgroundLockdown measures during the first wave of the COVID-19 pandemic in France led to serious public health concerns over people who use illicit drugs, especially in terms of mental health. We assessed changes in cannabis use during the first lockdown in France among daily cannabis users and associated correlates.MethodsCANNAVID is a French, national, cross-sectional web-based survey, conducted from 17 April to 11 May 2020. Daily cannabis users aged ≥ 18 years and living in France were invited to participate through advertisements. Respondents completed an ad hoc questionnaire on a dedicated online platform. We analyzed changes in cannabis use during the first lockdown (i.e.,stopped, decreased, unchanged, or increased) and performed a multinomial logistic regression analysis to evaluate correlates of these changes.ResultsOf the 4019 participants, 74.0% were men. Median age was 27 years (interquartile range: 22–37). With regard to cannabis use, 293 (7.3%) persons stopped, 1153 (28.7%) decreased, 1146 (28.5%) did not change, and 1427 (35.5%) increased their use during the lockdown. A multinomial logistic regression model revealed several sociodemographic, behavioral and health-related factors associated with changes in cannabis use. Compared with participants with an unchanged level of cannabis use during the lockdown, those who increased and those who stopped cannabis use were more likely to have increased tobacco and alcohol use and to have experienced depression and sleep disorders intensification. Those who stopped cannabis use were also more likely to have increased benzodiazepine use and to have experienced pain increase during lockdown.ConclusionsFrance’s first COVID-19-related lockdown had a differential impact on daily cannabis users’ consumption patterns. Most study respondents reported changes to their cannabis consumption pattern. Those who reported a stable cannabis use were more likely to report fewer negative changes. Specific interventions are needed for this population, as well as research to assess the long-term impacts of these changes.
Laparoscopic segmental colectomy with extensive D3 lymph node dissection: a good choice for right transverse colon cancer
Authors: Huang Xing 
Published: March 2022

Abstract
Background
Previous research was yet to establish a definite operation for transverse colon cancer (TCC); surgical procedure was often dictated by the surgeon’s preference in clinical practice. The main surgical methods could be summarized in two main points: segmental colectomy (transverse colectomy) and right hemicolectomy.

Method
The first patient was a 78-year-old woman, who was diagnosed with right TCC. Computed tomography revealed a right TCC and a very long transverse colon; laparoscopic exploration revealed an enlarged apical lymph node surrounding the ileocolic vessels. We performed a segmental colectomy with extensive apical lymph node dissection along the superior mesenteric vessels and its main branches for her. To distinguish it from the previous radical operations for TCC, we called this operation a segmental colectomy with extensive D3 lymph node dissection. Then, this surgical intervention was performed on 8 other TCC patients.

Results
The total operating time was 158 min. Pathological examination confirmed 2 apical lymph node metastases; among them, one apical lymph node metastasis was in group No.203. For all 9 patients, the median operative time was 160 min (range, 140–185 min), the average number of lymph node retrieval was 30 (range, 25–39), and the average number of apical lymph node (No.203, No.213, and No.223) retrieval was 5.9 (range, 0–11). Because of the preservation of the ileocecal junction and part of the ascending colon, all patients recovered uneventfully after surgery, and long-term diarrhea, water-electrolyte imbalance, and other Clavien–Dindo grade III or greater postoperative complications did not occur.

Conclusions
Our procedure combined the advantages of segmental colectomy and right hemicolectomy and gave consideration to oncological and functional outcomes. It may be an optimal choice for TCC patients with a very long transverse colon and preoperative diagnosis of lymph node metastasis.
Glycogen synthase kinase GSK3α promotes tumorigenesis by activating HIF1/VEGFA signaling pathway in NSCLC tumor
Authors: Cao Xiaonian , Wu Wei , Wang Dao , Sun Wei , Lai Senyan 
Published: March 2022

Abstract
Background
Lung cancer is one of the most common cancers and the leading cause of cancer-related death. Glycogen synthase kinase-3 (GSK-3) α, a member of the glycogen synthase kinase-3 family, reportedly plays a role in tumorigenesis. However, its biological function in tumorigenesis requires deeper exploration. Hypoxia is a major feature of solid tumor, along with decreasing availability of oxygen, inducing treatment resistance, and tumor progress.

Methods
Levels of GSK3α expression in clinical samples were detected using western blot and IHC assays, while its biological function and underlying mechanism of action in tumor progression were investigated using western blot, CCK8, cell cycle, colony formation, Transwell, ELISA and tube formation assays. Furthermore, we investigated the relationship between GSK3α expression and the HIF1α/VEGFA signaling pathway in vivo using a mouse xenograft model.

Results
GSK3α was significantly upregulated in NSCLC patients with cases that exhibited high GSK3α levels recording shorter survival times. Moreover, GSK3α overexpression promoted proliferation, migration, invasion and clone formation ability of NSCLC cells, while its silencing resulted in an opposite phenomenon. Moreover, GSK3α not only activated the HIF1α/VEGFA signaling pathway, but also regulated HIF1α stabilization independently via the PHDs-pVHL signaling pathway. Moreover, GSK3α-mediated tumor angiogenesis depended on HIF1α expression both in vitro and in vivo.

Conclusion
GSK3α functioned as an oncogene in NSCLC tumorigenesis by regulating the HIF1/VEGFA signaling pathway in an independent manner through the PHDs-pVHL signaling pathway. These findings were expected to provide novel sights to guide future development of therapies for effective treatment of NSCLC.
Traditional uses of wild and tended plants in maintaining ecosystem services in agricultural landscapes of the Eastern Cape Province in South Africa
Authors: Maroyi Alfred 
Published: March 2022

Abstract
Background
Many communities in developing countries rely on ecosystem services (ESs) associated with wild and cultivated plant species. Plant resources provide numerous ESs and goods that support human well-being and survival. The aim of this study was to identify and characterize wild and tended plant species, and also investigate how local communities in the Eastern Cape Province in South Africa perceive ESs associated with plant resources.

Methods
The study was conducted in six local municipalities in the Eastern Cape Province, between March 2016 and September 2021. Data on socio-economic characteristics of the participants, useful plants harvested from the wild and managed in home gardens were documented by means of questionnaires, observation and guided field walks with 196 participants. The ESs were identified using a free listing technique.

Results
A total of 163 plant species were recorded which provided 26 cultural, regulating and provisioning ESs. Provisioning ESs were the most cited with at least 25 plant species contributing towards generation of cash income, food, traditional and ethnoveterinary medicines. Important species recorded in this study with relative frequency of citation (RFC) values > 0.3 included Alepidea amatymbica, Allium cepa, Aloe ferox, Artemisia afra, Brassica oleracea, Capsicum annuum, Cucurbita moschata, Hypoxis hemerocallidea, Opuntia ficus-indica, Spinacia oleracea, Vachellia karroo and Zea mays.

Conclusion
Results of this study highlight the importance of plant resources to the well-being of local communities in the Eastern Cape within the context of provision of essential direct and indirect ESs such as food, medicinal products, construction materials, fodder, regulating, supporting and cultural services. The ESs are the basis for subsistence livelihoods in rural areas, particularly in developing countries such as South Africa. Therefore, such body of knowledge can be used as baseline data for provision of local support for natural resource management initiatives in the province and other areas of the country.
Utility of a novel integrated deep convolutional neural network for the segmentation of hip joint from computed tomography images in the preoperative planning of total hip arthroplasty
Authors: Wu Dong , Zhi Xin , Liu Xingyu , Zhang Yiling , Chai Wei 
Published: March 2022

Abstract
Purpose
Preoperative three-dimensional planning is important for total hip arthroplasty. To simulate the placement of joint implants on computed tomography (CT), pelvis and femur must be segmented. Accurate and rapid segmentation of the hip joint is challenging. This study aimed to develop a novel deep learning network, named Changmugu Net (CMG Net), which could achieve accurate segmentation of the femur and pelvis.

Methods
The overall deep neural network architecture of CMG Net employed three interrelated modules. CMG Net included the 2D U-net to separate the bony and soft tissues. The modular hierarchy method was used for the main femur segmentation to achieve better performance. A layer classifier was adopted to localise femur layers among a series of CT scan images. The first module was a modified 2D U-net, which separated bony and soft tissues; it provided intermediate supervision for the main femur segmentation. The second module was the main femur segmentation, which was used to distinguish the femur from the acetabulum. The third module was the layer classifier, which served as a post-processor for the second module.

Results
There was a much greater overlap in accuracy results with the “gold standard” segmentation than with competing networks. The dice overlap coefficient was 93.55% ± 5.57%; the mean surface distance was 1.34 ± 0.24 mm, and the Hausdorff distance was 4.19 ± 1.04 mm in the normal and diseased hips, which indicated greater accuracy than the other four competing networks. Moreover, the mean segmentation time of CMG Net was 25.87 ± 2.73 s, which was shorter than the times of the other four networks.

Conclusions
The prominent segmentation accuracy and run-time of CMG Net suggest that it is a reliable method for clinicians to observe anatomical structures of the hip joints, even in severely diseased cases.