bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis
Authors: Tan Dino B. A. , Tedja Chantalia , Kuster Lukas , Raymond Warren D. , Harsanyi Andreea , Chowalloor Priya V. , Misso Neil L. , Argawal Shashi , Bhoola Kanti D. , Keen Helen I. 
Published: May 2023

Abstract
Objective
Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides.

Methods
Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array.

Results
Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1β, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = −0.55), sTNFR1 (r = −0.352) and IL-6 (r = −0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05.

Conclusions
Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.
Levelling the playing field for the international migration of nurses: the India English Language Programme
Authors: Goldstone Ross , McCarthy Rose , Byrne Ged , Keen David 
Published: May 2023

Abstract
Background
This article presents evaluation findings of the India English Language Programme, an innovative programme aimed at providing Indian nurses with an opportunity to participate in an ethical and mutually beneficial learning programme aimed at supporting migration into the United Kingdom’s National Health Service (NHS). The programme provided 249 Indian nurses wishing to migrate to the NHS on an ‘earn, learn, and return’ basis with funding to support English language learning and accreditation sufficient to apply for Nursing and Midwifery Council (NMC) registration. The Programme provided English language training and pastoral support to candidates, in addition to the availability of remedial training and examination entry for those not meeting NMC proficiency requirements on their first attempt.

Methods
Descriptive statistical analysis of programme examination results and cost-effectiveness analysis is presented to demonstrate programme outputs and outcomes. Descriptive economic analysis of programme costings is presented alongside programme results to investigate the value-for-money provided by this programme.

Results
A total of 89 nurses were successful in meeting NMC proficiency requirements, representing a pass rate of 40%. Those undertaking OET training and examination(s) were more successful, compared to those undertaking British Council provision, with over half of candidates passing at the required level. This equates to an overall programme cost-per-pass of £4139 and represents a model to support health worker migration, in line with WHO guidelines, delivering individual learning and development, mutual health system gain, and value-for-money.

Conclusions
Taking place during the coronavirus pandemic, the programme evidences the effective delivery of online English language training to support health worker migration during a highly disruptive period for global health. This programme demonstrates an ethical and mutually beneficial pathway for English language improvement amongst internationally educated nurses to facilitate migration to and global health learning in the NHS. It provides a template through which healthcare leaders and nurse educators, working in policy and practice environments in the NHS and other English-speaking countries, can design future ethical health worker migration and training programmes to strengthen the global healthcare workforce.
Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease
Authors: Dai Mengjun , Li Kangbo , Sacirovic Mesud , Zemmrich Claudia , Buschmann Eva , Ritter Oliver , Bramlage Peter , Persson Anja Bondke , Buschmann Ivo , Hillmeister Philipp 
Published: May 2023

Abstract
Background
The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice.

Methods
Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants’ plasma. Treadmill testing with Gardner protocol was used to evaluate participants’ walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance.

Results
A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients’ PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity.

Conclusions
Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.
Vitamin D receptor gene polymorphism and polycystic ovary syndrome susceptibility
Authors: Albahlol Ibrahim A , Neamatallah Mustafa , Serria Mohamed Saad , El-Gilany Abdel-Hady , Setate Yomna A , Alkasaby Nashwa M. , Mostafa Sally Abdallah , Abdelaziz Mahmoud , Elazab Hossam , Ammar Omar A. 
Published: May 2023

AbstractBackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. This study was designed to investigate the associations of vitamin D receptor (VDR) gene variants with PCOS risk and the severity of the disease phenotype among Egyptian women.MethodsIn this study, 185 women with PCOS and 207 fertile women as controls were recruited. Cases were divided into phenotype groups based on their clinical and paraclinical features. Clinical and laboratory data were measured in the patient and control groups. All individuals were genotyped for nine single-nucleotide polymorphisms (SNPs) located across the VDR gene using TaqManallelic discrimination real-time polymerase chain reaction.ResultsWomen with PCOS were significantly (P ≤ 0.001) higher body mass index (BMI) (22.77 ± 2.5) than controls (21.68 ± 1.85 kg/m2). Women with PCOS had significantly higher anti-Mullerian hormone, prolactin, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH), free testosterone, total testosterone, and dehydroepiandrosterone sulfate levels than the control group (P ≤ 0.001). The level of FSH was significantly lower in women with PCOS than in the control group (P ≤ 0.001). Analysis of the VDR rs4516035, rs2107301, rs1544410 (BsmI), and rs731236 (TaqI) SNPs showed a significant association with PCOS phenotype A. Furthermore, rs2228570 (FokI), rs3782905, rs7975232 (ApaI), and rs739837 SNPs showed a significant association with PCOS phenotype C. Furthermore, rs11568820 SNP showed a significant association with PCOS phenotype D (P < 0.05).ConclusionsThe findings of this study indicate that variations in the VDR gene were associated with an increased risk of PCOS in Egyptian women.
Improved biosynthesis of heme in Bacillus subtilis through metabolic engineering assisted fed-batch fermentation
Authors: Yang Shaomei , Wang Anlong , Li Jiachang , Shao Yunhang , Sun Fengjie , Li Shucheng , Cao Kai , Liu Hongliang , Xiong Peng , Gao Zhengquan 
Published: May 2023

Abstract
Background
Heme is an iron/porphyrin complex compound, widely used in the health care, food, and pharmaceutical industries. It is more advantageous and attractive to develop microbial cell factories to produce heme by fermentation, with lower production costs and environmentally more friendly procedures than those of the traditional extraction based on animal blood. In this study, Bacillus subtilis, a typical industrial model microorganism of food safety grade, was used for the first time as the host to synthesize heme.

Results
The heme biosynthetic pathway was engineered as four modules, the endogenous C5 pathway, the heterologous C4 pathway, the uroporphyrinogen (urogen) III synthesis pathway, and the downstream synthesis pathway. Knockout of hemX encoding the negative effector of the concentration of HemA, overexpression of hemA encoding glutamyl-tRNA reductase, and knockout of rocG encoding the major glutamate dehydrogenase in the C5 pathway, resulted in an increase of 427% in heme production. Introduction of the heterologous C4 pathway showed a negligible effect on heme biosynthesis. Overexpression of hemCDB, which encoded hydroxymethylbilane synthase, urogen III synthase, and porphobilinogen synthase participating in the urogen III synthesis pathway, increased heme production by 39%. Knockouts of uroporphyrinogen methyltransferase gene nasF and both heme monooxygenase genes hmoA and hmoB in the downstream synthesis pathway increased heme production by 52%. The engineered B. subtilis produced 248.26 ± 6.97 mg/L of total heme with 221.83 ± 4.71 mg/L of extracellular heme during the fed-batch fermentation in 10 L fermenter.

Conclusions
Strengthening endogenous C5 pathway, urogen III synthesis pathway and downstream synthesis pathway promoted the biosynthesis of heme in B. subtilis. The engineered B. subtilis strain has great potential as a microbial cell factory for efficient industrial heme production.
Cost of inappropriate prescriptions for uncomplicated malaria in Ghana
Authors: Aryeetey Genevieve Cecilia , Nonvignon Justice , Malm Keziah , Owusu Richmond , Baabu Bright Sasu , Peprah Nana Yaw , Agyemang Samuel Agyei , Novignon Jacob , Amon Samuel , Dwomoh Duah , Aikins Moses 
Published: May 2023

AbstractBackgroundMalaria remains a common course of morbidity in many sub-Saharan African countries. While treatment options have improved in recent times, inappropriate prescription seems conventional among providers, increasing the burden on patients and society. This study examined the cost of inappropriate prescriptions for uncomplicated malaria treatment in Ghana.MethodsThis study used retrospective data collected from January to December 2016 in 27 selected facilities, under different ownership in three regions of the country, mainly Volta, Upper East and Brong Ahafo. Stratified random sampling technique was used to extract 1625 outpatient folders of patients diagnosed and treated for malaria. Two physicians independently reviewed patient folders according to the stated diagnoses. Malaria prescriptions were described as inappropriate when they do not adhere to the standard treatment guidelines. The economic cost was mainly treatment cost which was sourced as medication cost. Total and average costs for country were calculated using sample estimates and the total number of uncomplicated malaria cases that received inappropriate prescriptions.ResultsThe study revealed that patients received an average of two prescriptions per malaria episode. Artemether-lumefantrine (AL) was the major malaria medication (79.5%) prescribed to patients. Other medications usually antibiotics and vitamins and minerals were included in the prescription. More than 50% of prescribers did not follow the guidelines for prescribing medications to clients. By facility type, inappropriate prescription was high in the CHPS compounds (59.1%) and by ownership, government (58.3%), private (57.5%) and mission facilities (50.7%). Thus, about 55% of malaria prescriptions were evaluated as inappropriate during the review period, which translates into economic cost of approximately US$4.52 million for the entire country in 2016. The total cost of inappropriate prescription within the study sample was estimated at US$1,088.42 while the average cost was US$1.20.ConclusionInappropriate prescription for malaria is a major threat to malaria management in Ghana. It presents a huge economic burden to the health system. Training and strict enforcement of prescribers’ adherence to the standard treatment guideline is highly recommended.
The mediating effect of food choice upon associations between adolescent health-related quality of life and physical activity, social media use and abstinence from alcohol
Authors: Davison Jenny , Bunting Brendan , Stewart-Knox Barbara 
Published: May 2023

Abstract
Background
Understanding how health-related quality of life (HRQoL) is related to lifestyle factors during adolescence is crucial to effective health promotion. The aim of this analysis was to identify associations between HRQoL and lifestyle and to determine the degree to which they are mediated by food choices in adolescents.

Methods
The Wellbeing in Schools (NI) survey (N = 1609; 13–14 years) assessed HRQoL using the Kidscreen52. Food choice was assessed by Food Frequency Questionnaire (FFQ) and physical activity was assessed using the Physical Activity Questionnaire for Adolescents (PAQ-A). Social media and alcohol abstinence were self-reported.

Results
Path analysis indicated that fruit and vegetable intake was associated with higher HRQoL on dimensions of moods and emotions, parent relations and home life, financial resources, and social support and peers. Bread and diary intake was related to higher physical wellbeing. Protein was associated with higher psychological wellbeing, moods and emotions, self-perception, parent relations and home life, financial resources, and lower social support and peers. Junk food was related to lower moods and emotions. Males had higher psychological wellbeing, moods and emotions, parental relations and home life. Females had higher self-perception, autonomy, and social support and peers. Greater physical activity explained higher HRQoL on all dimensions. Less social media was associated with higher psychological wellbeing, moods and emotions, self-perception, parent relations and home life, and school environment. Alcohol abstinence was associated with higher physical wellbeing, psychological wellbeing, moods and emotions, self-perception, parent relations and home life, and school environment dimensions.

Conclusion
Intervention to promote HRQoL in adolescents should consider food choices whilst encouraging physical activity, discouraging social media and deterring alcohol, and targeting boys and girls separately.
The use of adjuvant chemotherapy is not associated with recurrence or cancer-specific death following curative resection for stage III rectal cancer: a competing risks analysis
Authors: Ng Kheng-Seong , Chan Charles , Rickard Matthew John Francis Xavier , Keshava Anil , Stewart Peter , Chapuis Pierre Henri 
Published: May 2023

Abstract
Background
The role of adjuvant chemotherapy (AC) in stage III rectal cancer (RC) has been argued based on evidence from its use in colon cancer. Previous trials have analysed disease-free and overall survivals as endpoints, rather than disease recurrence. This study compares the competing risks incidences of recurrence and cancer-specific death between patients who did and did not receive AC for stage III RC.

Methods
Consecutive patients who underwent a potentially curative resection for stage III RC (1995–2019) at Concord Hospital, Sydney, Australia, were studied. AC was considered following multidisciplinary discussion. Primary outcome measures were the competing risks incidences of disease recurrence and cancer-specific death. Associations between these outcomes and use of AC (and other variables) were tested by regression modelling.

Results
Some 338 patients (213 male, mean age 64.4 years [SD12.7]) were included. Of these, 208 received AC. The use of AC was associated with resection year (adjusted OR [aOR] 1.74, 95%CI 1.27–2.38); age ≥75 years (aOR0.04, 95%CI 0.02–0.12); peripheral vascular disease (aOR0.08, 95%CI 0.01–0.74); and postoperative abdomino-pelvic abscess (aOR0.23, 95%CI 0.07–0.81). One hundred fifty-seven patients (46.5%) were diagnosed with recurrence; death due to RC occurred in 119 (35.2%). After adjustment for the competing risk of non-cancer death, neither recurrence nor RC-specific death was associated with AC (HR0.97, 95%CI 0.70–1.33 and HR0.72, 95%CI 0.50–1.03, respectively).

Conclusion
This study found no significant difference in either recurrence or cancer-specific death between patients who did and did not receive AC following curative resection for stage III RC.
Comparison of clinical efficacy and surgical safety among three bone graft modalities in spinal tuberculosis: a network meta-analysis
Authors: Li Jian , Qin Xiuyu , Wang Jiani , Yang Wangzhe , Bai Junjun , Lv Jia 
Published: May 2023

Abstract
Background
Autogenous granular bone graft (AG), autogenous massive bone graft (AM), and titanium mesh bone graft (TM) are the three commonly utilized bone implant methods for spinal tuberculosis. However, the gold standard is still controversial. Therefore, this study aimed to compare the clinical efficacy and surgical safety of three primary bone graft modalities.

Methods
For systematic literature review, several databases, including PubMed, Embase, and Web of Science, were searched up to December 2022. Stata (version 14.0) was employed for data analysis.

Results
Our network meta-analysis included 517 patients from 7 articles whose qualities are acceptable based on our quality assessment criteria. In direct comparison, AG was associated with a shorter operation time (MD = 73.51; CI 30.65–116.37) and a lesser blood loss (MD = 214.30; CI 7.17–421.44) than AM. TM had fewer loss of Cobb angle than AG (MD = 1.45; CI 0.13–2.76) and AM (MD = 1.21; CI 0.42–1.99). Compared with AG, TM (MD = 0.96; CI 0.06–1.87) was related to a shorter bone graft fusion time. In indirect comparison, for the clinical parameters, the rank of CRP (from best to worst) was as follows: TM (58%) > AM (27%) > AG (15%), the rank of ESR (from best to worst) was as follows: AG (61%) > AM (21%) > TM (18%), and the rank of VAS (from best to worst) was as follows: AG (65%) > TM (33%) > AM (2%). In the aspect of surgical data, what is noteworthy is that AG showed less blood loss [AG (93%) > TM (6%) > AM (1%)], operative time [AG (97%) > TM (3%) > AM (0)], and complications [AG (75%) > TM (21%) > AM (4%)] than AM and TM. As for imaging parameters, the rank of the loss of Cobb angle (from best to worst) was as follows: TM (99%) > AM (1%) > AG (0). Moreover, TM showed a shorter bone graft fusion time than AM and AG: TM (96%) > AM (3%) > AG (1%).

Conclusions
The results indicated that AG might be the optional treatment for spinal tuberculosis owing to the outcomes of surgical safety. Moreover, TM is another right choice which can significantly reduce the loss of Cobb angle and shorten bone graft fusion time with long‐term follow‐up.
Three-dimensional multifrequency magnetic resonance elastography improves preoperative assessment of proliferative hepatocellular carcinoma
Authors: Liu Guixue , Ma Di , Wang Huafeng , Zhou Jiahao , Shen Zhehan , Yang Yuchen , Chen Yongjun , Sack Ingolf , Guo Jing , Li Ruokun , Yan Fuhua 
Published: May 2023

Abstract
Background
To investigate the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE).

Methods
This prospective study included 121 patients with 124 HCCs as training cohort, and validation cohort included 33 HCCs. They all underwent preoperative conventional magnetic resonance imaging (MRI) and tomoelastography based on 3D multifrequency MRE. Viscoelastic parameters of the tumor and liver were quantified as shear wave speed (c, m/s) and loss angle (φ, rad), representing stiffness and fluidity, respectively. Five MRI features were evaluated. Multivariate logistic regression analyses were used to determine predictors of proliferative HCC to construct corresponding nomograms.

Results
In training cohort, model 1 (Combining cirrhosis, hepatitis virus, rim APHE, peritumoral enhancement, and tumor margin) yielded an area under the curve (AUC), sensitivity, specificity, accuracy of 0.72, 58.73%,78.69%, 67.74%, respectively. When adding MRE properties (tumor c and tumor φ), established model 2, the AUC increased to 0.81 (95% CI 0.72–0.87), with sensitivity, specificity, accuracy of 71.43%, 81.97%, 75%, respectively. The C-index of nomogram of model 2 was 0.81, showing good performance for proliferative HCC. Therefore, integrating tumor c and tumor φ can significantly improve the performance of preoperative diagnosis of proliferative HCC (AUC increased from 0.72 to 0.81, p = 0.012). The same finding was observed in the validation cohort, with AUC increasing from 0.62 to 0.77 (p = 0.021).

Conclusions
Proliferative HCC exhibits low stiffness and high fluidity. Adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC.

Critical relevance statement
We investigated the viscoelastic signatures of proliferative hepatocellular carcinoma (HCC) using three-dimensional (3D) magnetic resonance elastography (MRE), and find that adding MRE properties (tumor c and tumor φ) can improve performance of conventional MRI for preoperative diagnosis of proliferative HCC.

Graphical Abstract