bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized 3D printing-assisted repair and reconstruction of neoplastic bone defects at irregular bone sites: exploration and practice in the treatment of scapular aneurysmal bone cysts
Authors: Luo Guochen , Zhang Yao , Wang Xiahua , Chen Shuaishuai , Li Dongyi , Yu Mingyang 
Published: November 2021

Abstract
Background
The irregular anatomical shape and complex structures of irregular bones make it more difficult to repair and reconstruct bone defects in irregular bones than in the long bones of the extremities. Three-dimensional (3D) printing technology can help to overcome the technical limitations of irregular bone repair by generating simulations that enable structural integration of the lesion area and bone structure of the donor site in all directions and at multiple angles. Thus, personalized and accurate treatment plans for restoring anatomical structure, muscle attachment points, and maximal function can be made. The present study aimed to investigate the ability of 3D printing technology to assist in the repair and reconstruction of scapular aneurysmal ABC defects.

Methods
The study included seven patients with ABCs of the scapula. Based on computed tomography (CT) data for the patient, the scapula (including the defect) and pelvis were reconstructed using Mimics Medical software. The reconstructed scapula model was printed using a 3D printer. Before the operation, the model was used to design the surgical approach and simulate the operation process, to determine the length and radius of the plate and the number and direction of screws, and to determine the bone mass of the ilium and develop reasonable strategies for segmentation and distribution. The operation time, amount of bleeding, length and radius of the plate, and direction and number of screws were recorded.

Results
The average duration of follow-up was 25.6 months, and none of the seven patients experienced recurrence during the follow-up period. The surgical approach, the length and radius of internal fixation, and the number and direction of screws were consistent with the designed operation plan. Patients gradually recovered the anatomical structure of the scapula and function of the shoulder joint.

Conclusions
In the treatment of bone defects caused by irregular bone tumors, 3D printing technology combined with surgery has the advantages of less trauma, short operation time, less bleeding and reducing the difficulty of operation, which can reduce the waste of bone graft, and more complete reconstruction of the anatomical structure of the defective bone.
Exploring healthcare staff narratives to understand the role of quality improvement methods in innovative practices during COVID-19
Authors: Khurshid Zuneera , McAuliffe Eilish , De Brún Aoife 
Published: November 2021

Abstract
Background
COVID-19 has impacted the context in which healthcare staff and teams operate and this has implications for quality improvement (QI) work. Contrary to the usual ambivalent relationship staff have with QI work, there have been examples of unprecedented staff engagement in implementing rapid changes during the pandemic indicating a change in important underlying factors that impact staff involvement in QI. The purpose of this study is to explore staff perspectives about how experience and skills of QI methods supported them in implementing innovative practices during COVID-19.

Methods
This is a qualitative narrative study based on narrative interviews to collect healthcare staff stories of implementing rapid change. The stories were identified through social media (Twitter) and a national health magazine issued by the Irish health service. Twenty staff members participated in the interviews. Interviews were audio recorded, transcribed, and anonymised. A four-step thematic analysis was conducted.

Results
The analysis revealed the transformational journey of healthcare staff from the initial shock and anxiety caused by COVID-19 to making sense of the situation, implementing rapid changes, and acknowledging COVID as a learning experience. Six themes were evident from the analysis: COVID anxiety and fear, emotional supports and coping mechanisms, person-centric changes, COVID as a ‘forcing function’ for change, a collective way of working and looking back and thinking ahead.

Conclusions
While most rapid changes during COVID-19 did not represent a systematic and explicit QI application, QI principles were evident throughout the stories and actions taken, including making small changes, testing changes, learning, reflecting as a team, and improving. Many staff members were able to retrospectively identify the relevance of QI principles. COVID-19 eliminated some traditional barriers to change leading to efficient solutions, thus highlighting a need to sustain these positive changes into routine practice to develop an adaptive healthcare system receptive to QI.
Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study
Authors: Wang Mu-Cyun , Li Chia-Ing , Liu Chiu-Shong , Lin Chih-Hsueh , Yang Shing-Yu , Li Tsai-Chung , Lin Cheng-Chieh 
Published: November 2021

AbstractBackgroundDyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.MethodsWe identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality.ResultsOver a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22–1.37), 1.05 (1.01–1.09), and 1.10 (1.03–1.16), respectively; those of cardiovascular mortality were 1.27 (1.16–1.39), 1.08 (1.02–1.15), and 1.16 (1.07–1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline.ConclusionsBlood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.
Characterization of a novel glucocorticoid-resistant human B-cell acute lymphoblastic leukemia cell line, with AMPK, mTOR and fatty acid synthesis pathway inhibition
Authors: Li Yuanyuan , Zuo Chuan , Gu Ling 
Published: November 2021

Abstract
Background
Acquired glucocorticoid (GC) resistance remains the main obstacle in acute lymphoblastic leukemia (ALL) therapy. The aim of the present study was to establish a novel GC-resistant B-ALL cell line and investigate its biological characteristics.

Methods
A cell culture technique was used to establish the GC-resistant cell line from the parental cell, NALM-6. Molecular and cellular biological techniques including flow cytometry, MTT assay, western blotting, DNA fingerprinting analysis and whole transcriptome sequencing (WTS) were used to characterize the GC-resistant cell lines. Nude mice were used for xenograft studies.

Results
The GC-resistant cell line, NALM-6/HDR, was established by culturing NALM-6 cells under hypoxia for 5 weeks with a single dexamethasone (Dex) treatment. We subcloned the NALM-6/HDR cell lines, and got 6 monoclone Dex-resistant cell lines, NALM-6/HDR-C1, C3, C4, C5, C6 and C9 with resistance index (RI) ranging from 20,000–50,000. NALM-6/HDR and its monoclone cell line, NALM-6/HDR-C5, exhibited moderate (RI 5–15) to high resistance (RI > 20) to Ara-c; low or no cross-resistance to L-Asp, VCR, DNR, and MTX (RI < 5). STR analysis confirmed that NALM-6/HDR and NALM-6/H were all derived from NALM-6. All these cells derived from NALM-6 showed similar morphology, growth curves, immunophenotype, chromosomal karyotype and tumorigenicity. WTS analysis revealed that the main metabolic differences between NALM-6 or NALM-6/H (GC-sensitive) and NALM-6/HDR (GC-resistant) were lipid and carbohydrates metabolism. Western blotting analysis showed that NALM-6/HDR cells had a low expression of GR and p-GR. Moreover, AMPK, mTORC1, glycolysis and de novo fatty acid synthesis (FAS) pathway were inhibited in NALM-6/HDR when compared with NALM-6.

Conclusions
NALM-6/HDR cell line may represent a subtype of B-ALL cells in patients who acquired GC and Ara-c resistance during the treatment. These patients may get little benefit from the available therapy target of AMPK, mTORC1, glycolysis and FAS pathway.
Causal effects on low Apgar at 5-min and stillbirth in a malaria maternal–fetal health outcome investigation: a large perinatal surveillance study in the Brazilian Amazon
Authors: Seijas-Chávez Julio Abel , Nolan Melissa S. , Lynn Mary K. , da Rocha Maria José Francalino , da Costa Araújo Muana , Fonseca Fernando Luiz Affonso , Laporta Gabriel Zorello 
Published: November 2021

Abstract
Background
Malaria elimination in Brazil poses several challenges, including the control of Plasmodium falciparum foci and the hidden burden of Plasmodium vivax in pregnancy. Maternal malaria and fetal health outcomes were investigated with a perinatal surveillance study in the municipality of Cruzeiro do Sul, Acre state, Brazilian Amazon. The research questions are: what are the causal effects of low birth weight on low Apgar at 5-min and of perinatal anaemia on stillbirth?

Methods
From November 2018 to October 2019, pregnant women of ≥ 22 weeks or puerperal mothers, who delivered at the referral maternity hospital (Juruá Women and Children’s Hospital), were recruited to participate in a malaria surveillance study. Clinical information was obtained from a questionnaire and abstracted from medical reports. Haemoglobin level and presence of malarial parasites were tested by haematology counter and light microscopy, respectively. Low Apgar at 5-min and stillbirth were the outcomes analysed in function of clinical data and epidemiologic risk factors for maternal malaria infection using both a model of additive and independent effects and a causal model with control of confounders and use of mediation.

Results
In total, 202 (7.2%; N = 2807) women had malaria during pregnancy. Nearly half of malaria infections during pregnancy (n = 94) were P. falciparum. A total of 27 women (1.03%; N = 2632) had perinatal malaria (19 P. vivax and 8 P. falciparum). Perinatal anaemia was demonstrated in 1144 women (41.2%; N = 2779) and low birth weight occurred in 212 newborns (3.1%; N = 2807). A total of 75 newborns (2.7%; N = 2807) had low (< 7) Apgar scores at 5-min., and stillbirth occurred in 23 instances (30.7%; n = 75). Low birth weight resulted in 7.1 higher odds of low Apgar at 5-min (OR = 7.05, 95% CI 3.86–12.88, p < 0.001) modulated by living in rural conditions, malaria during pregnancy, perinatal malaria, and perinatal anaemia. Stillbirth was associated with perinatal anaemia (OR = 2.56, 95% CI 1.02–6.42, p = 0.0444) modulated by living in rural conditions, falciparum malaria during pregnancy, perinatal malaria, and perinatal fever.

Conclusions
While Brazil continues its path towards malaria elimination, the population still faces major structural problems, including substandard living conditions. Here malaria infections on pregnant women were observed having indirect effects on fetal outcomes, contributing to low Apgar at 5-min and stillbirth. Finally, the utility of employing multiple statistical analysis methods to validate consistent trends is vital to ensure optimal public health intervention designs.
Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia
Authors: Jongdeepaisal Monnaphat , Ean Mom , Heng Chhoeun , Buntau Thoek , Tripura Rupam , Callery James J. , Peto Thomas J. , Conradis-Jansen Franca , von Seidlein Lorenz , Khonputsa Panarasri , Pongsoipetch Kulchada , Soviet Ung , Sovannaroth Siv , Pell Christopher , Maude Richard J. 
Published: November 2021

Abstract
Background
In the Greater Mekong Subregion, adults are at highest risk for malaria, particularly those who visit forests. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest goers against malaria.

Methods
Alongside a clinical trial of anti-malarial chemoprophylaxis in northern Cambodia, qualitative research was conducted, including in-depth interviews and observation, to explore the acceptability of malaria prophylaxis for forest goers, the implementation opportunities, and challenges of this strategy.

Results
Prophylaxis with artemether–lumefantrine for forest goers was found to be acceptable under trial conditions. Three factors played a major role: the community’s awareness and perception of the effectiveness of prophylaxis, their trust in the provider, and malaria as a local health concern. The findings highlight how uptake and adherence to prophylaxis are influenced by the perceived balance between benefits and burden of anti-malarials which are modulated by the seasonality of forest visits and its influence on malaria risk.

Conclusions
The implementation of anti-malarial prophylaxis needs to consider how the preventive medication can be incorporated into existing vector-control measures, malaria testing and treatment services. The next step in the roll out of anti-malarial prophylaxis for forest visitors will require support from local health workers.
Love bites: male frogs (Plectrohyla, Hylidae) use teeth scratching to deliver sodefrin precursor-like factors to females during amplexus
Authors: Schulte Lisa M. , Martel An , Cruz-Elizalde Raciel , Ramírez-Bautista Aurelio , Bossuyt Franky 
Published: November 2021

AbstractBackgroundEfficient transfer of chemical signals is important for successful mating in many animal species. Multiple evolutionary lineages of animals evolved direct sex pheromone transmission during traumatic mating—the wounding of the partner with specialized devices—which helps to avoid signal loss to the environment. Although such direct transmission modes of so-called allohormone pheromones are well-documented in invertebrates, they are considered rare in vertebrates. Males of several species of the frog genusPlectrohyla(Hylidae, Anura) have elongated teeth and develop swollen lips during the breeding season. Here we investigated the possibility that these structures are used to scratch the females’ skin and apply allohormone pheromones during traumatic mating in severalPlectrohylaspecies.ResultsOur behavioural observations revealed that males press their upper jaw onto the females’ dorsum during amplexus, leaving small skin scratches with their teeth. Histological examinations of the males’ lips identified specialized mucus glands, resembling known amphibian pheromone glands. Whole-transcriptome sequencing of these breeding glands showed high expression of sodefrin precursor-like factor (SPF) proteins, which are known to have a pheromone function in multiple amphibian species.ConclusionsOur study suggests SPF delivery via traumatic mating in several anuran species: the males have specialized breeding glands in the lips for production and secretion and use their elongated teeth as wounding devices for application. We hypothesize that these SPF proteins end up in the females’ circulatory system, where understanding their exact function will require further molecular, physiological and behavioural testing.
Effects of endplate coverage and intervertebral height change on heterotopic ossification following cervical disc replacement
Authors: Shen Yi-Wei , Yang Yi , Liu Hao , Rong Xin , Ding Chen , Meng Yang , Wang Bei-Yu , Hong Ying 
Published: November 2021

Abstract
Background
Heterotopic ossification (HO) is a common complication after cervical disc replacement (CDR). Biomechanical factors including endplate coverage and intervertebral disc height change may be related to HO formation. However, there is a dearth of quantitative analysis for endplate coverage, intervertebral height change and their combined effects on HO.

Methods
Patients who underwent single-level or two-level CDR with Prestige-LP were retrospectively reviewed. Clinical outcomes were evaluated through Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, and visual analogue scale (VAS) score. Radiological data, including the prosthesis-endplate depth ratio, intervertebral height change, posterior heterotopic ossification (PHO) and angular parameters, were collected. Logistic regression analysis was used to identify the potential risk factors. Receiver operating characteristic curves were plotted and the cut-off values of each potential factors were calculated.

Results
A total of 138 patients with 174 surgical segments were evaluated. Both the prosthesis-endplate depth ratio (P < 0.001) and post-operative disc height change (P < 0.001) were predictive factors for PHO formation. The area under the curve (AUC) of the prosthesis-endplate depth ratio, disc height change and their combined effects represented by the combined parameter (CP) were 0.728, 0.712 and 0.793, respectively. The risk of PHO significantly increased when the prosthesis-endplate depth ratio < 93.77% (P < 0.001, OR = 6.909, 95% CI 3.521–13.557), the intervertebral height change ≥ 1.8 mm (P < 0.001, OR = 5.303, 95% CI 2.592–10.849), or the CP representing the combined effect < 84.88 (P < 0.001, OR = 10.879, 95% CI 5.142–23.019).

Conclusions
Inadequate endplate coverage and excessive change of intervertebral height are both potential risk factors for the PHO after CDR. Endplate coverage less than 93.8% or intervertebral height change more than 1.8 mm would increase the risk of PHO. The combination of these two factors may exacerbate the non-uniform distribution of stress in the bone-implant interface and promote HO development.
Chronic wasting disease in Europe: new strains on the horizon
Authors: Tranulis Michael Andreas , Gavier-Widén Dolores , Våge Jørn , Nöremark Maria , Korpenfelt Sirkka-Liisa , Hautaniemi Maria , Pirisinu Laura , Nonno Romolo , Benestad Sylvie Lafond 
Published: November 2021

AbstractPrion diseases are fatal neurodegenerative disorders with known natural occurrence in humans and a few other mammalian species. The diseases are experimentally transmissible, and the agent is derived from the host-encoded cellular prion protein (PrPC), which is misfolded into a pathogenic conformer, designated PrPSc (scrapie). Aggregates of PrPSc molecules, constitute proteinaceous infectious particles, known as prions. Classical scrapie in sheep and goats and chronic wasting disease (CWD) in cervids are known to be infectious under natural conditions. In CWD, infected animals can shed prions via bodily excretions, allowing direct host-to-host transmission or indirectly via prion-contaminated environments. The robustness of prions means that transmission via the latter route can be highly successful and has meant that limiting the spread of CWD has proven difficult. In 2016, CWD was diagnosed for the first time in Europe, in reindeer (Rangifer tarandus) and European moose (Alces alces). Both were diagnosed in Norway, and, subsequently, more cases were detected in a semi-isolated wild reindeer population in the Nordfjella area, in which the first case was identified. This population was culled, and all reindeer (approximately 2400) were tested for CWD; 18 positive animals, in addition to the first diagnosed case, were found. After two years and around 25,900 negative tests from reindeer (about 6500 from wild and 19,400 from semi-domesticated) in Norway, a new case was diagnosed in a wild reindeer buck on Hardangervidda, south of the Nordfjella area, in 2020. Further cases of CWD were also identified in moose, with a total of eight in Norway, four in Sweden, and two cases in Finland. The mean age of these cases is 14.7 years, and the pathological features are different from North American CWD and from the Norwegian reindeer cases, resembling atypical prion diseases such as Nor98/atypical scrapie and H- and L-forms of BSE. In this review, these moose cases are referred to as atypical CWD. In addition, two cases were diagnosed in red deer (Cervus elaphus) in Norway. The emergence of CWD in Europe is a threat to European cervid populations, and, potentially, a food-safety challenge, calling for a swift, evidence-based response. Here, we review data on surveillance, epidemiology, and disease characteristics, including prion strain features of the newly identified European CWD agents.
Epigenetic activation of the elongator complex sensitizes gallbladder cancer to gemcitabine therapy
Authors: Xu Sunwang , Jiang Cen , Lin Ruirong , Wang Xiaopeng , Hu Xiaoqiang , Chen Wei , Chen Xiangjin , Chen Tao 
Published: November 2021

Abstract
Background
Gallbladder cancer (GBC) is known for its high malignancy and multidrug resistance. Previously, we uncovered that impaired integrity and stability of the elongator complex leads to GBC chemotherapy resistance, but whether its restoration can be an efficient therapeutic strategy for GBC remains unknown.

Methods
RT-qPCR, MS-qPCR and ChIP-qPCR were used to evaluate the direct association between ELP5 transcription and DNA methylation in tumour and non-tumour tissues of GBC. EMSA, chromatin accessibility assays, and luciferase assays were utilized to analysis the DNA methylation in interfering PAX5-DNA interactions. The functional experiments in vitro and in vivo were performed to investigate the effects of DNA demethylating agent decitabine (DAC) on the transcription activation of elongator complex and the enhanced sensitivity of gemcitabine in GBC cells. Tissue microarray contains GBC tumour tissues was used to evaluate the association between the expression of ELP5, DNMT3A and PAX5.

Results
We demonstrated that transcriptional repression of ELP5 in GBC was highly correlated with hypermethylation of the promoter. Mechanistically, epigenetic analysis revealed that DNA methyltransferase DNMT3A-catalysed hypermethylation blocked transcription factor PAX5 activation of ELP5 by disrupting PAX5-DNA interaction, resulting in repressed ELP5 transcription. Pharmacologically, the DNA demethylating agent DAC eliminated the hypermethylated CpG dinucleotides in the ELP5 promoter and then facilitated PAX5 binding and reactivated ELP5 transcription, leading to the enhanced function of the elongator complex. To target this mechanism, we employed a sequential combination therapy of DAC and gemcitabine to sensitize GBC cells to gemcitabine-therapy through epigenetic activation of the elongator complex.

Conclusions
Our findings suggest that ELP5 expression in GBC is controlled by DNA methylation-sensitive induction of PAX5. The sequential combination therapy of DAC and gemcitabine could be an efficient therapeutic strategy to overcome chemotherapy resistance in GBC.