bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human-centered design process and solutions to promote malaria testing and treatment seeking behavior in Guyana hinterlands
Authors: Yan Shirley D. , Simpson Joann , Mitchum Lyndsey , Orkis Jennifer , Davis TrishAnn , Wilson Sean , Trotman Neil , Imhoff Helen , Cox Horace , Hunter Gabrielle , Olapeju Bolanle , Adams Camille , Storey J. Douglas 
Published: December 2021

Abstract
Background
Malaria is a persistent public health challenge among miners and other hard-to-reach populations in Guyana’s hinterland, specifically in Regions 1, 7, 8, and 9. Despite an overall decrease in malaria prevalence throughout Guyana, it remains common among mining populations whose work conditions both contribute toward malaria transmission and make it difficult to seek timely, Ministry of Health (MoH) approved malaria testing and treatment services. In an effort to develop innovative approaches to address this public health challenge, an interdisciplinary team of public health professionals, designers, and mining organizations collaborated using a human-centered design (HCD) process facilitated by the USAID-funded Breakthrough ACTION Guyana project in partnership with the MoH.

Methods
This paper describes two phases: [1] Define and [2] Design & Test. In the Define phase, following a literature review, we conducted 108 qualitative interviews with miners, camp managers, trained malaria testers, health workers, and other key stakeholders to understand experiences and challenges when seeking malaria testing and treatment services. These interviews were synthesized into 11 insights on issues such as risk perception, malaria knowledge, preventive behaviors, traditional and self-treatment, adherence to the correct treatment, testing, and coordination and communication gaps. From these insights, during the Design & Test phase, we developed 33 “How might we…?” questions which led to 792 ideas, of which eight emergent concepts were prototyped and refined in the field with 145 miners, camp managers, and stakeholders.

Results
The five final prototypes included: “Little Mosquito, Big Problem” social behavior change campaign; rapid counseling cards; branded malaria testing and treatment services; innovations in treatment adherence; and a participants, content, and logistics approach.

Conclusion
When applying HCD to public health issues, there are both opportunities and challenges to reconcile gaps that may exist between the two disciplines. However, HCD provides additional tools and mindsets to generatively work with migrant and mobile mining communities to encourage malaria testing and treatment services.
Occupational risk factors for meniscal lesions: a systematic review and meta-analysis
Authors: Bahns Carolin , Bolm-Audorff Ulrich , Seidler Andreas , Romero Starke Karla , Ochsmann Elke 
Published: December 2021

AbstractBackgroundMeniscal lesions are common and are associated with the development of knee osteoarthritis. Knee-straining activities at work such as kneeling or squatting cause high biomechanical stresses on the knee joints that can lead to acute or chronic injuries. The objective of this systematic review is to update the evidence on the potential relationship between occupational risk factors and meniscal lesions.MethodsWe searched the Medline, Embase and Web of Science databases until August 2021 to identify epidemiological observational studies on the association between occupational risk factors and meniscal lesions. Study selection, data extraction and risk of bias assessment were performed independently by two reviewers. Effect measures were extracted from individual studies and pooled with random effects meta-analysis. Heterogeneity analyses were conducted. We used GRADE (Grades of Recommendations, Assessment, Development and Evaluation) to assess the overall quality of evidence.ResultsThe database search resulted in 11,006 references, and 46 additional studies were identified through hand search. Twenty-two studies (represented in 25 publications) met the predefined eligibility criteria and nine records were included in the meta-analysis. There was only one study with an overall low risk of bias. Significant associations between occupational risk factors and the development of meniscal lesions were found for kneeling (effect size (ES) 2.15, 95% CI 1.67–2.76), squatting (ES 2.01, 95% CI 1.34–3.03), climbing stairs (ES 2.28, 95% CI 1.58–3.30), lifting and carrying weights ≥ 10 kg (ES 1.63, 95% CI 1.35–1.96), lifting and carrying weights ≥ 25 kg (ES 1.56, 95% CI 1.08–2.24), playing football on a professional level (ES 5.22, 95% CI 3.24–8.41), working as a hard coal miner (ES 5.23, 95% CI 2.16–12.69) and floor layers (ES 1.99, 95% CI 1.43–2.78). The overall quality of evidence according GRADE was moderate to low.ConclusionWe found consistent evidence of an increased risk of meniscal lesions by occupational knee-straining exposures. Our findings are important for the development of preventive strategies to reduce work-related knee disorders and work absence.Trial registrationPROSPERO (registration no.CRD42020196279).
Polymicrobial synergy stimulates Porphyromonas gingivalis survival and gingipain expression in a multi-species subgingival community
Authors: Davies Julia R. , Kad Trupti , Neilands Jessica , Kinnby Bertil , Prgomet Zdenka , Bengtsson Torbjörn , Khalaf Hazem , Svensäter Gunnel 
Published: December 2021

Abstract
Background
Dysbiosis in subgingival microbial communities, resulting from increased inflammatory transudate from the gingival tissues, is an important factor in initiation and development of periodontitis. Dysbiotic communities are characterized by increased numbers of bacteria that exploit the serum-like transudate for nutrients, giving rise to a proteolytic community phenotype. Here we investigate the contribution of interactions between members of a sub-gingival community to survival and development of virulence in a serum environment—modelling that in the subgingival pocket.

Methods
Growth and proteolytic activity of three Porphyromonas gingivalis strains in nutrient broth or a serum environment were assessed using A600 and a fluorescent protease substrate, respectively. Adherence of P. gingivalis strains to serum-coated surfaces was studied with confocal microscopy and 2D-gel electrophoresis of bacterial supernatants used to investigate extracellular proteins. A model multi-species sub-gingival community containing Fusobacterium nucleatum, Streptococcus constellatus, Parvimonas micra with wild type or isogenic mutants of P. gingivalis was then created and growth and proteolytic activity in serum assessed as above. Community composition over time was monitored using culture techniques and qPCR.

Results
The P. gingivalis strains showed different growth rates in nutrient broth related to the level of proteolytic activity (largely gingipains) in the cultures. Despite being able to adhere to serum-coated surfaces, none of the strains was able to grow alone in a serum environment. Together in the subgingival consortium however, all the included species were able to grow in the serum environment and the community adopted a proteolytic phenotype. Inclusion of P. gingivalis strains lacking gingipains in the consortium revealed that community growth was facilitated by Rgp gingipain from P. gingivalis.

Conclusions
In the multi-species consortium, growth was facilitated by the wild-type and Rgp-expressing strains of P. gingivalis, suggesting that Rgp is involved in delivery of nutrients to the whole community through degradation of complex protein substrates in serum. Whereas they are constitutively expressed by P. gingivalis in nutrient broth, gingipain expression in the model periodontal pocket environment (serum) appeared to be orchestrated through signaling to P. gingivalis from other members of the community, a phenomenon which then promoted growth of the whole community.
Relationship between DMFT index and number of pregnancies: a cross-sectional study on enrollment phase of the Tabari Cohort Study
Authors: Gorji Nadia Elyassi , Nasiri Pegah , Shafaroudi Ali Malekzadeh , Shahhosseini Zohreh , Hamzehgardeshi Zeinab , Moosazadeh Mahmood 
Published: December 2021

Abstract
Background
People of all age and gender groups are at risk of dental diseases; however, some groups, such as pregnant women, are more vulnerable than others due to their specific physiological situations. The protection of maternal and fetal is critical. Therefore, the present study intended to investigate the relationship between the Decayed, Missing, and Filled Teeth (DMFT) index and the number of pregnancies.

Methods
The present cross-sectional study was performed using the Tabari Cohort Study (T.C.S.) data. Data of 5,496 women enrolled in the T.C.S. were included in the study. After obtaining the approval of the Ethics Committee, the related data on the variables of age, age at the first pregnancy, number of pregnancies, total number of teeth at the time of examination, number of DMFT, employment status, socioeconomic status, educational level, residence location, body mass index, and the status of diabetes mellitus, hypertension, and cardiovascular diseases were extracted. Finally, data analysis was performed in the STATA software (version 14).

Results
The mean DMFT index in women with 1, 2, 3, 4, 5, 6, and more than six pregnancies were obtained at 12.74 ± 7.11, 13.09 ± 7.06, 14.80 ± 7.81, 17.07 ± 8.11, 19.82 ± 9.02, 22.89 ± 8.98, and 26.17 ± 8.01, respectively (P < 0.001). Using the multivariate linear regression and adjusting the effect of potential confounding variables, it was found that the DMFT index increased by 34% for each unit increase in the number of pregnancies (β = 0.34, P < 0.001).

Conclusions
According to our results, there was a significant relationship between the DMFT index and the number of pregnancies. The DMFT index was increased with an increased number of pregnancies. Therefore, oral healthcare promotion should receive special attention in healthcare planning and related policies by raising awareness and providing easy access to dental services for women of childbearing age, especially pregnant women.
Maintenance of low driving pressure in patients with early acute respiratory distress syndrome significantly affects outcomes
Authors: Chang Hui-Chun , Ho Chung-Han , Kung Shu-Chen , Chen Wan-Lin , Wang Ching-Min , Cheng Kuo-Chen , Liu Wei-Lun , Hsu Han-Shui 
Published: December 2021

Abstract
Background
Driving pressure (∆P) is an important factor that predicts mortality in acute respiratory distress syndrome (ARDS). We test the hypothesis that serial changes in daily ΔP rather than Day 1 ΔP would better predict outcomes of patients with ARDS.

Methods
This retrospective cohort study enrolled patients admitted to five intensive care units (ICUs) at a medical center in Taiwan between March 2009 and January 2018 who met the criteria for ARDS and received the lung-protective ventilation strategy. ∆P was recorded daily for 3 consecutive days after the diagnosis of ARDS, and its correlation with 60-day survival was analyzed.

Results
A total of 224 patients were enrolled in the final analysis. The overall ICU and 60-day survival rates were 52.7% and 47.3%, respectively. ∆P on Days 1, 2, and 3 was significantly lower in the survival group than in the nonsurvival group (13.8 ± 3.4 vs. 14.8 ± 3.7, p = 0.0322, 14 ± 3.2 vs. 15 ± 3.5, p = 0.0194, 13.6 ± 3.2 vs. 15.1 ± 3.4, p = 0.0014, respectively). The patients were divided into four groups according to the daily changes in ∆P, namely, the low ∆P group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P < 14 cmH2O), decrement group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P < 14 cmH2O), high ∆P group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O), and increment group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O). The 60-day survival significantly differed among the four groups (log-rank test, p = 0.0271). Compared with the low ΔP group, patients in the decrement group did not have lower 60-day survival (adjusted hazard ratio 0.72; 95% confidence interval [CI] 0.31–1.68; p = 0.4448), while patients in the increment group had significantly lower 60-day survival (adjusted hazard ratio 1.96; 95% CI 1.11–3.44; p = 0.0198).

Conclusions
Daily ∆P remains an important predicting factor for survival in patients with ARDS. Serial changes in daily ΔP might be more informative than a single Day 1 ΔP value in predicting survival of patients with ARDS.
Delta radiomics analysis of Magnetic Resonance guided radiotherapy imaging data can enable treatment response prediction in pancreatic cancer
Authors: Tomaszewski M. R. , Latifi K. , Boyer E. , Palm R. F. , El Naqa I. , Moros E. G. , Hoffe S. E. , Rosenberg S. A. , Frakes J. M. , Gillies R. J. 
Published: December 2021

Abstract
Background
Magnetic Resonance Image guided Stereotactic body radiotherapy (MRgRT) is an emerging technology that is increasingly used in treatment of visceral cancers, such as pancreatic adenocarcinoma (PDAC). Given the variable response rates and short progression times of PDAC, there is an unmet clinical need for a method to assess early RT response that may allow better prescription personalization. We hypothesize that quantitative image feature analysis (radiomics) of the longitudinal MR scans acquired before and during MRgRT may be used to extract information related to early treatment response.

Methods
Histogram and texture radiomic features (n = 73) were extracted from the Gross Tumor Volume (GTV) in 0.35T MRgRT scans of 26 locally advanced and borderline resectable PDAC patients treated with 50 Gy RT in 5 fractions. Feature ratios between first (F1) and last (F5) fraction scan were correlated with progression free survival (PFS). Feature stability was assessed through region of interest (ROI) perturbation.

Results
Linear normalization of image intensity to median kidney value showed improved reproducibility of feature quantification. Histogram skewness change during treatment showed significant association with PFS (p = 0.005, HR = 2.75), offering a potential predictive biomarker of RT response. Stability analyses revealed a wide distribution of feature sensitivities to ROI delineation and was able to identify features that were robust to variability in contouring.

Conclusions
This study presents a proof-of-concept for the use of quantitative image analysis in MRgRT for treatment response prediction and providing an analysis pipeline that can be utilized in future MRgRT radiomic studies.
WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer
Authors: Menck Kerstin , Heinrichs Saskia , Wlochowitz Darius , Sitte Maren , Noeding Helen , Janshoff Andreas , Treiber Hannes , Ruhwedel Torben , Schatlo Bawarjan , von der Brelie Christian , Wiemann Stefan , Pukrop Tobias , Beißbarth Tim , Binder Claudia , Bleckmann Annalen 
Published: December 2021

Abstract
Background
Breast cancer has been associated with activation of the WNT signaling pathway, although no driver mutations in WNT genes have been found yet. Instead, a high expression of the alternative WNT receptor ROR2 was observed, in particular in breast cancer brain metastases. However, its respective ligand and downstream signaling in this context remained unknown.

Methods
We modulated the expression of ROR2 in human breast cancer cells and characterized their gene and protein expression by RNA-Seq, qRT-PCR, immunoblots and reverse phase protein array (RPPA) combined with network analyses to understand the molecular basis of ROR2 signaling in breast cancer. Using co-immunoprecipitations, we verified the interaction of ROR2 with the identified ligand, WNT11. The functional consequences of WNT11/ROR2 signaling for tumor cell aggressiveness were assessed by microscopy, impedance sensing as well as viability and invasion assays. To evaluate the translational significance of our findings, we performed gene set enrichment, expression and survival analyses on human breast cancer brain metastases.

Results
We found ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. ROR2 overexpression induced a BRCAness-like phenotype in a cell-context specific manner and rendered cells resistant to PARP inhibition. High levels of ROR2 were furthermore associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. On a molecular level, ROR2 overexpression upregulated several non-canonical WNT ligands, in particular WNT11. Co-immunoprecipitation confirmed that WNT11 indeed interacts with the cysteine-rich domain of ROR2 and triggers its invasion-promoting signaling via RHO/ROCK. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells.

Conclusions
Taken together, our study revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligand, WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.
Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study
Authors: Breda Luciana , Carbone Ilaria , Casciato Isabella , Gentile Cristina , Grasso Eleonora Agata , di Donato Giulia , Chiarelli Francesco , Verrotti Alberto 
Published: December 2021

Abstract
Background
A retrospective study was conducted in order to investigate and describe the characteristics of Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schӧnlein purpura, in the paediatric population of a community-based healthcare delivery system in the Italian region of Abruzzo.

Methods
This is a population-based retrospective chart review of the diagnosis of IgAV in children ages 0 to 18, admitted to the Department of Paediatrics of Chieti and Pescara between 1 January 2000 and 31 December 2016. All children enrolled presented with clinical symptoms and laboratory findings and met the EULAR/PRINTO/PRES 2008 criteria.

Results
Two-hundred-eight children met the criteria for IgAV, with the highest incidence reported among children below 7-years of age. A correlation with recent infections was found in 64% of the cohort; the onset was more frequently during the winter and fall. Purpura had a diffuse distribution in the majority of patients; joint impairment was the second most frequent symptom (43%), whereas the gastrointestinal tract was involved in 28% of patients.

Conclusions
Hereby, we confirm the relative benignity of IgAV in a cohort of Italian children; with regards to renal involvement, we report a better outcome compared to other studies. However, despite the low rate of renal disease, we observed a wide use of corticosteroids, especially for the treatment of persistent purpura.
Plastidial wax ester biosynthesis as a tool to synthesize shorter and more saturated wax esters
Authors: Vollheyde Katharina , Hornung Ellen , Herrfurth Cornelia , Ischebeck Till , Feussner Ivo 
Published: December 2021

AbstractBackgroundWax esters (WE) are neutral lipids that consist of a fatty alcohol esterified to a fatty acid. WE are valuable feedstocks in industry for producing lubricants, coatings, and cosmetics. They can be produced chemically from fossil fuel or plant-derived triacylglycerol. As fossil fuel resources are finite, the synthesis of WE in transgenic plants may serve as an alternative source. As chain length and desaturation of the alcohol and acyl moieties determine the physicochemical properties of WE and their field of application, tightly controlled and tailor-made WE synthesis in plants would be a sustainable, beneficial, and valuable commodity. Here, we report the expression of ten combinations of WE producing transgenes inArabidopsis thaliana. In order to study their suitability for WE productionin planta, we analyzed WE amount and composition in the transgenic plants.ResultsThe transgenes consisted of different combinations of aFATTY ACYL-COA/ACP REDUCTASE(FAR) and twoWAX SYNTHASES/ACYL-COA:DIACYLGLYCEROLO-ACYLTRANSFERASES(WSD), namelyWSD2andWSD5from the bacteriumMarinobacter aquaeoleoi. We generated constructs with and without plastidial transit peptides to access distinct alcohol and acyl substrate pools withinA. thalianacells. We observed WE formation with plastid and cytosol-localized FAR and WSD in seeds. A comparative WE analysis revealed the production of shorter and more saturated WE by plastid-localized WE biosynthesis compared to cytosolic WE synthesis.ConclusionsA shift of WE formation into seed plastids is a suitable approach for tailor-made WE production and can be used to synthesize WE that are mainly derived from mid- and long-chain saturated and monounsaturated substrates.
Improved methanol tolerance of Rhizomucor miehei lipase based on N‑glycosylation within the α-helix region and its application in biodiesel production
Authors: Tian Miao , Yang Lingmei , Wang Zhiyuan , Lv Pengmei , Fu Junying , Miao Changlin , Li Ming , Liu Tao , Luo Wen 
Published: December 2021

Abstract
Background
Liquid lipases are widely used to convert oil into biodiesel. Methanol-resistant lipases with high catalytic activity are the first choice for practical production. Rhizomucor miehei lipase (RML) is a single-chain α/β-type protein that is widely used in biodiesel preparation. Improving the catalytic activity and methanol tolerance of RML is necessary to realise the industrial production of biodiesel.

Results
In this study, a semi-rational design method was used to optimise the catalytic activity and methanol tolerance of ProRML. After N-glycosylation modification of the α-helix of the mature peptide in ProRML, the resulting mutants N218, N93, N115, N260, and N183 increased enzyme activity by 66.81, 13.54, 10.33, 3.69, and 2.39 times than that of WT, respectively. The residual activities of N218 and N260 were 88.78% and 86.08% after incubation in 50% methanol for 2.5 h, respectively. In addition, the biodiesel yield of all mutants was improved when methanol was added once and reacted for 24 h with colza oil as the raw material. N260 and N218 increased the biodiesel yield from 9.49% to 88.75% and 90.46%, respectively.

Conclusions
These results indicate that optimising N-glycosylation modification in the α-helix structure is an effective strategy for improving the performance of ProRML. This study provides an effective approach to improve the design of the enzyme and the properties of lipase mutants, thereby rendering them suitable for industrial biomass conversion.
Congenital ureterovaginal fistula: a rare case of single-system ectopic ureter with ipsilateral ectopic kidney managed by vaginal approach: a case report
Authors: Amenu Demisew , Asmare Andebet , Siraj Ahmed 
Published: December 2021

Abstract
Background
Diagnosing urinary incontinence from organic causes such as ectopic ureter is particularly important because of the potential for cure by surgical correction. The prevalence of ectopic ureter is uncertain because many are asymptomatic and the diagnosis is usually overlooked. Eighty percent of ectopic ureters in females are often associated with duplex kidney. However, an ectopic ureter draining a single-system ectopic dysplastic/atrophic but functioning kidney is rare, especially in females. The overall long-term continence rate after successful correction of ectopic ureter is satisfactory.

Case presentation
This case is reported to highlight a rare situation, where a 22-year-old nulligravid Ethiopian women presented with a complaint of continuous wetting of her underwear since childhood, but she had normal voiding pattern. Localized right pelvic kidney ultrasound and computed tomography scan with contrast revealed right ectopic ureter and atrophied ipsilateral pelvic kidney with good function. Surgical reimplantation through vaginal approach was performed, and the outcome was good. The patient’s subsequent follow-ups were uneventful.

Conclusion
An extramural vaginal ectopic ureter is better accessed through transvaginal approach than abdominal, especially when it is associated with pelvic ectopic kidney. This modified approach is less invasive and has lower morbidity and better success rate than a transabdominal approach.